NCBI Conserved Domain Search

First immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.

Pssm-ID: 409547 Cd Length: 99 Bit Score: 217.28 E-value: 1.06e-65

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223   38 GPVFLKEPTNRIDFSNSTGAEIECKASGNPMPEIIWIRSDGTAVGDVPGLRQISSDGKLVFPPFRAEDYRQEVHAQVYAC 117
Cdd:cd20955     1 GPVFLKEPTNRIDFSNSTGAEIECKASGNPMPEIIWIRSDGTAVGDVPGLRQISSDGKLVFPPFRAEDYRQEVHAQVYAC 80

                          90
                  ....*....|....*....
gi 386767223  118 LARNQFGSIISRDVHVRAV 136
Cdd:cd20955    81 LARNQFGSIISRDVHVRAV 99

Down syndrome cell adhesion molecule C terminal; This domain family is found in eukaryotes, and is approximately 120 amino acids in length. The family is found in association with pfam00047, pfam07679, pfam00041. The Down syndrome cell adhesion molecule (Dscam) belongs to a family of cell membrane molecules involved in the differentiation of the nervous system. This is the C terminal cytoplasmic tail region of Dscam.

Pssm-ID: 463546 Cd Length: 118 Bit Score: 205.64 E-value: 2.09e-61

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  1874 PGPEYDDPANCApEEDQYGSQYGGPYGQPYDHYGSRGSMGRRSIGSARN-PGNGSPEPPPPPPRNHDMSNSSFNDSKESN 1952
Cdd:pfam12355    3 PGPEYDDPANCA-EDDQYGSQYSGPYGAPYDHYGSRGSLGRRSVGSARNlPGNGSPEPPPPPPRNHDVSNSSFNDSKESN 81

                           90       100       110
                   ....*....|....*....|....*....|....*..
gi 386767223  1953 EISEAECDRDHGPRGNYGAVKRSPQPKDQRTTEEMRK 1989
Cdd:pfam12355   82 EISEAECDRDHLVNRNYGVGIRTMNSKDGMSTEEMRK 118

Seventh immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the seventh immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.

Pssm-ID: 409546 [Multi-domain] Cd Length: 96 Bit Score: 180.59 E-value: 7.07e-53

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  717 PPRWILEPTDKAFAQGSDAKVECKADGFPKPQVTWKKAVGDTPGEYKDLKKSDNIRVEE-GTLHVDNIQKTNEGYYLCEA 795
Cdd:cd20954     1 PPRWIVEPVDANVAAGQDVMLHCQADGFPTPTVTWKKATGSTPGEYKDLLYDPNVRILPnGTLVFGHVQKENEGHYLCEA 80

                          90
                  ....*....|....*.
gi 386767223  796 INGIGSGLSAVIMISV 811
Cdd:cd20954    81 KNGIGSGLSKVIFLKV 96

Fourth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.

Pssm-ID: 409548 [Multi-domain] Cd Length: 96 Bit Score: 172.36 E-value: 5.11e-50

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  431 PPVIRQAFQEETMEPGPSVFLKCVAGGNPTPEISWELDGKKIANNDRYQVGQYVTVNGDVVSYLNITSVHANDGGLYKCI 510
Cdd:cd20956     1 APVLLETFSEQTLQPGPSVSLKCVASGNPLPQITWTLDGFPIPESPRFRVGDYVTSDGDVVSYVNISSVRVEDGGEYTCT 80

                          90
                  ....*....|....*.
gi 386767223  511 AKSKVGVAEHSAKLNV 526
Cdd:cd20956    81 ATNDVGSVSHSARINV 96

Second immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. DSCAM is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.

Pssm-ID: 409545 Cd Length: 95 Bit Score: 171.57 E-value: 8.84e-50

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 386767223  267 SFAMLCQAQAFPLPIMRWYKFIEGTTRKQAVVLNDRVKQVSGTLIIKDAVVEDSGKYLCVVNNSVGGESVETVLTV 342
Cdd:cd20953    20 SIALLCPAQGYPAPSFRWYKFIEGTTRKQAVVLNDRVKQVSGTLIIKDAVVEDSGKYLCVVNNSVGGESVETVLTV 95

Fifth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fifth immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.

Pssm-ID: 409550 [Multi-domain] Cd Length: 89 Bit Score: 165.05 E-value: 1.47e-47

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  530 PYIRQMEKKAIVAGETLIVTCPVAGYPIDSIVWERDNRALPINRKQKVFPNGTLIIENVERNSDQATYTCVAKNQEGYSA 609
Cdd:cd20958     2 PFIRPMGNLTAVAGQTLRLHCPVAGYPISSITWEKDGRRLPLNHRQRVFPNGTLVIENVQRSSDEGEYTCTARNQQGQSA 81


                  ....*...
gi 386767223  610 RGSLEVQV 617
Cdd:cd20958    82 SRSVFVKV 89

Third immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the Constant 2 (C2)-set of IgSF domains; The members here are composed of the third immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. This group belongs to the C2-set of IgSF domains, having A, B, and E strands in one beta-sheet and A', G, F, C, and C' in the other. Unlike other Ig domain sets, the C2-set lacks the D strand.

Pssm-ID: 409549 [Multi-domain] Cd Length: 88 Bit Score: 148.45 E-value: 9.72e-42

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  345 PLSAKIDPPTQTVDFGRPAVFTCQYTGNPIKTVSWMKDGKAIGHS-------EPVLRIESVKKEDKGMYQCFVRNDQESA 417
Cdd:cd20957     1 PLSATIDPPVQTVDFGRTAVFNCSVTGNPIHTVLWMKDGKPLGHSsrvqilsEDVLVIPSVKREDKGMYQCFVRNDGDSA 80


                  ....*...
gi 386767223  418 EASAELKL 425
Cdd:cd20957    81 QATAELKL 88

Sixth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the sixth immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.

Pssm-ID: 409551 Cd Length: 94 Bit Score: 111.82 E-value: 7.42e-29

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  620 PPQIRPFDFGDEASNSGETMGIQCTVIKGDLPINITWVLNNHTLnSGDLDVVIGRMSSKSSTLNIDYIAAEHRGVYTCLA 699
Cdd:cd20959     1 PPRIIPFAFGEGAAQVGMRAQLHCGVPGGDLPLNIRWTLDGQPI-SDDLGITVSRLGRRSSILSIDSLEASHAGNYTCHA 79

                          90
                  ....*....|....*
gi 386767223  700 RNQAGESSYSAELKV 714
Cdd:cd20959    80 RNSAGSASYTAPLTV 94

Fibronectin type 3 domain [General function prediction only];

Pssm-ID: 442628 [Multi-domain] Cd Length: 603 Bit Score: 91.99 E-value: 1.56e-18

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  895 ATNAFGSDDASINMIV---QEVPEMPYALKVLDKSGRSVQLSWAQPydGNSPLDRYIIEfkRSRAS---WSEIDRVIvpg 968
Cdd:COG3401   211 ATDTGGESAPSNEVSVttpTTPPSAPTGLTATADTPGSVTLSWDPV--TESDATGYRVY--RSNSGdgpFTKVATVT--- 283

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  969 hTTEAQVQKLSPATTYNIRIVAENAIGT-SQSSEAVTIITAEEAPSgKPQNIKVEPVNQTTMRVTWKPPPrtewNGEILG 1047
Cdd:COG3401   284 -TTSYTDTGLTNGTTYYYRVTAVDAAGNeSAPSNVVSVTTDLTPPA-APSGLTATAVGSSSITLSWTASS----DADVTG 357

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223 1048 YYVgYKLSNTNSSYVfetinFITEEGKEHNLELQNLRVYTQYSVVIQAFNKIGAGPLSEEEKQFTAEGTPSQPPSDTACT 1127
Cdd:COG3401   358 YNV-YRSTSGGGTYT-----KIAETVTTTSYTDTGLTPGTTYYYKVTAVDAAGNESAPSEEVSATTASAASGESLTASVD 431

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223 1128 TLTSQTIrVGWVSPPLESANGVIKTYKVVYAPSDEWYDETkrhykkTASSDTVLHGLKKYTNYTMQVLATTAGGDGVRSV 1207
Cdd:COG3401   432 AVPLTDV-AGATAAASAASNPGVSAAVLADGGDTGNAVPF------TTTSSTVTATTTDTTTANLSVTTGSLVGGSGASS 504


                  .
gi 386767223 1208 P 1208
Cdd:COG3401   505 V 505

Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein fibronectin. Its tenth fibronectin type III repeat contains an RGD cell recognition sequence in a flexible loop between 2 strands. Approximately 2% of all animal proteins contain the FN3 repeat; including extracellular and intracellular proteins, membrane spanning cytokine receptors, growth hormone receptors, tyrosine phosphatase receptors, and adhesion molecules. FN3-like domains are also found in bacterial glycosyl hydrolases.

Pssm-ID: 238020 [Multi-domain] Cd Length: 93 Bit Score: 77.54 E-value: 7.22e-17

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  914 PEMPYALKVLDKSGRSVQLSWAQPYDGNSPLDRYIIEFKRSRAS-WSEIDRVivPGHTTEAQVQKLSPATTYNIRIVAEN 992
Cdd:cd00063     1 PSPPTNLRVTDVTSTSVTLSWTPPEDDGGPITGYVVEYREKGSGdWKEVEVT--PGSETSYTLTGLKPGTEYEFRVRAVN 78

                          90
                  ....*....|....*
gi 386767223  993 AIGTSQSSEAVTIIT 1007
Cdd:cd00063    79 GGGESPPSESVTVTT 93

Immunoglobulin (Ig) domain of Down Syndrome Cell Adhesion molecule (DSCAM); The members here are composed of the immunoglobulin (Ig) domain of Down Syndrome Cell Adhesion molecule (DSCAM). DSCAM is a cell adhesion molecule expressed largely in the developing nervous system. The gene encoding DSCAM is located at human chromosome 21q22, the locus associated with the intellectual disability phenotype of Down Syndrome. DSCAM is predicted to be the largest member of the IG superfamily. It has been demonstrated that DSCAM can mediate cation-independent homophilic intercellular adhesion.

Pssm-ID: 409398 Cd Length: 101 Bit Score: 74.83 E-value: 7.19e-16

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  826 ARRGEPAVLQCEAKGEKPIGILWNMNNMRLDPKNDNRYTIREEILSTGVMSSLSIKRTERSDSALFTCVATNAFGSDDAS 905
Cdd:cd05735    15 ATKGQKKEMSCTAHGEKPIIVRWEKEDTIINPSEMSRYLVTTKEVGDEVISTLQILPTVREDSGFFSCHAINSYGEDRGI 94


                  ....*..
gi 386767223  906 INMIVQE 912
Cdd:cd05735    95 IQLTVQE 101

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 73.06 E-value: 2.55e-15

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223   432 PVIRQAFQEETMEPGPSVFLKCVAGGNPTPEISWELDGKKIANNDRYQvgqyVTVNGDVVSyLNITSVHANDGGLYKCIA 511
Cdd:pfam07679    1 PKFTQKPKDVEVQEGESARFTCTVTGTPDPEVSWFKDGQPLRSSDRFK----VTYEGGTYT-LTISNVQPDDSGKYTCVA 75

                           90
                   ....*....|....*
gi 386767223   512 KSKVGVAEHSAKLNV 526
Cdd:pfam07679   76 TNSAGEAEASAELTV 90

Fibronectin type 3 domain [General function prediction only];

Pssm-ID: 442628 [Multi-domain] Cd Length: 603 Bit Score: 81.20 E-value: 3.41e-15

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223 1087 TQYSVVIQAFNKIGAGPLSEEeKQFTAEGTPSQPPSDTACTTLTSQTIRVGWVSPPLESANGviktYKVVYAPSDewyDE 1166
Cdd:COG3401   203 TTYYYRVAATDTGGESAPSNE-VSVTTPTTPPSAPTGLTATADTPGSVTLSWDPVTESDATG----YRVYRSNSG---DG 274

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223 1167 TKRHYKKTASSDTVLHGLKKYTNYTMQVLA-TTAGGDGVRSVPIHCQTEPDVPEAPTDVKALVMGNAAILVSWRPPAQPN 1245
Cdd:COG3401   275 PFTKVATVTTTSYTDTGLTNGTTYYYRVTAvDAAGNESAPSNVVSVTTDLTPPAAPSGLTATAVGSSSITLSWTASSDAD 354

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223 1246 giITQYTVYSKAEG-------AETETKTqkvphyqmSFEATELEKNKPYEFWVTASTTIG-EGQQSKSIVAMPSDQVPAK 1317
Cdd:COG3401   355 --VTGYNVYRSTSGggtytkiAETVTTT--------SYTDTGLTPGTTYYYKVTAVDAAGnESAPSEEVSATTASAASGE 424


                  ...
gi 386767223 1318 IAS 1320
Cdd:COG3401   425 SLT 427

Fibronectin type III domain;

Pssm-ID: 394996 [Multi-domain] Cd Length: 85 Bit Score: 72.06 E-value: 5.36e-15

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223   917 PYALKVLDKSGRSVQLSWAQPYDGNSPLDRYIIEFKRSRASWSEIdRVIVPGHTTEAQVQKLSPATTYNIRIVAENAIGT 996
Cdd:pfam00041    3 PSNLTVTDVTSTSLTVSWTPPPDGNGPITGYEVEYRPKNSGEPWN-EITVPGTTTSVTLTGLKPGTEYEVRVQAVNGGGE 81


                   ....
gi 386767223   997 SQSS 1000
Cdd:pfam00041   82 GPPS 85

Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein fibronectin. Its tenth fibronectin type III repeat contains an RGD cell recognition sequence in a flexible loop between 2 strands. Approximately 2% of all animal proteins contain the FN3 repeat; including extracellular and intracellular proteins, membrane spanning cytokine receptors, growth hormone receptors, tyrosine phosphatase receptors, and adhesion molecules. FN3-like domains are also found in bacterial glycosyl hydrolases.

Pssm-ID: 238020 [Multi-domain] Cd Length: 93 Bit Score: 71.76 E-value: 6.81e-15

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223 1014 GKPQNIKVEPVNQTTMRVTWKPPPrtEWNGEILGYYVGYKLSNTNSSYVFEtinfiTEEGKEHNLELQNLRVYTQYSVVI 1093
Cdd:cd00063     2 SPPTNLRVTDVTSTSVTLSWTPPE--DDGGPITGYVVEYREKGSGDWKEVE-----VTPGSETSYTLTGLKPGTEYEFRV 74

                          90
                  ....*....|....*....
gi 386767223 1094 QAFNKIGAGPLSEEEKQFT 1112
Cdd:cd00063    75 RAVNGGGESPPSESVTVTT 93

Fibronectin type III domain;

Pssm-ID: 394996 [Multi-domain] Cd Length: 85 Bit Score: 71.29 E-value: 9.25e-15

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  1014 GKPQNIKVEPVNQTTMRVTWKPPPrtEWNGEILGYYVGYKLSNTNssyvfETINFITEEGKEHNLELQNLRVYTQYSVVI 1093
Cdd:pfam00041    1 SAPSNLTVTDVTSTSLTVSWTPPP--DGNGPITGYEVEYRPKNSG-----EPWNEITVPGTTTSVTLTGLKPGTEYEVRV 73

                           90
                   ....*....|..
gi 386767223  1094 QAFNKIGAGPLS 1105
Cdd:pfam00041   74 QAVNGGGEGPPS 85

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 70.36 E-value: 2.09e-14

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223   815 PEFTEKLRNQTARRGEPAVLQCEAKGEKPIGILWNMNNMRLdpKNDNRYTIREEilstGVMSSLSIKRTERSDSALFTCV 894
Cdd:pfam07679    1 PKFTQKPKDVEVQEGESARFTCTVTGTPDPEVSWFKDGQPL--RSSDRFKVTYE----GGTYTLTISNVQPDDSGKYTCV 74

                           90
                   ....*....|....*.
gi 386767223   895 ATNAFGSDDASINMIV 910
Cdd:pfam07679   75 ATNSAGEAEASAELTV 90

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 69.90 E-value: 2.33e-14

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223   431 PPVIRQAFQEETMEPGPSVFLKCVAGGNPTPEISWELDGKKIANNDryqvgQYVTVNGDVVSYLNITSVHANDGGLYKCI 510
Cdd:pfam13927    1 KPVITVSPSSVTVREGETVTLTCEATGSPPPTITWYKNGEPISSGS-----TRSRSLSGSNSTLTISNVTRSDAGTYTCV 75


                   ..
gi 386767223   511 AK 512
Cdd:pfam13927   76 AS 77

Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein fibronectin. Its tenth fibronectin type III repeat contains an RGD cell recognition sequence in a flexible loop between 2 strands. Approximately 2% of all animal proteins contain the FN3 repeat; including extracellular and intracellular proteins, membrane spanning cytokine receptors, growth hormone receptors, tyrosine phosphatase receptors, and adhesion molecules. FN3-like domains are also found in bacterial glycosyl hydrolases.

Pssm-ID: 238020 [Multi-domain] Cd Length: 93 Bit Score: 68.29 E-value: 1.15e-13

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223 1218 PEAPTDVKALVMGNAAILVSWRPPAQPNGIITQYTVYSKAEGAETETKTQKVPHYQMSFEATELEKNKPYEFWVTASTTI 1297
Cdd:cd00063     1 PSPPTNLRVTDVTSTSVTLSWTPPEDDGGPITGYVVEYREKGSGDWKEVEVTPGSETSYTLTGLKPGTEYEFRVRAVNGG 80

                          90
                  ....*....|.
gi 386767223 1298 GEGQQSKSIVA 1308
Cdd:cd00063    81 GESPPSESVTV 91

Fibronectin type 3 domain [General function prediction only];

Pssm-ID: 442628 [Multi-domain] Cd Length: 603 Bit Score: 76.19 E-value: 1.41e-13

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  978 LSPATTYNIRIVAENAIGTSQSSEAVTIITAEEAPSgKPQNIKVEPVNQTTMRVTWKPPPrtewNGEILGYYVgYKLSNT 1057
Cdd:COG3401   199 IEPGTTYYYRVAATDTGGESAPSNEVSVTTPTTPPS-APTGLTATADTPGSVTLSWDPVT----ESDATGYRV-YRSNSG 272

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223 1058 NSSYV---FETINFITEEGKEHNlelqnlrvyTQYSVVIQAFNKIG-AGPLSEEEKqFTAEGTPSQPPSDTACTTLTSQT 1133
Cdd:COG3401   273 DGPFTkvaTVTTTSYTDTGLTNG---------TTYYYRVTAVDAAGnESAPSNVVS-VTTDLTPPAAPSGLTATAVGSSS 342

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223 1134 IRVGWVSppleSANGVIKTYKVVYAPSDEW-YDETKRHYKKTASSDTvlhGLKKYTNYTMQVLATTAGGD-GVRSVPIHC 1211
Cdd:COG3401   343 ITLSWTA----SSDADVTGYNVYRSTSGGGtYTKIAETVTTTSYTDT---GLTPGTTYYYKVTAVDAAGNeSAPSEEVSA 415

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223 1212 QTEPDVP-EAPTDVKALVMGNAAILVSWRPPAQPNGIITQYTVYSKAEGAEtetktqKVPHYQMSFEATELEKNKPYEFW 1290
Cdd:COG3401   416 TTASAASgESLTASVDAVPLTDVAGATAAASAASNPGVSAAVLADGGDTGN------AVPFTTTSSTVTATTTDTTTANL 489

                         330       340       350
                  ....*....|....*....|....*....|....*...
gi 386767223 1291 VTASTTIGEGQQSKSIVAMPSDQVPAKIASFDDTFTAT 1328
Cdd:COG3401   490 SVTTGSLVGGSGASSVTNSVSVIGASAAAAVGGAPDGT 527

Immunoglobulin (Ig)-like domain of myotilin, palladin, and myopalladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig)-like domain in myotilin, palladin, and myopalladin. Myotilin, palladin, and myopalladin function as scaffolds that regulate actin organization. Myotilin and myopalladin are most abundant in skeletal and cardiac muscle; palladin is ubiquitously expressed in the organs of developing vertebrates and plays a key role in cellular morphogenesis. The three family members each interact with specific molecular partners with all three binding to alpha-actinin; In addition, palladin also binds to vasodilator-stimulated phosphoprotein (VASP) and ezrin, myotilin binds to filamin and actin, and myopalladin also binds to nebulin and cardiac ankyrin repeat protein (CARP). This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409405 [Multi-domain] Cd Length: 91 Bit Score: 66.37 E-value: 5.26e-13

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  432 PVIRQAFQEETMEPGPSVFLKCVAGGNPTPEISWELDGKKIANNDRYQVgqYVTVNGdVVSyLNITSVHANDGGLYKCIA 511
Cdd:cd05744     1 PHFLQAPGDLEVQEGRLCRFDCKVSGLPTPDLFWQLNGKPVRPDSAHKM--LVRENG-RHS-LIIEPVTKRDAGIYTCIA 76

                          90
                  ....*....|....*
gi 386767223  512 KSKVGVAEHSAKLNV 526
Cdd:cd05744    77 RNRAGENSFNAELVV 91

Fifth immunoglobulin (Ig) domain of contactin; The members here are composed of the fifth immunoglobulin (Ig) domain of contactins. Contactins are neural cell adhesion molecules and are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module via contacts between Ig domains 1 and 4, and between Ig domains 2 and 3. Contactin-2 (TAG-1, axonin-1) may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. This group also includes contactin-1 and contactin-5. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-5 is expressed specifically in the rat postnatal nervous system, peaking at about 3 weeks postnatal, and a lack of contactin-5 (NB-2) results in an impairment of neuronal activity in the rat auditory system. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma.

Pssm-ID: 409358 [Multi-domain] Cd Length: 89 Bit Score: 66.33 E-value: 5.67e-13

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 386767223 1335 MPCLAVGAPQPEITWKiKGVE-FSANDRMRVLPDGSLLIKSVNRQDAGDYSCHAENSIAKDSITHKLIV 1402
Cdd:cd04969    22 IECKPKASPKPTISWS-KGTElLTNSSRICILPDGSLKIKNVTKSDEGKYTCFAVNFFGKANSTGSLSV 89

Fibronectin type 3 domain; One of three types of internal repeat within the plasma protein, fibronectin. The tenth fibronectin type III repeat contains a RGD cell recognition sequence in a flexible loop between 2 strands. Type III modules are present in both extracellular and intracellular proteins.

Pssm-ID: 214495 [Multi-domain] Cd Length: 83 Bit Score: 66.10 E-value: 6.06e-13

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223   1014 GKPQNIKVEPVNQTTMRVTWKPPPRTEWNGEILGYYVGYKLSNTNSSYVfetinfiTEEGKEHNLELQNLRVYTQYSVVI 1093
Cdd:smart00060    2 SPPSNLRVTDVTSTSVTLSWEPPPDDGITGYIVGYRVEYREEGSEWKEV-------NVTPSSTSYTLTGLKPGTEYEFRV 74


                    ....*....
gi 386767223   1094 QAFNKIGAG 1102
Cdd:smart00060   75 RAVNGAGEG 83

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 65.36 E-value: 1.25e-12

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 386767223  1331 EDAKMPCLAVGAPQPEITWKIKGVEFSANDRMRVLPDG---SLLIKSVNRQDAGDYSCHAENSIAKDSITHKLIV 1402
Cdd:pfam07679   16 ESARFTCTVTGTPDPEVSWFKDGQPLRSSDRFKVTYEGgtyTLTISNVQPDDSGKYTCVATNSAGEAEASAELTV 90

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.

Pssm-ID: 214653 [Multi-domain] Cd Length: 85 Bit Score: 64.83 E-value: 1.71e-12

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223    439 QEETMEPGPSVFLKCVAGGNPTPEISWELDG-KKIANNDRYQVgqyvtVNGDVVSYLNITSVHANDGGLYKCIAKSKVGV 517
Cdd:smart00410    2 PSVTVKEGESVTLSCEASGSPPPEVTWYKQGgKLLAESGRFSV-----SRSGSTSTLTISNVTPEDSGTYTCAATNSSGS 76


                    ....*....
gi 386767223    518 AEHSAKLNV 526
Cdd:smart00410   77 ASSGTTLTV 85

Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein fibronectin. Its tenth fibronectin type III repeat contains an RGD cell recognition sequence in a flexible loop between 2 strands. Approximately 2% of all animal proteins contain the FN3 repeat; including extracellular and intracellular proteins, membrane spanning cytokine receptors, growth hormone receptors, tyrosine phosphatase receptors, and adhesion molecules. FN3-like domains are also found in bacterial glycosyl hydrolases.

Pssm-ID: 238020 [Multi-domain] Cd Length: 93 Bit Score: 64.83 E-value: 2.26e-12

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223 1500 PKLPEKPRFIEVSSNSVSLHFKAWKDGGCPMSHFVVESKKRDQIEWNQISNNVKPDNNYVVLDLEPATWYNLRITAHNSA 1579
Cdd:cd00063     1 PSPPTNLRVTDVTSTSVTLSWTPPEDDGGPITGYVVEYREKGSGDWKEVEVTPGSETSYTLTGLKPGTEYEFRVRAVNGG 80


                  .
gi 386767223 1580 G 1580
Cdd:cd00063    81 G 81

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.

Pssm-ID: 214653 [Multi-domain] Cd Length: 85 Bit Score: 64.06 E-value: 3.52e-12

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223    352 PPTQTVDFGRPAVFTCQYTGNPIKTVSWMKDG-KAIGHSE----------PVLRIESVKKEDKGMYQCFVRNDQESAEAS 420
Cdd:smart00410    1 PPSVTVKEGESVTLSCEASGSPPPEVTWYKQGgKLLAESGrfsvsrsgstSTLTISNVTPEDSGTYTCAATNSSGSASSG 80


                    ....
gi 386767223    421 AELK 424
Cdd:smart00410   81 TTLT 84

Fibronectin type III domain;

Pssm-ID: 394996 [Multi-domain] Cd Length: 85 Bit Score: 63.97 E-value: 3.61e-12

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  1220 APTDVKALVMGNAAILVSWRPPAQPNGIITQYTVYSKAEGAETETKTQKVPHYQMSFEATELEKNKPYEFWVTASTTIGE 1299
Cdd:pfam00041    2 APSNLTVTDVTSTSLTVSWTPPPDGNGPITGYEVEYRPKNSGEPWNEITVPGTTTSVTLTGLKPGTEYEVRVQAVNGGGE 81


                   ....
gi 386767223  1300 GQQS 1303
Cdd:pfam00041   82 GPPS 85

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.

Pssm-ID: 214653 [Multi-domain] Cd Length: 85 Bit Score: 63.29 E-value: 5.25e-12

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223    822 RNQTARRGEPAVLQCEAKGEKPIGILWNMNNMRLdPKNDNRYTIREEilstGVMSSLSIKRTERSDSALFTCVATNAFGS 901
Cdd:smart00410    2 PSVTVKEGESVTLSCEASGSPPPEVTWYKQGGKL-LAESGRFSVSRS----GSTSTLTISNVTPEDSGTYTCAATNSSGS 76


                    ....*....
gi 386767223    902 DDASINMIV 910
Cdd:smart00410   77 ASSGTTLTV 85

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 63.05 E-value: 8.38e-12

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223   352 PPTQTVDFGRPAVFTCQYTGNPIKTVSWMKDGKAIGHSEPV----------LRIESVKKEDKGMYQCFVRNDQESAEASA 421
Cdd:pfam07679    7 PKDVEVQEGESARFTCTVTGTPDPEVSWFKDGQPLRSSDRFkvtyeggtytLTISNVQPDDSGKYTCVATNSAGEAEASA 86


                   ...
gi 386767223   422 ELK 424
Cdd:pfam07679   87 ELT 89

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409353 [Multi-domain] Cd Length: 70 Bit Score: 62.35 E-value: 9.95e-12

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 386767223 1333 AKMPCLAVGAPQPEITWKIKGVEFSANDRMR---VLPDGSLLIKSVNRQDAGDYSCHAENSI 1391
Cdd:cd00096     1 VTLTCSASGNPPPTITWYKNGKPLPPSSRDSrrsELGNGTLTISNVTLEDSGTYTCVASNSA 62

Fibronectin type 3 domain; One of three types of internal repeat within the plasma protein, fibronectin. The tenth fibronectin type III repeat contains a RGD cell recognition sequence in a flexible loop between 2 strands. Type III modules are present in both extracellular and intracellular proteins.

Pssm-ID: 214495 [Multi-domain] Cd Length: 83 Bit Score: 62.63 E-value: 1.10e-11

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223    914 PEMPYALKVLDKSGRSVQLSWAQPYDGN--SPLDRYIIEFKRSRASWSeidRVIVPGHTTEAQVQKLSPATTYNIRIVAE 991
Cdd:smart00060    1 PSPPSNLRVTDVTSTSVTLSWEPPPDDGitGYIVGYRVEYREEGSEWK---EVNVTPSSTSYTLTGLKPGTEYEFRVRAV 77


                    ....*.
gi 386767223    992 NAIGTS 997
Cdd:smart00060   78 NGAGEG 83

Fourth immunoglobulin (Ig)-like domain of hemolin, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain of hemolin and similar proteins. Hemolin, an insect immunoglobulin superfamily (IgSF) member containing four Ig-like domains, is a lipopolysaccharide-binding immune protein induced during bacterial infection. Hemolin shares significant sequence similarity with the first four Ig-like domains of the transmembrane cell adhesion molecules (CAMs) of the L1 family. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The fourth Ig-like domain of hemolin is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409570 [Multi-domain] Cd Length: 88 Bit Score: 61.64 E-value: 2.80e-11

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 386767223 1331 EDAKMPCLAVGAPQPEITWKIKGVEFSANDRMRVLPDGSLLIKSVNRQDAGDYSCHAENSIAKDSITHKLIV 1402
Cdd:cd20978    17 QDVTLPCQVTGVPQPKITWLHNGKPLQGPMERATVEDGTLTIINVQPEDTGYYGCVATNEIGDIYTETLLHV 88

Second Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the titin Z1z2 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409564 [Multi-domain] Cd Length: 91 Bit Score: 61.44 E-value: 3.15e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  431 PPVIRQAFQEETMEPGPSVFLKCVAGGNPTPEISWELDGKKIANNDRYQVGQyvtvNGDVVSYLnITSVHANDGGLYKCI 510
Cdd:cd20972     1 PPQFIQKLRSQEVAEGSKVRLECRVTGNPTPVVRWFCEGKELQNSPDIQIHQ----EGDLHSLI-IAEAFEEDTGRYSCL 75

                          90
                  ....*....|....*.
gi 386767223  511 AKSKVGVAEHSAKLNV 526
Cdd:cd20972    76 ATNSVGSDTTSAEIFV 91

agrin-responsive second immunoglobulin-like domains (Ig2) of the Muscle-specific kinase (MuSK) ectodomain; a member of the I-set of Ig superfamily domains; The members here are composed of the second immunoglobulin-like (Ig) domains of the Muscle-specific kinase (MuSK) ectodomain. MuSK is a receptor tyrosine kinase specifically expressed in skeletal muscle, where it plays a central role in the formation and maintenance of the neuromuscular junction (NMJ). MuSK is activated by agrin, a neuron-derived heparan sulfate proteoglycan. The activation of MUSK in myotubes regulates the formation of NMJs through the regulation of different processes including the specific expression of genes in subsynaptic nuclei, the reorganization of the actin cytoskeleton and the clustering of the acetylcholine receptors (AChR) in the postsynaptic membrane. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the MuSK lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409560 [Multi-domain] Cd Length: 88 Bit Score: 61.10 E-value: 3.45e-11

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223 1333 AKMPCLAVGAPQPEITWkIKGVE-FSANDRMRVLPDGSLLIKSVNRQDAGDYSCHAENSI 1391
Cdd:cd20968    17 AVLPCTTMGNPKPSVSW-IKGDDlIKENNRIAVLESGSLRIHNVQKEDAGQYRCVAKNSL 75

Fibronectin type 3 domain [General function prediction only];

Pssm-ID: 442628 [Multi-domain] Cd Length: 603 Bit Score: 68.11 E-value: 3.94e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223 1112 TAEGTPSQPPSDTACTTLTSQTIRVGWVSPPLESANGVIKTYKVVYAPSDEWYDETKRHYKKTASSDTVLHGL--KKYTN 1189
Cdd:COG3401   125 ATTATAVAGGAATAGTYALGAGLYGVDGANASGTTASSVAGAGVVVSPDTSATAAVATTSLTVTSTTLVDGGGdiEPGTT 204

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223 1190 YTMQVLATTAGGDGVRSVPIHCQTEPDVPEAPTDVKALVMGNAAILVSWRPPAQPNgiITQYTVYSKAEGAETETKTQKV 1269
Cdd:COG3401   205 YYYRVAATDTGGESAPSNEVSVTTPTTPPSAPTGLTATADTPGSVTLSWDPVTESD--ATGYRVYRSNSGDGPFTKVATV 282

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*...
gi 386767223 1270 PhyQMSFEATELEKNKPYEFWVTASTTIG-EGQQSKSIVAMPSDQVPA 1316
Cdd:COG3401   283 T--TTSYTDTGLTNGTTYYYRVTAVDAAGnESAPSNVVSVTTDLTPPA 328

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409353 [Multi-domain] Cd Length: 70 Bit Score: 60.42 E-value: 4.18e-11

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 386767223  272 CQAQAFPLPIMRWYKfiEGTTRKQAVVLNDRVKQVSGTLIIKDAVVEDSGKYLCVVNNSVGGESVETV 339
Cdd:cd00096     5 CSASGNPPPTITWYK--NGKPLPPSSRDSRRSELGNGTLTISNVTLEDSGTYTCVASNSAGGSASASV 70

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.

Pssm-ID: 214653 [Multi-domain] Cd Length: 85 Bit Score: 60.60 E-value: 6.08e-11

                            10        20        30        40        50        60        70
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 386767223   1331 EDAKMPCLAVGAPQPEITW-KIKGVEFSANDRMRVLPDG---SLLIKSVNRQDAGDYSCHAENSIAKDSITHKLIV 1402
Cdd:smart00410   10 ESVTLSCEASGSPPPEVTWyKQGGKLLAESGRFSVSRSGstsTLTISNVTPEDSGTYTCAATNSSGSASSGTTLTV 85

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 59.89 E-value: 7.45e-11

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 386767223   350 IDPPTQTVDFGRPAVFTCQYTGNPIKTVSWMKDGKAIGH----------SEPVLRIESVKKEDKGMYQCFVRN 412
Cdd:pfam13927    6 VSPSSVTVREGETVTLTCEATGSPPPTITWYKNGEPISSgstrsrslsgSNSTLTISNVTRSDAGTYTCVASN 78

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 59.89 E-value: 8.46e-11

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 386767223   530 PYIRQMEKKAIVA-GETLIVTCPVAGYPIDSIVWERDNRALPINRKQK---VFPNGTLIIENVERnSDQATYTCVAKN 603
Cdd:pfam13927    2 PVITVSPSSVTVReGETVTLTCEATGSPPPTITWYKNGEPISSGSTRSrslSGSNSTLTISNVTR-SDAGTYTCVASN 78

Fifth Ig-like domain of Roundabout (Robo) homolog 1/2, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fifth Ig-like domain of Roundabout (Robo) homolog 1/2 and similar domains. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, -2, and -3), and three mammalian Slit homologs (Slit-1,-2, -3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, -2, and -3 are expressed by commissural neurons in the vertebrate spinal cord and Slits 1, -2, -3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of slit responsiveness, antagonizes slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be is the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. The fifth Ig-like domain of Robo 1 and 2 is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors

Pssm-ID: 409544 [Multi-domain] Cd Length: 87 Bit Score: 60.20 E-value: 8.50e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  351 DPPTQTVDFGRPAVFTCQYTGNPIKTVSWMKDGKAIGHSEP--------VLRIESVKKEDKGMYQCFVRNDQESAEASAE 422
Cdd:cd20952     5 GPQNQTVAVGGTVVLNCQATGEPVPTISWLKDGVPLLGKDErittlengSLQIKGAEKSDTGEYTCVALNLSGEATWSAV 84


                  .
gi 386767223  423 L 423
Cdd:cd20952    85 L 85

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409353 [Multi-domain] Cd Length: 70 Bit Score: 59.27 E-value: 1.10e-10

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 386767223  449 VFLKCVAGGNPTPEISWELDGKKIANNDRYQVgqyvtVNGDVVSYLNITSVHANDGGLYKCIAKSKVGVAEHS 521
Cdd:cd00096     1 VTLTCSASGNPPPTITWYKNGKPLPPSSRDSR-----RSELGNGTLTISNVTLEDSGTYTCVASNSAGGSASA 68

Immunoglobulin domain I1 of the titin I-band and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin domain I1 of the titin I-band and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. The two sheets are linked together by a conserved disulfide bond between B strand and F strand. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The Ig I1 domain of the titin I-band is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409543 [Multi-domain] Cd Length: 94 Bit Score: 59.74 E-value: 1.44e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  815 PEFTEKLRNQTARRGEPAVLQCEAKGE-KPIgILWNMNNMRLDP-KNDNRYTIREEilstGVMSSLSIKRTERSDSALFT 892
Cdd:cd20951     1 PEFIIRLQSHTVWEKSDAKLRVEVQGKpDPE-VKWYKNGVPIDPsSIPGKYKIESE----YGVHVLHIRRVTVEDSAVYS 75

                          90
                  ....*....|....*....
gi 386767223  893 CVATNAFGSDDASINMIVQ 911
Cdd:cd20951    76 AVAKNIHGEASSSASVVVE 94

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 59.19 E-value: 1.71e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223   532 IRQMEKKAIVAGETLIVTCPVAGYPIDSIVWERDNRALPINRKQKVFPNG---TLIIENVERnSDQATYTCVAKNQEGyS 608
Cdd:pfam07679    4 TQKPKDVEVQEGESARFTCTVTGTPDPEVSWFKDGQPLRSSDRFKVTYEGgtyTLTISNVQP-DDSGKYTCVATNSAG-E 81


                   ....*....
gi 386767223   609 ARGSLEVQV 617
Cdd:pfam07679   82 AEASAELTV 90

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409353 [Multi-domain] Cd Length: 70 Bit Score: 58.49 E-value: 2.25e-10

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 386767223  546 LIVTCPVAGYPIDSIVWERDNRALPINRKQKVF---PNGTLIIENVERnSDQATYTCVAKNQEGYSARGSL 613
Cdd:cd00096     1 VTLTCSASGNPPPTITWYKNGKPLPPSSRDSRRselGNGTLTISNVTL-EDSGTYTCVASNSAGGSASASV 70

Third immunoglobulin (Ig)-like domain of Neural Cell Adhesion Molecule 1 (NCAM-1); member of the I-set of IgSF domains; The members here are composed of the third immunoglobulin (Ig)-like domain of Neural Cell Adhesion Molecule (NCAM-1). NCAM plays important roles in the development and regeneration of the central nervous system, in synaptogenesis and neural migration. NCAM mediates cell-cell and cell-substratum recognition and adhesion via homophilic (NCAM-NCAM), and heterophilic (NCAM-non-NCAM), interactions. NCAM is expressed as three major isoforms having different intracellular extensions. The extracellular portion of NCAM has five N-terminal Ig-like domains and two fibronectin type III domains. The double zipper adhesion complex model for NCAM homophilic binding involves Ig1, Ig2, and Ig3. By this model, Ig1 and Ig2 mediate dimerization of NCAM molecules situated on the same cell surface (cis interactions), and Ig3 domains mediate interactions between NCAM molecules expressed on the surface of opposing cells (trans interactions) through binding to the Ig1 and Ig2 domains. The adhesive ability of NCAM is modulated by the addition of polysialic acid chains to the fifth Ig-like domain.

Pssm-ID: 143207 [Multi-domain] Cd Length: 95 Bit Score: 59.18 E-value: 2.44e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  431 PPVI--RQAFQEETMEPGPSVFLKCVAGGNPTPEISWELDGKKIANNDryqvgQYVTVNGDvVSYLNITSVHANDGGLYK 508
Cdd:cd05730     1 PPTIraRQSEVNATANLGQSVTLACDADGFPEPTMTWTKDGEPIESGE-----EKYSFNED-GSEMTILDVDKLDEAEYT 74

                          90
                  ....*....|....*....
gi 386767223  509 CIAKSKVGVAEHSAKLNVY 527
Cdd:cd05730    75 CIAENKAGEQEAEIHLKVF 93

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 58.35 E-value: 2.48e-10

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 386767223  1331 EDAKMPCLAVGAPQPEITWKIKGVEFSAND---RMRVLPDGSLLIKSVNRQDAGDYSCHAEN 1389
Cdd:pfam13927   17 ETVTLTCEATGSPPPTITWYKNGEPISSGStrsRSLSGSNSTLTISNVTRSDAGTYTCVASN 78

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 58.35 E-value: 2.65e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223   814 PPEFTEKLRNQTARRGEPAVLQCEAKGEKPIGILWNMNNMrldPKNDNRYTIREEILSTgvmSSLSIKRTERSDSALFTC 893
Cdd:pfam13927    1 KPVITVSPSSVTVREGETVTLTCEATGSPPPTITWYKNGE---PISSGSTRSRSLSGSN---STLTISNVTRSDAGTYTC 74


                   ....
gi 386767223   894 VATN 897
Cdd:pfam13927   75 VASN 78

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 58.81 E-value: 2.75e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223   718 PRWILEPTDKAFAQGSDAKVECKADGFPKPQVTWKKavGDTPgeykdLKKSDNIRV----EEGTLHVDNIQKTNEGYYLC 793
Cdd:pfam07679    1 PKFTQKPKDVEVQEGESARFTCTVTGTPDPEVSWFK--DGQP-----LRSSDRFKVtyegGTYTLTISNVQPDDSGKYTC 73


                   ....*...
gi 386767223   794 EAINGIGS 801
Cdd:pfam07679   74 VATNSAGE 81

First immunoglobulin (Ig) domain of contactin-5; member of the I-set of Ig superfamily domains; The members here are composed of the first immunoglobulin (Ig) domain of the neural cell adhesion molecule contactin-5. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains, anchored to the membrane by glycosylphosphatidylinositol. The different contactins show different expression patterns in the central nervous system. In rats, a lack of contactin-5 (NB-2) results in an impairment of the neuronal activity in the auditory system. Contactin-5 is expressed specifically in the postnatal nervous system, peaking at about 3 weeks postnatal. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala; lower levels of expression have been detected in the corpus callosum, caudate nucleus, and spinal cord. This group belongs to the I-set of IgSF domains.

Pssm-ID: 409435 Cd Length: 96 Bit Score: 58.80 E-value: 2.89e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223   38 GPVFLKEPTNRIDFSNSTGAEI--ECKASGNPMPEIIWIRsDGTAVGDVPGLRQISSDGKLVFP-PFRAEDYRQevhaqv 114
Cdd:cd05848     1 GPVFVQEPDDAIFPTDSDEKKVilNCEARGNPVPTYRWLR-NGTEIDTESDYRYSLIDGNLIISnPSEVKDSGR------ 73

                          90
                  ....*....|....*.
gi 386767223  115 YACLARNQFGSIISRD 130
Cdd:cd05848    74 YQCLATNSIGSILSRE 89

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409353 [Multi-domain] Cd Length: 70 Bit Score: 58.11 E-value: 2.98e-10

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 386767223  363 AVFTCQYTGNPIKTVSWMKDGKAIGHSEP----------VLRIESVKKEDKGMYQCFVRNDQESAEAS 420
Cdd:cd00096     1 VTLTCSASGNPPPTITWYKNGKPLPPSSRdsrrselgngTLTISNVTLEDSGTYTCVASNSAGGSASA 68

Second immunoglobulin (Ig)-like domain of a Follistatin-related protein 5, and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig)-like domain found in human Follistatin-related protein 5 (FSTL5) and a follistatin-like molecule encoded by the CNS-related Mahya gene. Mahya genes have been retained in certain Bilaterian branches during evolution. They are conserved in Hymenoptera and Deuterostomes, but are absent from other metazoan species such as fruit fly and nematode. Mahya proteins are secretory, with a follistatin-like domain (Kazal-type serine/threonine protease inhibitor domain and EF-hand calcium-binding domain), two Ig-like domains, and a novel C-terminal domain. Mahya may be involved in learning and memory and in processing of sensory information in Hymenoptera and vertebrates. Follistatin is a secreted, multidomain protein that binds activins with high affinity and antagonizes their signaling.

Pssm-ID: 409399 [Multi-domain] Cd Length: 93 Bit Score: 58.81 E-value: 3.06e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  432 PVIRQAFQEETMEPGPSVFLKCVAGGNPTPEISWELDGKKIANNdryQVGQY-VTVNGdvvSYLNITSVHANDGGLYKCI 510
Cdd:cd05736     1 PVIRVYPEFQAKEPGVEASLRCHAEGIPLPRVQWLKNGMDINPK---LSKQLtLIANG---SELHISNVRYEDTGAYTCI 74

                          90
                  ....*....|....*.
gi 386767223  511 AKSKVGVAEHSAKLNV 526
Cdd:cd05736    75 AKNEGGVDEDISSLFV 90

Immunoglobulin (Ig)-like domain of Down Syndrome Cell Adhesion molecule (DSCAM); The members here are composed of the immunoglobulin (Ig)-like domain of Down Syndrome Cell Adhesion molecule (DSCAM). DSCAM is a cell adhesion molecule expressed largely in the developing nervous system. The gene encoding DSCAM is located at human chromosome 21q22, the locus associated with the intellectual disability phenotype of Down Syndrome. DSCAM is predicted to be the largest member of the IG superfamily. It has been demonstrated that DSCAM can mediate cation-independent homophilic intercellular adhesion.

Pssm-ID: 409397 [Multi-domain] Cd Length: 97 Bit Score: 58.66 E-value: 3.50e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  717 PPRWILEPTDKAFAQGSDAKVECKADGFPKPQVTWKKAVG-DTPGEYKDLKKSDNIRV-EEGTLHVDNIQKTNEGYYLCE 794
Cdd:cd05734     1 PPRFVVQPNDQDGIYGKAVVLNCSADGYPPPTIVWKHSKGsGVPQFQHIVPLNGRIQLlSNGSLLIKHVLEEDSGYYLCK 80

                          90
                  ....*....|....*..
gi 386767223  795 AINGIGSGLSAVIMISV 811
Cdd:cd05734    81 VSNDVGADISKSMYLTV 97

Sixth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the sixth immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.

Pssm-ID: 409551 Cd Length: 94 Bit Score: 58.27 E-value: 3.78e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  431 PPVIRQAFQEETMEPGPSVFLKC-VAGGNPTPEISWELDGKKIANNdryqVGQYVTVNGDVVSYLNITSVHANDGGLYKC 509
Cdd:cd20959     2 PRIIPFAFGEGAAQVGMRAQLHCgVPGGDLPLNIRWTLDGQPISDD----LGITVSRLGRRSSILSIDSLEASHAGNYTC 77

                          90
                  ....*....|....*..
gi 386767223  510 IAKSKVGVAEHSAKLNV 526
Cdd:cd20959    78 HARNSAGSASYTAPLTV 94

Fifth immunoglobulin (Ig) domain of contactin; The members here are composed of the fifth immunoglobulin (Ig) domain of contactins. Contactins are neural cell adhesion molecules and are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module via contacts between Ig domains 1 and 4, and between Ig domains 2 and 3. Contactin-2 (TAG-1, axonin-1) may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. This group also includes contactin-1 and contactin-5. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-5 is expressed specifically in the rat postnatal nervous system, peaking at about 3 weeks postnatal, and a lack of contactin-5 (NB-2) results in an impairment of neuronal activity in the rat auditory system. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma.

Pssm-ID: 409358 [Multi-domain] Cd Length: 89 Bit Score: 58.24 E-value: 3.98e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  730 AQGSDAKVECKADGFPKPQVTWKKavGDtpgeyKDLKKSDNIRV-EEGTLHVDNIQKTNEGYYLCEAINGIGSGLSAVIM 808
Cdd:cd04969    15 AKGGDVIIECKPKASPKPTISWSK--GT-----ELLTNSSRICIlPDGSLKIKNVTKSDEGKYTCFAVNFFGKANSTGSL 87


                  .
gi 386767223  809 I 809
Cdd:cd04969    88 S 88

Fourth immunoglobulin (Ig)-like domain of peroxidasin; The members here are composed of the fourth immunoglobulin (Ig)-like domain in peroxidasin. Peroxidasin has a peroxidase domain and interacting extracellular motifs containing four Ig-like domains. It has been suggested that peroxidasin is secreted, and has functions related to the stabilization of the extracellular matrix. It may play a part in various other important processes such as removal and destruction of cells which have undergone programmed cell death and protection of the organism against non-self.

Pssm-ID: 143223 Cd Length: 69 Bit Score: 57.58 E-value: 4.39e-10

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 386767223 1334 KMPCLAVGAPQPEITWKIKGVEFSANDRMRVLPDGSLLIKSVNRQDAGDYSCHAENSIAKDSITHKL 1400
Cdd:cd05746     2 QIPCSAQGDPEPTITWNKDGVQVTESGKFHISPEGYLAIRDVGVADQGRYECVARNTIGYASVSMVL 68

Second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of the Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, and Robo3), and three mammalian Slit homologs (Slit-1,Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit-2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409389 [Multi-domain] Cd Length: 87 Bit Score: 58.18 E-value: 4.50e-10

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 386767223 1331 EDAKMPCLA-VGAPQPEITWKIKGVEF-SANDRMRVLPDGSLLIKSVNRQDAGDYSCHAENSI-AKDSITHKLIV 1402
Cdd:cd05724    13 EMAVLECSPpRGHPEPTVSWRKDGQPLnLDNERVRIVDDGNLLIAEARKSDEGTYKCVATNMVgERESRAARLSV 87

Fifth Ig-like domain of Roundabout (Robo) homolog 1/2, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fifth Ig-like domain of Roundabout (Robo) homolog 1/2 and similar domains. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, -2, and -3), and three mammalian Slit homologs (Slit-1,-2, -3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, -2, and -3 are expressed by commissural neurons in the vertebrate spinal cord and Slits 1, -2, -3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of slit responsiveness, antagonizes slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be is the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. The fifth Ig-like domain of Robo 1 and 2 is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors

Pssm-ID: 409544 [Multi-domain] Cd Length: 87 Bit Score: 57.89 E-value: 5.17e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  263 VVDQSFAMLCQAQAFPLPIMRWYKfiEGttrKQAVVLNDRVKQV-SGTLIIKDAVVEDSGKYLCVVNNSVGGESVETVLT 341
Cdd:cd20952    12 AVGGTVVLNCQATGEPVPTISWLK--DG---VPLLGKDERITTLeNGSLQIKGAEKSDTGEYTCVALNLSGEATWSAVLD 86


                  .
gi 386767223  342 V 342
Cdd:cd20952    87 V 87

Fifth Ig-like domain of Roundabout (Robo) homolog 1/2, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fifth Ig-like domain of Roundabout (Robo) homolog 1/2 and similar domains. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, -2, and -3), and three mammalian Slit homologs (Slit-1,-2, -3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, -2, and -3 are expressed by commissural neurons in the vertebrate spinal cord and Slits 1, -2, -3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of slit responsiveness, antagonizes slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be is the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. The fifth Ig-like domain of Robo 1 and 2 is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors

Pssm-ID: 409544 [Multi-domain] Cd Length: 87 Bit Score: 57.89 E-value: 5.64e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  433 VIRQAFQEETMEPGPSVFLKCVAGGNPTPEISWELDGKKIA-NNDRYQVGQyvtvNGDvvsyLNITSVHANDGGLYKCIA 511
Cdd:cd20952     1 IILQGPQNQTVAVGGTVVLNCQATGEPVPTISWLKDGVPLLgKDERITTLE----NGS----LQIKGAEKSDTGEYTCVA 72

                          90
                  ....*....|....*
gi 386767223  512 KSKVGVAEHSAKLNV 526
Cdd:cd20952    73 LNLSGEATWSAVLDV 87

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 57.19 E-value: 6.21e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223   717 PPRWILEPTDKAFAQGSDAKVECKADGFPKPQVTWKKaVGDTPGEYKDLKKSDNIrvEEGTLHVDNIQKTNEGYYLCEAI 796
Cdd:pfam13927    1 KPVITVSPSSVTVREGETVTLTCEATGSPPPTITWYK-NGEPISSGSTRSRSLSG--SNSTLTISNVTRSDAGTYTCVAS 77


                   .
gi 386767223   797 N 797
Cdd:pfam13927   78 N 78

Fifth Ig-like domain of Roundabout (Robo) homolog 1/2, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fifth Ig-like domain of Roundabout (Robo) homolog 1/2 and similar domains. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, -2, and -3), and three mammalian Slit homologs (Slit-1,-2, -3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, -2, and -3 are expressed by commissural neurons in the vertebrate spinal cord and Slits 1, -2, -3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of slit responsiveness, antagonizes slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be is the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. The fifth Ig-like domain of Robo 1 and 2 is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors

Pssm-ID: 409544 [Multi-domain] Cd Length: 87 Bit Score: 57.51 E-value: 7.13e-10

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 386767223  540 IVAGETLIVTCPVAGYPIDSIVWERDNRALPI-NRKQKVFPNGTLIIENVERNsDQATYTCVAKNQEG-YSARGSLEV 615
Cdd:cd20952    11 VAVGGTVVLNCQATGEPVPTISWLKDGVPLLGkDERITTLENGSLQIKGAEKS-DTGEYTCVALNLSGeATWSAVLDV 87

Third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, Robo3), and three mammalian Slit homologs (Slit-1,Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, and Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409390 [Multi-domain] Cd Length: 83 Bit Score: 57.41 E-value: 7.20e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  823 NQTARRGEPAVLQCEAKGEKPIGILWNMNNMRLdPKndNRYTIREEilstgvmSSLSIKRTERSDSALFTCVATNAFGSD 902
Cdd:cd05725     6 NQVVLVDDSAEFQCEVGGDPVPTVRWRKEDGEL-PK--GRYEILDD-------HSLKIRKVTAGDMGSYTCVAENMVGKI 75


                  ....*...
gi 386767223  903 DASINMIV 910
Cdd:cd05725    76 EASATLTV 83

Immunoglobulin (Ig)-like ectodomain of the LRIG1 (Leucine-rich Repeats And Immunoglobulin-like Domains Protein 1) and similar proteins; member of the I-set of IgSF domains; The members here are composed of subgroup of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. The ectodomain of LRIG1 has two distinct regions: the proposed 15 LRRs and three Ig-like domains closer to the membrane. LRIG1 has been reported to interact with many receptor tyrosine kinases, GDNF/c-Ret, E-cadherin, JAK/STAT, c-Met, and the EGFR family signaling systems. Immunoglobulin Superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The structure of the LRIG1 extracellular Ig domain lacks a C" strand and thus is better described as a member of the I-set of IgSF domains.

Pssm-ID: 409420 [Multi-domain] Cd Length: 91 Bit Score: 57.24 E-value: 8.37e-10

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 386767223 1333 AKMPCLAVGAPQPEITW-KIKGVEFSA--NDRMRVLP-DGSLLIKSVNRQDAGDYSCHAENSIAKDSITHKLIVL 1403
Cdd:cd05763    17 ARLECAATGHPTPQIAWqKDGGTDFPAarERRMHVMPeDDVFFIVDVKIEDTGVYSCTAQNSAGSISANATLTVL 91

Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein fibronectin. Its tenth fibronectin type III repeat contains an RGD cell recognition sequence in a flexible loop between 2 strands. Approximately 2% of all animal proteins contain the FN3 repeat; including extracellular and intracellular proteins, membrane spanning cytokine receptors, growth hormone receptors, tyrosine phosphatase receptors, and adhesion molecules. FN3-like domains are also found in bacterial glycosyl hydrolases.

Pssm-ID: 238020 [Multi-domain] Cd Length: 93 Bit Score: 57.12 E-value: 9.35e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223 1120 PPSDTACTTLTSQTIRVGWVSPPleSANGVIKTYKVVYAPSDEwydETKRHYKKTASSDT--VLHGLKKYTNYTMQVLAT 1197
Cdd:cd00063     3 PPTNLRVTDVTSTSVTLSWTPPE--DDGGPITGYVVEYREKGS---GDWKEVEVTPGSETsyTLTGLKPGTEYEFRVRAV 77

                          90
                  ....*....|....*.
gi 386767223 1198 TAGGDGVRSVPIHCQT 1213
Cdd:cd00063    78 NGGGESPPSESVTVTT 93

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.

Pssm-ID: 214653 [Multi-domain] Cd Length: 85 Bit Score: 57.13 E-value: 1.00e-09

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223    541 VAGETLIVTCPVAGYPIDSIVWERDNRALPINRK----QKVFPNGTLIIENVERnSDQATYTCVAKNQEGySARGSLEVQ 616
Cdd:smart00410    7 KEGESVTLSCEASGSPPPEVTWYKQGGKLLAESGrfsvSRSGSTSTLTISNVTP-EDSGTYTCAATNSSG-SASSGTTLT 84


                    .
gi 386767223    617 V 617
Cdd:smart00410   85 V 85

Third immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the Constant 2 (C2)-set of IgSF domains; The members here are composed of the third immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. This group belongs to the C2-set of IgSF domains, having A, B, and E strands in one beta-sheet and A', G, F, C, and C' in the other. Unlike other Ig domain sets, the C2-set lacks the D strand.

Pssm-ID: 409549 [Multi-domain] Cd Length: 88 Bit Score: 57.16 E-value: 1.01e-09

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 386767223  542 AGETLIVTCPVAGYPIDSIVWERDNRALPINRKQKVFPNGTLIIENVERNsDQATYTCVAKNqEGYSARGSLEVQV 617
Cdd:cd20957    15 FGRTAVFNCSVTGNPIHTVLWMKDGKPLGHSSRVQILSEDVLVIPSVKRE-DKGMYQCFVRN-DGDSAQATAELKL 88

Fourth Ig-like domain from smooth muscle myosin light chain kinase and similar domains ; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain from smooth muscle myosin light chain kinase (MYLK) and similar domains. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of this group shows that the fourth Ig-like domain from myosin light chain kinase lacks this strand and thus belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409568 [Multi-domain] Cd Length: 90 Bit Score: 56.87 E-value: 1.12e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  431 PPVIRQAFQEETMEPGPSVFLKCVAGGNPTPEISWELDGKKIA-NNDRYQVGQyvtvngdVVSYLNITSVHANDGGLYKC 509
Cdd:cd20976     1 APSFSSVPKDLEAVEGQDFVAQCSARGKPVPRITWIRNAQPLQyAADRSTCEA-------GVGELHIQDVLPEDHGTYTC 73

                          90
                  ....*....|....*..
gi 386767223  510 IAKSKVGVAEHSAKLNV 526
Cdd:cd20976    74 LAKNAAGQVSCSAWVTV 90

agrin-responsive first immunoglobulin-like domains (Ig1) of the MuSK ectodomain; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin-like domains (Ig1) of the Muscle-specific kinase (MuSK). MuSK is a receptor tyrosine kinase specifically expressed in skeletal muscle, where it plays a central role in the formation and maintenance of the neuromuscular junction (NMJ). MuSK is activated by agrin, a neuron-derived heparan sulfate proteoglycan. The activation of MUSK in myotubes regulates the formation of NMJs through the regulation of different processes including the specific expression of genes in subsynaptic nuclei, the reorganization of the actin cytoskeleton and the clustering of the acetylcholine receptors (AChR) in the postsynaptic membrane. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the MuSK lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409562 [Multi-domain] Cd Length: 92 Bit Score: 57.13 E-value: 1.21e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  432 PVIRQAFQEETM--EPGPSVFLKCVAGGNPTPEISWELDGKKI-ANNDRYQVGQyvtvNGDVvsyLNITSVHANDGGLYK 508
Cdd:cd20970     1 PVISTPQPSFTVtaREGENATFMCRAEGSPEPEISWTRNGNLIiEFNTRYIVRE----NGTT---LTIRNIRRSDMGIYL 73

                          90
                  ....*....|....*....
gi 386767223  509 CIAKSKV-GVAEHSAKLNV 526
Cdd:cd20970    74 CIASNGVpGSVEKRITLQV 92

Fifth Ig-like domain of Roundabout (Robo) homolog 1/2, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fifth Ig-like domain of Roundabout (Robo) homolog 1/2 and similar domains. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, -2, and -3), and three mammalian Slit homologs (Slit-1,-2, -3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, -2, and -3 are expressed by commissural neurons in the vertebrate spinal cord and Slits 1, -2, -3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of slit responsiveness, antagonizes slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be is the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. The fifth Ig-like domain of Robo 1 and 2 is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors

Pssm-ID: 409544 [Multi-domain] Cd Length: 87 Bit Score: 56.74 E-value: 1.38e-09

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 386767223 1332 DAKMPCLAVGAPQPEITWKIKGVEFSAND-RMRVLPDGSLLIKSVNRQDAGDYSCHAENSIAKDSITHKLIV 1402
Cdd:cd20952    16 TVVLNCQATGEPVPTISWLKDGVPLLGKDeRITTLENGSLQIKGAEKSDTGEYTCVALNLSGEATWSAVLDV 87

Third immunoglobulin (Ig) domain of contactin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig) domain of contactins. Contactins are neural cell adhesion molecules and are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module via contacts between Ig domains 1 and 4, and between Ig domains 2 and 3. Contactin-2 (TAG-1, axonin-1) may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. This group also includes contactin-1 and contactin-5. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-5 is expressed specifically in the rat postnatal nervous system, peaking at about 3 weeks postnatal, and a lack of contactin-5 (NB-2) results in an impairment of neuronal activity in the rat auditory system. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma. This group belongs to the I-set of IgSF domains.

Pssm-ID: 409357 [Multi-domain] Cd Length: 88 Bit Score: 56.79 E-value: 1.40e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223 1315 PAKIASFDDTFTATFKEDAKMPCLAVGAPQPEITW-KIKGVEFSANDRMRvlPDGSLLIKSVNRQDAGDYSCHAENSIAK 1393
Cdd:cd04968     1 PSIKVRFPADTYALKGQTVTLECFALGNPVPQIKWrKVDGSPSSQWEITT--SEPVLEIPNVQFEDEGTYECEAENSRGK 78


                  ....*....
gi 386767223 1394 DSITHKLIV 1402
Cdd:cd04968    79 DTVQGRIIV 87

Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein fibronectin. Its tenth fibronectin type III repeat contains an RGD cell recognition sequence in a flexible loop between 2 strands. Approximately 2% of all animal proteins contain the FN3 repeat; including extracellular and intracellular proteins, membrane spanning cytokine receptors, growth hormone receptors, tyrosine phosphatase receptors, and adhesion molecules. FN3-like domains are also found in bacterial glycosyl hydrolases.

Pssm-ID: 238020 [Multi-domain] Cd Length: 93 Bit Score: 56.74 E-value: 1.44e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223 1405 PPQSPHVTLSATTTDALTVKLKPHEGDTAPLHGYTLHYKPEF-GEWET-SEVSVDSQKHNIEGLLCGSRYQVYATGFNNI 1482
Cdd:cd00063     1 PSPPTNLRVTDVTSTSVTLSWTPPEDDGGPITGYVVEYREKGsGDWKEvEVTPGSETSYTLTGLKPGTEYEFRVRAVNGG 80

                          90
                  ....*....|...
gi 386767223 1483 GAGEASDILNTRT 1495
Cdd:cd00063    81 GESPPSESVTVTT 93

Third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM); The members here are composed of the third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM). L1 belongs to the L1 subfamily of cell adhesion molecules (CAMs) and is comprised of an extracellular region having six Ig-like domains, five fibronectin type III domains, a transmembrane region and an intracellular domain. L1 is primarily expressed in the nervous system and is involved in its development and function. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, or spastic paraplegia type 1, that involves abnormalities of axonal growth. This group also contains the chicken neuron-glia cell adhesion molecule, Ng-CAM.

Pssm-ID: 409460 [Multi-domain] Cd Length: 83 Bit Score: 56.07 E-value: 2.05e-09

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 386767223  543 GETLIVTCPVAGYPIDSIVWERDNRALPINRKQKVFPNGTLIIENVERnSDQATYTCVAKNQEGySARGSLEVQV 617
Cdd:cd05876    10 GQSLVLECIAEGLPTPTVKWLRPSGPLPPDRVKYQNHNKTLQLLNVGE-SDDGEYVCLAENSLG-SARHAYYVTV 82

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.

Pssm-ID: 214653 [Multi-domain] Cd Length: 85 Bit Score: 55.97 E-value: 2.14e-09

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223    259 SYARVVDQSFAMLCQAQAFPLPIMRWYKfiegtTRKQAVVLNDRVKQV----SGTLIIKDAVVEDSGKYLCVVNNSVGGE 334
Cdd:smart00410    3 SVTVKEGESVTLSCEASGSPPPEVTWYK-----QGGKLLAESGRFSVSrsgsTSTLTISNVTPEDSGTYTCAATNSSGSA 77


                    ....*...
gi 386767223    335 SVETVLTV 342
Cdd:smart00410   78 SSGTTLTV 85

agrin-responsive second immunoglobulin-like domains (Ig2) of the Muscle-specific kinase (MuSK) ectodomain; a member of the I-set of Ig superfamily domains; The members here are composed of the second immunoglobulin-like (Ig) domains of the Muscle-specific kinase (MuSK) ectodomain. MuSK is a receptor tyrosine kinase specifically expressed in skeletal muscle, where it plays a central role in the formation and maintenance of the neuromuscular junction (NMJ). MuSK is activated by agrin, a neuron-derived heparan sulfate proteoglycan. The activation of MUSK in myotubes regulates the formation of NMJs through the regulation of different processes including the specific expression of genes in subsynaptic nuclei, the reorganization of the actin cytoskeleton and the clustering of the acetylcholine receptors (AChR) in the postsynaptic membrane. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the MuSK lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409560 [Multi-domain] Cd Length: 88 Bit Score: 56.10 E-value: 2.45e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  724 PTDKAFAQGSDAKVECKADGFPKPQVTWKKavGDTPgeykdLKKSDNIRV-EEGTLHVDNIQKTNEGYYLCEAINGIGSG 802
Cdd:cd20968     6 PTNVTIIEGLKAVLPCTTMGNPKPSVSWIK--GDDL-----IKENNRIAVlESGSLRIHNVQKEDAGQYRCVAKNSLGIA 78

                          90
                  ....*....|
gi 386767223  803 LSAVIMISVQ 812
Cdd:cd20968    79 YSKPVTIEVE 88

Third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, Robo3), and three mammalian Slit homologs (Slit-1,Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, and Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409390 [Multi-domain] Cd Length: 83 Bit Score: 55.48 E-value: 2.80e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  532 IRQMEKKAIVAGETLIVTCPVAGYPIDSIVWERDNRALPINRKQkVFPNGTLIIENVErNSDQATYTCVAKNQEG-YSAR 610
Cdd:cd05725     1 VKRPQNQVVLVDDSAEFQCEVGGDPVPTVRWRKEDGELPKGRYE-ILDDHSLKIRKVT-AGDMGSYTCVAENMVGkIEAS 78


                  ....*
gi 386767223  611 GSLEV 615
Cdd:cd05725    79 ATLTV 83

Fourth Ig domain of the neural cell adhesion molecule contactin-2, and similar domains; The members here are composed of the fourth Ig domain of the neural cell adhesion molecule contactin-2. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-2 (also called TAG-1, axonin-1) facilitates cell adhesion by homophilic binding between molecules in apposed membranes. The first four Ig domains form the intermolecular binding fragment which arranges as a compact U-shaped module by contacts between Ig domains 1 and 4, and domains 2 and 3. It has been proposed that a linear zipper-like array forms, from contactin-2 molecules alternatively provided by the two apposed membranes.

Pssm-ID: 143205 [Multi-domain] Cd Length: 85 Bit Score: 55.68 E-value: 2.82e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  446 GPSVFLKCVAGGNPTPEISWELDGKKIANNDRYQVgqyvtVNGDvvsyLNITSVHANDGGLYKCIAKSKVGVAEHSAKLN 525
Cdd:cd05728    14 GSSLRWECKASGNPRPAYRWLKNGQPLASENRIEV-----EAGD----LRITKLSLSDSGMYQCVAENKHGTIYASAELA 84


                  .
gi 386767223  526 V 526
Cdd:cd05728    85 V 85

Third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, Robo3), and three mammalian Slit homologs (Slit-1,Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, and Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409390 [Multi-domain] Cd Length: 83 Bit Score: 55.48 E-value: 3.05e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223 1310 PSDQVpakiASFDDTftATFKedakmpCLAVGAPQPEITWKIKGVEFSANdRMRVLPDGSLLIKSVNRQDAGDYSCHAEN 1389
Cdd:cd05725     4 PQNQV----VLVDDS--AEFQ------CEVGGDPVPTVRWRKEDGELPKG-RYEILDDHSLKIRKVTAGDMGSYTCVAEN 70

                          90
                  ....*....|...
gi 386767223 1390 SIAKDSITHKLIV 1402
Cdd:cd05725    71 MVGKIEASATLTV 83

Immunoglobulin (Ig)-like domain of myotilin, palladin, and myopalladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig)-like domain in myotilin, palladin, and myopalladin. Myotilin, palladin, and myopalladin function as scaffolds that regulate actin organization. Myotilin and myopalladin are most abundant in skeletal and cardiac muscle; palladin is ubiquitously expressed in the organs of developing vertebrates and plays a key role in cellular morphogenesis. The three family members each interact with specific molecular partners with all three binding to alpha-actinin; In addition, palladin also binds to vasodilator-stimulated phosphoprotein (VASP) and ezrin, myotilin binds to filamin and actin, and myopalladin also binds to nebulin and cardiac ankyrin repeat protein (CARP). This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409405 [Multi-domain] Cd Length: 91 Bit Score: 55.58 E-value: 3.64e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223 1315 PAKIASFDDtFTATFKEDAKMPCLAVGAPQPEITWKIKG--VEFSANDRMRVLPDG--SLLIKSVNRQDAGDYSCHAENS 1390
Cdd:cd05744     1 PHFLQAPGD-LEVQEGRLCRFDCKVSGLPTPDLFWQLNGkpVRPDSAHKMLVRENGrhSLIIEPVTKRDAGIYTCIARNR 79

                          90
                  ....*....|..
gi 386767223 1391 IAKDSITHKLIV 1402
Cdd:cd05744    80 AGENSFNAELVV 91

Fifth immunoglobulin (Ig) domain of contactin; The members here are composed of the fifth immunoglobulin (Ig) domain of contactins. Contactins are neural cell adhesion molecules and are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module via contacts between Ig domains 1 and 4, and between Ig domains 2 and 3. Contactin-2 (TAG-1, axonin-1) may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. This group also includes contactin-1 and contactin-5. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-5 is expressed specifically in the rat postnatal nervous system, peaking at about 3 weeks postnatal, and a lack of contactin-5 (NB-2) results in an impairment of neuronal activity in the rat auditory system. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma.

Pssm-ID: 409358 [Multi-domain] Cd Length: 89 Bit Score: 55.54 E-value: 3.75e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  534 QMEKKAIVA-GETLIVTCPVAGYPIDSIVWERDNRALPINRKQKVFPNGTLIIENVERnSDQATYTCVAKNQEGY-SARG 611
Cdd:cd04969     7 PVKKKILAAkGGDVIIECKPKASPKPTISWSKGTELLTNSSRICILPDGSLKIKNVTK-SDEGKYTCFAVNFFGKaNSTG 85


                  ....
gi 386767223  612 SLEV 615
Cdd:cd04969    86 SLSV 89

Fourth immunoglobulin (Ig)-like domain of hemolin, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain of hemolin and similar proteins. Hemolin, an insect immunoglobulin superfamily (IgSF) member containing four Ig-like domains, is a lipopolysaccharide-binding immune protein induced during bacterial infection. Hemolin shares significant sequence similarity with the first four Ig-like domains of the transmembrane cell adhesion molecules (CAMs) of the L1 family. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The fourth Ig-like domain of hemolin is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409570 [Multi-domain] Cd Length: 88 Bit Score: 55.48 E-value: 3.87e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  718 PRWILEP-TDKAFAQGSDAKVECKADGFPKPQVTW---KKAVGDTPGEYKdlkksdnirVEEGTLHVDNIQKTNEGYYLC 793
Cdd:cd20978     1 PKFIQKPeKNVVVKGGQDVTLPCQVTGVPQPKITWlhnGKPLQGPMERAT---------VEDGTLTIINVQPEDTGYYGC 71


                  ....*..
gi 386767223  794 EAINGIG 800
Cdd:cd20978    72 VATNEIG 78

Third immunoglobulin (Ig) domain of contactin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig) domain of contactins. Contactins are neural cell adhesion molecules and are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module via contacts between Ig domains 1 and 4, and between Ig domains 2 and 3. Contactin-2 (TAG-1, axonin-1) may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. This group also includes contactin-1 and contactin-5. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-5 is expressed specifically in the rat postnatal nervous system, peaking at about 3 weeks postnatal, and a lack of contactin-5 (NB-2) results in an impairment of neuronal activity in the rat auditory system. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma. This group belongs to the I-set of IgSF domains.

Pssm-ID: 409357 [Multi-domain] Cd Length: 88 Bit Score: 55.25 E-value: 4.02e-09

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 386767223  724 PTDKAFAQGSDAKVECKADGFPKPQVTWKKAVGDTPGEYKdlkksdnIRVEEGTLHVDNIQKTNEGYYLCEAINGIG 800
Cdd:cd04968     8 PADTYALKGQTVTLECFALGNPVPQIKWRKVDGSPSSQWE-------ITTSEPVLEIPNVQFEDEGTYECEAENSRG 77

Fourth immunoglobulin (Ig)-like domain of hemolin, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain of hemolin and similar proteins. Hemolin, an insect immunoglobulin superfamily (IgSF) member containing four Ig-like domains, is a lipopolysaccharide-binding immune protein induced during bacterial infection. Hemolin shares significant sequence similarity with the first four Ig-like domains of the transmembrane cell adhesion molecules (CAMs) of the L1 family. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The fourth Ig-like domain of hemolin is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409570 [Multi-domain] Cd Length: 88 Bit Score: 55.09 E-value: 4.30e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  530 PYIRQMEKKAIVA--GETLIVTCPVAGYPIDSIVWERDNRALPINRKQKVFPNGTLIIENVeRNSDQATYTCVAKNQEGY 607
Cdd:cd20978     1 PKFIQKPEKNVVVkgGQDVTLPCQVTGVPQPKITWLHNGKPLQGPMERATVEDGTLTIINV-QPEDTGYYGCVATNEIGD 79

Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor, and similar domains; member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor. FGF receptors bind FGF signaling polypeptides. FGFs participate in multiple processes such as morphogenesis, development, and angiogenesis. FGFs bind to four FGF receptor tyrosine kinases (FGFR1, FGFR2, FGFR3, FGFR4). Receptor diversity is controlled by alternative splicing producing splice variants with different ligand binding characteristics and different expression patterns. FGFRs have an extracellular region comprised of three Ig-like domains, a single transmembrane helix, and an intracellular tyrosine kinase domain. Ligand binding and specificity reside in the Ig-like domains 2 and 3, and the linker region that connects these two. FGFR activation and signaling depend on FGF-induced dimerization, a process involving cell surface heparin or heparin sulfate proteoglycans. This group also contains fibroblast growth factor (FGF) receptor like-1(FGFRL1). FGFRL1 does not have a protein tyrosine kinase domain at its C-terminus; neither does its cytoplasmic domain appear to interact with a signaling partner. It has been suggested that FGFRL1 may not have any direct signaling function, but instead acts as a decoy receptor trapping FGFs and preventing them from binding other receptors.

Pssm-ID: 409393 [Multi-domain] Cd Length: 95 Bit Score: 55.30 E-value: 4.44e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  446 GPSVFLKCVAGGNPTPEISWELDGKKIANNDRYQVGQyvtvNGDVVSYLNITSVHANDGGLYKCIAKSKVGVAEHSAKLN 525
Cdd:cd05729    19 ANKVRLECGAGGNPMPNITWLKDGKEFKKEHRIGGTK----VEEKGWSLIIERAIPRDKGKYTCIVENEYGSINHTYDVD 94


                  .
gi 386767223  526 V 526
Cdd:cd05729    95 V 95

Fourth immunoglobulin (Ig)-like domain in neogenin, and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain in neogenin and related proteins. Neogenin is a cell surface protein which is expressed in the developing nervous system of vertebrate embryos in the growing nerve cells. It is also expressed in other embryonic tissues, and may play a general role in developmental processes such as cell migration, cell-cell recognition, and tissue growth regulation. Included in this group is the tumor suppressor protein DCC which is deleted in colorectal carcinoma. DCC and neogenin each have four Ig-like domains followed by six fibronectin type III domains, a transmembrane domain, and an intracellular domain. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409388 Cd Length: 84 Bit Score: 54.89 E-value: 4.49e-09

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 386767223  364 VFTCQYTGNPIKTVSWMKDGKAIGHS-------EPVLRIESVKKEDKGMYQCFVRNDQESAEASAEL 423
Cdd:cd05723    16 VFECEVTGKPTPTVKWVKNGDVVIPSdyfkivkEHNLQVLGLVKSDEGFYQCIAENDVGNAQASAQL 82

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409353 [Multi-domain] Cd Length: 70 Bit Score: 54.26 E-value: 5.83e-09

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 386767223  735 AKVECKADGFPKPQVTWKKAVGDTPGEYKDLKKSDNirvEEGTLHVDNIQKTNEGYYLCEAINGIGSGLSAVI 807
Cdd:cd00096     1 VTLTCSASGNPPPTITWYKNGKPLPPSSRDSRRSEL---GNGTLTISNVTLEDSGTYTCVASNSAGGSASASV 70

Fibronectin type 3 domain; One of three types of internal repeat within the plasma protein, fibronectin. The tenth fibronectin type III repeat contains a RGD cell recognition sequence in a flexible loop between 2 strands. Type III modules are present in both extracellular and intracellular proteins.

Pssm-ID: 214495 [Multi-domain] Cd Length: 83 Bit Score: 54.54 E-value: 6.02e-09

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223   1218 PEAPTDVKALVMGNAAILVSWRPPAQPNGI--ITQYTVYSKAEGaeTETKTQKVPHYQMSFEATELEKNKPYEFWVTAST 1295
Cdd:smart00060    1 PSPPSNLRVTDVTSTSVTLSWEPPPDDGITgyIVGYRVEYREEG--SEWKEVNVTPSSTSYTLTGLKPGTEYEFRVRAVN 78


                    ....*
gi 386767223   1296 TIGEG 1300
Cdd:smart00060   79 GAGEG 83

Fourth immunoglobulin (Ig)-like domain of L1, Ng-CAM (Neuron-glia CAM cell adhesion molecule), and NrCAM (Ng-CAM-related); The members here are composed of the fourth immunoglobulin (Ig)-like domain of L1, Ng-CAM (Neuron-glia CAM cell adhesion molecule), and NrCAM (Ng-CAM-related). These proteins belong to the L1 subfamily of cell adhesion molecules (CAMs) and are comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region and an intracellular domain. These molecules are primarily expressed in the nervous system. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, or spastic paraplegia type 1, that involves abnormalities of axonal growth.

Pssm-ID: 409367 [Multi-domain] Cd Length: 89 Bit Score: 54.76 E-value: 6.16e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  719 RWILEPTDKAFAQGSDAKVECKADGFPKPQVTW---KKAVGDTPGEYKDlkksdniRVEEGTLHVDNIQKTNEGYYLCEA 795
Cdd:cd04978     1 YWIIEPPSLVLSPGETGELICEAEGNPQPTITWrlnGVPIEPAPEDMRR-------TVDGRTLIFSNLQPNDTAVYQCNA 73


                  ....*
gi 386767223  796 INGIG 800
Cdd:cd04978    74 SNVHG 78

Fourth Ig domain of the neural cell adhesion molecule contactin-2, and similar domains; The members here are composed of the fourth Ig domain of the neural cell adhesion molecule contactin-2. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-2 (also called TAG-1, axonin-1) facilitates cell adhesion by homophilic binding between molecules in apposed membranes. The first four Ig domains form the intermolecular binding fragment which arranges as a compact U-shaped module by contacts between Ig domains 1 and 4, and domains 2 and 3. It has been proposed that a linear zipper-like array forms, from contactin-2 molecules alternatively provided by the two apposed membranes.

Pssm-ID: 143205 [Multi-domain] Cd Length: 85 Bit Score: 54.53 E-value: 6.54e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  350 IDPPTQT-VDFGRPAVFTCQYTGNPIKTVSWMKDGKAIGHSEPV------LRIESVKKEDKGMYQCFVRNDQESAEASAE 422
Cdd:cd05728     3 LKVISDTeADIGSSLRWECKASGNPRPAYRWLKNGQPLASENRIeveagdLRITKLSLSDSGMYQCVAENKHGTIYASAE 82


                  ...
gi 386767223  423 LKL 425
Cdd:cd05728    83 LAV 85

Third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, Robo3), and three mammalian Slit homologs (Slit-1,Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, and Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409390 [Multi-domain] Cd Length: 83 Bit Score: 54.32 E-value: 6.80e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  723 EPTDKAFAQGSDAKVECKADGFPKPQVTWKKAVGDTP-GEYKDLkksdnirvEEGTLHVDNIQKTNEGYYLCEAINGIGS 801
Cdd:cd05725     3 RPQNQVVLVDDSAEFQCEVGGDPVPTVRWRKEDGELPkGRYEIL--------DDHSLKIRKVTAGDMGSYTCVAENMVGK 74

Fibronectin type III domain;

Pssm-ID: 394996 [Multi-domain] Cd Length: 85 Bit Score: 54.34 E-value: 7.22e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  1503 PEKPRFIEVSSNSVSLHFKAWKDGGCPMSHFVVE-SKKRDQIEWNQIsNNVKPDNNYVVLDLEPATWYNLRITAHNSAGF 1581
Cdd:pfam00041    3 PSNLTVTDVTSTSLTVSWTPPPDGNGPITGYEVEyRPKNSGEPWNEI-TVPGTTTSVTLTGLKPGTEYEVRVQAVNGGGE 81

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 54.57 E-value: 8.70e-09

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 386767223   272 CQAQAFPLPIMRWYKfiEGTTRKQAVVLNDRVKQVSGTLIIKDAVVEDSGKYLCVVNNSVGGESVETVLTV 342
Cdd:pfam07679   22 CTVTGTPDPEVSWFK--DGQPLRSSDRFKVTYEGGTYTLTISNVQPDDSGKYTCVATNSAGEAEASAELTV 90

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 54.11 E-value: 9.21e-09

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 386767223   259 SYARVVDQSFAMLCQAQAFPLPIMRWYKfiEGTTRKQAVVLNDRVKQVSGTLIIKDAVVEDSGKYLCVVNN 329
Cdd:pfam13927   10 SVTVREGETVTLTCEATGSPPPTITWYK--NGEPISSGSTRSRSLSGSNSTLTISNVTRSDAGTYTCVASN 78

Third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM), and similar domains; The members here are composed of the third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM). L1 belongs to the L1 subfamily of cell adhesion molecules (CAMs) and is comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region and an intracellular domain. L1 is primarily expressed in the nervous system and is involved in its development and function. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, and spastic paraplegia type 1, that involves abnormalities of axonal growth. This group also contains the chicken neuron-glia cell adhesion molecule, Ng-CAM and human neurofascin.

Pssm-ID: 409394 [Multi-domain] Cd Length: 83 Bit Score: 53.95 E-value: 9.48e-09

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 386767223  731 QGSDAKVECKADGFPKPQVTWKKAVGDTPgeyKDLKKSDNIRveeGTLHVDNIQKTNEGYYLCEAINGIGS 801
Cdd:cd05731     9 RGGVLLLECIAEGLPTPDIRWIKLGGELP---KGRTKFENFN---KTLKIENVSEADSGEYQCTASNTMGS 73

Fourth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.

Pssm-ID: 409548 [Multi-domain] Cd Length: 96 Bit Score: 54.49 E-value: 1.10e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223 1324 TFTATFKEDAKMP-------CLAVGAPQPEITWKIKGVEFSANDRMR----VLPDGSLL----IKSVNRQDAGDYSCHAE 1388
Cdd:cd20956     3 VLLETFSEQTLQPgpsvslkCVASGNPLPQITWTLDGFPIPESPRFRvgdyVTSDGDVVsyvnISSVRVEDGGEYTCTAT 82

                          90
                  ....*....|
gi 386767223 1389 NSIAkdSITH 1398
Cdd:cd20956    83 NDVG--SVSH 90

Second Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the titin Z1z2 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409564 [Multi-domain] Cd Length: 91 Bit Score: 54.13 E-value: 1.37e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  814 PPEFTEKLRNQTARRGEPAVLQCEAKGEKPIGILWNMNNMRLDPKNDNrytireEILSTGVMSSLSIKRTERSDSALFTC 893
Cdd:cd20972     1 PPQFIQKLRSQEVAEGSKVRLECRVTGNPTPVVRWFCEGKELQNSPDI------QIHQEGDLHSLIIAEAFEEDTGRYSC 74

                          90
                  ....*....|....*..
gi 386767223  894 VATNAFGSDDASINMIV 910
Cdd:cd20972    75 LATNSVGSDTTSAEIFV 91

Fifth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fifth immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.

Pssm-ID: 409550 [Multi-domain] Cd Length: 89 Bit Score: 53.73 E-value: 1.65e-08

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 386767223 1326 TATFKEDAKMPCLAVGAPQPEITWKIKGVEFSANDRMRVLPDGSLLIKSVNR-QDAGDYSCHAENS 1390
Cdd:cd20958    11 TAVAGQTLRLHCPVAGYPISSITWEKDGRRLPLNHRQRVFPNGTLVIENVQRsSDEGEYTCTARNQ 76

Fifth immunoglobulin (Ig)-like domain of Kirrel (kin of irregular chiasm-like) 3, and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the fifth immunoglobulin (Ig)-like domain of Kirrel (kin of irregular chiasm-like) 3 (also known as Neph2). This protein has five Ig-like domains, one transmembrane domain, and a cytoplasmic tail. Included in this group is mammalian Kirrel (also known as Neph1), Kirrel2 (also known as Neph3), and Drosophila RST (also known as irregular chiasm C-roughest) protein. These proteins contain multiple Ig domains, have properties of cell adhesion molecules, and are important in organ development.

Pssm-ID: 319310 Cd Length: 98 Bit Score: 53.69 E-value: 1.74e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  813 APPEFTeKLRNQTARRGEPAVLQCEAKGE-KPIGILWNMNNMRLDPKNDNRYTIREEILSTGVMSSLSIKRTERSD-SAL 890
Cdd:cd05758     1 GPPIIT-AEATQPAILGEKARLECLVFSSpPPDRIVWSWDEGFLESGSSGRFSVETFPTEPGVISVLHISGTQRSDfQTS 79

                          90
                  ....*....|....*...
gi 386767223  891 FTCVATNAFGSDDASINM 908
Cdd:cd05758    80 FNCSAWNRFGEGTAIVSL 97

Fibronectin type 3 domain; One of three types of internal repeat within the plasma protein, fibronectin. The tenth fibronectin type III repeat contains a RGD cell recognition sequence in a flexible loop between 2 strands. Type III modules are present in both extracellular and intracellular proteins.

Pssm-ID: 214495 [Multi-domain] Cd Length: 83 Bit Score: 53.39 E-value: 1.76e-08

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223   1120 PPSDTACTTLTSQTIRVGWVSPPLESANGVIKTYKVVYAPSDewyDETKRHYKKTASSDTVLHGLKKYTNYTMQVLATTA 1199
Cdd:smart00060    3 PPSNLRVTDVTSTSVTLSWEPPPDDGITGYIVGYRVEYREEG---SEWKEVNVTPSSTSYTLTGLKPGTEYEFRVRAVNG 79


                    ....
gi 386767223   1200 GGDG 1203
Cdd:smart00060   80 AGEG 83

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.

Pssm-ID: 214653 [Multi-domain] Cd Length: 85 Bit Score: 53.28 E-value: 1.77e-08

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223    724 PTDKAFAQGSDAKVECKADGFPKPQVTWKKavgdtpGEYKDLKKSDNIRVEE----GTLHVDNIQKTNEGYYLCEAINGI 799
Cdd:smart00410    1 PPSVTVKEGESVTLSCEASGSPPPEVTWYK------QGGKLLAESGRFSVSRsgstSTLTISNVTPEDSGTYTCAATNSS 74


                    ..
gi 386767223    800 GS 801
Cdd:smart00410   75 GS 76

Third immunoglobulin (Ig)-like domain of peroxidasin; The members here are composed of the third immunoglobulin (Ig)-like domain in peroxidasin. Peroxidasin has a peroxidase domain and interacting extracellular motifs containing four Ig-like domains. It has been suggested that peroxidasin is secreted and has functions related to the stabilization of the extracellular matrix. It may play a part in various other important processes such as removal and destruction of cells which have undergone programmed cell death and protection of the organism against non-self.

Pssm-ID: 143222 [Multi-domain] Cd Length: 74 Bit Score: 53.02 E-value: 2.04e-08

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 386767223 1336 PCLAVGAPQPEITWKIKGVEFSANDRMRVLPDGSLLIKSVNRQDAGDYSCHAENSIAKDSITHKLIV 1402
Cdd:cd05745     8 LCEAQGYPQPVIAWTKGGSQLSVDRRHLVLSSGTLRISRVALHDQGQYECQAVNIVGSQRTVAQLTV 74

Third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM), and similar domains; The members here are composed of the third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM). L1 belongs to the L1 subfamily of cell adhesion molecules (CAMs) and is comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region and an intracellular domain. L1 is primarily expressed in the nervous system and is involved in its development and function. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, and spastic paraplegia type 1, that involves abnormalities of axonal growth. This group also contains the chicken neuron-glia cell adhesion molecule, Ng-CAM and human neurofascin.

Pssm-ID: 409394 [Multi-domain] Cd Length: 83 Bit Score: 53.18 E-value: 2.11e-08

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 386767223  446 GPSVFLKCVAGGNPTPEISWELDGKKIANnDRYQVGQYVTVngdvvsyLNITSVHANDGGLYKCIAKSKVGVAEH 520
Cdd:cd05731    10 GGVLLLECIAEGLPTPDIRWIKLGGELPK-GRTKFENFNKT-------LKIENVSEADSGEYQCTASNTMGSARH 76

Second C-terminal immunoglobulin (Ig)-like domain of palladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of palladin. Palladin belongs to the palladin-myotilin-myopalladin family. Proteins belonging to this family contain multiple Ig-like domains and function as scaffolds, modulating actin cytoskeleton. Palladin binds to alpha-actinin ezrin, vasodilator-stimulated phosphoprotein VASP, SPIN90 (also known as DIP or mDia interacting protein), and Src. Palladin also binds F-actin directly, via its Ig3 domain. Palladin is expressed as several alternatively spliced isoforms, having various combinations of Ig-like domains, in a cell-type-specific manner. It has been suggested that palladin's different Ig-like domains may be specialized for distinct functions. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409582 Cd Length: 91 Bit Score: 53.18 E-value: 2.32e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  432 PVIRQAFQEETMEPGPSVFLKCVAGGNPTPEISWELDGKKIANNDRYQVgqYVTVNGdvVSYLNITSVHANDGGLYKCIA 511
Cdd:cd20990     1 PHFLQAPGDLTVQEGKLCRMDCKVSGLPTPDLSWQLDGKPIRPDSAHKM--LVRENG--VHSLIIEPVTSRDAGIYTCIA 76

                          90
                  ....*....|....*
gi 386767223  512 KSKVGVAEHSAKLNV 526
Cdd:cd20990    77 TNRAGQNSFNLELVV 91

Second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of the Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, and Robo3), and three mammalian Slit homologs (Slit-1,Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit-2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409389 [Multi-domain] Cd Length: 87 Bit Score: 52.79 E-value: 3.05e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  722 LEPTDKAFAQGSDAKVECKAD-GFPKPQVTWKKavgdtPGEYKDLkksDNIR---VEEGTLHVDNIQKTNEGYYLCEAIN 797
Cdd:cd05724     2 VEPSDTQVAVGEMAVLECSPPrGHPEPTVSWRK-----DGQPLNL---DNERvriVDDGNLLIAEARKSDEGTYKCVATN 73

                          90
                  ....*....|....
gi 386767223  798 GIGSGLSAVIMISV 811
Cdd:cd05724    74 MVGERESRAARLSV 87

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 52.64 E-value: 3.18e-08

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 386767223   636 GETMGIQCTVIkGDLPINITWVLNNHTLNSGDlDVVIgRMSSKSSTLNIDYIAAEHRGVYTCLARNQAGESSYSAELKV 714
Cdd:pfam07679   15 GESARFTCTVT-GTPDPEVSWFKDGQPLRSSD-RFKV-TYEGGTYTLTISNVQPDDSGKYTCVATNSAGEAEASAELTV 90

Seventh immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the seventh immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.

Pssm-ID: 409546 [Multi-domain] Cd Length: 96 Bit Score: 52.70 E-value: 4.08e-08

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 386767223 1332 DAKMPCLAVGAPQPEITWKiKGV--------EFSANDRMRVLPDGSLLIKSVNRQDAGDYSCHAENSI 1391
Cdd:cd20954    18 DVMLHCQADGFPTPTVTWK-KATgstpgeykDLLYDPNVRILPNGTLVFGHVQKENEGHYLCEAKNGI 84

First immunoglobulin (Ig)-like domain in neogenin, and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the first immunoglobulin (Ig)-like domain in neogenin and related proteins. Neogenin is a cell surface protein which is expressed in the developing nervous system of vertebrate embryos in the growing nerve cells. It is also expressed in other embryonic tissues and may play a general role in developmental processes such as cell migration, cell-cell recognition, and tissue growth regulation. Included in this group is the tumor suppressor protein DCC which is deleted in colorectal carcinoma. DCC and neogenin each have four Ig-like domains followed by six fibronectin type III domains, a transmembrane domain, and an intracellular domain. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409387 Cd Length: 97 Bit Score: 52.87 E-value: 4.11e-08

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 386767223 1335 MPCLAVGAPQPEITWKIKGV--EFSANDRMRVLPDGSLLIKSV-----NRQDAGDYSCHAEN 1389
Cdd:cd05722    21 LNCSAESDPPPKIEWKKDGVllNLVSDERRQQLPNGSLLITSVvhskhNKPDEGFYQCVAQN 82

Fourth immunoglobulin (Ig)-like domain of L1, Ng-CAM (Neuron-glia CAM cell adhesion molecule), and NrCAM (Ng-CAM-related); The members here are composed of the fourth immunoglobulin (Ig)-like domain of L1, Ng-CAM (Neuron-glia CAM cell adhesion molecule), and NrCAM (Ng-CAM-related). These proteins belong to the L1 subfamily of cell adhesion molecules (CAMs) and are comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region and an intracellular domain. These molecules are primarily expressed in the nervous system. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, or spastic paraplegia type 1, that involves abnormalities of axonal growth.

Pssm-ID: 409367 [Multi-domain] Cd Length: 89 Bit Score: 52.45 E-value: 4.17e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  439 QEETMEPGPSVFLKCVAGGNPTPEISWELDGKKIANNDRYQVgqyVTVNGDVVSYLNITSvhaNDGGLYKCIAKSKVGVA 518
Cdd:cd04978     7 PSLVLSPGETGELICEAEGNPQPTITWRLNGVPIEPAPEDMR---RTVDGRTLIFSNLQP---NDTAVYQCNASNVHGYL 80


                  ....*...
gi 386767223  519 EHSAKLNV 526
Cdd:cd04978    81 LANAFLHV 88

Fibronectin type III domain;

Pssm-ID: 394996 [Multi-domain] Cd Length: 85 Bit Score: 52.42 E-value: 4.27e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  1120 PPSDTACTTLTSQTIRVGWVSPPleSANGVIKTYKVVYAPSDEwyDETKRHYKKTASSDTV-LHGLKKYTNYTMQVLATT 1198
Cdd:pfam00041    2 APSNLTVTDVTSTSLTVSWTPPP--DGNGPITGYEVEYRPKNS--GEPWNEITVPGTTTSVtLTGLKPGTEYEVRVQAVN 77


                   ....*...
gi 386767223  1199 AGGDGVRS 1206
Cdd:pfam00041   78 GGGEGPPS 85

Immunoglobulin (Ig)-like I-set domain of Neural Cell Adhesion Molecule 1 (NCAM-1) and similar proteins; The members here are composed of the fourth immunoglobulin (Ig)-like domain of Neural Cell Adhesion Molecule (NCAM-1). NCAM plays important roles in the development and regeneration of the central nervous system, in synaptogenesis and neural migration. NCAM mediates cell-cell and cell-substratum recognition and adhesion via homophilic (NCAM-NCAM), and heterophilic (NCAM-non-NCAM), interactions. NCAM is expressed as three major isoforms having different intracellular extensions. The extracellular portion of NCAM has five N-terminal Ig-like domains and two fibronectin type III domains. The double zipper adhesion complex model for NCAM homophilic binding involves Ig1, Ig2, and Ig3. By this model, Ig1 and Ig2 mediate dimerization of NCAM molecules situated on the same cell surface (cis interactions), and Ig3 domains mediate interactions between NCAM molecules expressed on the surface of opposing cells (trans interactions), through binding to the Ig1 and Ig2 domains. The adhesive ability of NCAM is modulated by the addition of polysialic acid chains to the fifth Ig-like domain. Also included in this group is NCAM-2 (also known as OCAM/mamFas II and RNCAM) NCAM-2 is differentially expressed in the developing and mature olfactory epithelium (OE). One of the unique features of I-set domains is the lack of a C" strand. The structures of this group show that the Ig domain lacks this strand and thus is a member of the I-set of Ig domains.

Pssm-ID: 409395 [Multi-domain] Cd Length: 96 Bit Score: 52.53 E-value: 5.05e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  432 PVIRQAFQEETMEPGpSVFLKCVAGGNPTPEISWELDGKKIANNDRYQVGQyVTVNGDV-VSYLNITSVHANDGGLYKCI 510
Cdd:cd05732     3 PKITYLENQTAVELE-QITLTCEAEGDPIPEITWRRATRGISFEEGDLDGR-IVVRGHArVSSLTLKDVQLTDAGRYDCE 80

                          90
                  ....*....|....*.
gi 386767223  511 AKSKVGVAEHSAKLNV 526
Cdd:cd05732    81 ASNRIGGDQQSMYLEV 96

Fifth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fifth immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.

Pssm-ID: 409550 [Multi-domain] Cd Length: 89 Bit Score: 52.18 E-value: 5.32e-08

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 386767223  360 GRPAVFTCQYTGNPIKTVSWMKDGKA--IGHSEPV-----LRIESV-KKEDKGMYQCFVRNDQ-ESAEASAELK 424
Cdd:cd20958    15 GQTLRLHCPVAGYPISSITWEKDGRRlpLNHRQRVfpngtLVIENVqRSSDEGEYTCTARNQQgQSASRSVFVK 88

Third immunoglobulin (Ig) domain of contactin-1; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig) domain of the neural cell adhesion molecule contactin-1. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-1 is differentially expressed in tumor tissues and may through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma. This group belongs to the I-set of IgSF domains.

Pssm-ID: 143259 Cd Length: 88 Bit Score: 51.95 E-value: 6.07e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  431 PPVIRQAFQEETMEPGPSVFLKCVAGGNPTPEISWeldgKKIanNDRYQVGQYVTVNGDVVSYLNItsvHANDGGLYKCI 510
Cdd:cd05851     1 PADINVKFKDTYALKGQNVTLECFALGNPVPVIRW----RKI--LEPMPATAEISMSGAVLKIFNI---QPEDEGTYECE 71

                          90
                  ....*....|....*.
gi 386767223  511 AKSKVGVAEHSAKLNV 526
Cdd:cd05851    72 AENIKGKDKHQARVYV 87

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 51.41 E-value: 6.51e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223   620 PPQIRPFdFGDEASNSGETMGIQCTVIKGDLPiNITWVLNNHTLNSGDldVVIGRMSSKSSTLNIDYIAAEHRGVYTCLA 699
Cdd:pfam13927    1 KPVITVS-PSSVTVREGETVTLTCEATGSPPP-TITWYKNGEPISSGS--TRSRSLSGSNSTLTISNVTRSDAGTYTCVA 76


                   ..
gi 386767223   700 RN 701
Cdd:pfam13927   77 SN 78

Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor, and similar domains; member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor. FGF receptors bind FGF signaling polypeptides. FGFs participate in multiple processes such as morphogenesis, development, and angiogenesis. FGFs bind to four FGF receptor tyrosine kinases (FGFR1, FGFR2, FGFR3, FGFR4). Receptor diversity is controlled by alternative splicing producing splice variants with different ligand binding characteristics and different expression patterns. FGFRs have an extracellular region comprised of three Ig-like domains, a single transmembrane helix, and an intracellular tyrosine kinase domain. Ligand binding and specificity reside in the Ig-like domains 2 and 3, and the linker region that connects these two. FGFR activation and signaling depend on FGF-induced dimerization, a process involving cell surface heparin or heparin sulfate proteoglycans. This group also contains fibroblast growth factor (FGF) receptor like-1(FGFRL1). FGFRL1 does not have a protein tyrosine kinase domain at its C-terminus; neither does its cytoplasmic domain appear to interact with a signaling partner. It has been suggested that FGFRL1 may not have any direct signaling function, but instead acts as a decoy receptor trapping FGFs and preventing them from binding other receptors.

Pssm-ID: 409393 [Multi-domain] Cd Length: 95 Bit Score: 52.22 E-value: 6.67e-08

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 386767223  261 ARVVDQSFAMLCQAQAFPLPIMRWYKfiEGTTRKQAVVLN-DRVKQVSGTLIIKDAVVEDSGKYLCVVNNSVG 332
Cdd:cd05729    15 ALPAANKVRLECGAGGNPMPNITWLK--DGKEFKKEHRIGgTKVEEKGWSLIIERAIPRDKGKYTCIVENEYG 85

Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor_like-1(FGFRL1); member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor like-1(FGFRL1). FGFRL1 is comprised of a signal peptide, three extracellular Ig-like modules, a transmembrane segment, and a short intracellular domain. FGFRL1 is expressed preferentially in skeletal tissues. Similar to FGF receptors, the expressed protein interacts specifically with heparin and with FGF2. FGFRL1 does not have a protein tyrosine kinase domain at its C-terminus; neither does its cytoplasmic domain appear to interact with a signaling partner. It has been suggested that FGFRL1 may not have any direct signaling function, but instead acts as a decoy receptor trapping FGFs and preventing them from binding other receptors.

Pssm-ID: 409442 Cd Length: 92 Bit Score: 51.40 E-value: 1.05e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  443 MEP-GPSVFLKCVAGGNPTPEISWELDGKKIannDRYQVGQyvtvNGDVVSYLNITSVHANDGGLYKCIAKSKVGVAEHS 521
Cdd:cd05856    15 ARPvGSSVRLKCVASGNPRPDITWLKDNKPL---TPPEIGE----NKKKKWTLSLKNLKPEDSGKYTCHVSNRAGEINAT 87


                  ....*
gi 386767223  522 AKLNV 526
Cdd:cd05856    88 YKVDV 92

Immunoglobulin I-set domain of the Leucine-rich repeat and immunoglobin-like domain-containing protein 1 (Lingo-1); The members here are composed of the immunoglobulin I-set (IgI) domain of the Leucine-rich repeat and immunoglobin-like domain-containing protein 1 (Lingo-1). Human Lingo-1 is a central nervous system-specific transmembrane glycoprotein also known as LERN-1, which functions as a negative regulator of neuronal survival, axonal regeneration, and oligodendrocyte differentiation and myelination. Lingo-1 is a key component of the Nogo receptor signaling complex (RTN4R/NGFR) in RhoA activation responsible for some inhibition of axonal regeneration by myelin-associated factors. The ligand-binding ectodomain of human Lingo-1 contains a bimodular, kinked structure composed of leucine-rich repeat (LRR) and immunoglobulin (Ig)-like modules. Diseases associated with Lingo-1 include mental retardation, autosomal recessive 64 and essential tremor. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the Lingo-1 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409561 Cd Length: 92 Bit Score: 51.24 E-value: 1.13e-07

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 386767223 1337 CLAVGAPQPEITWKIKG---VEFSANDRMRVLPDGSLLIKSVNRQDAGDYSCHAENSIAKDSITHKLIV 1402
Cdd:cd20969    24 CRADGDPPPAILWLSPRkhlVSAKSNGRLTVFPDGTLEVRYAQVQDNGTYLCIAANAGGNDSMPAHLHV 92

Third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, Robo3), and three mammalian Slit homologs (Slit-1,Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, and Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409390 [Multi-domain] Cd Length: 83 Bit Score: 50.86 E-value: 1.20e-07

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 386767223  352 PPTQTVDFGRPAVFTCQYTGNPIKTVSW------MKDGKAIGHSEPVLRIESVKKEDKGMYQCFVRNDQESAEASAEL 423
Cdd:cd05725     4 PQNQVVLVDDSAEFQCEVGGDPVPTVRWrkedgeLPKGRYEILDDHSLKIRKVTAGDMGSYTCVAENMVGKIEASATL 81

Fourth immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; Members here are composed the fourth immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, Robo3), and three mammalian Slit homologs (Slit-1, Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, and Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409391 [Multi-domain] Cd Length: 98 Bit Score: 51.50 E-value: 1.28e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  719 RWILEPTDKAFAQGSDAKVECKADGFPKPQVTWKK-AVGDTPGEYKDLKKSDNIRVEE-GTLHVDNIQKTNEGYYLCEAI 796
Cdd:cd05726     1 QFVVKPRDQVVALGRTVTFQCETKGNPQPAIFWQKeGSQNLLFPYQPPQPSSRFSVSPtGDLTITNVQRSDVGYYICQAL 80


                  ....*...
gi 386767223  797 NGIGSGLS 804
Cdd:cd05726    81 NVAGSILA 88

Immunoglobulin (Ig)-like I-set domain of Neural Cell Adhesion Molecule 1 (NCAM-1); The members here are composed of the fourth Ig domain of Neural Cell Adhesion Molecule 1(NCAM-1). NCAM plays important roles in the development and regeneration of the central nervous system, in synaptogenesis and neural migration. NCAM mediates cell-cell and cell-substratum recognition and adhesion via homophilic (NCAM-NCAM) and heterophilic (NCAM-non-NCAM) interactions. NCAM is expressed as three major isoforms having different intracellular extensions. The extracellular portion of NCAM has five N-terminal Ig-like domains and two fibronectin type III domains. The double zipper adhesion complex model for NCAM homophilic binding involves Ig1, Ig2, and Ig3. By this model, Ig1 and Ig2 mediate dimerization of NCAM molecules situated on the same cell surface (cis interactions), and Ig3 domains mediate interactions between NCAM molecules expressed on the surface of opposing cells (trans interactions), through binding to the Ig1 and Ig2 domains. The adhesive ability of NCAM is modulated by the addition of polysialic acid chains to the fifth Ig-like domain. One of the unique features of I-set domains is the lack of a C" strand. The structures of this group show that the Ig domain lacks this strand and thus is a member of the I-set of Ig domains.

Pssm-ID: 143277 [Multi-domain] Cd Length: 97 Bit Score: 51.52 E-value: 1.33e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  432 PVIRQAFQEETMEPGPSVFLKCVAGGNPTPEISWELDGKKIANNDRYQVGQYVTVNGDVVSYLNITSVHANDGGLYKCIA 511
Cdd:cd05869     3 PKITYVENQTAMELEEQITLTCEASGDPIPSITWRTSTRNISSEEKTLDGHIVVRSHARVSSLTLKYIQYTDAGEYLCTA 82

                          90
                  ....*....|....*
gi 386767223  512 KSKVGVAEHSAKLNV 526
Cdd:cd05869    83 SNTIGQDSQSMYLEV 97

Immunoglobulin (Ig)-like I-set domain of Neural Cell Adhesion Molecule 1 (NCAM-1) and similar proteins; The members here are composed of the fourth immunoglobulin (Ig)-like domain of Neural Cell Adhesion Molecule (NCAM-1). NCAM plays important roles in the development and regeneration of the central nervous system, in synaptogenesis and neural migration. NCAM mediates cell-cell and cell-substratum recognition and adhesion via homophilic (NCAM-NCAM), and heterophilic (NCAM-non-NCAM), interactions. NCAM is expressed as three major isoforms having different intracellular extensions. The extracellular portion of NCAM has five N-terminal Ig-like domains and two fibronectin type III domains. The double zipper adhesion complex model for NCAM homophilic binding involves Ig1, Ig2, and Ig3. By this model, Ig1 and Ig2 mediate dimerization of NCAM molecules situated on the same cell surface (cis interactions), and Ig3 domains mediate interactions between NCAM molecules expressed on the surface of opposing cells (trans interactions), through binding to the Ig1 and Ig2 domains. The adhesive ability of NCAM is modulated by the addition of polysialic acid chains to the fifth Ig-like domain. Also included in this group is NCAM-2 (also known as OCAM/mamFas II and RNCAM) NCAM-2 is differentially expressed in the developing and mature olfactory epithelium (OE). One of the unique features of I-set domains is the lack of a C" strand. The structures of this group show that the Ig domain lacks this strand and thus is a member of the I-set of Ig domains.

Pssm-ID: 409395 [Multi-domain] Cd Length: 96 Bit Score: 50.99 E-value: 1.48e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223 1326 TATFKEDAKMPCLAVGAPQPEITWK--IKGVEFSANDrmrvlPDG-----------SLLIKSVNRQDAGDYSCHAENSIA 1392
Cdd:cd05732    12 TAVELEQITLTCEAEGDPIPEITWRraTRGISFEEGD-----LDGrivvrgharvsSLTLKDVQLTDAGRYDCEASNRIG 86


                  ...
gi 386767223 1393 KDS 1395
Cdd:cd05732    87 GDQ 89

C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin, and similar domains; member of the I-set IgSF domains; The members here are composed of the C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin and similar proteins, including Caenorhabditis elegans and Aplysia californica Twitchin, Drosophila melanogaster Projectin, and similar proteins. These are very large muscle proteins containing multiple immunoglobulin (Ig)-like and fibronectin type III (FN3) domains and a single kinase domain near the C-terminus. In humans these proteins are called Titin. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The Ig-like domain of the Twitchin is a member of the I-set IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins (titin, telokin, and twitchin), the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D.

Pssm-ID: 409541 [Multi-domain] Cd Length: 89 Bit Score: 50.79 E-value: 1.72e-07

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223 1331 EDAKMPCLAVGAPQPEITWKIKGVEFSAN----DRMRVLPDGsLLIKSVNRQDAGDYSCHAE--NSIAKD 1394
Cdd:cd20949    15 QSATILCEVKGEPQPNVTWHFNGQPISASvadmSKYRILADG-LLINKVTQDDTGEYTCRAYqvNSIASD 83

Immunoglobulin (Ig)-like domain of myotilin, palladin, and myopalladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig)-like domain in myotilin, palladin, and myopalladin. Myotilin, palladin, and myopalladin function as scaffolds that regulate actin organization. Myotilin and myopalladin are most abundant in skeletal and cardiac muscle; palladin is ubiquitously expressed in the organs of developing vertebrates and plays a key role in cellular morphogenesis. The three family members each interact with specific molecular partners with all three binding to alpha-actinin; In addition, palladin also binds to vasodilator-stimulated phosphoprotein (VASP) and ezrin, myotilin binds to filamin and actin, and myopalladin also binds to nebulin and cardiac ankyrin repeat protein (CARP). This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409405 [Multi-domain] Cd Length: 91 Bit Score: 50.96 E-value: 1.75e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  628 FGDEASNSGETMGIQCTViKGDLPINITWVLNNHTLNSGDLDVVIGRmSSKSSTLNIDYIAAEHRGVYTCLARNQAGESS 707
Cdd:cd05744     7 PGDLEVQEGRLCRFDCKV-SGLPTPDLFWQLNGKPVRPDSAHKMLVR-ENGRHSLIIEPVTKRDAGIYTCIARNRAGENS 84


                  ....*..
gi 386767223  708 YSAELKV 714
Cdd:cd05744    85 FNAELVV 91

Third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, Robo3), and three mammalian Slit homologs (Slit-1,Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, and Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409390 [Multi-domain] Cd Length: 83 Bit Score: 50.47 E-value: 1.81e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  439 QEETMEPGPSVFLKCVAGGNPTPEISWELDGKKIANNdRYQVGQYVTvngdvvsyLNITSVHANDGGLYKCIAKSKVGVA 518
Cdd:cd05725     5 QNQVVLVDDSAEFQCEVGGDPVPTVRWRKEDGELPKG-RYEILDDHS--------LKIRKVTAGDMGSYTCVAENMVGKI 75


                  ....*...
gi 386767223  519 EHSAKLNV 526
Cdd:cd05725    76 EASATLTV 83

First immunoglobulin (Ig) domain of contactin; member of the I-set of (Ig) superfamily domains; The members here are composed of the first immunoglobulin (Ig) domain of contactins. Contactins are neural cell adhesion molecules and are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module via contacts between Ig domains 1 and 4, and between Ig domains 2 and 3. Contactin-2 (TAG-1, axonin-1) may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. This group also includes contactin-1 and contactin-5. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-5 is expressed specifically in the rat postnatal nervous system, peaking at about 3 weeks postnatal, and a lack of contactin-5 (NB-2) results in an impairment of neuronal activity in the rat auditory system. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma. This group belongs to the I-set of IgSF domains.

Pssm-ID: 409356 [Multi-domain] Cd Length: 96 Bit Score: 51.09 E-value: 1.82e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223   38 GPVFLKEPTNRI--DFSNSTGAEIECKASGNPMPEIIWIRsDGTAVGDVPGLRQISSDGKLVFP-PFRAEDyrqevhAQV 114
Cdd:cd04967     1 GPVFEEQPDDTIfpEDSDEKKVALNCRARANPVPSYRWLM-NGTEIDLESDYRYSLVDGTLVISnPSKAKD------AGH 73

                          90       100
                  ....*....|....*....|
gi 386767223  115 YACLARNQFGSIISRDVHVR 134
Cdd:cd04967    74 YQCLATNTVGSVLSREATLQ 93

Immunoglobulin (Ig)-like I-set domain of Neural Cell Adhesion Molecule 1 (NCAM-1) and similar proteins; The members here are composed of the fourth immunoglobulin (Ig)-like domain of Neural Cell Adhesion Molecule (NCAM-1). NCAM plays important roles in the development and regeneration of the central nervous system, in synaptogenesis and neural migration. NCAM mediates cell-cell and cell-substratum recognition and adhesion via homophilic (NCAM-NCAM), and heterophilic (NCAM-non-NCAM), interactions. NCAM is expressed as three major isoforms having different intracellular extensions. The extracellular portion of NCAM has five N-terminal Ig-like domains and two fibronectin type III domains. The double zipper adhesion complex model for NCAM homophilic binding involves Ig1, Ig2, and Ig3. By this model, Ig1 and Ig2 mediate dimerization of NCAM molecules situated on the same cell surface (cis interactions), and Ig3 domains mediate interactions between NCAM molecules expressed on the surface of opposing cells (trans interactions), through binding to the Ig1 and Ig2 domains. The adhesive ability of NCAM is modulated by the addition of polysialic acid chains to the fifth Ig-like domain. Also included in this group is NCAM-2 (also known as OCAM/mamFas II and RNCAM) NCAM-2 is differentially expressed in the developing and mature olfactory epithelium (OE). One of the unique features of I-set domains is the lack of a C" strand. The structures of this group show that the Ig domain lacks this strand and thus is a member of the I-set of Ig domains.

Pssm-ID: 409395 [Multi-domain] Cd Length: 96 Bit Score: 50.60 E-value: 2.24e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  813 APPEFTeKLRNQTARRGEPAVLQCEAKGEKPIGILW-----NMNNMRLDPknDNRYTIREEILstgvMSSLSIKRTERSD 887
Cdd:cd05732     1 VQPKIT-YLENQTAVELEQITLTCEAEGDPIPEITWrratrGISFEEGDL--DGRIVVRGHAR----VSSLTLKDVQLTD 73

                          90
                  ....*....|....*....
gi 386767223  888 SALFTCVATNAFGSDDASI 906
Cdd:cd05732    74 AGRYDCEASNRIGGDQQSM 92

Immunoglobulin (Ig)-like domain of human neurofascin (NF); member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the first immunoglobulin (Ig)-like domain of human neurofascin (NF). NF belongs to the L1 subfamily of cell adhesion molecules (CAMs) and is comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region, and a cytoplasmic domain. NF has many alternatively spliced isoforms having different temporal expression patterns during development. NF participates in axon subcellular targeting and synapse formation, however little is known of the functions of the different isoforms. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lacks a C" strand.

Pssm-ID: 409459 Cd Length: 95 Bit Score: 50.36 E-value: 2.50e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223   59 IECKASGNPMPEIIWIR-SDGTAVGDVPGLRQISSDGKLVFPPF---RAEDYRQEvhaqvYACLARNQFGSIISRDVHVR 134
Cdd:cd05875    21 IECEAKGNPVPTFHWTRnGKFFNVAKDPRVSMRRRSGTLVIDFRgggRPEDYEGE-----YQCFARNKFGTALSNKIRLQ 95

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409353 [Multi-domain] Cd Length: 70 Bit Score: 49.64 E-value: 2.70e-07

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 386767223  641 IQCTViKGDLPINITWVLNNHTLNSGDLDvvIGRMSSKSSTLNIDYIAAEHRGVYTCLARNQAGESSYS 709
Cdd:cd00096     3 LTCSA-SGNPPPTITWYKNGKPLPPSSRD--SRRSELGNGTLTISNVTLEDSGTYTCVASNSAGGSASA 68

First immunoglobulin (Ig)-like domain in neogenin, and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the first immunoglobulin (Ig)-like domain in neogenin and related proteins. Neogenin is a cell surface protein which is expressed in the developing nervous system of vertebrate embryos in the growing nerve cells. It is also expressed in other embryonic tissues and may play a general role in developmental processes such as cell migration, cell-cell recognition, and tissue growth regulation. Included in this group is the tumor suppressor protein DCC which is deleted in colorectal carcinoma. DCC and neogenin each have four Ig-like domains followed by six fibronectin type III domains, a transmembrane domain, and an intracellular domain. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409387 Cd Length: 97 Bit Score: 50.55 E-value: 2.83e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  817 FTEKLRNQTARRGEPAVLQCEAKGEKPIGILWNMNNMRLDPKNDNRYtireEILSTG--VMSSLSIKRTERSDSALFTCV 894
Cdd:cd05722     4 FLSEPSDIVAMRGGPVVLNCSAESDPPPKIEWKKDGVLLNLVSDERR----QQLPNGslLITSVVHSKHNKPDEGFYQCV 79


                  ....*...
gi 386767223  895 ATN-AFGS 901
Cdd:cd05722    80 AQNeSLGS 87

agrin-responsive first immunoglobulin-like domains (Ig1) of the MuSK ectodomain; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin-like domains (Ig1) of the Muscle-specific kinase (MuSK). MuSK is a receptor tyrosine kinase specifically expressed in skeletal muscle, where it plays a central role in the formation and maintenance of the neuromuscular junction (NMJ). MuSK is activated by agrin, a neuron-derived heparan sulfate proteoglycan. The activation of MUSK in myotubes regulates the formation of NMJs through the regulation of different processes including the specific expression of genes in subsynaptic nuclei, the reorganization of the actin cytoskeleton and the clustering of the acetylcholine receptors (AChR) in the postsynaptic membrane. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the MuSK lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409562 [Multi-domain] Cd Length: 92 Bit Score: 50.20 E-value: 2.85e-07

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 386767223 1324 TFTATFKEDAKMPCLAVGAPQPEITWKIKGVEFSA-NDRMRVLPDGSLL-IKSVNRQDAGDYSCHAEN 1389
Cdd:cd20970    11 TVTAREGENATFMCRAEGSPEPEISWTRNGNLIIEfNTRYIVRENGTTLtIRNIRRSDMGIYLCIASN 78

Immunoglobulin (Ig)-like domain of myotilin, palladin, and myopalladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig)-like domain in myotilin, palladin, and myopalladin. Myotilin, palladin, and myopalladin function as scaffolds that regulate actin organization. Myotilin and myopalladin are most abundant in skeletal and cardiac muscle; palladin is ubiquitously expressed in the organs of developing vertebrates and plays a key role in cellular morphogenesis. The three family members each interact with specific molecular partners with all three binding to alpha-actinin; In addition, palladin also binds to vasodilator-stimulated phosphoprotein (VASP) and ezrin, myotilin binds to filamin and actin, and myopalladin also binds to nebulin and cardiac ankyrin repeat protein (CARP). This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409405 [Multi-domain] Cd Length: 91 Bit Score: 50.19 E-value: 3.06e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  352 PPTQTVDFGRPAVFTCQYTGNPIKTVSWMKDGKAI----GHSEPV-------LRIESVKKEDKGMYQCFVRNDQESAEAS 420
Cdd:cd05744     7 PGDLEVQEGRLCRFDCKVSGLPTPDLFWQLNGKPVrpdsAHKMLVrengrhsLIIEPVTKRDAGIYTCIARNRAGENSFN 86


                  ...
gi 386767223  421 AEL 423
Cdd:cd05744    87 AEL 89

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409353 [Multi-domain] Cd Length: 70 Bit Score: 49.25 E-value: 3.25e-07

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 386767223   57 AEIECKASGNPMPEIIWIRSDGT-AVGDVPGLRQISSDGKLVFPPFRAEDyrqevhAQVYACLARNQFGSIISRDV 131
Cdd:cd00096     1 VTLTCSASGNPPPTITWYKNGKPlPPSSRDSRRSELGNGTLTISNVTLED------SGTYTCVASNSAGGSASASV 70

Immunoglobulin (Ig)-like I-set domain of Neural Cell Adhesion Molecule 1 (NCAM-1) and similar proteins; The members here are composed of the fourth immunoglobulin (Ig)-like domain of Neural Cell Adhesion Molecule (NCAM-1). NCAM plays important roles in the development and regeneration of the central nervous system, in synaptogenesis and neural migration. NCAM mediates cell-cell and cell-substratum recognition and adhesion via homophilic (NCAM-NCAM), and heterophilic (NCAM-non-NCAM), interactions. NCAM is expressed as three major isoforms having different intracellular extensions. The extracellular portion of NCAM has five N-terminal Ig-like domains and two fibronectin type III domains. The double zipper adhesion complex model for NCAM homophilic binding involves Ig1, Ig2, and Ig3. By this model, Ig1 and Ig2 mediate dimerization of NCAM molecules situated on the same cell surface (cis interactions), and Ig3 domains mediate interactions between NCAM molecules expressed on the surface of opposing cells (trans interactions), through binding to the Ig1 and Ig2 domains. The adhesive ability of NCAM is modulated by the addition of polysialic acid chains to the fifth Ig-like domain. Also included in this group is NCAM-2 (also known as OCAM/mamFas II and RNCAM) NCAM-2 is differentially expressed in the developing and mature olfactory epithelium (OE). One of the unique features of I-set domains is the lack of a C" strand. The structures of this group show that the Ig domain lacks this strand and thus is a member of the I-set of Ig domains.

Pssm-ID: 409395 [Multi-domain] Cd Length: 96 Bit Score: 50.22 E-value: 3.35e-07

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 386767223  731 QGSDAKVECKADGFPKPQVTWKKAVGDTPGEYKDLKKSDNIRVEEG--TLHVDNIQKTNEGYYLCEAINGIG 800
Cdd:cd05732    15 ELEQITLTCEAEGDPIPEITWRRATRGISFEEGDLDGRIVVRGHARvsSLTLKDVQLTDAGRYDCEASNRIG 86

Fibronectin type 3 domain; One of three types of internal repeat within the plasma protein, fibronectin. The tenth fibronectin type III repeat contains a RGD cell recognition sequence in a flexible loop between 2 strands. Type III modules are present in both extracellular and intracellular proteins.

Pssm-ID: 214495 [Multi-domain] Cd Length: 83 Bit Score: 49.54 E-value: 3.51e-07

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223   1500 PKLPEKPRFIEVSSNSVSLHFKAWKDGGCpmSHFVVE---SKKRDQIEWNQISNNVkPDNNYVVLDLEPATWYNLRITAH 1576
Cdd:smart00060    1 PSPPSNLRVTDVTSTSVTLSWEPPPDDGI--TGYIVGyrvEYREEGSEWKEVNVTP-SSTSYTLTGLKPGTEYEFRVRAV 77


                    ....
gi 386767223   1577 NSAG 1580
Cdd:smart00060   78 NGAG 81

Fourth immunoglobulin (Ig)-like domain of hemolin, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain of hemolin and similar proteins. Hemolin, an insect immunoglobulin superfamily (IgSF) member containing four Ig-like domains, is a lipopolysaccharide-binding immune protein induced during bacterial infection. Hemolin shares significant sequence similarity with the first four Ig-like domains of the transmembrane cell adhesion molecules (CAMs) of the L1 family. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The fourth Ig-like domain of hemolin is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409570 [Multi-domain] Cd Length: 88 Bit Score: 49.70 E-value: 3.88e-07

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 386767223  352 PPTQTV-DFGRPAVFTCQYTGNPIKTVSWMKDGKAIGHSEP-------VLRIESVKKEDKGMYQC 408
Cdd:cd20978     7 PEKNVVvKGGQDVTLPCQVTGVPQPKITWLHNGKPLQGPMEratvedgTLTIINVQPEDTGYYGC 71

Fourth immunoglobulin (Ig)-like domain of L1, Ng-CAM (Neuron-glia CAM cell adhesion molecule), and NrCAM (Ng-CAM-related); The members here are composed of the fourth immunoglobulin (Ig)-like domain of L1, Ng-CAM (Neuron-glia CAM cell adhesion molecule), and NrCAM (Ng-CAM-related). These proteins belong to the L1 subfamily of cell adhesion molecules (CAMs) and are comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region and an intracellular domain. These molecules are primarily expressed in the nervous system. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, or spastic paraplegia type 1, that involves abnormalities of axonal growth.

Pssm-ID: 409367 [Multi-domain] Cd Length: 89 Bit Score: 49.37 E-value: 4.47e-07

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 386767223 1331 EDAKMPCLAVGAPQPEITWKIKGV---EFSANDRMRVLPDgSLLIKSVNRQDAGDYSCHAEN 1389
Cdd:cd04978    15 ETGELICEAEGNPQPTITWRLNGVpiePAPEDMRRTVDGR-TLIFSNLQPNDTAVYQCNASN 75

Fourth Ig domain of the neural cell adhesion molecule contactin-2, and similar domains; The members here are composed of the fourth Ig domain of the neural cell adhesion molecule contactin-2. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-2 (also called TAG-1, axonin-1) facilitates cell adhesion by homophilic binding between molecules in apposed membranes. The first four Ig domains form the intermolecular binding fragment which arranges as a compact U-shaped module by contacts between Ig domains 1 and 4, and domains 2 and 3. It has been proposed that a linear zipper-like array forms, from contactin-2 molecules alternatively provided by the two apposed membranes.

Pssm-ID: 143205 [Multi-domain] Cd Length: 85 Bit Score: 49.52 E-value: 4.63e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  720 WILEPTDKAFAQGSDAKVECKADGFPKPQVTWKKAvgdtpGEykDLKKSDNIRVEEGTLHVDNIQKTNEGYYLCEAINGI 799
Cdd:cd05728     2 WLKVISDTEADIGSSLRWECKASGNPRPAYRWLKN-----GQ--PLASENRIEVEAGDLRITKLSLSDSGMYQCVAENKH 74


                  ..
gi 386767223  800 GS 801
Cdd:cd05728    75 GT 76

Fifth immunoglobulin (Ig) domain of contactin-1; The members here are composed of the fifth immunoglobulin (Ig) domain of the neural cell adhesion molecule contactin-1. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-1 is differentially expressed in tumor tissues and may through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma.

Pssm-ID: 409438 Cd Length: 89 Bit Score: 49.61 E-value: 4.73e-07

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 386767223 1337 CLAVGAPQPEITWKiKGVEFSAND-RMRVLPDGSLLIKSVNRQDAGDYSCHAENSIAKDSITHKLIV 1402
Cdd:cd05852    24 CKPKAAPKPKFSWS-KGTELLVNNsRISIWDDGSLEILNITKLDEGSYTCFAENNRGKANSTGVLSV 89

Second immunoglobulin (Ig)-like domain of the receptor protein tyrosine phosphatase (RPTP)-F; member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain found in the receptor protein tyrosine phosphatase (RPTP)-F, also known as LAR. LAR belongs to the RPTP type IIa subfamily. Members of this subfamily are cell adhesion molecule-like proteins involved in central nervous system (CNS) development. They have large extracellular portions comprised of multiple Ig-like domains and two to nine fibronectin type III (FNIII) domains and a cytoplasmic portion having two tandem phosphatase domains.

Pssm-ID: 409400 [Multi-domain] Cd Length: 91 Bit Score: 49.63 E-value: 4.80e-07

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 386767223 1333 AKMPCLAVGAPQPEITWKIKGV---EFSANDRMRVLPDGSLLIKSVNRQDAGDYSCHAENS 1390
Cdd:cd05738    17 ATMLCAASGNPDPEISWFKDFLpvdTATSNGRIKQLRSGALQIENSEESDQGKYECVATNS 77

Immunoglobulin (Ig)-like ectodomain of the LRIG1 (Leucine-rich Repeats And Immunoglobulin-like Domains Protein 1) and similar proteins; member of the I-set of IgSF domains; The members here are composed of subgroup of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. The ectodomain of LRIG1 has two distinct regions: the proposed 15 LRRs and three Ig-like domains closer to the membrane. LRIG1 has been reported to interact with many receptor tyrosine kinases, GDNF/c-Ret, E-cadherin, JAK/STAT, c-Met, and the EGFR family signaling systems. Immunoglobulin Superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The structure of the LRIG1 extracellular Ig domain lacks a C" strand and thus is better described as a member of the I-set of IgSF domains.

Pssm-ID: 409420 [Multi-domain] Cd Length: 91 Bit Score: 49.54 E-value: 4.80e-07

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 386767223  724 PTDKAFAQGSDAKVECKADGFPKPQVTWKKAVG-DTPGEYkdlKKSDNIRVEEGTLHVDNIQKTNEGYYLCEAINGIGS 801
Cdd:cd05763     6 PHDITIRAGSTARLECAATGHPTPQIAWQKDGGtDFPAAR---ERRMHVMPEDDVFFIVDVKIEDTGVYSCTAQNSAGS 81

Third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM), and similar domains; The members here are composed of the third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM). L1 belongs to the L1 subfamily of cell adhesion molecules (CAMs) and is comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region and an intracellular domain. L1 is primarily expressed in the nervous system and is involved in its development and function. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, and spastic paraplegia type 1, that involves abnormalities of axonal growth. This group also contains the chicken neuron-glia cell adhesion molecule, Ng-CAM and human neurofascin.

Pssm-ID: 409394 [Multi-domain] Cd Length: 83 Bit Score: 49.33 E-value: 4.82e-07

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 386767223  543 GETLIVTCPVAGYPIDSIVWERDNRALPINRKQKVFPNGTLIIENVErNSDQATYTCVAKNQEGySARGSLEVQV 617
Cdd:cd05731    10 GGVLLLECIAEGLPTPDIRWIKLGGELPKGRTKFENFNKTLKIENVS-EADSGEYQCTASNTMG-SARHTISVTV 82

Immunoglobulin (Ig)-like domain of titin and similar proteins; The members here are composed of the immunoglobulin (Ig)-like domain found in titin-like proteins and similar proteins. Titin (also called connectin) is a fibrous sarcomeric protein specifically found in vertebrate striated muscle. Titin is a giant protein; depending on isoform composition, it ranges from 2970 to 3700 kDa, and is of a length that spans half a sarcomere. Titin largely consists of multiple repeats of Ig-like and fibronectin type 3 (FN-III)-like domains. Titin connects the ends of myosin thick filaments to Z disks and extends along the thick filament to the H zone. It appears to function similarly to an elastic band, keeping the myosin filaments centered in the sarcomere during muscle contraction or stretching. Within the sarcomere, titin is also attached to or is associated with myosin binding protein C (MyBP-C). MyBP-C appears to contribute to the generation of passive tension by titin and like titin has repeated Ig-like and FN-III domains. Also included in this group are worm twitchin and insect projectin, thick filament proteins of invertebrate muscle which also have repeated Ig-like and FN-III domains.

Pssm-ID: 409406 [Multi-domain] Cd Length: 82 Bit Score: 49.13 E-value: 5.30e-07

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 386767223 1340 VGAPQPEITWKIKGVEFSANDRMRV---LPDGSLLIKSVNRQDAGDYSCHAENSIAKDSITHKLIV 1402
Cdd:cd05748    17 KGRPTPTVTWSKDGQPLKETGRVQIettASSTSLVIKNAKRSDSGKYTLTLKNSAGEKSATINVKV 82

Immunoglobulin (Ig)-like I-set domain of Neural Cell Adhesion Molecule 2 (NCAM-2); The members here are composed of the fourth Ig domain of Neural Cell Adhesion Molecule NCAM-2 (also known as OCAM/mamFas II and RNCAM). NCAM-2 is organized similarly to NCAM, including five N-terminal Ig-like domains and two fibronectin type III domains. NCAM-2 is differentially expressed in the developing and mature olfactory epithelium (OE), and may function like NCAM, as an adhesion molecule. One of the unique features of I-set domains is the lack of a C" strand. The structures of this group show that the Ig domain lacks this strand and thus is a member of the I-set of Ig domains.

Pssm-ID: 143278 [Multi-domain] Cd Length: 98 Bit Score: 49.59 E-value: 5.34e-07

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 386767223  731 QGSDAKVECKADGFPKPQVTWKKAV-GDTpgeYKDLKKSDNIRVE------EGTLHVDNIQKTNEGYYLCEAINGIG 800
Cdd:cd05870    15 ENGAATLSCKAEGEPIPEITWKRASdGHT---FSEGDKSPDGRIEvkgqhgESSLHIKDVKLSDSGRYDCEAASRIG 88

agrin-responsive first immunoglobulin-like domains (Ig1) of the MuSK ectodomain; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin-like domains (Ig1) of the Muscle-specific kinase (MuSK). MuSK is a receptor tyrosine kinase specifically expressed in skeletal muscle, where it plays a central role in the formation and maintenance of the neuromuscular junction (NMJ). MuSK is activated by agrin, a neuron-derived heparan sulfate proteoglycan. The activation of MUSK in myotubes regulates the formation of NMJs through the regulation of different processes including the specific expression of genes in subsynaptic nuclei, the reorganization of the actin cytoskeleton and the clustering of the acetylcholine receptors (AChR) in the postsynaptic membrane. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the MuSK lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409562 [Multi-domain] Cd Length: 92 Bit Score: 49.04 E-value: 6.47e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  722 LEPTDKAFAQGSDAKVECKADGFPKPQVTWKKavgdtpgeykdlkksDNIRVEEG-----------TLHVDNIQKTNEGY 790
Cdd:cd20970     7 QPSFTVTAREGENATFMCRAEGSPEPEISWTR---------------NGNLIIEFntryivrengtTLTIRNIRRSDMGI 71

                          90       100
                  ....*....|....*....|.
gi 386767223  791 YLCEAINGIGSGLSAVIMISV 811
Cdd:cd20970    72 YLCIASNGVPGSVEKRITLQV 92

agrin-responsive second immunoglobulin-like domains (Ig2) of the Muscle-specific kinase (MuSK) ectodomain; a member of the I-set of Ig superfamily domains; The members here are composed of the second immunoglobulin-like (Ig) domains of the Muscle-specific kinase (MuSK) ectodomain. MuSK is a receptor tyrosine kinase specifically expressed in skeletal muscle, where it plays a central role in the formation and maintenance of the neuromuscular junction (NMJ). MuSK is activated by agrin, a neuron-derived heparan sulfate proteoglycan. The activation of MUSK in myotubes regulates the formation of NMJs through the regulation of different processes including the specific expression of genes in subsynaptic nuclei, the reorganization of the actin cytoskeleton and the clustering of the acetylcholine receptors (AChR) in the postsynaptic membrane. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the MuSK lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409560 [Multi-domain] Cd Length: 88 Bit Score: 48.78 E-value: 7.41e-07

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 386767223  352 PPTQ-TVDFGRPAVFTCQYTGNPIKTVSWMKDGKAIGHSEPV-------LRIESVKKEDKGMYQCFVRNDQESA 417
Cdd:cd20968     5 PPTNvTIIEGLKAVLPCTTMGNPKPSVSWIKGDDLIKENNRIavlesgsLRIHNVQKEDAGQYRCVAKNSLGIA 78

Immunoglobulin (Ig)-like domain of human titin C terminus and similar proteins; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the fifth immunoglobulin (Ig)-like domain from the C-terminus of human titin x and similar proteins. Titin (also called connectin) is a fibrous sarcomeric protein specifically found in vertebrate striated muscle. Titin is gigantic; depending on isoform composition it ranges from 2970 to 3700 kDa, and is of a length that spans half a sarcomere. Titin largely consists of multiple repeats of Ig-like and fibronectin type 3 (FN-III)-like domains. Titin connects the ends of myosin thick filaments to Z disks and extends along the thick filament to the H zone and appears to function similar to an elastic band, keeping the myosin filaments centered in the sarcomere during muscle contraction or stretching. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 143224 [Multi-domain] Cd Length: 92 Bit Score: 48.89 E-value: 7.67e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  343 TAPLSAKIDPPTQTVDFGRPAVFTCQYTGNPIKTVSWMKDGKAIGHS----------EPVLRIESVKKEDKGMYQCFVRN 412
Cdd:cd05747     1 TLPATILTKPRSLTVSEGESARFSCDVDGEPAPTVTWMREGQIIVSSqrhqitsteyKSTFEISKVQMSDEGNYTVVVEN 80

                          90
                  ....*....|.
gi 386767223  413 DQESAEASAEL 423
Cdd:cd05747    81 SEGKQEAQFTL 91

Fibronectin type 3 domain; One of three types of internal repeat within the plasma protein, fibronectin. The tenth fibronectin type III repeat contains a RGD cell recognition sequence in a flexible loop between 2 strands. Type III modules are present in both extracellular and intracellular proteins.

Pssm-ID: 214495 [Multi-domain] Cd Length: 83 Bit Score: 48.76 E-value: 7.74e-07

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223   1405 PPQSPHVTLSATTTDALTVKLKP--HEGDTAPLHGYTLHYKPEFGEWETSEVSVDSQKHNIEGLLCGSRYQVYATGFNNI 1482
Cdd:smart00060    1 PSPPSNLRVTDVTSTSVTLSWEPppDDGITGYIVGYRVEYREEGSEWKEVNVTPSSTSYTLTGLKPGTEYEFRVRAVNGA 80


                    ...
gi 386767223   1483 GAG 1485
Cdd:smart00060   81 GEG 83

Fourth Ig-like domain from smooth muscle myosin light chain kinase and similar domains ; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain from smooth muscle myosin light chain kinase (MYLK) and similar domains. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of this group shows that the fourth Ig-like domain from myosin light chain kinase lacks this strand and thus belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409568 [Multi-domain] Cd Length: 90 Bit Score: 48.79 E-value: 7.76e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223 1315 PAKIASFDDTFTATFKEDAKMPCLAVGAPQPEITWKIKGVEFS-ANDRMRVLPD-GSLLIKSVNRQDAGDYSCHAENSIA 1392
Cdd:cd20976     1 APSFSSVPKDLEAVEGQDFVAQCSARGKPVPRITWIRNAQPLQyAADRSTCEAGvGELHIQDVLPEDHGTYTCLAKNAAG 80

                          90
                  ....*....|
gi 386767223 1393 KDSITHKLIV 1402
Cdd:cd20976    81 QVSCSAWVTV 90

agrin-responsive second immunoglobulin-like domains (Ig2) of the Muscle-specific kinase (MuSK) ectodomain; a member of the I-set of Ig superfamily domains; The members here are composed of the second immunoglobulin-like (Ig) domains of the Muscle-specific kinase (MuSK) ectodomain. MuSK is a receptor tyrosine kinase specifically expressed in skeletal muscle, where it plays a central role in the formation and maintenance of the neuromuscular junction (NMJ). MuSK is activated by agrin, a neuron-derived heparan sulfate proteoglycan. The activation of MUSK in myotubes regulates the formation of NMJs through the regulation of different processes including the specific expression of genes in subsynaptic nuclei, the reorganization of the actin cytoskeleton and the clustering of the acetylcholine receptors (AChR) in the postsynaptic membrane. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the MuSK lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409560 [Multi-domain] Cd Length: 88 Bit Score: 48.78 E-value: 8.01e-07

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 386767223  540 IVAGETLIVTCPVAGYPIDSIVWERDNRALPINRKQKVFPNGTLIIENVERnSDQATYTCVAKNQEG--YSARGSLEVQ 616
Cdd:cd20968    11 IIEGLKAVLPCTTMGNPKPSVSWIKGDDLIKENNRIAVLESGSLRIHNVQK-EDAGQYRCVAKNSLGiaYSKPVTIEVE 88

Fourth immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM); The members here are composed of the fourth immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM). L1 is comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region, and an intracellular domain. L1 is primarily expressed in the nervous system and is involved in its development and function. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, and spastic paraplegia type 1, that involves abnormalities of axonal growth. This group also contains the chicken neuron-glia cell adhesion molecule, Ng-CAM.

Pssm-ID: 409453 [Multi-domain] Cd Length: 89 Bit Score: 48.74 E-value: 8.37e-07

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 386767223  720 WILEPTDKAFAQGSDAKVECKADGFPKPQVTWKKAVGDTPGEYKDLKKsdniRVEEGTLHVDNIQKTNEGYYLCEAIN 797
Cdd:cd05867     2 WTRRPQSHLYGPGETARLDCQVEGIPTPNITWSINGAPIEGTDPDPRR----HVSSGALILTDVQPSDTAVYQCEARN 75

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.

Pssm-ID: 214653 [Multi-domain] Cd Length: 85 Bit Score: 48.66 E-value: 8.38e-07

                            10        20        30        40        50        60        70
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 386767223    636 GETMGIQCTViKGDLPINITWVLNNHTLNSGDLDVVIgRMSSKSSTLNIDYIAAEHRGVYTCLARNQAGESSYSAELKV 714
Cdd:smart00410    9 GESVTLSCEA-SGSPPPEVTWYKQGGKLLAESGRFSV-SRSGSTSTLTISNVTPEDSGTYTCAATNSSGSASSGTTLTV 85

immunoglobulin-like domain of telokin and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig) domain in telokin, the C-terminal domain of myosin light chain kinase which is identical to telokin, and similar proteins. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the telokin Ig domain lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409565 [Multi-domain] Cd Length: 88 Bit Score: 48.72 E-value: 8.98e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  435 RQAFQEETMEPGPSVFLKCVAGGNPTPEISWELDGKKIANNDRYQVGQyvtvNGDVVSYLNITSVHANDGGLYKCIAKSK 514
Cdd:cd20973     1 IQTLRDKEVVEGSAARFDCKVEGYPDPEVKWMKDDNPIVESRRFQIDQ----DEDGLCSLIISDVCGDDSGKYTCKAVNS 76

                          90
                  ....*....|..
gi 386767223  515 VGVAEHSAKLNV 526
Cdd:cd20973    77 LGEATCSAELTV 88

First immunoglobulin (Ig)-like constant domain in Robo (roundabout) receptors, and similar domains; The members here are composed of the first immunoglobulin (Ig)-like domain in Roundabout (Robo) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, and Robo3), and three mammalian Slit homologs (Slit1, Slit2, Slit3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit1, Slit2,and Slit3 are expressed at the ventral midline. Robo3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be is the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site.

Pssm-ID: 409490 [Multi-domain] Cd Length: 99 Bit Score: 49.09 E-value: 9.77e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  815 PEFTEKLRNQTARRGEPAVLQCEAKGEKPIGILWNMNNMRLDPKNDNRYTiREEILSTGVMSSLSI--KRTERSDSALFT 892
Cdd:cd07693     1 PRIVEHPSDLIVSKGDPATLNCKAEGRPTPTIQWLKNGQPLETDKDDPRS-HRIVLPSGSLFFLRVvhGRKGRSDEGVYV 79

                          90
                  ....*....|....*..
gi 386767223  893 CVATNAFG---SDDASI 906
Cdd:cd07693    80 CVAHNSLGeavSRNASL 96

Immunoglobulin (Ig)-like I-set domain of Neural Cell Adhesion Molecule 1 (NCAM-1); The members here are composed of the fourth Ig domain of Neural Cell Adhesion Molecule 1(NCAM-1). NCAM plays important roles in the development and regeneration of the central nervous system, in synaptogenesis and neural migration. NCAM mediates cell-cell and cell-substratum recognition and adhesion via homophilic (NCAM-NCAM) and heterophilic (NCAM-non-NCAM) interactions. NCAM is expressed as three major isoforms having different intracellular extensions. The extracellular portion of NCAM has five N-terminal Ig-like domains and two fibronectin type III domains. The double zipper adhesion complex model for NCAM homophilic binding involves Ig1, Ig2, and Ig3. By this model, Ig1 and Ig2 mediate dimerization of NCAM molecules situated on the same cell surface (cis interactions), and Ig3 domains mediate interactions between NCAM molecules expressed on the surface of opposing cells (trans interactions), through binding to the Ig1 and Ig2 domains. The adhesive ability of NCAM is modulated by the addition of polysialic acid chains to the fifth Ig-like domain. One of the unique features of I-set domains is the lack of a C" strand. The structures of this group show that the Ig domain lacks this strand and thus is a member of the I-set of Ig domains.

Pssm-ID: 143277 [Multi-domain] Cd Length: 97 Bit Score: 48.82 E-value: 9.89e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223 1317 KIASFDDTFTATFKEDAKMPCLAVGAPQPEITWKIKGVEFSAND-----RMRVLPD---GSLLIKSVNRQDAGDYSCHAE 1388
Cdd:cd05869     4 KITYVENQTAMELEEQITLTCEASGDPIPSITWRTSTRNISSEEktldgHIVVRSHarvSSLTLKYIQYTDAGEYLCTAS 83


                  ....*..
gi 386767223 1389 NSIAKDS 1395
Cdd:cd05869    84 NTIGQDS 90

Immunoglobulin (Ig)-like domain of myotilin, palladin, and myopalladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig)-like domain in myotilin, palladin, and myopalladin. Myotilin, palladin, and myopalladin function as scaffolds that regulate actin organization. Myotilin and myopalladin are most abundant in skeletal and cardiac muscle; palladin is ubiquitously expressed in the organs of developing vertebrates and plays a key role in cellular morphogenesis. The three family members each interact with specific molecular partners with all three binding to alpha-actinin; In addition, palladin also binds to vasodilator-stimulated phosphoprotein (VASP) and ezrin, myotilin binds to filamin and actin, and myopalladin also binds to nebulin and cardiac ankyrin repeat protein (CARP). This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409405 [Multi-domain] Cd Length: 91 Bit Score: 48.65 E-value: 1.04e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  718 PRWILEPTDKAFAQGSDAKVECKADGFPKPQVTWKKAvgdtpGEYKDLKKSDNIRVEEG---TLHVDNIQKTNEGYYLCE 794
Cdd:cd05744     1 PHFLQAPGDLEVQEGRLCRFDCKVSGLPTPDLFWQLN-----GKPVRPDSAHKMLVRENgrhSLIIEPVTKRDAGIYTCI 75


                  ....*.
gi 386767223  795 AINGIG 800
Cdd:cd05744    76 ARNRAG 81

Third immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the Constant 2 (C2)-set of IgSF domains; The members here are composed of the third immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. This group belongs to the C2-set of IgSF domains, having A, B, and E strands in one beta-sheet and A', G, F, C, and C' in the other. Unlike other Ig domain sets, the C2-set lacks the D strand.

Pssm-ID: 409549 [Multi-domain] Cd Length: 88 Bit Score: 48.30 E-value: 1.13e-06

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 386767223 1326 TATFKEDAKMPCLAVGAPQPEITWKIKGVEFSANDRMRVLPDGSLLIKSVNRQDAGDYSCHAEN 1389
Cdd:cd20957    12 TVDFGRTAVFNCSVTGNPIHTVLWMKDGKPLGHSSRVQILSEDVLVIPSVKREDKGMYQCFVRN 75

Third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, Robo3), and three mammalian Slit homologs (Slit-1,Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, and Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409390 [Multi-domain] Cd Length: 83 Bit Score: 48.16 E-value: 1.13e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  263 VVDQSFAMLCQAQAFPLPIMRWYKFIEGTTRKQAVVLNDRvkqvsgTLIIKDAVVEDSGKYLCVVNNSVGGESVETVLTV 342
Cdd:cd05725    10 LVDDSAEFQCEVGGDPVPTVRWRKEDGELPKGRYEILDDH------SLKIRKVTAGDMGSYTCVAENMVGKIEASATLTV 83

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409353 [Multi-domain] Cd Length: 70 Bit Score: 47.71 E-value: 1.19e-06

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 386767223  832 AVLQCEAKGEKPIGILWNMNNMRLDPKNDNRYTIREEIlstgvmSSLSIKRTERSDSALFTCVATNAFGSDDASI 906
Cdd:cd00096     1 VTLTCSASGNPPPTITWYKNGKPLPPSSRDSRRSELGN------GTLTISNVTLEDSGTYTCVASNSAGGSASAS 69

Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor; member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor. FGF receptors bind FGF signaling polypeptides. FGFs participate in multiple processes such as morphogenesis, development, and angiogenesis. FGFs bind to four FGF receptor tyrosine kinases (FGFR1, FGFR2, FGFR3, FGFR4). Receptor diversity is controlled by alternative splicing producing splice variants with different ligand binding characteristics and different expression patterns. FGFRs have an extracellular region comprised of three IG-like domains, a single transmembrane helix, and an intracellular tyrosine kinase domain. Ligand binding and specificity reside in the Ig-like domains 2 and 3, and the linker region that connects these two. FGFR activation and signaling depend on FGF-induced dimerization, a process involving cell surface heparin or heparin sulfate proteoglycans.

Pssm-ID: 409443 [Multi-domain] Cd Length: 95 Bit Score: 48.70 E-value: 1.19e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  446 GPSVFLKCVAGGNPTPEISWELDGKKIANNDRyqVGQYVTVNGDvvSYLNITSVHANDGGLYKCIAKSKVGVAEHSAKLN 525
Cdd:cd05857    19 ANTVKFRCPAAGNPTPTMRWLKNGKEFKQEHR--IGGYKVRNQH--WSLIMESVVPSDKGNYTCVVENEYGSINHTYHLD 94


                  .
gi 386767223  526 V 526
Cdd:cd05857    95 V 95

Fibronectin type III domain;

Pssm-ID: 394996 [Multi-domain] Cd Length: 85 Bit Score: 48.18 E-value: 1.23e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  1405 PPQSPHVTlsATTTDALTVKLKPHEGDTAPLHGYTLHYKPEFGEWETSEVSVDSQKH--NIEGLLCGSRYQVYATGFNNI 1482
Cdd:pfam00041    2 APSNLTVT--DVTSTSLTVSWTPPPDGNGPITGYEVEYRPKNSGEPWNEITVPGTTTsvTLTGLKPGTEYEVRVQAVNGG 79


                   ....*.
gi 386767223  1483 GAGEAS 1488
Cdd:pfam00041   80 GEGPPS 85

First immunoglobulin (Ig)-like constant domain in Robo (roundabout) receptors, and similar domains; The members here are composed of the first immunoglobulin (Ig)-like domain in Roundabout (Robo) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, and Robo3), and three mammalian Slit homologs (Slit1, Slit2, Slit3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit1, Slit2,and Slit3 are expressed at the ventral midline. Robo3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be is the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site.

Pssm-ID: 409490 [Multi-domain] Cd Length: 99 Bit Score: 48.32 E-value: 1.49e-06

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 386767223   57 AEIECKASGNPMPEIIWIRsDG----TAVGDVPGLRQISSDGKLVFppFRAEDYRQ-EVHAQVYACLARNQFGSIISRD 130
Cdd:cd07693    18 ATLNCKAEGRPTPTIQWLK-NGqpleTDKDDPRSHRIVLPSGSLFF--LRVVHGRKgRSDEGVYVCVAHNSLGEAVSRN 93

Second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of the Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, and Robo3), and three mammalian Slit homologs (Slit-1,Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit-2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409389 [Multi-domain] Cd Length: 87 Bit Score: 47.78 E-value: 1.79e-06

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 386767223  540 IVAGETLIVTC-PVAGYPIDSIVWERDNRALPI-NRKQKVFPNGTLIIENVERnSDQATYTCVAKNQEG 606
Cdd:cd05724     9 VAVGEMAVLECsPPRGHPEPTVSWRKDGQPLNLdNERVRIVDDGNLLIAEARK-SDEGTYKCVATNMVG 76

Immunoglobulin-like domain of human nephrin and similar proteins; member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin-like domain in human nephrin and similar proteins. Nephrin is an integral component of the slit diaphragm and is a central component of the glomerular ultrafilter. Nephrin plays a structural role and has a role in signaling. Nephrin is a transmembrane protein having a short intracellular portion, an extracellular portion comprised of eight Ig-like domains, and one fibronectin type III-like domain. The extracellular portions of nephrin from neighboring foot processes of separate podocyte cells may interact with each other, and in association with other components of the slit diaphragm form a porous molecular sieve within the slit pore. The intracellular portion of nephrin is associated with linker proteins, which connect nephrin to the actin cytoskeleton. The intracellular portion is tyrosine phosphorylated, and mediates signaling from the slit diaphragm into the podocytes.

Pssm-ID: 143250 Cd Length: 109 Bit Score: 48.39 E-value: 1.87e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  811 VQAPPEFTeklrnQTARRGE---PAVLQCEAKGEKPIGILWNMNNMRLDPKNDnRYTirEEILSTGVM--SSLSIKRTER 885
Cdd:cd05773     7 LQKGPQLR-----KVASRGDgssDANLVCQAQGVPRVQFRWAKNGVPLDLGNP-RYE--ETTEHTGTVhtSILTIINVSA 78

                          90       100       110
                  ....*....|....*....|....*....|.
gi 386767223  886 S-DSALFTCVATNAFGSDDASINMIVQEVPE 915
Cdd:cd05773    79 AlDYALFTCTAHNSLGEDSLDIQLVSTSRPD 109

Immunoglobulin (Ig)-like domain of Down Syndrome Cell Adhesion molecule (DSCAM); The members here are composed of the immunoglobulin (Ig)-like domain of Down Syndrome Cell Adhesion molecule (DSCAM). DSCAM is a cell adhesion molecule expressed largely in the developing nervous system. The gene encoding DSCAM is located at human chromosome 21q22, the locus associated with the intellectual disability phenotype of Down Syndrome. DSCAM is predicted to be the largest member of the IG superfamily. It has been demonstrated that DSCAM can mediate cation-independent homophilic intercellular adhesion.

Pssm-ID: 409397 [Multi-domain] Cd Length: 97 Bit Score: 47.87 E-value: 1.97e-06

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 386767223  272 CQAQAFPLPIMRWyKFIEGTTRKQ---AVVLNDRVKQVS-GTLIIKDAVVEDSGKYLCVVNNSVGGE-SVETVLTV 342
Cdd:cd05734    23 CSADGYPPPTIVW-KHSKGSGVPQfqhIVPLNGRIQLLSnGSLLIKHVLEEDSGYYLCKVSNDVGADiSKSMYLTV 97

Third immunoglobulin (Ig)-like domain of Neural Cell Adhesion Molecule 1 (NCAM-1); member of the I-set of IgSF domains; The members here are composed of the third immunoglobulin (Ig)-like domain of Neural Cell Adhesion Molecule (NCAM-1). NCAM plays important roles in the development and regeneration of the central nervous system, in synaptogenesis and neural migration. NCAM mediates cell-cell and cell-substratum recognition and adhesion via homophilic (NCAM-NCAM), and heterophilic (NCAM-non-NCAM), interactions. NCAM is expressed as three major isoforms having different intracellular extensions. The extracellular portion of NCAM has five N-terminal Ig-like domains and two fibronectin type III domains. The double zipper adhesion complex model for NCAM homophilic binding involves Ig1, Ig2, and Ig3. By this model, Ig1 and Ig2 mediate dimerization of NCAM molecules situated on the same cell surface (cis interactions), and Ig3 domains mediate interactions between NCAM molecules expressed on the surface of opposing cells (trans interactions) through binding to the Ig1 and Ig2 domains. The adhesive ability of NCAM is modulated by the addition of polysialic acid chains to the fifth Ig-like domain.

Pssm-ID: 143207 [Multi-domain] Cd Length: 95 Bit Score: 48.00 E-value: 2.06e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  823 NQTARRGEPAVLQCEAKGEKPIGILWNMNNMRLDpKNDNRYTIREEilstgvMSSLSIKRTERSDSALFTCVATNAFGSD 902
Cdd:cd05730    12 NATANLGQSVTLACDADGFPEPTMTWTKDGEPIE-SGEEKYSFNED------GSEMTILDVDKLDEAEYTCIAENKAGEQ 84


                  ....*...
gi 386767223  903 DASINMIV 910
Cdd:cd05730    85 EAEIHLKV 92

Third immunoglobulin (Ig) domain of contactin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig) domain of contactins. Contactins are neural cell adhesion molecules and are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module via contacts between Ig domains 1 and 4, and between Ig domains 2 and 3. Contactin-2 (TAG-1, axonin-1) may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. This group also includes contactin-1 and contactin-5. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-5 is expressed specifically in the rat postnatal nervous system, peaking at about 3 weeks postnatal, and a lack of contactin-5 (NB-2) results in an impairment of neuronal activity in the rat auditory system. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma. This group belongs to the I-set of IgSF domains.

Pssm-ID: 409357 [Multi-domain] Cd Length: 88 Bit Score: 47.54 E-value: 2.16e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  432 PVIRQAFQEETME-PGPSVFLKCVAGGNPTPEISW-ELDGKKIANNDRYQVGqyvtvngdvvSYLNITSVHANDGGLYKC 509
Cdd:cd04968     1 PSIKVRFPADTYAlKGQTVTLECFALGNPVPQIKWrKVDGSPSSQWEITTSE----------PVLEIPNVQFEDEGTYEC 70

                          90
                  ....*....|....*...
gi 386767223  510 IAKSKVGVAEHSAKLNVY 527
Cdd:cd04968    71 EAENSRGKDTVQGRIIVQ 88

Fourth immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; Members here are composed the fourth immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, Robo3), and three mammalian Slit homologs (Slit-1, Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, and Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409391 [Multi-domain] Cd Length: 98 Bit Score: 48.03 E-value: 2.18e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223 1307 VAMPSDQVPAKIAsfddtfTATFkedakmPCLAVGAPQPEITWKIKGVE---FS-----ANDRMRVLPDGSLLIKSVNRQ 1378
Cdd:cd05726     3 VVKPRDQVVALGR------TVTF------QCETKGNPQPAIFWQKEGSQnllFPyqppqPSSRFSVSPTGDLTITNVQRS 70

                          90
                  ....*....|.
gi 386767223 1379 DAGDYSCHAEN 1389
Cdd:cd05726    71 DVGYYICQALN 81

Fourth immunoglobulin (Ig)-like domain of peroxidasin; The members here are composed of the fourth immunoglobulin (Ig)-like domain in peroxidasin. Peroxidasin has a peroxidase domain and interacting extracellular motifs containing four Ig-like domains. It has been suggested that peroxidasin is secreted, and has functions related to the stabilization of the extracellular matrix. It may play a part in various other important processes such as removal and destruction of cells which have undergone programmed cell death and protection of the organism against non-self.

Pssm-ID: 143223 Cd Length: 69 Bit Score: 46.79 E-value: 2.26e-06

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 386767223  449 VFLKCVAGGNPTPEISWELDGKKIANNDRYQVGQYvtvngdvvSYLNITSVHANDGGLYKCIAKSKVGVAEHSAKL 524
Cdd:cd05746     1 VQIPCSAQGDPEPTITWNKDGVQVTESGKFHISPE--------GYLAIRDVGVADQGRYECVARNTIGYASVSMVL 68

Fourth immunoglobulin (Ig)-like domain of peroxidasin; The members here are composed of the fourth immunoglobulin (Ig)-like domain in peroxidasin. Peroxidasin has a peroxidase domain and interacting extracellular motifs containing four Ig-like domains. It has been suggested that peroxidasin is secreted, and has functions related to the stabilization of the extracellular matrix. It may play a part in various other important processes such as removal and destruction of cells which have undergone programmed cell death and protection of the organism against non-self.

Pssm-ID: 143223 Cd Length: 69 Bit Score: 46.79 E-value: 2.32e-06

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 386767223  272 CQAQAFPLPIMRWykfiegttRKQAVVLNDRVK-QVS--GTLIIKDAVVEDSGKYLCVVNNSVGGESVETVLT 341
Cdd:cd05746     5 CSAQGDPEPTITW--------NKDGVQVTESGKfHISpeGYLAIRDVGVADQGRYECVARNTIGYASVSMVLS 69

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

Pssm-ID: 464026 [Multi-domain] Cd Length: 79 Bit Score: 47.00 E-value: 2.33e-06

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 386767223   349 KIDPPTQTVDFGRPAVFTCQYTGNPIKTVSWMKDGKAI--GHSEPVLRIESvkkEDKGMYQCFVRNDQ 414
Cdd:pfam13895    3 VLTPSPTVVTEGEPVTLTCSAPGNPPPSYTWYKDGSAIssSPNFFTLSVSA---EDSGTYTCVARNGR 67

Second C-terminal immunoglobulin (Ig)-like domain of palladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of palladin. Palladin belongs to the palladin-myotilin-myopalladin family. Proteins belonging to this family contain multiple Ig-like domains and function as scaffolds, modulating actin cytoskeleton. Palladin binds to alpha-actinin ezrin, vasodilator-stimulated phosphoprotein VASP, SPIN90 (also known as DIP or mDia interacting protein), and Src. Palladin also binds F-actin directly, via its Ig3 domain. Palladin is expressed as several alternatively spliced isoforms, having various combinations of Ig-like domains, in a cell-type-specific manner. It has been suggested that palladin's different Ig-like domains may be specialized for distinct functions. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409582 Cd Length: 91 Bit Score: 47.40 E-value: 2.47e-06

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 386767223 1334 KMPCLAVGAPQPEITWKIKG--VEFSANDRMRVLPDG--SLLIKSVNRQDAGDYSCHAENSIAKDSITHKLIV 1402
Cdd:cd20990    19 RMDCKVSGLPTPDLSWQLDGkpIRPDSAHKMLVRENGvhSLIIEPVTSRDAGIYTCIATNRAGQNSFNLELVV 91

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 47.18 E-value: 2.71e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223    39 PVFLKEPTNRIDFSNSTgAEIECKASGNPMPEIIWIRSDGTAV-GDVPGLRQISSDGKLVFPPFRAEDyrqevhAQVYAC 117
Cdd:pfam13927    2 PVITVSPSSVTVREGET-VTLTCEATGSPPPTITWYKNGEPISsGSTRSRSLSGSNSTLTISNVTRSD------AGTYTC 74


                   ....
gi 386767223   118 LARN 121
Cdd:pfam13927   75 VASN 78

Immunoglobulin (Ig)-like domain of the human basement membrane heparan sulfate proteoglycan perlecan and similar proteins; The members here are composed of the immunoglobulin (Ig)-like domain of the human basement membrane heparan sulfate proteoglycan perlecan, also known as HSPG2, and similar proteins. Perlecan consists of five domains: domain I has three putative heparan sulfate attachment sites, domain II has four LDL receptor-like repeats, and one Ig-like repeat, domain III resembles the short arm of laminin chains, domain IV has multiple Ig-like repeats (21 repeats in human perlecan), and domain V resembles the globular G domain of the laminin A chain and internal repeats of EGF. Perlecan may participate in a variety of biological functions including cell binding, LDL-metabolism, basement membrane assembly and selective permeability, calcium binding, and growth- and neurite-promoting activities.

Pssm-ID: 143220 Cd Length: 78 Bit Score: 47.10 E-value: 2.88e-06

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 386767223  732 GSDAKVECKADGFPKPQVTWKKAVGDTPGEYKDLKKSDNIRveeGTLHVDNIQKTNEGYYLCEAINGIG 800
Cdd:cd05743     1 GETVEFTCVATGVPTPIINWRLNWGHVPDSARVSITSEGGY---GTLTIRDVKESDQGAYTCEAINTRG 66

C-terminal immunoglobulin (Ig)-like domain of myomesin and M-protein; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of myomesin and M-protein (also known as myomesin-2). Myomesin and M-protein are both structural proteins localized to the M-band, a transverse structure in the center of the sarcomere, and are candidates for M-band bridges. Both proteins are modular, consisting mainly of repetitive Ig-like and fibronectin type III (FnIII) domains. Myomesin is expressed in all types of vertebrate striated muscle; M-protein has a muscle-type specific expression pattern. Myomesin is present in both slow and fast fibers; M-protein is present only in fast fibers. It has been suggested that myomesin acts as a molecular spring with alternative splicing as a means of modifying its elasticity.

Pssm-ID: 319300 Cd Length: 92 Bit Score: 47.20 E-value: 2.97e-06

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 386767223  442 TMEPGPSVFLKCVAGGNPTPEISWELDGKKIANNDRYQV----GQYVtvngdvvsYLNITSVHANDGGLYKCIAKSKVG 516
Cdd:cd05737    12 TIMEGKTLNLTCNVWGDPPPEVSWLKNDQALAFLDHCNLkveaGRTV--------YFTINGVSSEDSGKYGLVVKNKYG 82

Immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM) and similar proteins; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the first immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM). L1 belongs to the L1 subfamily of cell adhesion molecules (CAMs) and is comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region and an intracellular domain. L1 is primarily expressed in the nervous system and is involved in its development and function. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, or spastic paraplegia type 1, that involves abnormalities of axonal growth. This group also contains NrCAM [Ng(neuronglia)CAM-related cell adhesion molecule], which is primarily expressed in the nervous system, and human neurofascin. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lacks a C" strand.

Pssm-ID: 409396 [Multi-domain] Cd Length: 94 Bit Score: 47.40 E-value: 2.98e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223   59 IECKASGNPMPEIIWIRsDGT--AVGDVPGLRQISSDGKLV--FPPFRAEDYRQEvhaqvYACLARNQFGSIISRDVHVR 134
Cdd:cd05733    21 IKCEAKGNPQPTFRWTK-DGKffDPAKDPRVSMRRRSGTLVidNHNGGPEDYQGE-----YQCYASNELGTAISNEIRLV 94

Second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of the Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, and Robo3), and three mammalian Slit homologs (Slit-1,Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit-2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409389 [Multi-domain] Cd Length: 87 Bit Score: 47.01 E-value: 3.10e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  442 TMEPGPSVflkcvagGNPTPEISWELDGKKIA--NNDRYQVGqyvtvNGDVVsylnITSVHANDGGLYKCIAKSKVGVAE 519
Cdd:cd05724    16 VLECSPPR-------GHPEPTVSWRKDGQPLNldNERVRIVD-----DGNLL----IAEARKSDEGTYKCVATNMVGERE 79


                  ....*...
gi 386767223  520 HS-AKLNV 526
Cdd:cd05724    80 SRaARLSV 87

Second immunoglobulin (Ig)-like domain of protein tyrosine kinase (PTK) 7; The members here are composed of the second immunoglobulin (Ig)-like domain in protein tyrosine kinase (PTK) 7, also known as CCK4. PTK7 is a subfamily of the receptor protein tyrosine kinase family, and is referred to as an RPTK-like molecule. RPTKs transduce extracellular signals across the cell membrane and play important roles in regulating cell proliferation, migration, and differentiation. PTK7 is organized as an extracellular portion having seven Ig-like domains, a single transmembrane region, and a cytoplasmic tyrosine kinase-like domain. PTK7 is considered a pseudokinase as it has several unusual residues in some of the highly conserved tyrosine kinase (TK) motifs; it is predicted to lack TK activity. PTK7 may function as a cell-adhesion molecule. PTK7 mRNA is expressed at high levels in placenta, melanocytes, liver, lung, pancreas, and kidney. PTK7 is overexpressed in several cancers, including melanoma and colon cancer lines.

Pssm-ID: 409417 Cd Length: 95 Bit Score: 47.23 E-value: 3.33e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223   39 PVFLKEPTNRIDFSNSTGAEIECKASGNPMPEIIWIRsDGTAVGDVPGLRQISSDGK-LVFPPFRAEdyrqevHAQVYAC 117
Cdd:cd05760     1 PVVLKHPASAAEIQPSSRVTLRCHIDGHPRPTYQWFR-DGTPLSDGQGNYSVSSKERtLTLRSAGPD------DSGLYYC 73

                          90
                  ....*....|...
gi 386767223  118 LARNQFGSIISRD 130
Cdd:cd05760    74 CAHNAFGSVCSSQ 86

Third immunoglobulin (Ig)-like domain of peroxidasin; The members here are composed of the third immunoglobulin (Ig)-like domain in peroxidasin. Peroxidasin has a peroxidase domain and interacting extracellular motifs containing four Ig-like domains. It has been suggested that peroxidasin is secreted and has functions related to the stabilization of the extracellular matrix. It may play a part in various other important processes such as removal and destruction of cells which have undergone programmed cell death and protection of the organism against non-self.

Pssm-ID: 143222 [Multi-domain] Cd Length: 74 Bit Score: 46.47 E-value: 3.44e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  446 GPSVFLKCVAGGNPTPEISWELDGKKIANNDRYQVGQYVTvngdvvsyLNITSVHANDGGLYKCIAKSKVGVAEHSAKLN 525
Cdd:cd05745     2 GQTVDFLCEAQGYPQPVIAWTKGGSQLSVDRRHLVLSSGT--------LRISRVALHDQGQYECQAVNIVGSQRTVAQLT 73


                  .
gi 386767223  526 V 526
Cdd:cd05745    74 V 74

Immunoglobulin domain I1 of the titin I-band and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin domain I1 of the titin I-band and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. The two sheets are linked together by a conserved disulfide bond between B strand and F strand. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The Ig I1 domain of the titin I-band is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409543 [Multi-domain] Cd Length: 94 Bit Score: 47.03 E-value: 3.45e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  355 QTVDFGRPAVFTCQYTGNPIKTVSWMKDGKAI-GHSEP------------VLRIESVKKEDKGMYQCFVRNDQESAEASA 421
Cdd:cd20951    10 HTVWEKSDAKLRVEVQGKPDPEVKWYKNGVPIdPSSIPgkykieseygvhVLHIRRVTVEDSAVYSAVAKNIHGEASSSA 89


                  ..
gi 386767223  422 EL 423
Cdd:cd20951    90 SV 91

Immunoglobulin (Ig)-like domain of Down Syndrome Cell Adhesion molecule (DSCAM); The members here are composed of the immunoglobulin (Ig)-like domain of Down Syndrome Cell Adhesion molecule (DSCAM). DSCAM is a cell adhesion molecule expressed largely in the developing nervous system. The gene encoding DSCAM is located at human chromosome 21q22, the locus associated with the intellectual disability phenotype of Down Syndrome. DSCAM is predicted to be the largest member of the IG superfamily. It has been demonstrated that DSCAM can mediate cation-independent homophilic intercellular adhesion.

Pssm-ID: 409397 [Multi-domain] Cd Length: 97 Bit Score: 47.10 E-value: 3.54e-06

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 386767223 1337 CLAVGAPQPEITWKI---KGV-EFSA----NDRMRVLPDGSLLIKSVNRQDAGDYSCHAENSIAKD 1394
Cdd:cd05734    23 CSADGYPPPTIVWKHskgSGVpQFQHivplNGRIQLLSNGSLLIKHVLEEDSGYYLCKVSNDVGAD 88

Immunoglobulin (Ig)-like domain in neuregulins; The members here are composed of the immunoglobulin (Ig)-like domain in neuregulins (NRGs). NRGs are signaling molecules which participate in cell-cell interactions in the nervous system, breast, heart, and other organ systems, and are implicated in the pathology of diseases including schizophrenia, multiple sclerosis, and breast cancer. There are four members of the neuregulin gene family (NRG-1, NRG-2, NRG-3, and NRG-4). The NRG-1 protein, binds to and activates the tyrosine kinases receptors ErbB3 and ErbB4, initiating signaling cascades. The other NRGs proteins bind one or the other or both of these ErbBs. NRG-1 has multiple functions: in the brain it regulates various processes such as radial glia formation and neuronal migration, dendritic development, and expression of neurotransmitters receptors, while in the peripheral nervous system NRG-1 regulates processes such as target cell differentiation, and Schwann cell survival. There are many NRG-1 isoforms which arise from the alternative splicing of mRNA. Less is known of the functions of the other NRGs. NRG-2 and NRG-3 are expressed predominantly in the nervous system. NRG-2 is expressed by motor neurons and terminal Schwann cells, and is concentrated near synaptic sites and may be a signal that regulates synaptic differentiation. NRG-4 has been shown to direct pancreatic islet cell development towards the delta-cell lineage.

Pssm-ID: 409408 [Multi-domain] Cd Length: 92 Bit Score: 47.12 E-value: 3.78e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  820 KLRNQTARRGEPAVLQCEAKGEKP-IGILWNMNNMRLDPKNDNRYTIREEILStgvmSSLSIKRTERSDSALFTCVATNA 898
Cdd:cd05750     5 EMKSQTVQEGSKLVLKCEATSENPsPRYRWFKDGKELNRKRPKNIKIRNKKKN----SELQINKAKLEDSGEYTCVVENI 80

                          90
                  ....*....|..
gi 386767223  899 FGSDDASINMIV 910
Cdd:cd05750    81 LGKDTVTGNVTV 92

agrin-responsive first immunoglobulin-like domains (Ig1) of the MuSK ectodomain; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin-like domains (Ig1) of the Muscle-specific kinase (MuSK). MuSK is a receptor tyrosine kinase specifically expressed in skeletal muscle, where it plays a central role in the formation and maintenance of the neuromuscular junction (NMJ). MuSK is activated by agrin, a neuron-derived heparan sulfate proteoglycan. The activation of MUSK in myotubes regulates the formation of NMJs through the regulation of different processes including the specific expression of genes in subsynaptic nuclei, the reorganization of the actin cytoskeleton and the clustering of the acetylcholine receptors (AChR) in the postsynaptic membrane. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the MuSK lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409562 [Multi-domain] Cd Length: 92 Bit Score: 47.12 E-value: 3.82e-06

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 386767223  543 GETLIVTCPVAGYPIDSIVWERD-NRALPINRKQKVFPNGT-LIIENVeRNSDQATYTCVAKNQEGYSARGSLEVQV 617
Cdd:cd20970    17 GENATFMCRAEGSPEPEISWTRNgNLIIEFNTRYIVRENGTtLTIRNI-RRSDMGIYLCIASNGVPGSVEKRITLQV 92

Immunoglobulin (Ig)-like I-set domain of Neural Cell Adhesion Molecule 2 (NCAM-2); The members here are composed of the fourth Ig domain of Neural Cell Adhesion Molecule NCAM-2 (also known as OCAM/mamFas II and RNCAM). NCAM-2 is organized similarly to NCAM, including five N-terminal Ig-like domains and two fibronectin type III domains. NCAM-2 is differentially expressed in the developing and mature olfactory epithelium (OE), and may function like NCAM, as an adhesion molecule. One of the unique features of I-set domains is the lack of a C" strand. The structures of this group show that the Ig domain lacks this strand and thus is a member of the I-set of Ig domains.

Pssm-ID: 143278 [Multi-domain] Cd Length: 98 Bit Score: 47.28 E-value: 3.94e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  432 PVIRQAFQEETMEPGpSVFLKCVAGGNPTPEISWE--LDGKKIANNDRYQVGQyVTVNGDV-VSYLNITSVHANDGGLYK 508
Cdd:cd05870     3 PHIIQLKNETTVENG-AATLSCKAEGEPIPEITWKraSDGHTFSEGDKSPDGR-IEVKGQHgESSLHIKDVKLSDSGRYD 80

                          90
                  ....*....|....*...
gi 386767223  509 CIAKSKVGVAEHSAKLNV 526
Cdd:cd05870    81 CEAASRIGGHQKSMYLDI 98

Fifth Ig-like domain of Roundabout (Robo) homolog 1/2, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fifth Ig-like domain of Roundabout (Robo) homolog 1/2 and similar domains. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, -2, and -3), and three mammalian Slit homologs (Slit-1,-2, -3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, -2, and -3 are expressed by commissural neurons in the vertebrate spinal cord and Slits 1, -2, -3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of slit responsiveness, antagonizes slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be is the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. The fifth Ig-like domain of Robo 1 and 2 is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors

Pssm-ID: 409544 [Multi-domain] Cd Length: 87 Bit Score: 46.72 E-value: 4.08e-06

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 386767223  823 NQTARRGEPAVLQCEAKGEKPIGILWnMNNMRLDPKNDNRYTIREEilstgvmSSLSIKRTERSDSALFTCVATNAFGS 901
Cdd:cd20952     8 NQTVAVGGTVVLNCQATGEPVPTISW-LKDGVPLLGKDERITTLEN-------GSLQIKGAEKSDTGEYTCVALNLSGE 78

Immunoglobulin (Ig)-like domain in neuregulins; The members here are composed of the immunoglobulin (Ig)-like domain in neuregulins (NRGs). NRGs are signaling molecules which participate in cell-cell interactions in the nervous system, breast, heart, and other organ systems, and are implicated in the pathology of diseases including schizophrenia, multiple sclerosis, and breast cancer. There are four members of the neuregulin gene family (NRG-1, NRG-2, NRG-3, and NRG-4). The NRG-1 protein, binds to and activates the tyrosine kinases receptors ErbB3 and ErbB4, initiating signaling cascades. The other NRGs proteins bind one or the other or both of these ErbBs. NRG-1 has multiple functions: in the brain it regulates various processes such as radial glia formation and neuronal migration, dendritic development, and expression of neurotransmitters receptors, while in the peripheral nervous system NRG-1 regulates processes such as target cell differentiation, and Schwann cell survival. There are many NRG-1 isoforms which arise from the alternative splicing of mRNA. Less is known of the functions of the other NRGs. NRG-2 and NRG-3 are expressed predominantly in the nervous system. NRG-2 is expressed by motor neurons and terminal Schwann cells, and is concentrated near synaptic sites and may be a signal that regulates synaptic differentiation. NRG-4 has been shown to direct pancreatic islet cell development towards the delta-cell lineage.

Pssm-ID: 409408 [Multi-domain] Cd Length: 92 Bit Score: 46.74 E-value: 4.12e-06

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 386767223  272 CQAQA-FPLPIMRWYKFIEGTTRKQAVVLNDRVKQVSGTLIIKDAVVEDSGKYLCVVNNSVGGESVETVLTV 342
Cdd:cd05750    21 CEATSeNPSPRYRWFKDGKELNRKRPKNIKIRNKKKNSELQINKAKLEDSGEYTCVVENILGKDTVTGNVTV 92

Eighth immunoglobulin (Ig)-like domain of human myosin light-chain kinase (MLCK) and similar protein; member of the I-set of IgSF domains; The members here are composed of the eighth immunoglobulin (Ig)-like domain of human myosin light-chain kinase (MLCK) and similar proteins. Myosin light-chain kinase (MLCK) is a key regulator of different forms of cell motility involving actin and myosin II. Agonist stimulation of smooth muscle cells increases cytosolic Ca2+ which binds calmodulin. This Ca2+-calmodulin complex in turn binds to and activates MLCK. Activated MLCK leads to the phosphorylation of the 20 kDa myosin regulatory light chain (RLC) of myosin II and the stimulation of actin-activated myosin MgATPase activity. MLCK is widely present in vertebrate tissues; it phosphorylates the 20 kDa RLC of both smooth and nonmuscle myosin II. Phosphorylation leads to the activation of the myosin motor domain and altered structural properties of myosin II. In smooth muscle MLCK it is involved in initiating contraction. In nonmuscle cells, MLCK may participate in cell division and cell motility; it has been suggested MLCK plays a role in cardiomyocyte differentiation and contraction through regulation of nonmuscle myosin II.

Pssm-ID: 409419 Cd Length: 99 Bit Score: 47.26 E-value: 4.19e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  814 PPEFTEKLRNQTARRGEPAVLQCEAKGEKPIGILWnmnnMRLdpkndnRYTIRE----EILSTGVMSSLSIKRTERSDSA 889
Cdd:cd05762     1 PPQIIQFPEDMKVRAGESVELFCKVTGTQPITCTW----MKF------RKQIQEgegiKIENTENSSKLTITEGQQEHCG 70

                          90       100
                  ....*....|....*....|....*...
gi 386767223  890 LFTCVATNAFGSDDASINMIVQEVPEMP 917
Cdd:cd05762    71 CYTLEVENKLGSRQAQVNLTVVDKPDPP 98

Fourth immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM); The members here are composed of the fourth immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM). L1 is comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region, and an intracellular domain. L1 is primarily expressed in the nervous system and is involved in its development and function. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, and spastic paraplegia type 1, that involves abnormalities of axonal growth. This group also contains the chicken neuron-glia cell adhesion molecule, Ng-CAM.

Pssm-ID: 409453 [Multi-domain] Cd Length: 89 Bit Score: 46.81 E-value: 4.58e-06

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 386767223 1331 EDAKMPCLAVGAPQPEITWKIKG--VEFSANDRMRVLPDGSLLIKSVNRQDAGDYSCHAEN 1389
Cdd:cd05867    15 ETARLDCQVEGIPTPNITWSINGapIEGTDPDPRRHVSSGALILTDVQPSDTAVYQCEARN 75

Second immunoglobulin (Ig)-like domain of a Follistatin-related protein 5, and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig)-like domain found in human Follistatin-related protein 5 (FSTL5) and a follistatin-like molecule encoded by the CNS-related Mahya gene. Mahya genes have been retained in certain Bilaterian branches during evolution. They are conserved in Hymenoptera and Deuterostomes, but are absent from other metazoan species such as fruit fly and nematode. Mahya proteins are secretory, with a follistatin-like domain (Kazal-type serine/threonine protease inhibitor domain and EF-hand calcium-binding domain), two Ig-like domains, and a novel C-terminal domain. Mahya may be involved in learning and memory and in processing of sensory information in Hymenoptera and vertebrates. Follistatin is a secreted, multidomain protein that binds activins with high affinity and antagonizes their signaling.

Pssm-ID: 409399 [Multi-domain] Cd Length: 93 Bit Score: 46.87 E-value: 4.82e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  815 PEFTEKLRNQTARRGEPAVLQCEAKGEKPIGILWNMNNMRLDPKNDNRYTireeILSTGvmSSLSIKRTERSDSALFTCV 894
Cdd:cd05736     1 PVIRVYPEFQAKEPGVEASLRCHAEGIPLPRVQWLKNGMDINPKLSKQLT----LIANG--SELHISNVRYEDTGAYTCI 74

                          90
                  ....*....|....*...
gi 386767223  895 ATNAFGSDDASINMIVQE 912
Cdd:cd05736    75 AKNEGGVDEDISSLFVED 92

Second Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the titin Z1z2 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409564 [Multi-domain] Cd Length: 91 Bit Score: 46.81 E-value: 5.08e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  717 PPRWILEPTDKAFAQGSDAKVECKADGFPKPQVTWKKavgdtpgEYKDLKKSDNIRV-EEGTLHVDNIQKTNE---GYYL 792
Cdd:cd20972     1 PPQFIQKLRSQEVAEGSKVRLECRVTGNPTPVVRWFC-------EGKELQNSPDIQIhQEGDLHSLIIAEAFEedtGRYS 73


                  ....*....
gi 386767223  793 CEAINGIGS 801
Cdd:cd20972    74 CLATNSVGS 82

Immunoglobulin domain of human Synaptic Adhesion-Like Molecule 5 (SALM5) and similar proteins; member of the I-set of IgSF domains; This group contains the immunoglobulin domain of human Synaptic Adhesion-Like Molecule 5 (SALM5) and similar proteins. The SALM (for synaptic adhesion-like molecules; also known as Lrfn for leucine-rich repeat and fibronectin type III domain containing) family of adhesion molecules consists of five known members: SALM1/Lrfn2, SALM2/Lrfn1, SALM3/Lrfn4, SALM4/Lrfn3, and SALM5/Lrfn5. SALMs share a similar domain structure, containing leucine-rich repeats (LRRs), an immunoglobulin (Ig) domain, and a fibronectin III (FNIII) domain, followed by a transmembrane domain and a C-terminal PDZ-binding motif. SALM5 is implicated in autism spectrum disorders (ASDs) and schizophrenia, induces presynaptic differentiation in contacting axons. SALM5 interacts with the Ig domains of LAR (Leukocyte common Antigen-Related) family receptor protein tyrosine phosphatases (LAR-RPTPs; LAR, PTPdelta, and PTPsigma). In addition, PTPdelta is implicated in ASDs, ADHD, bipolar disorder, and restless leg syndrome. Studies have shown that LAR-RPTPs are novel and splicing-dependent presynaptic ligands for SALM5, and that they mediate SALM5-dependent presynaptic differentiation. Furthermore, SALM5 maintains AMPA receptor (AMPAR)-mediated excitatory synaptic transmission through mechanisms involving the interaction of SALM5 with LAR-RPTPs. This group belongs to the I-set of immunoglobulin superfamily (IgSF) domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.

Pssm-ID: 409421 [Multi-domain] Cd Length: 88 Bit Score: 46.31 E-value: 6.40e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  432 PVIRQAFQEETMEPGPSVFLKCVAGGNPTPEISW-ELDGKKIANNDRYQVGQyvtvNGDvvsyLNITSVHANDGGLYKCI 510
Cdd:cd05764     1 PLITRHTHELRVLEGQRATLRCKARGDPEPAIHWiSPEGKLISNSSRTLVYD----NGT----LDILITTVKDTGAFTCI 72

                          90
                  ....*....|....*.
gi 386767223  511 AKSKVGVAEHSAKLNV 526
Cdd:cd05764    73 ASNPAGEATARVELHI 88

Fourth immunoglobulin (Ig)-like domain of NrCAM (NgCAM-related cell adhesion molecule); The members here are composed of the fourth immunoglobulin (Ig)-like domain of NrCAM (NgCAM-related cell adhesion molecule). NrCAM belongs to the L1 subfamily of cell adhesion molecules (CAMs) and is comprised of an extracellular region having six IG-like domains and five fibronectin type III domains, a transmembrane region, and an intracellular domain. NrCAM is primarily expressed in the nervous system.

Pssm-ID: 409454 Cd Length: 89 Bit Score: 46.13 E-value: 6.70e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  720 WILEPTDKAFAQGSDAKVECKADGFPKPQVTWKkavgdTPGEYKDLKKSDNIRVEEG-TLHVDNIQKTNEGYYLCEAING 798
Cdd:cd05868     2 WITAPTNLVLSPGEDGTLICRANGNPKPSISWL-----TNGVPIEIAPTDPSRKVDGdTIIFSKVQERSSAVYQCNASNE 76


                  ..
gi 386767223  799 IG 800
Cdd:cd05868    77 YG 78

First immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.

Pssm-ID: 409547 Cd Length: 99 Bit Score: 46.63 E-value: 6.91e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  718 PRWILEPTDKA-FAQGSDAKVECKADGFPKPQVTWKK----AVGDTPGEYKdlKKSDNIRVEEGTLHVDNIQKTNEGYYL 792
Cdd:cd20955     2 PVFLKEPTNRIdFSNSTGAEIECKASGNPMPEIIWIRsdgtAVGDVPGLRQ--ISSDGKLVFPPFRAEDYRQEVHAQVYA 79

                          90
                  ....*....|..
gi 386767223  793 CEAINGIGSGLS 804
Cdd:cd20955    80 CLARNQFGSIIS 91

Fourth immunoglobulin (Ig)-like domain of L1, Ng-CAM (Neuron-glia CAM cell adhesion molecule), and NrCAM (Ng-CAM-related); The members here are composed of the fourth immunoglobulin (Ig)-like domain of L1, Ng-CAM (Neuron-glia CAM cell adhesion molecule), and NrCAM (Ng-CAM-related). These proteins belong to the L1 subfamily of cell adhesion molecules (CAMs) and are comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region and an intracellular domain. These molecules are primarily expressed in the nervous system. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, or spastic paraplegia type 1, that involves abnormalities of axonal growth.

Pssm-ID: 409367 [Multi-domain] Cd Length: 89 Bit Score: 46.29 E-value: 7.38e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223   42 LKEPTNrIDFSNSTGAEIECKASGNPMPEIIWiRSDGTAVGDVPGLRQISSDGK-LVFPPFraedyrQEVHAQVYACLAR 120
Cdd:cd04978     3 IIEPPS-LVLSPGETGELICEAEGNPQPTITW-RLNGVPIEPAPEDMRRTVDGRtLIFSNL------QPNDTAVYQCNAS 74

                          90
                  ....*....|....*
gi 386767223  121 NQFGSIISRD-VHVR 134
Cdd:cd04978    75 NVHGYLLANAfLHVL 89

Third immunoglobulin (Ig)-like domain of peroxidasin; The members here are composed of the third immunoglobulin (Ig)-like domain in peroxidasin. Peroxidasin has a peroxidase domain and interacting extracellular motifs containing four Ig-like domains. It has been suggested that peroxidasin is secreted and has functions related to the stabilization of the extracellular matrix. It may play a part in various other important processes such as removal and destruction of cells which have undergone programmed cell death and protection of the organism against non-self.

Pssm-ID: 143222 [Multi-domain] Cd Length: 74 Bit Score: 45.70 E-value: 7.39e-06

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 386767223  543 GETLIVTCPVAGYPIDSIVWERDNRALPINRKQKVFPNGTLIIENVERNsDQATYTCVAKNQEG 606
Cdd:cd05745     2 GQTVDFLCEAQGYPQPVIAWTKGGSQLSVDRRHLVLSSGTLRISRVALH-DQGQYECQAVNIVG 64

Fourth immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; Members here are composed the fourth immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, Robo3), and three mammalian Slit homologs (Slit-1, Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, and Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409391 [Multi-domain] Cd Length: 98 Bit Score: 46.49 E-value: 7.53e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  439 QEETMEPGPSVFLKCVAGGNPTPEISWELDGKKI--------ANNDRYQVGQyvtvNGDvvsyLNITSVHANDGGLYKCI 510
Cdd:cd05726     7 RDQVVALGRTVTFQCETKGNPQPAIFWQKEGSQNllfpyqppQPSSRFSVSP----TGD----LTITNVQRSDVGYYICQ 78

                          90
                  ....*....|....*...
gi 386767223  511 AKSKVGVAEHSAKLNVYG 528
Cdd:cd05726    79 ALNVAGSILAKAQLEVTD 96

Immunoglobulin domain I1 of the titin I-band and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin domain I1 of the titin I-band and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. The two sheets are linked together by a conserved disulfide bond between B strand and F strand. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The Ig I1 domain of the titin I-band is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409543 [Multi-domain] Cd Length: 94 Bit Score: 46.26 E-value: 7.60e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  432 PVIRQAFQEETMEPGPSVFLKCVAGGNPTPEISWELDGKKIANNDryQVGQYVTVNGDVVSYLNITSVHANDGGLYKCIA 511
Cdd:cd20951     1 PEFIIRLQSHTVWEKSDAKLRVEVQGKPDPEVKWYKNGVPIDPSS--IPGKYKIESEYGVHVLHIRRVTVEDSAVYSAVA 78

                          90
                  ....*....|....*
gi 386767223  512 KSKVGVAEHSAKLNV 526
Cdd:cd20951    79 KNIHGEASSSASVVV 93

First immunoglobulin (Ig) domain of contactin-5; member of the I-set of Ig superfamily domains; The members here are composed of the first immunoglobulin (Ig) domain of the neural cell adhesion molecule contactin-5. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains, anchored to the membrane by glycosylphosphatidylinositol. The different contactins show different expression patterns in the central nervous system. In rats, a lack of contactin-5 (NB-2) results in an impairment of the neuronal activity in the auditory system. Contactin-5 is expressed specifically in the postnatal nervous system, peaking at about 3 weeks postnatal. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala; lower levels of expression have been detected in the corpus callosum, caudate nucleus, and spinal cord. This group belongs to the I-set of IgSF domains.

Pssm-ID: 409435 Cd Length: 96 Bit Score: 46.47 E-value: 7.74e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223 1315 PAKIASFDDTFTATFKEDAK--MPCLAVGAPQPEITWKIKGVEFSANDRMRV-LPDGSLLIKSVNR-QDAGDYSCHAENS 1390
Cdd:cd05848     2 PVFVQEPDDAIFPTDSDEKKviLNCEARGNPVPTYRWLRNGTEIDTESDYRYsLIDGNLIISNPSEvKDSGRYQCLATNS 81


                  .
gi 386767223 1391 I 1391
Cdd:cd05848    82 I 82

Sixth immunoglobulin (Ig) domain of contactin; The members here are composed of the sixth immunoglobulin (Ig) domain of contactins. Contactins are neural cell adhesion molecules and are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module via contacts between Ig domains 1 and 4, and between Ig domains 2 and 3. Contactin-2 (TAG-1, axonin-1) may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. This group also includes contactin-1 and contactin-5. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-5 is expressed specifically in the rat postnatal nervous system, peaking at about 3 weeks postnatal, and a lack of contactin-5 (NB-2) results in an impairment of neuronal activity in the rat auditory system. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma.

Pssm-ID: 409359 Cd Length: 102 Bit Score: 46.39 E-value: 8.39e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  430 DPPVIRQAFQEETMEPGPSVFLKCVAGGNPTPEIS--WELDGKKI---ANNDRYQVGQYVTVNGDvvsyLNITSVHANDG 504
Cdd:cd04970     1 DATRITLAPSNADITVGENATLQCHASHDPTLDLTftWSFNGVPIdleKIEGHYRRRYGKDSNGD----LEIVNAQLKHA 76

                          90       100
                  ....*....|....*....|....*.
gi 386767223  505 GLYKCIAKSKVGVAEHSAKLNVYGLP 530
Cdd:cd04970    77 GRYTCTAQTVVDSDSASATLVVRGPP 102

Immunoglobulin (Ig)-like domain of titin and similar proteins; The members here are composed of the immunoglobulin (Ig)-like domain found in titin-like proteins and similar proteins. Titin (also called connectin) is a fibrous sarcomeric protein specifically found in vertebrate striated muscle. Titin is a giant protein; depending on isoform composition, it ranges from 2970 to 3700 kDa, and is of a length that spans half a sarcomere. Titin largely consists of multiple repeats of Ig-like and fibronectin type 3 (FN-III)-like domains. Titin connects the ends of myosin thick filaments to Z disks and extends along the thick filament to the H zone. It appears to function similarly to an elastic band, keeping the myosin filaments centered in the sarcomere during muscle contraction or stretching. Within the sarcomere, titin is also attached to or is associated with myosin binding protein C (MyBP-C). MyBP-C appears to contribute to the generation of passive tension by titin and like titin has repeated Ig-like and FN-III domains. Also included in this group are worm twitchin and insect projectin, thick filament proteins of invertebrate muscle which also have repeated Ig-like and FN-III domains.

Pssm-ID: 409406 [Multi-domain] Cd Length: 82 Bit Score: 45.66 E-value: 8.87e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  825 TARRGEPAVLQCEAKGEKPIGILWNMNNMRLdpKNDNRYTIReeilSTGVMSSLSIKRTERSDSALFTCVATNAFGSDDA 904
Cdd:cd05748     3 VVRAGESLRLDIPIKGRPTPTVTWSKDGQPL--KETGRVQIE----TTASSTSLVIKNAKRSDSGKYTLTLKNSAGEKSA 76


                  ....*.
gi 386767223  905 SINMIV 910
Cdd:cd05748    77 TINVKV 82

Fifth immunoglobulin (Ig) domain of contactin; The members here are composed of the fifth immunoglobulin (Ig) domain of contactins. Contactins are neural cell adhesion molecules and are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module via contacts between Ig domains 1 and 4, and between Ig domains 2 and 3. Contactin-2 (TAG-1, axonin-1) may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. This group also includes contactin-1 and contactin-5. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-5 is expressed specifically in the rat postnatal nervous system, peaking at about 3 weeks postnatal, and a lack of contactin-5 (NB-2) results in an impairment of neuronal activity in the rat auditory system. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma.

Pssm-ID: 409358 [Multi-domain] Cd Length: 89 Bit Score: 45.91 E-value: 8.90e-06

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 386767223  360 GRPAVFTCQYTGNPIKTVSWMKDGKAIGHSEPV-------LRIESVKKEDKGMYQCFVRNDQESAEASAEL 423
Cdd:cd04969    17 GGDVIIECKPKASPKPTISWSKGTELLTNSSRIcilpdgsLKIKNVTKSDEGKYTCFAVNFFGKANSTGSL 87

Immunoglobulin (Ig)-like domain of vascular endothelial growth factor (VEGF) receptor (R) and similar proteins; member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig)-like domain of vascular endothelial growth factor (VEGF) receptor (R) and related proteins. The VEGFRs have an extracellular component with seven Ig-like domains, a transmembrane segment, and an intracellular tyrosine kinase domain interrupted by a kinase-insert domain. The VEGFR family consists of three members: VEGFR-1 (Flt-1), VEGFR-2 (KDR/Flk-1) and VEGFR-3 (Flt-4). VEGF-A interacts with both VEGFR-1 and VEGFR-2. VEGFR-1 binds strongest to VEGF; VEGF-2 binds more weakly. VEGFR-3 appears not to bind VEGF, but binds other members of the VEGF family (VEGF-C and -D). VEGFRs bind VEGFs with high affinity with the IG-like domains. VEGF-A is important to the growth and maintenance of vascular endothelial cells and to the development of new blood- and lymphatic-vessels in physiological and pathological states. VEGFR-2 is a major mediator of the mitogenic, angiogenic, and microvascular permeability-enhancing effects of VEGF-A. VEGFR-1 may play an inhibitory part in these processes by binding VEGF and interfering with its interaction with VEGFR-2. VEGFR-1 has a signaling role in mediating monocyte chemotaxis. VEGFR-1 and VEGFR-2 may mediate a chemotactic and a survival signal in hematopoietic stem cells or leukemia cells. VEGFR-3 has been shown to be involved in tumor angiogenesis and growth. This group also contains alpha-type platelet-derived growth factor receptor precursor (PDGFR)-alpha (CD140a), and PDGFR-beta (CD140b). PDGFRs alpha and beta have an extracellular component with five Ig-like domains, a transmembrane segment, and a cytoplasmic portion that has protein tyrosine kinase activity.

Pssm-ID: 409404 Cd Length: 102 Bit Score: 46.38 E-value: 9.14e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  822 RNQTARRGEPAVLQCEAKGEKPIGIlwNMNNMRLDPKNDNRYTIREEIL-----STGVMSSLSIKRTERSDSALFTCVAT 896
Cdd:cd05742    10 EPTVLPQGETLVLNCTANVNLNEVV--DFQWTYPSEKEGKLALLKPDIKvdwsePGEFVSTLTIPEATLKDSGTYTCAAR 87

                          90
                  ....*....|....
gi 386767223  897 NAFGSDDASINMIV 910
Cdd:cd05742    88 SGVMKKEKQTSVSV 101

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

Pssm-ID: 464026 [Multi-domain] Cd Length: 79 Bit Score: 45.46 E-value: 9.64e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223   721 ILEPTDKAFAQGSDAKVECKADGFPKPQVTWKKavGDTPgeykdLKKSDNirveegtLHVDNIQKTNEGYYLCEAINGIG 800
Cdd:pfam13895    3 VLTPSPTVVTEGEPVTLTCSAPGNPPPSYTWYK--DGSA-----ISSSPN-------FFTLSVSAEDSGTYTCVARNGRG 68

                           90
                   ....*....|.
gi 386767223   801 SGLSAVIMISV 811
Cdd:pfam13895   69 GKVSNPVELTV 79

Fourth immunoglobulin (Ig)-like domain of hemolin, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain of hemolin and similar proteins. Hemolin, an insect immunoglobulin superfamily (IgSF) member containing four Ig-like domains, is a lipopolysaccharide-binding immune protein induced during bacterial infection. Hemolin shares significant sequence similarity with the first four Ig-like domains of the transmembrane cell adhesion molecules (CAMs) of the L1 family. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The fourth Ig-like domain of hemolin is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409570 [Multi-domain] Cd Length: 88 Bit Score: 45.85 E-value: 9.74e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  815 PEFTEKLRNQTARR-GEPAVLQCEAKGEKPIGILWNMNNMRLDpKNDNRYTIREeilstgvmSSLSIKRTERSDSALFTC 893
Cdd:cd20978     1 PKFIQKPEKNVVVKgGQDVTLPCQVTGVPQPKITWLHNGKPLQ-GPMERATVED--------GTLTIINVQPEDTGYYGC 71


                  ....*..
gi 386767223  894 VATNAFG 900
Cdd:cd20978    72 VATNEIG 78

Sixth immunoglobulin (Ig) domain of contactin; The members here are composed of the sixth immunoglobulin (Ig) domain of contactins. Contactins are neural cell adhesion molecules and are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module via contacts between Ig domains 1 and 4, and between Ig domains 2 and 3. Contactin-2 (TAG-1, axonin-1) may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. This group also includes contactin-1 and contactin-5. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-5 is expressed specifically in the rat postnatal nervous system, peaking at about 3 weeks postnatal, and a lack of contactin-5 (NB-2) results in an impairment of neuronal activity in the rat auditory system. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma.

Pssm-ID: 409359 Cd Length: 102 Bit Score: 46.00 E-value: 1.00e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223 1315 PAKIASFDDTFTATFKEDAKMPCLAVGAPQPEIT--WKIKGVEFSAND------RMRVLPD-GSLLIKSVNRQDAGDYSC 1385
Cdd:cd04970     2 ATRITLAPSNADITVGENATLQCHASHDPTLDLTftWSFNGVPIDLEKieghyrRRYGKDSnGDLEIVNAQLKHAGRYTC 81

                          90       100
                  ....*....|....*....|.
gi 386767223 1386 HAENSIAKDSITHKLIVLAPP 1406
Cdd:cd04970    82 TAQTVVDSDSASATLVVRGPP 102

Fourth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.

Pssm-ID: 409548 [Multi-domain] Cd Length: 96 Bit Score: 46.01 E-value: 1.03e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  814 PPEFTEKLRNQTARRGEPAVLQCEAKGEKPIGILWNMNNMRLdPKNDnRYTIREEILSTG-VMSSLSIKRTERSDSALFT 892
Cdd:cd20956     1 APVLLETFSEQTLQPGPSVSLKCVASGNPLPQITWTLDGFPI-PESP-RFRVGDYVTSDGdVVSYVNISSVRVEDGGEYT 78


                  ....*....
gi 386767223  893 CVATNAFGS 901
Cdd:cd20956    79 CTATNDVGS 87

First immunoglobulin (Ig)-like constant domain in Robo (roundabout) receptors, and similar domains; The members here are composed of the first immunoglobulin (Ig)-like domain in Roundabout (Robo) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, and Robo3), and three mammalian Slit homologs (Slit1, Slit2, Slit3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit1, Slit2,and Slit3 are expressed at the ventral midline. Robo3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be is the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site.

Pssm-ID: 409490 [Multi-domain] Cd Length: 99 Bit Score: 46.01 E-value: 1.12e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  718 PRWILEPTDKAFAQGSDAKVECKADGFPKPQVTWKKAvGDTPGEYKDLKKSDNIRVEEGTLHVDNI-----QKTNEGYYL 792
Cdd:cd07693     1 PRIVEHPSDLIVSKGDPATLNCKAEGRPTPTIQWLKN-GQPLETDKDDPRSHRIVLPSGSLFFLRVvhgrkGRSDEGVYV 79

                          90
                  ....*....|...
gi 386767223  793 CEAINGIGSGLSA 805
Cdd:cd07693    80 CVAHNSLGEAVSR 92

Second immunoglobulin (Ig)-like domain of the receptor protein tyrosine phosphatase (RPTP)-F; member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain found in the receptor protein tyrosine phosphatase (RPTP)-F, also known as LAR. LAR belongs to the RPTP type IIa subfamily. Members of this subfamily are cell adhesion molecule-like proteins involved in central nervous system (CNS) development. They have large extracellular portions comprised of multiple Ig-like domains and two to nine fibronectin type III (FNIII) domains and a cytoplasmic portion having two tandem phosphatase domains.

Pssm-ID: 409400 [Multi-domain] Cd Length: 91 Bit Score: 45.39 E-value: 1.28e-05

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 386767223  270 MLCQAQAFPLPIMRWYK-FIEGTTRKQavvlNDRVKQV-SGTLIIKDAVVEDSGKYLCVVNNSVG 332
Cdd:cd05738    19 MLCAASGNPDPEISWFKdFLPVDTATS----NGRIKQLrSGALQIENSEESDQGKYECVATNSAG 79

First immunoglobulin (Ig)-like constant domain in Robo (roundabout) receptors, and similar domains; The members here are composed of the first immunoglobulin (Ig)-like domain in Roundabout (Robo) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, and Robo3), and three mammalian Slit homologs (Slit1, Slit2, Slit3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit1, Slit2,and Slit3 are expressed at the ventral midline. Robo3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be is the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site.

Pssm-ID: 409490 [Multi-domain] Cd Length: 99 Bit Score: 45.62 E-value: 1.33e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  530 PYIRQMEKKAIVA-GETLIVTCPVAGYPIDSIVWERDNRALPINRKQK-----VFPNGTL----IIENVERNSDQATYTC 599
Cdd:cd07693     1 PRIVEHPSDLIVSkGDPATLNCKAEGRPTPTIQWLKNGQPLETDKDDPrshriVLPSGSLfflrVVHGRKGRSDEGVYVC 80

                          90
                  ....*....|....*...
gi 386767223  600 VAKNQ--EGYSARGSLEV 615
Cdd:cd07693    81 VAHNSlgEAVSRNASLEV 98

Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor; member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor. FGF receptors bind FGF signaling polypeptides. FGFs participate in multiple processes such as morphogenesis, development, and angiogenesis. FGFs bind to four FGF receptor tyrosine kinases (FGFR1, FGFR2, FGFR3, FGFR4). Receptor diversity is controlled by alternative splicing producing splice variants with different ligand binding characteristics and different expression patterns. FGFRs have an extracellular region comprised of three IG-like domains, a single transmembrane helix, and an intracellular tyrosine kinase domain. Ligand binding and specificity reside in the Ig-like domains 2 and 3, and the linker region that connects these two. FGFR activation and signaling depend on FGF-induced dimerization, a process involving cell surface heparin or heparin sulfate proteoglycans.

Pssm-ID: 409443 [Multi-domain] Cd Length: 95 Bit Score: 45.61 E-value: 1.33e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  534 QMEKK--AIVAGETLIVTCPVAGYPIDSIVWERDNRalPINRKQKV------FPNGTLIIENVERnSDQATYTCVAKNQE 605
Cdd:cd05857     8 KMEKKlhAVPAANTVKFRCPAAGNPTPTMRWLKNGK--EFKQEHRIggykvrNQHWSLIMESVVP-SDKGNYTCVVENEY 84


                  .
gi 386767223  606 G 606
Cdd:cd05857    85 G 85

Second immunoglobulin (Ig)-like domain of a Follistatin-related protein 5, and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig)-like domain found in human Follistatin-related protein 5 (FSTL5) and a follistatin-like molecule encoded by the CNS-related Mahya gene. Mahya genes have been retained in certain Bilaterian branches during evolution. They are conserved in Hymenoptera and Deuterostomes, but are absent from other metazoan species such as fruit fly and nematode. Mahya proteins are secretory, with a follistatin-like domain (Kazal-type serine/threonine protease inhibitor domain and EF-hand calcium-binding domain), two Ig-like domains, and a novel C-terminal domain. Mahya may be involved in learning and memory and in processing of sensory information in Hymenoptera and vertebrates. Follistatin is a secreted, multidomain protein that binds activins with high affinity and antagonizes their signaling.

Pssm-ID: 409399 [Multi-domain] Cd Length: 93 Bit Score: 45.33 E-value: 1.34e-05

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 386767223  349 KIDPPTQTVDFGRPAVFTCQYTGNPIKTVSWMKDGKAIGHSEP----------VLRIESVKKEDKGMYQCFVRND 413
Cdd:cd05736     4 RVYPEFQAKEPGVEASLRCHAEGIPLPRVQWLKNGMDINPKLSkqltliangsELHISNVRYEDTGAYTCIAKNE 78

Third immunoglobulin (Ig)-like domain of Neural Cell Adhesion Molecule 1 (NCAM-1); member of the I-set of IgSF domains; The members here are composed of the third immunoglobulin (Ig)-like domain of Neural Cell Adhesion Molecule (NCAM-1). NCAM plays important roles in the development and regeneration of the central nervous system, in synaptogenesis and neural migration. NCAM mediates cell-cell and cell-substratum recognition and adhesion via homophilic (NCAM-NCAM), and heterophilic (NCAM-non-NCAM), interactions. NCAM is expressed as three major isoforms having different intracellular extensions. The extracellular portion of NCAM has five N-terminal Ig-like domains and two fibronectin type III domains. The double zipper adhesion complex model for NCAM homophilic binding involves Ig1, Ig2, and Ig3. By this model, Ig1 and Ig2 mediate dimerization of NCAM molecules situated on the same cell surface (cis interactions), and Ig3 domains mediate interactions between NCAM molecules expressed on the surface of opposing cells (trans interactions) through binding to the Ig1 and Ig2 domains. The adhesive ability of NCAM is modulated by the addition of polysialic acid chains to the fifth Ig-like domain.

Pssm-ID: 143207 [Multi-domain] Cd Length: 95 Bit Score: 45.69 E-value: 1.41e-05

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 386767223  532 IRQMEKKAIV-AGETLIVTCPVAGYPIDSIVWERDNRALPINRKQKVF--PNGTLIIENVERNsDQATYTCVAKNQEG 606
Cdd:cd05730     6 ARQSEVNATAnLGQSVTLACDADGFPEPTMTWTKDGEPIESGEEKYSFneDGSEMTILDVDKL-DEAEYTCIAENKAG 82

agrin-responsive first immunoglobulin-like domains (Ig1) of the MuSK ectodomain; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin-like domains (Ig1) of the Muscle-specific kinase (MuSK). MuSK is a receptor tyrosine kinase specifically expressed in skeletal muscle, where it plays a central role in the formation and maintenance of the neuromuscular junction (NMJ). MuSK is activated by agrin, a neuron-derived heparan sulfate proteoglycan. The activation of MUSK in myotubes regulates the formation of NMJs through the regulation of different processes including the specific expression of genes in subsynaptic nuclei, the reorganization of the actin cytoskeleton and the clustering of the acetylcholine receptors (AChR) in the postsynaptic membrane. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the MuSK lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409562 [Multi-domain] Cd Length: 92 Bit Score: 45.19 E-value: 1.53e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  820 KLRNQTARRGEPAVLQCEAKGEKPIGILWNMNNMRLDPKNDnrytiREEILSTGVMssLSIKRTERSDSALFTCVATN-A 898
Cdd:cd20970     8 PSFTVTAREGENATFMCRAEGSPEPEISWTRNGNLIIEFNT-----RYIVRENGTT--LTIRNIRRSDMGIYLCIASNgV 80

                          90
                  ....*....|..
gi 386767223  899 FGSDDASINMIV 910
Cdd:cd20970    81 PGSVEKRITLQV 92

Immunoglobulin (Ig)-like domain in neuregulins; The members here are composed of the immunoglobulin (Ig)-like domain in neuregulins (NRGs). NRGs are signaling molecules which participate in cell-cell interactions in the nervous system, breast, heart, and other organ systems, and are implicated in the pathology of diseases including schizophrenia, multiple sclerosis, and breast cancer. There are four members of the neuregulin gene family (NRG-1, NRG-2, NRG-3, and NRG-4). The NRG-1 protein, binds to and activates the tyrosine kinases receptors ErbB3 and ErbB4, initiating signaling cascades. The other NRGs proteins bind one or the other or both of these ErbBs. NRG-1 has multiple functions: in the brain it regulates various processes such as radial glia formation and neuronal migration, dendritic development, and expression of neurotransmitters receptors, while in the peripheral nervous system NRG-1 regulates processes such as target cell differentiation, and Schwann cell survival. There are many NRG-1 isoforms which arise from the alternative splicing of mRNA. Less is known of the functions of the other NRGs. NRG-2 and NRG-3 are expressed predominantly in the nervous system. NRG-2 is expressed by motor neurons and terminal Schwann cells, and is concentrated near synaptic sites and may be a signal that regulates synaptic differentiation. NRG-4 has been shown to direct pancreatic islet cell development towards the delta-cell lineage.

Pssm-ID: 409408 [Multi-domain] Cd Length: 92 Bit Score: 45.19 E-value: 1.56e-05

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 386767223  354 TQTVDFGRPAVFTCQYTG-NPIKTVSWMKDGKAIGHSEPV------------LRIESVKKEDKGMYQCFVRN 412
Cdd:cd05750     8 SQTVQEGSKLVLKCEATSeNPSPRYRWFKDGKELNRKRPKnikirnkkknseLQINKAKLEDSGEYTCVVEN 79

Immunoglobulin (Ig)-like ectodomain of the LRIG1 (Leucine-rich Repeats And Immunoglobulin-like Domains Protein 1) and similar proteins; member of the I-set of IgSF domains; The members here are composed of subgroup of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. The ectodomain of LRIG1 has two distinct regions: the proposed 15 LRRs and three Ig-like domains closer to the membrane. LRIG1 has been reported to interact with many receptor tyrosine kinases, GDNF/c-Ret, E-cadherin, JAK/STAT, c-Met, and the EGFR family signaling systems. Immunoglobulin Superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The structure of the LRIG1 extracellular Ig domain lacks a C" strand and thus is better described as a member of the I-set of IgSF domains.

Pssm-ID: 409420 [Multi-domain] Cd Length: 91 Bit Score: 44.92 E-value: 2.00e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223   41 FLKEPTNrIDFSNSTGAEIECKASGNPMPEIIWIRSDGTavgDVPGLRQ-----ISSDGKLVFPPFRAEDyrqevhAQVY 115
Cdd:cd05763     2 FTKTPHD-ITIRAGSTARLECAATGHPTPQIAWQKDGGT---DFPAARErrmhvMPEDDVFFIVDVKIED------TGVY 71

                          90
                  ....*....|.
gi 386767223  116 ACLARNQFGSI 126
Cdd:cd05763    72 SCTAQNSAGSI 82

Second Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the titin Z1z2 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409564 [Multi-domain] Cd Length: 91 Bit Score: 44.88 E-value: 2.07e-05

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 386767223 1334 KMPCLAVGAPQPEITWKIKGVEFSANDRMRVLPDG---SLLIKSVNRQDAGDYSCHAENSIAKDSITHKLIV 1402
Cdd:cd20972    20 RLECRVTGNPTPVVRWFCEGKELQNSPDIQIHQEGdlhSLIIAEAFEEDTGRYSCLATNSVGSDTTSAEIFV 91

C-terminal immunoglobulin (Ig)-like domain of myotilin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of myotilin. Mytolin belongs to the palladin-myotilin-myopalladin family. Proteins belonging to the latter family contain multiple Ig-like domains and function as scaffolds, modulating the actin cytoskeleton. Myotilin is most abundant in skeletal and cardiac muscle and is involved in maintaining sarcomere integrity. It binds to alpha-actinin, filamin, and actin. Mutations in myotilin lead to muscle disorders. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409473 Cd Length: 92 Bit Score: 44.76 E-value: 2.20e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  718 PRWILEPTDKAFAQGSDAKVECKADGFPKPQVTWKKAvgdtpgeykdlKKSDNIRVEEGTLHVDN-------IQ---KTN 787
Cdd:cd05892     1 PMFIQKPQNKKVLEGDPVRLECQISAIPPPQIFWKKN-----------NEMLQYNTDRISLYQDNcgricllIQnanKKD 69

                          90
                  ....*....|...
gi 386767223  788 EGYYLCEAINGIG 800
Cdd:cd05892    70 AGWYTVSAVNEAG 82

Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor, and similar domains; member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor. FGF receptors bind FGF signaling polypeptides. FGFs participate in multiple processes such as morphogenesis, development, and angiogenesis. FGFs bind to four FGF receptor tyrosine kinases (FGFR1, FGFR2, FGFR3, FGFR4). Receptor diversity is controlled by alternative splicing producing splice variants with different ligand binding characteristics and different expression patterns. FGFRs have an extracellular region comprised of three Ig-like domains, a single transmembrane helix, and an intracellular tyrosine kinase domain. Ligand binding and specificity reside in the Ig-like domains 2 and 3, and the linker region that connects these two. FGFR activation and signaling depend on FGF-induced dimerization, a process involving cell surface heparin or heparin sulfate proteoglycans. This group also contains fibroblast growth factor (FGF) receptor like-1(FGFRL1). FGFRL1 does not have a protein tyrosine kinase domain at its C-terminus; neither does its cytoplasmic domain appear to interact with a signaling partner. It has been suggested that FGFRL1 may not have any direct signaling function, but instead acts as a decoy receptor trapping FGFs and preventing them from binding other receptors.

Pssm-ID: 409393 [Multi-domain] Cd Length: 95 Bit Score: 44.90 E-value: 2.26e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  347 SAKIDPPTQTVDFGRPAVFTCQYTGNPIKTVSWMKDGK---AIGHSEP--------VLRIESVKKEDKGMYQCFVRNDQE 415
Cdd:cd05729     6 TEKMEEREHALPAANKVRLECGAGGNPMPNITWLKDGKefkKEHRIGGtkveekgwSLIIERAIPRDKGKYTCIVENEYG 85

                          90
                  ....*....|
gi 386767223  416 SAEASAELKL 425
Cdd:cd05729    86 SINHTYDVDV 95

C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin, and similar domains; member of the I-set IgSF domains; The members here are composed of the C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin and similar proteins, including Caenorhabditis elegans and Aplysia californica Twitchin, Drosophila melanogaster Projectin, and similar proteins. These are very large muscle proteins containing multiple immunoglobulin (Ig)-like and fibronectin type III (FN3) domains and a single kinase domain near the C-terminus. In humans these proteins are called Titin. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The Ig-like domain of the Twitchin is a member of the I-set IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins (titin, telokin, and twitchin), the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D.

Pssm-ID: 409541 [Multi-domain] Cd Length: 89 Bit Score: 44.63 E-value: 2.38e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  817 FTEKLRNQTARRGEPAVLQCEAKGEKPIGILWNMNNMRLdpKNDNRYTIREEILSTGvmssLSIKRTERSDSALFTCVAT 896
Cdd:cd20949     2 FTENAYVTTVKEGQSATILCEVKGEPQPNVTWHFNGQPI--SASVADMSKYRILADG----LLINKVTQDDTGEYTCRAY 75


                  ....
gi 386767223  897 NAFG 900
Cdd:cd20949    76 QVNS 79

Immunoglobulin (Ig)-like domain of the human basement membrane heparan sulfate proteoglycan perlecan and similar proteins; The members here are composed of the immunoglobulin (Ig)-like domain of the human basement membrane heparan sulfate proteoglycan perlecan, also known as HSPG2, and similar proteins. Perlecan consists of five domains: domain I has three putative heparan sulfate attachment sites, domain II has four LDL receptor-like repeats, and one Ig-like repeat, domain III resembles the short arm of laminin chains, domain IV has multiple Ig-like repeats (21 repeats in human perlecan), and domain V resembles the globular G domain of the laminin A chain and internal repeats of EGF. Perlecan may participate in a variety of biological functions including cell binding, LDL-metabolism, basement membrane assembly and selective permeability, calcium binding, and growth- and neurite-promoting activities.

Pssm-ID: 143220 Cd Length: 78 Bit Score: 44.40 E-value: 2.46e-05

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 386767223  543 GETLIVTCPVAGYPIDSIVWERDNRALPINRKQKVFPN---GTLIIENVeRNSDQATYTCVAKNQEGY 607
Cdd:cd05743     1 GETVEFTCVATGVPTPIINWRLNWGHVPDSARVSITSEggyGTLTIRDV-KESDQGAYTCEAINTRGM 67

Fourth immunoglobulin (Ig)-like domain of L1, Ng-CAM (Neuron-glia CAM cell adhesion molecule), and NrCAM (Ng-CAM-related); The members here are composed of the fourth immunoglobulin (Ig)-like domain of L1, Ng-CAM (Neuron-glia CAM cell adhesion molecule), and NrCAM (Ng-CAM-related). These proteins belong to the L1 subfamily of cell adhesion molecules (CAMs) and are comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region and an intracellular domain. These molecules are primarily expressed in the nervous system. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, or spastic paraplegia type 1, that involves abnormalities of axonal growth.

Pssm-ID: 409367 [Multi-domain] Cd Length: 89 Bit Score: 44.75 E-value: 2.48e-05

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 386767223  543 GETLIVTCPVAGYPIDSIVWERDNR---ALPINRKQKVFPnGTLIIENVERNsDQATYTCVAKNQEGY 607
Cdd:cd04978    14 GETGELICEAEGNPQPTITWRLNGVpiePAPEDMRRTVDG-RTLIFSNLQPN-DTAVYQCNASNVHGY 79

Immunoglobulin (Ig)-like ectodomain of the LRIG1 (Leucine-rich Repeats And Immunoglobulin-like Domains Protein 1) and similar proteins; member of the I-set of IgSF domains; The members here are composed of subgroup of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. The ectodomain of LRIG1 has two distinct regions: the proposed 15 LRRs and three Ig-like domains closer to the membrane. LRIG1 has been reported to interact with many receptor tyrosine kinases, GDNF/c-Ret, E-cadherin, JAK/STAT, c-Met, and the EGFR family signaling systems. Immunoglobulin Superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The structure of the LRIG1 extracellular Ig domain lacks a C" strand and thus is better described as a member of the I-set of IgSF domains.

Pssm-ID: 409420 [Multi-domain] Cd Length: 91 Bit Score: 44.53 E-value: 2.63e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  442 TMEPGPSVFLKCVAGGNPTPEISWELDGKK---IANNDRYQVgqyvtVNGDVVSYlnITSVHANDGGLYKCIAKSKVGVA 518
Cdd:cd05763    10 TIRAGSTARLECAATGHPTPQIAWQKDGGTdfpAARERRMHV-----MPEDDVFF--IVDVKIEDTGVYSCTAQNSAGSI 82


                  ....*...
gi 386767223  519 EHSAKLNV 526
Cdd:cd05763    83 SANATLTV 90

Fifth immunoglobulin (Ig)-like domain of Kirrel (kin of irregular chiasm-like) 3 protein; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the fifth immunoglobulin (Ig)-like domain of Kirrel (kin of irregular chiasm-like) 3 protein (also known as Neph2). This protein has five Ig-like domains, one transmembrane domain, and a cytoplasmic tail. Included in this group is mammalian Kirrel (Neph1). These proteins contain multiple Ig domains, have properties of cell adhesion molecules, and are important in organ development. Neph1 and 2 may mediate axonal guidance and synapse formation in certain areas of the CNS. In the kidney they participate in the formation of the slit diaphragm.

Pssm-ID: 409479 Cd Length: 98 Bit Score: 44.94 E-value: 2.66e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  824 QTARRGEPAVLQCE-AKGEKPIGILWNMNNMRLDPKNDNRYTIREEILSTGVMSSLSIKRTERSD-SALFTCVATNAFGS 901
Cdd:cd05898    11 QYAVRGERGKVKCFiGSTPPPDRIAWAWKENVLESGTLERYTVERTSTGSGVLSTLTINNIMEADfQTHYNCTAWNSFGS 90


                  ....*..
gi 386767223  902 DDASINM 908
Cdd:cd05898    91 GTAIIQL 97

Third immunoglobulin (Ig)-like domain of Neural Cell Adhesion Molecule 1 (NCAM-1); member of the I-set of IgSF domains; The members here are composed of the third immunoglobulin (Ig)-like domain of Neural Cell Adhesion Molecule (NCAM-1). NCAM plays important roles in the development and regeneration of the central nervous system, in synaptogenesis and neural migration. NCAM mediates cell-cell and cell-substratum recognition and adhesion via homophilic (NCAM-NCAM), and heterophilic (NCAM-non-NCAM), interactions. NCAM is expressed as three major isoforms having different intracellular extensions. The extracellular portion of NCAM has five N-terminal Ig-like domains and two fibronectin type III domains. The double zipper adhesion complex model for NCAM homophilic binding involves Ig1, Ig2, and Ig3. By this model, Ig1 and Ig2 mediate dimerization of NCAM molecules situated on the same cell surface (cis interactions), and Ig3 domains mediate interactions between NCAM molecules expressed on the surface of opposing cells (trans interactions) through binding to the Ig1 and Ig2 domains. The adhesive ability of NCAM is modulated by the addition of polysialic acid chains to the fifth Ig-like domain.

Pssm-ID: 143207 [Multi-domain] Cd Length: 95 Bit Score: 44.54 E-value: 2.70e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223 1326 TATFKEDAKMPCLAVGAPQPEITWKIKGVEF-SANDRMRVLPDGS-LLIKSVNRQDAGDYSCHAENSIAKDSITHKLIVL 1403
Cdd:cd05730    14 TANLGQSVTLACDADGFPEPTMTWTKDGEPIeSGEEKYSFNEDGSeMTILDVDKLDEAEYTCIAENKAGEQEAEIHLKVF 93


                  .
gi 386767223 1404 A 1404
Cdd:cd05730    94 A 94

Seventh immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the seventh immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.

Pssm-ID: 409546 [Multi-domain] Cd Length: 96 Bit Score: 44.61 E-value: 2.94e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223   39 PVFLKEPTnriDFSNSTGAEI--ECKASGNPMPEIIWIRSDGTAVGDVPGLR-----QISSDGKLVFppfraeDYRQEVH 111
Cdd:cd20954     2 PRWIVEPV---DANVAAGQDVmlHCQADGFPTPTVTWKKATGSTPGEYKDLLydpnvRILPNGTLVF------GHVQKEN 72

                          90
                  ....*....|....*...
gi 386767223  112 AQVYACLARNQFGSIISR 129
Cdd:cd20954    73 EGHYLCEAKNGIGSGLSK 90

First immunoglobulin (Ig)-like domain in neogenin, and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the first immunoglobulin (Ig)-like domain in neogenin and related proteins. Neogenin is a cell surface protein which is expressed in the developing nervous system of vertebrate embryos in the growing nerve cells. It is also expressed in other embryonic tissues and may play a general role in developmental processes such as cell migration, cell-cell recognition, and tissue growth regulation. Included in this group is the tumor suppressor protein DCC which is deleted in colorectal carcinoma. DCC and neogenin each have four Ig-like domains followed by six fibronectin type III domains, a transmembrane domain, and an intracellular domain. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409387 Cd Length: 97 Bit Score: 44.78 E-value: 2.97e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  717 PPRWILEPTDKAFAQGSDAKVECKADGFPKPQVTWKKAvgdtpGEYKDLKKSDNIRV-EEGTLHVDNIQ-----KTNEGY 790
Cdd:cd05722     1 ELYFLSEPSDIVAMRGGPVVLNCSAESDPPPKIEWKKD-----GVLLNLVSDERRQQlPNGSLLITSVVhskhnKPDEGF 75

                          90
                  ....*....|....*
gi 386767223  791 YLCEAING-IGSGLS 804
Cdd:cd05722    76 YQCVAQNEsLGSIVS 90

Fifth Ig-like domain of Roundabout (Robo) homolog 1/2, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fifth Ig-like domain of Roundabout (Robo) homolog 1/2 and similar domains. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, -2, and -3), and three mammalian Slit homologs (Slit-1,-2, -3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, -2, and -3 are expressed by commissural neurons in the vertebrate spinal cord and Slits 1, -2, -3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of slit responsiveness, antagonizes slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be is the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. The fifth Ig-like domain of Robo 1 and 2 is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors

Pssm-ID: 409544 [Multi-domain] Cd Length: 87 Bit Score: 44.41 E-value: 2.97e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  723 EPTDKAFAQGSDAKVECKADGFPKPQVTWKKAVGDTPGEYKDLKKSDNirveeGTLHVDNIQKTNEGYYLCEAINGIGSG 802
Cdd:cd20952     5 GPQNQTVAVGGTVVLNCQATGEPVPTISWLKDGVPLLGKDERITTLEN-----GSLQIKGAEKSDTGEYTCVALNLSGEA 79


                  ....*.
gi 386767223  803 L-SAVI 807
Cdd:cd20952    80 TwSAVL 85

Fourth immunoglobulin (Ig)-like domain of hemolin, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain of hemolin and similar proteins. Hemolin, an insect immunoglobulin superfamily (IgSF) member containing four Ig-like domains, is a lipopolysaccharide-binding immune protein induced during bacterial infection. Hemolin shares significant sequence similarity with the first four Ig-like domains of the transmembrane cell adhesion molecules (CAMs) of the L1 family. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The fourth Ig-like domain of hemolin is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409570 [Multi-domain] Cd Length: 88 Bit Score: 44.31 E-value: 3.00e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  442 TMEPGPSVFLKCVAGGNPTPEISWELDGKKI-ANNDRYQVGQyvtvngdvvSYLNITSVHANDGGLYKCIAKSKVGVAEH 520
Cdd:cd20978    12 VVKGGQDVTLPCQVTGVPQPKITWLHNGKPLqGPMERATVED---------GTLTIINVQPEDTGYYGCVATNEIGDIYT 82


                  ....*.
gi 386767223  521 SAKLNV 526
Cdd:cd20978    83 ETLLHV 88

agrin-responsive second immunoglobulin-like domains (Ig2) of the Muscle-specific kinase (MuSK) ectodomain; a member of the I-set of Ig superfamily domains; The members here are composed of the second immunoglobulin-like (Ig) domains of the Muscle-specific kinase (MuSK) ectodomain. MuSK is a receptor tyrosine kinase specifically expressed in skeletal muscle, where it plays a central role in the formation and maintenance of the neuromuscular junction (NMJ). MuSK is activated by agrin, a neuron-derived heparan sulfate proteoglycan. The activation of MUSK in myotubes regulates the formation of NMJs through the regulation of different processes including the specific expression of genes in subsynaptic nuclei, the reorganization of the actin cytoskeleton and the clustering of the acetylcholine receptors (AChR) in the postsynaptic membrane. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the MuSK lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409560 [Multi-domain] Cd Length: 88 Bit Score: 44.16 E-value: 3.07e-05

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 386767223  446 GPSVFLKCVAGGNPTPEISWELDGKKIANNDRYQVGQyvtvNGDvvsyLNITSVHANDGGLYKCIAKSKVGVA 518
Cdd:cd20968    14 GLKAVLPCTTMGNPKPSVSWIKGDDLIKENNRIAVLE----SGS----LRIHNVQKEDAGQYRCVAKNSLGIA 78

Third immunoglobulin (Ig) domain of contactin-1; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig) domain of the neural cell adhesion molecule contactin-1. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-1 is differentially expressed in tumor tissues and may through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma. This group belongs to the I-set of IgSF domains.

Pssm-ID: 143259 Cd Length: 88 Bit Score: 44.24 E-value: 3.15e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  717 PPRWILEPTDKAFAQGSDAKVECKADGFPKPQVTWKKAVGDTPGeykdlkkSDNIRVEEGTLHVDNIQKTNEGYYLCEAI 796
Cdd:cd05851     1 PADINVKFKDTYALKGQNVTLECFALGNPVPVIRWRKILEPMPA-------TAEISMSGAVLKIFNIQPEDEGTYECEAE 73


                  .
gi 386767223  797 N 797
Cdd:cd05851    74 N 74

Third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM); The members here are composed of the third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM). L1 belongs to the L1 subfamily of cell adhesion molecules (CAMs) and is comprised of an extracellular region having six Ig-like domains, five fibronectin type III domains, a transmembrane region and an intracellular domain. L1 is primarily expressed in the nervous system and is involved in its development and function. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, or spastic paraplegia type 1, that involves abnormalities of axonal growth. This group also contains the chicken neuron-glia cell adhesion molecule, Ng-CAM.

Pssm-ID: 409460 [Multi-domain] Cd Length: 83 Bit Score: 44.13 E-value: 3.18e-05

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 386767223  731 QGSDAKVECKADGFPKPQVTWKKAVGDTPGEykDLKKSDNIRveegTLHVDNIQKTNEGYYLCEAINGIGS 801
Cdd:cd05876     9 RGQSLVLECIAEGLPTPTVKWLRPSGPLPPD--RVKYQNHNK----TLQLLNVGESDDGEYVCLAENSLGS 73

First immunoglobulin (Ig)-like domain of neural cell adhesion molecule NCAM-1, and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the first immunoglobulin (Ig)-like domain of neural cell adhesion molecule NCAM-1. NCAM-1 plays important roles in the development and regeneration of the central nervous system, in synaptogenesis and neural migration. NCAM mediates cell-cell and cell-substratum recognition and adhesion via homophilic (NCAM-NCAM) and heterophilic (NCAM-nonNCAM) interactions. NCAM is expressed as three major isoforms having different intracellular extensions. The extracellular portion of NCAM has five N-terminal Ig-like domains and two fibronectin type III domains. The double zipper adhesion complex model for NCAM homophilic binding involves the Ig1, Ig2, and Ig3 domains. By this model, Ig1 and Ig2 mediate dimerization of NCAM molecules situated on the same cell surface (cis interactions), and Ig3 domains mediate interactions between NCAM molecules expressed on the surface of opposing cells (trans interactions), through binding to the Ig1 and Ig2 domains. The adhesive ability of NCAM is modulated by the addition of polysialic acid chains to the fifth Ig-like domain. Also included in this group is NCAM-2 (also known as OCAM/mamFas II and RNCAM). NCAM-2 is differentially expressed in the developing and mature olfactory epithelium (OE). This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409366 Cd Length: 95 Bit Score: 44.55 E-value: 3.20e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  442 TMEPGPSVFLKCVAGGNPTpEISW-ELDGKKIANNDryqvGQYVTVN-GDVVSYLNITSVHANDGGLYKCIAKSKVGV-A 518
Cdd:cd04977    11 EISVGESKFFLCKVSGDAK-NINWvSPNGEKVLTKH----GNLKVVNhGSVLSSLTIYNANINDAGIYKCVATNGKGTeS 85


                  ....*....
gi 386767223  519 EHSAKLNVY 527
Cdd:cd04977    86 EATVKLDII 94

Fifth immunoglobulin (Ig) domain of contactin-1; The members here are composed of the fifth immunoglobulin (Ig) domain of the neural cell adhesion molecule contactin-1. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-1 is differentially expressed in tumor tissues and may through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma.

Pssm-ID: 409438 Cd Length: 89 Bit Score: 44.22 E-value: 3.38e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  718 PRWILEPTDKAF--AQGSDAKVECKADGFPKPQVTWKKAVgdtpgeyKDLKKSDNIRV-EEGTLHVDNIQKTNEGYYLCE 794
Cdd:cd05852     1 PTFEFNPMKKKIlaAKGGRVIIECKPKAAPKPKFSWSKGT-------ELLVNNSRISIwDDGSLEILNITKLDEGSYTCF 73

                          90
                  ....*....|....
gi 386767223  795 AINGIGSGLSAVIM 808
Cdd:cd05852    74 AENNRGKANSTGVL 87

Third immunoglobulin (Ig)-like domain of the receptor protein tyrosine phosphatase (RPTP)-F (also known as LAR), type IIa; member of the I-set of IgSF domains; The members here are composed of the third immunoglobulin (Ig)-like domain found in the receptor protein tyrosine phosphatase (RPTP)-F, also known as LAR. LAR belongs to the RPTP type IIa subfamily. Members of this subfamily are cell adhesion molecule-like proteins involved in central nervous system (CNS) development. They have large extracellular portions comprised of multiple Ig-like domains and two to nine fibronectin type III (FNIII) domains and a cytoplasmic portion having two tandem phosphatase domains. Included in this group is Drosophila LAR (DLAR).

Pssm-ID: 409401 Cd Length: 82 Bit Score: 43.74 E-value: 3.79e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  440 EETMePGPSVFLKCVAGGNPTPEISWELDGKKIANNDRYQVGQyvtvngDVVSYLNITSvHANdgglYKCIAKSKVGVAE 519
Cdd:cd05739     7 HEVM-PGGSVNLTCVAVGAPMPYVKWMKGGEELTKEDEMPVGR------NVLELTNIYE-SAN----YTCVAISSLGMIE 74


                  ....*..
gi 386767223  520 HSAKLNV 526
Cdd:cd05739    75 ATAQVTV 81

C-terminal immunoglobulin (Ig)-like domain of myotilin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of myotilin. Mytolin belongs to the palladin-myotilin-myopalladin family. Proteins belonging to the latter family contain multiple Ig-like domains and function as scaffolds, modulating the actin cytoskeleton. Myotilin is most abundant in skeletal and cardiac muscle and is involved in maintaining sarcomere integrity. It binds to alpha-actinin, filamin, and actin. Mutations in myotilin lead to muscle disorders. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409473 Cd Length: 92 Bit Score: 43.99 E-value: 4.19e-05

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 386767223 1331 EDAKMPCLAVGAPQPEITWKIKGVEFSAN-DRMRVLPDGS----LLIKSVNRQDAGDYSCHAENSIAKDSITHKLIV 1402
Cdd:cd05892    16 DPVRLECQISAIPPPQIFWKKNNEMLQYNtDRISLYQDNCgricLLIQNANKKDAGWYTVSAVNEAGVVSCNARLDV 92

Third immunoglobulin (Ig) domain of contactin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig) domain of contactins. Contactins are neural cell adhesion molecules and are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module via contacts between Ig domains 1 and 4, and between Ig domains 2 and 3. Contactin-2 (TAG-1, axonin-1) may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. This group also includes contactin-1 and contactin-5. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-5 is expressed specifically in the rat postnatal nervous system, peaking at about 3 weeks postnatal, and a lack of contactin-5 (NB-2) results in an impairment of neuronal activity in the rat auditory system. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma. This group belongs to the I-set of IgSF domains.

Pssm-ID: 409357 [Multi-domain] Cd Length: 88 Bit Score: 44.08 E-value: 4.30e-05

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 386767223  367 CQYTGNPIKTVSWMK-DG-----KAIGHSEPVLRIESVKKEDKGMYQCFVRN 412
Cdd:cd04968    23 CFALGNPVPQIKWRKvDGspssqWEITTSEPVLEIPNVQFEDEGTYECEAEN 74

Second immunoglobulin (Ig)-like domain of a Follistatin-related protein 5, and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig)-like domain found in human Follistatin-related protein 5 (FSTL5) and a follistatin-like molecule encoded by the CNS-related Mahya gene. Mahya genes have been retained in certain Bilaterian branches during evolution. They are conserved in Hymenoptera and Deuterostomes, but are absent from other metazoan species such as fruit fly and nematode. Mahya proteins are secretory, with a follistatin-like domain (Kazal-type serine/threonine protease inhibitor domain and EF-hand calcium-binding domain), two Ig-like domains, and a novel C-terminal domain. Mahya may be involved in learning and memory and in processing of sensory information in Hymenoptera and vertebrates. Follistatin is a secreted, multidomain protein that binds activins with high affinity and antagonizes their signaling.

Pssm-ID: 409399 [Multi-domain] Cd Length: 93 Bit Score: 44.17 E-value: 4.34e-05

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 386767223 1330 KEDAKMPCLAVGAPQPEITWKIKGVEFSAN--DRMRVLPDGS-LLIKSVNRQDAGDYSCHAENSIAKDSITHKLIV 1402
Cdd:cd05736    15 GVEASLRCHAEGIPLPRVQWLKNGMDINPKlsKQLTLIANGSeLHISNVRYEDTGAYTCIAKNEGGVDEDISSLFV 90

Fourth Ig-like domain from smooth muscle myosin light chain kinase and similar domains ; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain from smooth muscle myosin light chain kinase (MYLK) and similar domains. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of this group shows that the fourth Ig-like domain from myosin light chain kinase lacks this strand and thus belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409568 [Multi-domain] Cd Length: 90 Bit Score: 43.78 E-value: 4.47e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  352 PPTQTVDFGRPAVFTCQYTGNPIKTVSWMKDGKAIGHS------EP---VLRIESVKKEDKGMYQCFVRNDQESAEASAE 422
Cdd:cd20976     8 PKDLEAVEGQDFVAQCSARGKPVPRITWIRNAQPLQYAadrstcEAgvgELHIQDVLPEDHGTYTCLAKNAAGQVSCSAW 87


                  .
gi 386767223  423 L 423
Cdd:cd20976    88 V 88

immunoglobulin-like domain of telokin and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig) domain in telokin, the C-terminal domain of myosin light chain kinase which is identical to telokin, and similar proteins. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the telokin Ig domain lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409565 [Multi-domain] Cd Length: 88 Bit Score: 43.72 E-value: 4.61e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  726 DKAFAQGSDAKVECKADGFPKPQVTWKKavgdtpgEYKDLKKSDNIRV---EEG--TLHVDNIQKTNEGYYLCEAINGIG 800
Cdd:cd20973     6 DKEVVEGSAARFDCKVEGYPDPEVKWMK-------DDNPIVESRRFQIdqdEDGlcSLIISDVCGDDSGKYTCKAVNSLG 78

Third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM); The members here are composed of the third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM). L1 belongs to the L1 subfamily of cell adhesion molecules (CAMs) and is comprised of an extracellular region having six Ig-like domains, five fibronectin type III domains, a transmembrane region and an intracellular domain. L1 is primarily expressed in the nervous system and is involved in its development and function. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, or spastic paraplegia type 1, that involves abnormalities of axonal growth. This group also contains the chicken neuron-glia cell adhesion molecule, Ng-CAM.

Pssm-ID: 409460 [Multi-domain] Cd Length: 83 Bit Score: 43.75 E-value: 4.74e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  446 GPSVFLKCVAGGNPTPEISW-ELDGKKIANNDRYQVGQyvtvngdvvSYLNITSVHANDGGLYKCIAKSKVGVAEHSAKL 524
Cdd:cd05876    10 GQSLVLECIAEGLPTPTVKWlRPSGPLPPDRVKYQNHN---------KTLQLLNVGESDDGEYVCLAENSLGSARHAYYV 80


                  ..
gi 386767223  525 NV 526
Cdd:cd05876    81 TV 82

Immunoglobulin (Ig) constant domain of the complement receptor of the immunoglobulin superfamily (CRIg); The members here are composed of the Immunoglobulin (Ig) constant domain of the complement receptor of the immunoglobulin superfamily (CRIg). The N-terminal domain of CRIg (also referred to as Z39Ig and V-set and Ig domain-containing 4 (VSIG4)) belongs to the IgV family of immunoglobulin-like domains while the C-terminal domain of CRIg belongs to the IgC family of immunoglobulin-like domains. CRIg plays a role in the complement system, an inhibitor of the alternative pathway convertases, and a negative regulator of T cell activation. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins such as T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins such as butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond.

Pssm-ID: 409504 Cd Length: 86 Bit Score: 43.59 E-value: 4.88e-05

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 386767223  269 AMLCQAQAFPLPIMRWYKfiEGTTRKQAVVLNDRvkqvsGTLIIKDAVVEDSGKYLCVVNNSVGGE 334
Cdd:cd16082    17 SLQCQAWGSPPISYVWYK--EQTNNQEPIKVAAL-----STLLFKPAVVADSGSYFCTAKGRVGSE 75

Immunoglobulin domain; Members of the immunoglobulin superfamily are found in hundreds of proteins of different functions. Examples include antibodies, the giant muscle kinase titin and receptor tyrosine kinases. Immunoglobulin-like domains may be involved in protein-protein and protein-ligand interactions.

Pssm-ID: 395002 Cd Length: 86 Bit Score: 43.72 E-value: 5.11e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223   822 RNQTARRGEPAVLQCEAK-GEKPIGILWNMNNMRLD-----PKNDNRYTIreeilstgvmSSLSIKRTERSDSALFTCVA 895
Cdd:pfam00047    4 PTVTVLEGDSATLTCSAStGSPGPDVTWSKEGGTLIeslkvKHDNGRTTQ----------SSLLISNVTKEDAGTYTCVV 73

                           90
                   ....*....|...
gi 386767223   896 TNAFGSDDASINM 908
Cdd:pfam00047   74 NNPGGSATLSTSL 86

Immunoglobulin (Ig)-like domain of titin and similar proteins; The members here are composed of the immunoglobulin (Ig)-like domain found in titin-like proteins and similar proteins. Titin (also called connectin) is a fibrous sarcomeric protein specifically found in vertebrate striated muscle. Titin is a giant protein; depending on isoform composition, it ranges from 2970 to 3700 kDa, and is of a length that spans half a sarcomere. Titin largely consists of multiple repeats of Ig-like and fibronectin type 3 (FN-III)-like domains. Titin connects the ends of myosin thick filaments to Z disks and extends along the thick filament to the H zone. It appears to function similarly to an elastic band, keeping the myosin filaments centered in the sarcomere during muscle contraction or stretching. Within the sarcomere, titin is also attached to or is associated with myosin binding protein C (MyBP-C). MyBP-C appears to contribute to the generation of passive tension by titin and like titin has repeated Ig-like and FN-III domains. Also included in this group are worm twitchin and insect projectin, thick filament proteins of invertebrate muscle which also have repeated Ig-like and FN-III domains.

Pssm-ID: 409406 [Multi-domain] Cd Length: 82 Bit Score: 43.35 E-value: 5.11e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  540 IVAGETLIVTCPVAGYPIDSIVWERDNRALPINRKQKVFP---NGTLIIENVERnSDQATYTCVAKNQEGySARGSLEVQ 616
Cdd:cd05748     4 VRAGESLRLDIPIKGRPTPTVTWSKDGQPLKETGRVQIETtasSTSLVIKNAKR-SDSGKYTLTLKNSAG-EKSATINVK 81


                  .
gi 386767223  617 V 617
Cdd:cd05748    82 V 82

First immunoglobulin (Ig)-like constant domain in Robo (roundabout) receptors, and similar domains; The members here are composed of the first immunoglobulin (Ig)-like domain in Roundabout (Robo) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, and Robo3), and three mammalian Slit homologs (Slit1, Slit2, Slit3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit1, Slit2,and Slit3 are expressed at the ventral midline. Robo3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be is the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site.

Pssm-ID: 409490 [Multi-domain] Cd Length: 99 Bit Score: 44.08 E-value: 5.47e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  451 LKCVAGGNPTPEISWELDGKKIANNDRYQVGQYVTVNGDVVSYLNItsVHA----NDGGLYKCIAKSKVGVA-EHSAKLN 525
Cdd:cd07693    20 LNCKAEGRPTPTIQWLKNGQPLETDKDDPRSHRIVLPSGSLFFLRV--VHGrkgrSDEGVYVCVAHNSLGEAvSRNASLE 97


                  .
gi 386767223  526 V 526
Cdd:cd07693    98 V 98

Third immunoglobulin (Ig)-like domain of peroxidasin; The members here are composed of the third immunoglobulin (Ig)-like domain in peroxidasin. Peroxidasin has a peroxidase domain and interacting extracellular motifs containing four Ig-like domains. It has been suggested that peroxidasin is secreted and has functions related to the stabilization of the extracellular matrix. It may play a part in various other important processes such as removal and destruction of cells which have undergone programmed cell death and protection of the organism against non-self.

Pssm-ID: 143222 [Multi-domain] Cd Length: 74 Bit Score: 43.00 E-value: 5.51e-05

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 386767223  731 QGSDAKVECKADGFPKPQVTWKKAVGDTPGEYKDLKKSdnirveEGTLHVDNIQKTNEGYYLCEAINGIGS 801
Cdd:cd05745     1 EGQTVDFLCEAQGYPQPVIAWTKGGSQLSVDRRHLVLS------SGTLRISRVALHDQGQYECQAVNIVGS 65

Third immunoglobulin (Ig) domain of contactin-1; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig) domain of the neural cell adhesion molecule contactin-1. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-1 is differentially expressed in tumor tissues and may through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma. This group belongs to the I-set of IgSF domains.

Pssm-ID: 143259 Cd Length: 88 Bit Score: 43.47 E-value: 5.72e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223 1315 PAKI-ASFDDTFtATFKEDAKMPCLAVGAPQPEITWK--IKGVEFSANDRMrvlpDGSLL-IKSVNRQDAGDYSCHAENS 1390
Cdd:cd05851     1 PADInVKFKDTY-ALKGQNVTLECFALGNPVPVIRWRkiLEPMPATAEISM----SGAVLkIFNIQPEDEGTYECEAENI 75


                  ....*....
gi 386767223 1391 IAKDsiTHK 1399
Cdd:cd05851    76 KGKD--KHQ 82

Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor, and similar domains; member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor. FGF receptors bind FGF signaling polypeptides. FGFs participate in multiple processes such as morphogenesis, development, and angiogenesis. FGFs bind to four FGF receptor tyrosine kinases (FGFR1, FGFR2, FGFR3, FGFR4). Receptor diversity is controlled by alternative splicing producing splice variants with different ligand binding characteristics and different expression patterns. FGFRs have an extracellular region comprised of three Ig-like domains, a single transmembrane helix, and an intracellular tyrosine kinase domain. Ligand binding and specificity reside in the Ig-like domains 2 and 3, and the linker region that connects these two. FGFR activation and signaling depend on FGF-induced dimerization, a process involving cell surface heparin or heparin sulfate proteoglycans. This group also contains fibroblast growth factor (FGF) receptor like-1(FGFRL1). FGFRL1 does not have a protein tyrosine kinase domain at its C-terminus; neither does its cytoplasmic domain appear to interact with a signaling partner. It has been suggested that FGFRL1 may not have any direct signaling function, but instead acts as a decoy receptor trapping FGFs and preventing them from binding other receptors.

Pssm-ID: 409393 [Multi-domain] Cd Length: 95 Bit Score: 43.75 E-value: 5.75e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  530 PYIRQMEK-----KAIVAGETLIVTCPVAGYPIDSIVWERDNRAL-PINR------KQKVFpngTLIIENVeRNSDQATY 597
Cdd:cd05729     1 PRFTDTEKmeereHALPAANKVRLECGAGGNPMPNITWLKDGKEFkKEHRiggtkvEEKGW---SLIIERA-IPRDKGKY 76


                  ....*....
gi 386767223  598 TCVAKNQEG 606
Cdd:cd05729    77 TCIVENEYG 85

immunoglobulin-like domain of telokin and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig) domain in telokin, the C-terminal domain of myosin light chain kinase which is identical to telokin, and similar proteins. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the telokin Ig domain lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409565 [Multi-domain] Cd Length: 88 Bit Score: 43.72 E-value: 5.83e-05

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 386767223 1333 AKMPCLAVGAPQPEITWKIKGVEFSANDRMRVLPDG----SLLIKSVNRQDAGDYSCHAENSIAKDSITHKLIV 1402
Cdd:cd20973    15 ARFDCKVEGYPDPEVKWMKDDNPIVESRRFQIDQDEdglcSLIISDVCGDDSGKYTCKAVNSLGEATCSAELTV 88

Immunoglobulin (Ig) domain of Down Syndrome Cell Adhesion molecule (DSCAM); The members here are composed of the immunoglobulin (Ig) domain of Down Syndrome Cell Adhesion molecule (DSCAM). DSCAM is a cell adhesion molecule expressed largely in the developing nervous system. The gene encoding DSCAM is located at human chromosome 21q22, the locus associated with the intellectual disability phenotype of Down Syndrome. DSCAM is predicted to be the largest member of the IG superfamily. It has been demonstrated that DSCAM can mediate cation-independent homophilic intercellular adhesion.

Pssm-ID: 409398 Cd Length: 101 Bit Score: 44.02 E-value: 5.87e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223 1313 QVPAKIASFDDTFTATFKEDAKMPCLAVGAPQPEITWKiKGVEFSANDRM-------RVLPD---GSLLIKSVNRQDAGD 1382
Cdd:cd05735     1 KIPAMITSYPNTTLATKGQKKEMSCTAHGEKPIIVRWE-KEDTIINPSEMsrylvttKEVGDeviSTLQILPTVREDSGF 79

                          90       100
                  ....*....|....*....|
gi 386767223 1383 YSCHAENSIAKDSITHKLIV 1402
Cdd:cd05735    80 FSCHAINSYGEDRGIIQLTV 99

Second Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the titin Z1z2 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409564 [Multi-domain] Cd Length: 91 Bit Score: 43.34 E-value: 6.50e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  352 PPTQTVDFGRPAVFTCQYTGNPIKTVSWMKDGKAIgHSEPVLRIES-----------VKKEDKGMYQCFVRNDQESAEAS 420
Cdd:cd20972     8 LRSQEVAEGSKVRLECRVTGNPTPVVRWFCEGKEL-QNSPDIQIHQegdlhsliiaeAFEEDTGRYSCLATNSVGSDTTS 86


                  ...
gi 386767223  421 AEL 423
Cdd:cd20972    87 AEI 89

Fourth immunoglobulin (Ig)-like domain in neogenin, and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain in neogenin and related proteins. Neogenin is a cell surface protein which is expressed in the developing nervous system of vertebrate embryos in the growing nerve cells. It is also expressed in other embryonic tissues, and may play a general role in developmental processes such as cell migration, cell-cell recognition, and tissue growth regulation. Included in this group is the tumor suppressor protein DCC which is deleted in colorectal carcinoma. DCC and neogenin each have four Ig-like domains followed by six fibronectin type III domains, a transmembrane domain, and an intracellular domain. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409388 Cd Length: 84 Bit Score: 43.34 E-value: 6.50e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  438 FQEETMEpgpsVFLKCVAGGNPTPEISWELDGKKIANNDRYQVgqyvtVNGdvvSYLNITSVHANDGGLYKCIAKSKVGV 517
Cdd:cd05723     8 YAHESMD----IVFECEVTGKPTPTVKWVKNGDVVIPSDYFKI-----VKE---HNLQVLGLVKSDEGFYQCIAENDVGN 75


                  ....*..
gi 386767223  518 AEHSAKL 524
Cdd:cd05723    76 AQASAQL 82

First immunoglobulin (Ig)-like constant domain in Robo (roundabout) receptors, and similar domains; The members here are composed of the first immunoglobulin (Ig)-like domain in Roundabout (Robo) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, and Robo3), and three mammalian Slit homologs (Slit1, Slit2, Slit3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit1, Slit2,and Slit3 are expressed at the ventral midline. Robo3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be is the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site.

Pssm-ID: 409490 [Multi-domain] Cd Length: 99 Bit Score: 43.69 E-value: 6.64e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  352 PPTQTVDFGRPAVFTCQYTGNPIKTVSWMKDG------KAIGHSEPV---------LRIESVKK--EDKGMYQCFVRN-- 412
Cdd:cd07693     7 PSDLIVSKGDPATLNCKAEGRPTPTIQWLKNGqpletdKDDPRSHRIvlpsgslffLRVVHGRKgrSDEGVYVCVAHNsl 86

                          90
                  ....*....|..
gi 386767223  413 -DQESAEASAEL 423
Cdd:cd07693    87 gEAVSRNASLEV 98

Fourth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.

Pssm-ID: 409548 [Multi-domain] Cd Length: 96 Bit Score: 43.70 E-value: 6.93e-05

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 386767223   61 CKASGNPMPEIIWIRsDGTAVGDVPGLRQ---ISSDGKLV----FPPFRAEDyrqevhAQVYACLARNQFGSI 126
Cdd:cd20956    23 CVASGNPLPQITWTL-DGFPIPESPRFRVgdyVTSDGDVVsyvnISSVRVED------GGEYTCTATNDVGSV 88

Second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of the Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, and Robo3), and three mammalian Slit homologs (Slit-1,Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit-2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409389 [Multi-domain] Cd Length: 87 Bit Score: 43.16 E-value: 6.93e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  263 VVDQSFAMLCQA-QAFPLPIMRWYKfiEGTTrkqAVVLNDRVKQVS-GTLIIKDAVVEDSGKYLCVVNNSVGG-ESVETV 339
Cdd:cd05724    10 AVGEMAVLECSPpRGHPEPTVSWRK--DGQP---LNLDNERVRIVDdGNLLIAEARKSDEGTYKCVATNMVGErESRAAR 84


                  ...
gi 386767223  340 LTV 342
Cdd:cd05724    85 LSV 87

Third immunoglobulin (Ig)-like domain of Neural Cell Adhesion Molecule 1 (NCAM-1); member of the I-set of IgSF domains; The members here are composed of the third immunoglobulin (Ig)-like domain of Neural Cell Adhesion Molecule (NCAM-1). NCAM plays important roles in the development and regeneration of the central nervous system, in synaptogenesis and neural migration. NCAM mediates cell-cell and cell-substratum recognition and adhesion via homophilic (NCAM-NCAM), and heterophilic (NCAM-non-NCAM), interactions. NCAM is expressed as three major isoforms having different intracellular extensions. The extracellular portion of NCAM has five N-terminal Ig-like domains and two fibronectin type III domains. The double zipper adhesion complex model for NCAM homophilic binding involves Ig1, Ig2, and Ig3. By this model, Ig1 and Ig2 mediate dimerization of NCAM molecules situated on the same cell surface (cis interactions), and Ig3 domains mediate interactions between NCAM molecules expressed on the surface of opposing cells (trans interactions) through binding to the Ig1 and Ig2 domains. The adhesive ability of NCAM is modulated by the addition of polysialic acid chains to the fifth Ig-like domain.

Pssm-ID: 143207 [Multi-domain] Cd Length: 95 Bit Score: 43.38 E-value: 7.10e-05

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 386767223  739 CKADGFPKPQVTWKKavGDTPGEYKDLKKSDNirvEEGT-LHVDNIQKTNEGYYLCEAINGIG 800
Cdd:cd05730    25 CDADGFPEPTMTWTK--DGEPIESGEEKYSFN---EDGSeMTILDVDKLDEAEYTCIAENKAG 82

Immunoglobulin (Ig)-like domain of Down Syndrome Cell Adhesion molecule (DSCAM); The members here are composed of the immunoglobulin (Ig)-like domain of Down Syndrome Cell Adhesion molecule (DSCAM). DSCAM is a cell adhesion molecule expressed largely in the developing nervous system. The gene encoding DSCAM is located at human chromosome 21q22, the locus associated with the intellectual disability phenotype of Down Syndrome. DSCAM is predicted to be the largest member of the IG superfamily. It has been demonstrated that DSCAM can mediate cation-independent homophilic intercellular adhesion.

Pssm-ID: 409397 [Multi-domain] Cd Length: 97 Bit Score: 43.64 E-value: 7.49e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  814 PPEFTEKLRNQTARRGEPAVLQCEAKGEKPIGILWNMNNMRLDPKNDNRYTI--REEILSTGvmsSLSIKRTERSDSALF 891
Cdd:cd05734     1 PPRFVVQPNDQDGIYGKAVVLNCSADGYPPPTIVWKHSKGSGVPQFQHIVPLngRIQLLSNG---SLLIKHVLEEDSGYY 77

                          90
                  ....*....|.
gi 386767223  892 TCVATNAFGSD 902
Cdd:cd05734    78 LCKVSNDVGAD 88

Fourth immunoglobulin (Ig)-like domain of L1, Ng-CAM (Neuron-glia CAM cell adhesion molecule), and NrCAM (Ng-CAM-related); The members here are composed of the fourth immunoglobulin (Ig)-like domain of L1, Ng-CAM (Neuron-glia CAM cell adhesion molecule), and NrCAM (Ng-CAM-related). These proteins belong to the L1 subfamily of cell adhesion molecules (CAMs) and are comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region and an intracellular domain. These molecules are primarily expressed in the nervous system. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, or spastic paraplegia type 1, that involves abnormalities of axonal growth.

Pssm-ID: 409367 [Multi-domain] Cd Length: 89 Bit Score: 43.21 E-value: 7.55e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  349 KIDPPTQTVDFGRPAVFTCQYTGNPIKTVSWMKDGKAIgHSEP----------VLRIESVKKEDKGMYQCFVRNDQESAE 418
Cdd:cd04978     3 IIEPPSLVLSPGETGELICEAEGNPQPTITWRLNGVPI-EPAPedmrrtvdgrTLIFSNLQPNDTAVYQCNASNVHGYLL 81


                  ....*
gi 386767223  419 ASAEL 423
Cdd:cd04978    82 ANAFL 86

Immunoglobulin (Ig)-like domain of myotilin, palladin, and myopalladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig)-like domain in myotilin, palladin, and myopalladin. Myotilin, palladin, and myopalladin function as scaffolds that regulate actin organization. Myotilin and myopalladin are most abundant in skeletal and cardiac muscle; palladin is ubiquitously expressed in the organs of developing vertebrates and plays a key role in cellular morphogenesis. The three family members each interact with specific molecular partners with all three binding to alpha-actinin; In addition, palladin also binds to vasodilator-stimulated phosphoprotein (VASP) and ezrin, myotilin binds to filamin and actin, and myopalladin also binds to nebulin and cardiac ankyrin repeat protein (CARP). This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409405 [Multi-domain] Cd Length: 91 Bit Score: 43.25 E-value: 7.68e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  531 YIRQMEKKAIVAGETLIVTCPVAGYPIDSIVWERDNRALPINRKQKVFPNG----TLIIENVERnSDQATYTCVAKNQEG 606
Cdd:cd05744     3 FLQAPGDLEVQEGRLCRFDCKVSGLPTPDLFWQLNGKPVRPDSAHKMLVREngrhSLIIEPVTK-RDAGIYTCIARNRAG 81

Fourth immunoglobulin (Ig)-like domain of NrCAM (NgCAM-related cell adhesion molecule); The members here are composed of the fourth immunoglobulin (Ig)-like domain of NrCAM (NgCAM-related cell adhesion molecule). NrCAM belongs to the L1 subfamily of cell adhesion molecules (CAMs) and is comprised of an extracellular region having six IG-like domains and five fibronectin type III domains, a transmembrane region, and an intracellular domain. NrCAM is primarily expressed in the nervous system.

Pssm-ID: 409454 Cd Length: 89 Bit Score: 43.43 E-value: 7.70e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  443 MEPGPSVFLKCVAGGNPTPEISWELDGK--KIANNDRYQvgqyvTVNGDVVSYlniTSVHANDGGLYKCIAKSKVGVAEH 520
Cdd:cd05868    11 LSPGEDGTLICRANGNPKPSISWLTNGVpiEIAPTDPSR-----KVDGDTIIF---SKVQERSSAVYQCNASNEYGYLLA 82


                  ....*.
gi 386767223  521 SAKLNV 526
Cdd:cd05868    83 NAFVNV 88

Fourth Ig-like domain from smooth muscle myosin light chain kinase and similar domains ; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain from smooth muscle myosin light chain kinase (MYLK) and similar domains. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of this group shows that the fourth Ig-like domain from myosin light chain kinase lacks this strand and thus belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409568 [Multi-domain] Cd Length: 90 Bit Score: 43.39 E-value: 7.80e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  814 PPEFTEKLRNQTARRGEPAVLQCEAKGeKPIG-ILWNMNNMRLDpKNDNRYTIREEIlstgvmSSLSIKRTERSDSALFT 892
Cdd:cd20976     1 APSFSSVPKDLEAVEGQDFVAQCSARG-KPVPrITWIRNAQPLQ-YAADRSTCEAGV------GELHIQDVLPEDHGTYT 72

                          90
                  ....*....|....*...
gi 386767223  893 CVATNAFGSDDASINMIV 910
Cdd:cd20976    73 CLAKNAAGQVSCSAWVTV 90

Second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of the Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, and Robo3), and three mammalian Slit homologs (Slit-1,Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit-2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409389 [Multi-domain] Cd Length: 87 Bit Score: 43.16 E-value: 8.27e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  349 KIDPPTQTVDFGRPAVFTCQY-TGNPIKTVSWMKDGKAIGHSEPVLR--------IESVKKEDKGMYQCFVRN---DQES 416
Cdd:cd05724     1 RVEPSDTQVAVGEMAVLECSPpRGHPEPTVSWRKDGQPLNLDNERVRivddgnllIAEARKSDEGTYKCVATNmvgERES 80


                  ...
gi 386767223  417 AEA 419
Cdd:cd05724    81 RAA 83

Third immunoglobulin (Ig)-like domain of Neural Cell Adhesion Molecule 1 (NCAM-1); member of the I-set of IgSF domains; The members here are composed of the third immunoglobulin (Ig)-like domain of Neural Cell Adhesion Molecule (NCAM-1). NCAM plays important roles in the development and regeneration of the central nervous system, in synaptogenesis and neural migration. NCAM mediates cell-cell and cell-substratum recognition and adhesion via homophilic (NCAM-NCAM), and heterophilic (NCAM-non-NCAM), interactions. NCAM is expressed as three major isoforms having different intracellular extensions. The extracellular portion of NCAM has five N-terminal Ig-like domains and two fibronectin type III domains. The double zipper adhesion complex model for NCAM homophilic binding involves Ig1, Ig2, and Ig3. By this model, Ig1 and Ig2 mediate dimerization of NCAM molecules situated on the same cell surface (cis interactions), and Ig3 domains mediate interactions between NCAM molecules expressed on the surface of opposing cells (trans interactions) through binding to the Ig1 and Ig2 domains. The adhesive ability of NCAM is modulated by the addition of polysialic acid chains to the fifth Ig-like domain.

Pssm-ID: 143207 [Multi-domain] Cd Length: 95 Bit Score: 43.38 E-value: 8.38e-05

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 386767223  356 TVDFGRPAVFTCQYTGNPIKTVSWMKDGKAIGHSE---------PVLRIESVKKEDKGMYQCFVRNDQESAEASAELKL 425
Cdd:cd05730    14 TANLGQSVTLACDADGFPEPTMTWTKDGEPIESGEekysfnedgSEMTILDVDKLDEAEYTCIAENKAGEQEAEIHLKV 92

Fourth immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM); The members here are composed of the fourth immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM). L1 is comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region, and an intracellular domain. L1 is primarily expressed in the nervous system and is involved in its development and function. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, and spastic paraplegia type 1, that involves abnormalities of axonal growth. This group also contains the chicken neuron-glia cell adhesion molecule, Ng-CAM.

Pssm-ID: 409453 [Multi-domain] Cd Length: 89 Bit Score: 42.96 E-value: 8.50e-05

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 386767223  445 PGPSVFLKCVAGGNPTPEISWELDGKKIANNDRYQvgQYVTVNGDVVsylnITSVHANDGGLYKCIAKSKVG 516
Cdd:cd05867    13 PGETARLDCQVEGIPTPNITWSINGAPIEGTDPDP--RRHVSSGALI----LTDVQPSDTAVYQCEARNRHG 78

Second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of the Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, and Robo3), and three mammalian Slit homologs (Slit-1,Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit-2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409389 [Multi-domain] Cd Length: 87 Bit Score: 43.16 E-value: 8.60e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  822 RNQTARRGEPAVLQCEA-KGEKPIGILWNMNNMRLDPKNdNRYTIREEilstgvmSSLSIKRTERSDSALFTCVATNAFG 900
Cdd:cd05724     5 SDTQVAVGEMAVLECSPpRGHPEPTVSWRKDGQPLNLDN-ERVRIVDD-------GNLLIAEARKSDEGTYKCVATNMVG 76

Third immunoglobulin (Ig)-like domain of peroxidasin; The members here are composed of the third immunoglobulin (Ig)-like domain in peroxidasin. Peroxidasin has a peroxidase domain and interacting extracellular motifs containing four Ig-like domains. It has been suggested that peroxidasin is secreted and has functions related to the stabilization of the extracellular matrix. It may play a part in various other important processes such as removal and destruction of cells which have undergone programmed cell death and protection of the organism against non-self.

Pssm-ID: 143222 [Multi-domain] Cd Length: 74 Bit Score: 42.62 E-value: 8.66e-05

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 386767223  266 QSFAMLCQAQAFPLPIMRWykfiegtTRKQAVVLNDRVKQV--SGTLIIKDAVVEDSGKYLCVVNNSVGGESVETVLTV 342
Cdd:cd05745     3 QTVDFLCEAQGYPQPVIAW-------TKGGSQLSVDRRHLVlsSGTLRISRVALHDQGQYECQAVNIVGSQRTVAQLTV 74

First immunoglobulin (Ig)-like domain in neogenin, and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the first immunoglobulin (Ig)-like domain in neogenin and related proteins. Neogenin is a cell surface protein which is expressed in the developing nervous system of vertebrate embryos in the growing nerve cells. It is also expressed in other embryonic tissues and may play a general role in developmental processes such as cell migration, cell-cell recognition, and tissue growth regulation. Included in this group is the tumor suppressor protein DCC which is deleted in colorectal carcinoma. DCC and neogenin each have four Ig-like domains followed by six fibronectin type III domains, a transmembrane domain, and an intracellular domain. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409387 Cd Length: 97 Bit Score: 43.24 E-value: 8.75e-05

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 386767223  541 VAGETLIVTCPVAGYPIDSIVWERDNR--ALPINRKQKVFPNGTLIIENVER----NSDQATYTCVAKN 603
Cdd:cd05722    14 MRGGPVVLNCSAESDPPPKIEWKKDGVllNLVSDERRQQLPNGSLLITSVVHskhnKPDEGFYQCVAQN 82

First immunoglobulin (Ig) domain of contactin-1; member of the I-set of Ig superfamily domains; The members here are composed of the first immunoglobulin (Ig) domain of the neural cell adhesion molecule contactin-1. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma. This group belongs to the I-set of IgSF domains.

Pssm-ID: 409436 [Multi-domain] Cd Length: 95 Bit Score: 43.40 E-value: 9.10e-05

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 386767223  265 DQSFAMLCQAQAFPLPIMRWYKfiegtTRKQAVVLNDRVKQVSGTLIIKDA-VVEDSGKYLCVVNNSVG 332
Cdd:cd05849    19 EGKVSVNCRARANPFPIYKWRK-----NNLDIDLTNDRYSMVGGNLVINNPdKYKDAGRYVCIVSNIYG 82

Fourth immunoglobulin (Ig)-like domain of hemolin, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain of hemolin and similar proteins. Hemolin, an insect immunoglobulin superfamily (IgSF) member containing four Ig-like domains, is a lipopolysaccharide-binding immune protein induced during bacterial infection. Hemolin shares significant sequence similarity with the first four Ig-like domains of the transmembrane cell adhesion molecules (CAMs) of the L1 family. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The fourth Ig-like domain of hemolin is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409570 [Multi-domain] Cd Length: 88 Bit Score: 42.76 E-value: 9.88e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223   39 PVFLKEPTNRIDFSNSTGAEIECKASGNPMPEIIWIRsDGTAVGDVPGLRQIsSDGKLVFPPFRAEDYRqevhaqVYACL 118
Cdd:cd20978     1 PKFIQKPEKNVVVKGGQDVTLPCQVTGVPQPKITWLH-NGKPLQGPMERATV-EDGTLTIINVQPEDTG------YYGCV 72

                          90
                  ....*....|
gi 386767223  119 ARNQFGSIIS 128
Cdd:cd20978    73 ATNEIGDIYT 82

immunoglobulin-like domain of telokin and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig) domain in telokin, the C-terminal domain of myosin light chain kinase which is identical to telokin, and similar proteins. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the telokin Ig domain lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409565 [Multi-domain] Cd Length: 88 Bit Score: 42.95 E-value: 9.98e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  356 TVDFGRPAVFTCQYTGNPIKTVSWMKDGKAIGHSEPV-----------LRIESVKKEDKGMYQCFVRNDQESAEASAELK 424
Cdd:cd20973     8 EVVEGSAARFDCKVEGYPDPEVKWMKDDNPIVESRRFqidqdedglcsLIISDVCGDDSGKYTCKAVNSLGEATCSAELT 87


                  .
gi 386767223  425 L 425
Cdd:cd20973    88 V 88

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.

Pssm-ID: 214653 [Multi-domain] Cd Length: 85 Bit Score: 42.88 E-value: 1.00e-04

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223     57 AEIECKASGNPMPEIIWIRSDGTAVGDVPGLRQISSDGK--LVFPPFRAEDyrqevhAQVYACLARNQFGSIISR-DVHV 133
Cdd:smart00410   12 VTLSCEASGSPPPEVTWYKQGGKLLAESGRFSVSRSGSTstLTISNVTPED------SGTYTCAATNSSGSASSGtTLTV 85

Immunoglobulin (Ig)-like domain of NrCAM (Ng (neuronglia) CAM-related cell adhesion molecule); member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the first immunoglobulin (Ig)-like domain of NrCAM (Ng (neuronglia) CAM-related cell adhesion molecule). NrCAM belongs to the L1 subfamily of cell adhesion molecules (CAMs) and is comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region, and an intracellular domain. NrCAM is primarily expressed in the nervous system.

Pssm-ID: 409458 Cd Length: 95 Bit Score: 43.05 E-value: 1.07e-04

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 386767223   59 IECKASGNPMPEIIWIRsDGTA--VGDVPGLRQISSDGKLVFPPFRAEdyRQEVHAQVYACLARNQFGSIISRDVHVR 134
Cdd:cd05874    21 IQCEAKGKPPPSFSWTR-NGTHfdIDKDPKVTMKPNTGTLVINIMNGE--KAEAYEGVYQCTARNERGAAVSNNIVIR 95

Immunoglobulin (Ig)-like domain of human titin C terminus and similar proteins; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the fifth immunoglobulin (Ig)-like domain from the C-terminus of human titin x and similar proteins. Titin (also called connectin) is a fibrous sarcomeric protein specifically found in vertebrate striated muscle. Titin is gigantic; depending on isoform composition it ranges from 2970 to 3700 kDa, and is of a length that spans half a sarcomere. Titin largely consists of multiple repeats of Ig-like and fibronectin type 3 (FN-III)-like domains. Titin connects the ends of myosin thick filaments to Z disks and extends along the thick filament to the H zone and appears to function similar to an elastic band, keeping the myosin filaments centered in the sarcomere during muscle contraction or stretching. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 143224 [Multi-domain] Cd Length: 92 Bit Score: 42.73 E-value: 1.12e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223 1314 VPAKIASFDDTFTATFKEDAKMPCLAVGAPQPEITWKIKGVEFSANDRMRVLP---DGSLLIKSVNRQDAGDYSCHAENS 1390
Cdd:cd05747     2 LPATILTKPRSLTVSEGESARFSCDVDGEPAPTVTWMREGQIIVSSQRHQITSteyKSTFEISKVQMSDEGNYTVVVENS 81


                  ...
gi 386767223 1391 IAK 1393
Cdd:cd05747    82 EGK 84

Fourth Ig-like domain from smooth muscle myosin light chain kinase and similar domains ; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain from smooth muscle myosin light chain kinase (MYLK) and similar domains. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of this group shows that the fourth Ig-like domain from myosin light chain kinase lacks this strand and thus belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409568 [Multi-domain] Cd Length: 90 Bit Score: 42.62 E-value: 1.15e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  620 PPQIRPFdFGDEASNSGETMGIQCTVIKGDLPiNITWVLNnhtlnSGDLDVVIGRMSSKSST--LNIDYIAAEHRGVYTC 697
Cdd:cd20976     1 APSFSSV-PKDLEAVEGQDFVAQCSARGKPVP-RITWIRN-----AQPLQYAADRSTCEAGVgeLHIQDVLPEDHGTYTC 73

                          90
                  ....*....|....*..
gi 386767223  698 LARNQAGESSYSAELKV 714
Cdd:cd20976    74 LAKNAAGQVSCSAWVTV 90

Fourth immunoglobulin (Ig)-like domain of NrCAM (NgCAM-related cell adhesion molecule); The members here are composed of the fourth immunoglobulin (Ig)-like domain of NrCAM (NgCAM-related cell adhesion molecule). NrCAM belongs to the L1 subfamily of cell adhesion molecules (CAMs) and is comprised of an extracellular region having six IG-like domains and five fibronectin type III domains, a transmembrane region, and an intracellular domain. NrCAM is primarily expressed in the nervous system.

Pssm-ID: 409454 Cd Length: 89 Bit Score: 42.66 E-value: 1.16e-04

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 386767223 1331 EDAKMPCLAVGAPQPEITWKIKGV--EFSANDRMRVLPDGSLLIKSVNRQDAGDYSCHAEN 1389
Cdd:cd05868    15 EDGTLICRANGNPKPSISWLTNGVpiEIAPTDPSRKVDGDTIIFSKVQERSSAVYQCNASN 75

Fourth immunoglobulin (Ig)-like domain of hemolin, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain of hemolin and similar proteins. Hemolin, an insect immunoglobulin superfamily (IgSF) member containing four Ig-like domains, is a lipopolysaccharide-binding immune protein induced during bacterial infection. Hemolin shares significant sequence similarity with the first four Ig-like domains of the transmembrane cell adhesion molecules (CAMs) of the L1 family. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The fourth Ig-like domain of hemolin is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409570 [Multi-domain] Cd Length: 88 Bit Score: 42.76 E-value: 1.19e-04

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 386767223  272 CQAQAFPLPIMRWY---KFIEGTtrkqavvlNDRVKQVSGTLIIKDAVVEDSGKYLCVVNNSVGGESVETVLTV 342
Cdd:cd20978    23 CQVTGVPQPKITWLhngKPLQGP--------MERATVEDGTLTIINVQPEDTGYYGCVATNEIGDIYTETLLHV 88

Second C-terminal immunoglobulin (Ig)-like domain of palladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of palladin. Palladin belongs to the palladin-myotilin-myopalladin family. Proteins belonging to this family contain multiple Ig-like domains and function as scaffolds, modulating actin cytoskeleton. Palladin binds to alpha-actinin ezrin, vasodilator-stimulated phosphoprotein VASP, SPIN90 (also known as DIP or mDia interacting protein), and Src. Palladin also binds F-actin directly, via its Ig3 domain. Palladin is expressed as several alternatively spliced isoforms, having various combinations of Ig-like domains, in a cell-type-specific manner. It has been suggested that palladin's different Ig-like domains may be specialized for distinct functions. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409582 Cd Length: 91 Bit Score: 42.78 E-value: 1.23e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  815 PEFTEKLRNQTARRGEPAVLQCEAKGEKPIGILWNMNNMRLDPKNDNRYTIREeilsTGVmSSLSIKRTERSDSALFTCV 894
Cdd:cd20990     1 PHFLQAPGDLTVQEGKLCRMDCKVSGLPTPDLSWQLDGKPIRPDSAHKMLVRE----NGV-HSLIIEPVTSRDAGIYTCI 75

                          90
                  ....*....|....*.
gi 386767223  895 ATNAFGSDDASINMIV 910
Cdd:cd20990    76 ATNRAGQNSFNLELVV 91

Immunoglobulin (Ig)-like I-set domain of Neural Cell Adhesion Molecule 1 (NCAM-1); The members here are composed of the fourth Ig domain of Neural Cell Adhesion Molecule 1(NCAM-1). NCAM plays important roles in the development and regeneration of the central nervous system, in synaptogenesis and neural migration. NCAM mediates cell-cell and cell-substratum recognition and adhesion via homophilic (NCAM-NCAM) and heterophilic (NCAM-non-NCAM) interactions. NCAM is expressed as three major isoforms having different intracellular extensions. The extracellular portion of NCAM has five N-terminal Ig-like domains and two fibronectin type III domains. The double zipper adhesion complex model for NCAM homophilic binding involves Ig1, Ig2, and Ig3. By this model, Ig1 and Ig2 mediate dimerization of NCAM molecules situated on the same cell surface (cis interactions), and Ig3 domains mediate interactions between NCAM molecules expressed on the surface of opposing cells (trans interactions), through binding to the Ig1 and Ig2 domains. The adhesive ability of NCAM is modulated by the addition of polysialic acid chains to the fifth Ig-like domain. One of the unique features of I-set domains is the lack of a C" strand. The structures of this group show that the Ig domain lacks this strand and thus is a member of the I-set of Ig domains.

Pssm-ID: 143277 [Multi-domain] Cd Length: 97 Bit Score: 43.04 E-value: 1.28e-04

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 386767223  739 CKADGFPKPQVTWKKAVGDTPGEYKDLK-----KSDnIRVEEGTLhvDNIQKTNEGYYLCEAINGIGSGLSAV 806
Cdd:cd05869    24 CEASGDPIPSITWRTSTRNISSEEKTLDghivvRSH-ARVSSLTL--KYIQYTDAGEYLCTASNTIGQDSQSM 93

Immunoglobulin (Ig)-like domain of human neurofascin (NF); member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the first immunoglobulin (Ig)-like domain of human neurofascin (NF). NF belongs to the L1 subfamily of cell adhesion molecules (CAMs) and is comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region, and a cytoplasmic domain. NF has many alternatively spliced isoforms having different temporal expression patterns during development. NF participates in axon subcellular targeting and synapse formation, however little is known of the functions of the different isoforms. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lacks a C" strand.

Pssm-ID: 409459 Cd Length: 95 Bit Score: 42.66 E-value: 1.29e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  431 PPVIRQAFQEETMEPGPSVFLKCVAGGNPTPEISWELDGK--KIANNDRYQVGQYvtvNGDVVSYLNITSVHANDGGLYK 508
Cdd:cd05875     1 PTITKQSAKDYIVDPRDNILIECEAKGNPVPTFHWTRNGKffNVAKDPRVSMRRR---SGTLVIDFRGGGRPEDYEGEYQ 77

                          90
                  ....*....|
gi 386767223  509 CIAKSKVGVA 518
Cdd:cd05875    78 CFARNKFGTA 87

First immunoglobulin (Ig) domain of contactin; member of the I-set of (Ig) superfamily domains; The members here are composed of the first immunoglobulin (Ig) domain of contactins. Contactins are neural cell adhesion molecules and are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module via contacts between Ig domains 1 and 4, and between Ig domains 2 and 3. Contactin-2 (TAG-1, axonin-1) may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. This group also includes contactin-1 and contactin-5. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-5 is expressed specifically in the rat postnatal nervous system, peaking at about 3 weeks postnatal, and a lack of contactin-5 (NB-2) results in an impairment of neuronal activity in the rat auditory system. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma. This group belongs to the I-set of IgSF domains.

Pssm-ID: 409356 [Multi-domain] Cd Length: 96 Bit Score: 43.00 E-value: 1.29e-04

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 386767223  834 LQCEAKGEKPIGILWNMNNMRLDPKNDNRYTIreeILSTGVMSSLSikrtERSDSALFTCVATNAFGS 901
Cdd:cd04967    24 LNCRARANPVPSYRWLMNGTEIDLESDYRYSL---VDGTLVISNPS----KAKDAGHYQCLATNTVGS 84

Immunoglobulin (Ig)-like I-set domain of Neural Cell Adhesion Molecule 2 (NCAM-2); The members here are composed of the fourth Ig domain of Neural Cell Adhesion Molecule NCAM-2 (also known as OCAM/mamFas II and RNCAM). NCAM-2 is organized similarly to NCAM, including five N-terminal Ig-like domains and two fibronectin type III domains. NCAM-2 is differentially expressed in the developing and mature olfactory epithelium (OE), and may function like NCAM, as an adhesion molecule. One of the unique features of I-set domains is the lack of a C" strand. The structures of this group show that the Ig domain lacks this strand and thus is a member of the I-set of Ig domains.

Pssm-ID: 143278 [Multi-domain] Cd Length: 98 Bit Score: 43.04 E-value: 1.30e-04

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 386767223 1333 AKMPCLAVGAPQPEITWK--IKGVEFSANDRMrvlPDG-----------SLLIKSVNRQDAGDYSCHAENSI 1391
Cdd:cd05870    19 ATLSCKAEGEPIPEITWKraSDGHTFSEGDKS---PDGrievkgqhgesSLHIKDVKLSDSGRYDCEAASRI 87

Fourth immunoglobulin (Ig)-like domain of peroxidasin; The members here are composed of the fourth immunoglobulin (Ig)-like domain in peroxidasin. Peroxidasin has a peroxidase domain and interacting extracellular motifs containing four Ig-like domains. It has been suggested that peroxidasin is secreted, and has functions related to the stabilization of the extracellular matrix. It may play a part in various other important processes such as removal and destruction of cells which have undergone programmed cell death and protection of the organism against non-self.

Pssm-ID: 143223 Cd Length: 69 Bit Score: 41.78 E-value: 1.40e-04

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 386767223  548 VTCPVAGYPIDSIVWERDNRALPINRKQKVFPNGTLIIENVErNSDQATYTCVAKNQEGYSA 609
Cdd:cd05746     3 IPCSAQGDPEPTITWNKDGVQVTESGKFHISPEGYLAIRDVG-VADQGRYECVARNTIGYAS 63

Second immunoglobulin (Ig)-like domain of a Follistatin-related protein 5, and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig)-like domain found in human Follistatin-related protein 5 (FSTL5) and a follistatin-like molecule encoded by the CNS-related Mahya gene. Mahya genes have been retained in certain Bilaterian branches during evolution. They are conserved in Hymenoptera and Deuterostomes, but are absent from other metazoan species such as fruit fly and nematode. Mahya proteins are secretory, with a follistatin-like domain (Kazal-type serine/threonine protease inhibitor domain and EF-hand calcium-binding domain), two Ig-like domains, and a novel C-terminal domain. Mahya may be involved in learning and memory and in processing of sensory information in Hymenoptera and vertebrates. Follistatin is a secreted, multidomain protein that binds activins with high affinity and antagonizes their signaling.

Pssm-ID: 409399 [Multi-domain] Cd Length: 93 Bit Score: 42.63 E-value: 1.41e-04

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 386767223  724 PTDKAFAQGSDAKVECKADGFPKPQVTW-KKAVGDTPgeykDLKKSDNIRVEEGTLHVDNIQKTNEGYYLCEAINGIG 800
Cdd:cd05736     7 PEFQAKEPGVEASLRCHAEGIPLPRVQWlKNGMDINP----KLSKQLTLIANGSELHISNVRYEDTGAYTCIAKNEGG 80

First immunoglobulin (Ig) domain of contactin-2; member of the I-set of Ig superfamily domains; The members here are composed of the first immunoglobulin (Ig) domain of the neural cell adhesion molecule contactin-2-like. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-2 (TAG-1, axonin-1) facilitates cell adhesion by homophilic binding between molecules in apposed membranes. It may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module by contacts between IG domains 1 and 4, and domains 2 and 3. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-2 is also expressed in retinal amacrine cells in the developing chick retina, corresponding to the period of formation and maturation of AC processes. This group belongs to the I-set of IgSF domains.

Pssm-ID: 409437 [Multi-domain] Cd Length: 97 Bit Score: 42.60 E-value: 1.41e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223   38 GPVFLKEPTNRIDFSNSTGAEI--ECKASGNPMPEIIWiRSDGTAVGDVPGLRQISSDGKLVFP-PFRAEDyrqevhAQV 114
Cdd:cd05850     2 GPVFEEQPSSTLFPEGSAEEKVtlACRARASPPATYRW-KMNGTELKMEPDSRYRLVAGNLVISnPVKAKD------AGS 74

                          90       100
                  ....*....|....*....|
gi 386767223  115 YACLARNQFGSIISRDVHVR 134
Cdd:cd05850    75 YQCLASNRRGTVVSREASLR 94

Immunoglobulin I-set domain of the Leucine-rich repeat and immunoglobin-like domain-containing protein 1 (Lingo-1); The members here are composed of the immunoglobulin I-set (IgI) domain of the Leucine-rich repeat and immunoglobin-like domain-containing protein 1 (Lingo-1). Human Lingo-1 is a central nervous system-specific transmembrane glycoprotein also known as LERN-1, which functions as a negative regulator of neuronal survival, axonal regeneration, and oligodendrocyte differentiation and myelination. Lingo-1 is a key component of the Nogo receptor signaling complex (RTN4R/NGFR) in RhoA activation responsible for some inhibition of axonal regeneration by myelin-associated factors. The ligand-binding ectodomain of human Lingo-1 contains a bimodular, kinked structure composed of leucine-rich repeat (LRR) and immunoglobulin (Ig)-like modules. Diseases associated with Lingo-1 include mental retardation, autosomal recessive 64 and essential tremor. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the Lingo-1 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409561 Cd Length: 92 Bit Score: 42.76 E-value: 1.42e-04

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 386767223  731 QGSDAKVECKADGFPKPQVTWKkavgdTPGEYK-DLKKSDNIRV-EEGTLHVDNIQKTNEGYYLCEAINGIG 800
Cdd:cd20969    16 EGHTVQFVCRADGDPPPAILWL-----SPRKHLvSAKSNGRLTVfPDGTLEVRYAQVQDNGTYLCIAANAGG 82

Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor, and similar domains; member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor. FGF receptors bind FGF signaling polypeptides. FGFs participate in multiple processes such as morphogenesis, development, and angiogenesis. FGFs bind to four FGF receptor tyrosine kinases (FGFR1, FGFR2, FGFR3, FGFR4). Receptor diversity is controlled by alternative splicing producing splice variants with different ligand binding characteristics and different expression patterns. FGFRs have an extracellular region comprised of three Ig-like domains, a single transmembrane helix, and an intracellular tyrosine kinase domain. Ligand binding and specificity reside in the Ig-like domains 2 and 3, and the linker region that connects these two. FGFR activation and signaling depend on FGF-induced dimerization, a process involving cell surface heparin or heparin sulfate proteoglycans. This group also contains fibroblast growth factor (FGF) receptor like-1(FGFRL1). FGFRL1 does not have a protein tyrosine kinase domain at its C-terminus; neither does its cytoplasmic domain appear to interact with a signaling partner. It has been suggested that FGFRL1 may not have any direct signaling function, but instead acts as a decoy receptor trapping FGFs and preventing them from binding other receptors.

Pssm-ID: 409393 [Multi-domain] Cd Length: 95 Bit Score: 42.59 E-value: 1.45e-04

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 386767223 1334 KMPCLAVGAPQPEITWKIKGVEFSANDRMRVLPDG----SLLIKSVNRQDAGDYSCHAENSIAKDSITHKLIV 1402
Cdd:cd05729    23 RLECGAGGNPMPNITWLKDGKEFKKEHRIGGTKVEekgwSLIIERAIPRDKGKYTCIVENEYGSINHTYDVDV 95

Third immunoglobulin (Ig)-like domain of Neural Cell Adhesion Molecule 1 (NCAM-1); member of the I-set of IgSF domains; The members here are composed of the third immunoglobulin (Ig)-like domain of Neural Cell Adhesion Molecule (NCAM-1). NCAM plays important roles in the development and regeneration of the central nervous system, in synaptogenesis and neural migration. NCAM mediates cell-cell and cell-substratum recognition and adhesion via homophilic (NCAM-NCAM), and heterophilic (NCAM-non-NCAM), interactions. NCAM is expressed as three major isoforms having different intracellular extensions. The extracellular portion of NCAM has five N-terminal Ig-like domains and two fibronectin type III domains. The double zipper adhesion complex model for NCAM homophilic binding involves Ig1, Ig2, and Ig3. By this model, Ig1 and Ig2 mediate dimerization of NCAM molecules situated on the same cell surface (cis interactions), and Ig3 domains mediate interactions between NCAM molecules expressed on the surface of opposing cells (trans interactions) through binding to the Ig1 and Ig2 domains. The adhesive ability of NCAM is modulated by the addition of polysialic acid chains to the fifth Ig-like domain.

Pssm-ID: 143207 [Multi-domain] Cd Length: 95 Bit Score: 42.61 E-value: 1.48e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  264 VDQSFAMLCQAQAFPLPIMRWykfiegtTRKQAVVLNDRVKQV----SGTLIIKDAVVEDSGKYLCVVNNSVGGESVETV 339
Cdd:cd05730    17 LGQSVTLACDADGFPEPTMTW-------TKDGEPIESGEEKYSfnedGSEMTILDVDKLDEAEYTCIAENKAGEQEAEIH 89


                  ....*
gi 386767223  340 LTVTA 344
Cdd:cd05730    90 LKVFA 94

First immunoglobulin (Ig) domain of contactin-5; member of the I-set of Ig superfamily domains; The members here are composed of the first immunoglobulin (Ig) domain of the neural cell adhesion molecule contactin-5. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains, anchored to the membrane by glycosylphosphatidylinositol. The different contactins show different expression patterns in the central nervous system. In rats, a lack of contactin-5 (NB-2) results in an impairment of the neuronal activity in the auditory system. Contactin-5 is expressed specifically in the postnatal nervous system, peaking at about 3 weeks postnatal. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala; lower levels of expression have been detected in the corpus callosum, caudate nucleus, and spinal cord. This group belongs to the I-set of IgSF domains.

Pssm-ID: 409435 Cd Length: 96 Bit Score: 42.62 E-value: 1.56e-04

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 386767223  265 DQSFAMLCQAQAFPLPIMRWykFIEGTtrKQAVVLNDRVKQVSGTLIIKDAV-VEDSGKYLCVVNNSVG 332
Cdd:cd05848    19 EKKVILNCEARGNPVPTYRW--LRNGT--EIDTESDYRYSLIDGNLIISNPSeVKDSGRYQCLATNSIG 83

Second immunoglobulin (Ig)-like domain of the receptor protein tyrosine phosphatase (RPTP)-F; member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain found in the receptor protein tyrosine phosphatase (RPTP)-F, also known as LAR. LAR belongs to the RPTP type IIa subfamily. Members of this subfamily are cell adhesion molecule-like proteins involved in central nervous system (CNS) development. They have large extracellular portions comprised of multiple Ig-like domains and two to nine fibronectin type III (FNIII) domains and a cytoplasmic portion having two tandem phosphatase domains.

Pssm-ID: 409400 [Multi-domain] Cd Length: 91 Bit Score: 42.31 E-value: 1.59e-04

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 386767223  545 TLIVTCPVAGYPIDSIVWERDnrALPI-----NRKQKVFPNGTLIIENVERnSDQATYTCVAKNQEG--YSARGSLEVQ 616
Cdd:cd05738    16 TATMLCAASGNPDPEISWFKD--FLPVdtatsNGRIKQLRSGALQIENSEE-SDQGKYECVATNSAGtrYSAPANLYVR 91

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

Pssm-ID: 464026 [Multi-domain] Cd Length: 79 Bit Score: 42.00 E-value: 1.60e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223   534 QMEKKAIVAGETLIVTCPVAGYPIDSIVWERDNRALPinrkqkvfPNGTLIIENVErNSDQATYTCVAKNQEGYSARGSL 613
Cdd:pfam13895    5 TPSPTVVTEGEPVTLTCSAPGNPPPSYTWYKDGSAIS--------SSPNFFTLSVS-AEDSGTYTCVARNGRGGKVSNPV 75


                   ....
gi 386767223   614 EVQV 617
Cdd:pfam13895   76 ELTV 79

agrin-responsive first immunoglobulin-like domains (Ig1) of the MuSK ectodomain; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin-like domains (Ig1) of the Muscle-specific kinase (MuSK). MuSK is a receptor tyrosine kinase specifically expressed in skeletal muscle, where it plays a central role in the formation and maintenance of the neuromuscular junction (NMJ). MuSK is activated by agrin, a neuron-derived heparan sulfate proteoglycan. The activation of MUSK in myotubes regulates the formation of NMJs through the regulation of different processes including the specific expression of genes in subsynaptic nuclei, the reorganization of the actin cytoskeleton and the clustering of the acetylcholine receptors (AChR) in the postsynaptic membrane. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the MuSK lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409562 [Multi-domain] Cd Length: 92 Bit Score: 42.50 E-value: 1.66e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  249 PSFSSDYNSFSYARVVDQSFAMLCQAQAFPLPIMRWYKfiEGTTRkQAVVLNDRVKQVSGTLIIKDAVVEDSGKYLCVVN 328
Cdd:cd20970     1 PVISTPQPSFTVTAREGENATFMCRAEGSPEPEISWTR--NGNLI-IEFNTRYIVRENGTTLTIRNIRRSDMGIYLCIAS 77

                          90
                  ....*....|....
gi 386767223  329 NSVGGeSVETVLTV 342
Cdd:cd20970    78 NGVPG-SVEKRITL 90

First immunoglobulin (Ig)-like constant domain in Robo (roundabout) receptors, and similar domains; The members here are composed of the first immunoglobulin (Ig)-like domain in Roundabout (Robo) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, and Robo3), and three mammalian Slit homologs (Slit1, Slit2, Slit3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit1, Slit2,and Slit3 are expressed at the ventral midline. Robo3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be is the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site.

Pssm-ID: 409490 [Multi-domain] Cd Length: 99 Bit Score: 42.54 E-value: 1.68e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223 1306 IVAMPSDQVPAKiasfddtftatfKEDAKMPCLAVGAPQPEITWKIKGVEF-----SANDRMRVLPDGSLLIKSV----- 1375
Cdd:cd07693     3 IVEHPSDLIVSK------------GDPATLNCKAEGRPTPTIQWLKNGQPLetdkdDPRSHRIVLPSGSLFFLRVvhgrk 70

                          90
                  ....*....|....*.
gi 386767223 1376 NRQDAGDYSCHAENSI 1391
Cdd:cd07693    71 GRSDEGVYVCVAHNSL 86

Immunoglobulin (Ig)-like domain of titin and similar proteins; The members here are composed of the immunoglobulin (Ig)-like domain found in titin-like proteins and similar proteins. Titin (also called connectin) is a fibrous sarcomeric protein specifically found in vertebrate striated muscle. Titin is a giant protein; depending on isoform composition, it ranges from 2970 to 3700 kDa, and is of a length that spans half a sarcomere. Titin largely consists of multiple repeats of Ig-like and fibronectin type 3 (FN-III)-like domains. Titin connects the ends of myosin thick filaments to Z disks and extends along the thick filament to the H zone. It appears to function similarly to an elastic band, keeping the myosin filaments centered in the sarcomere during muscle contraction or stretching. Within the sarcomere, titin is also attached to or is associated with myosin binding protein C (MyBP-C). MyBP-C appears to contribute to the generation of passive tension by titin and like titin has repeated Ig-like and FN-III domains. Also included in this group are worm twitchin and insect projectin, thick filament proteins of invertebrate muscle which also have repeated Ig-like and FN-III domains.

Pssm-ID: 409406 [Multi-domain] Cd Length: 82 Bit Score: 41.81 E-value: 1.77e-04

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  457 GNPTPEISWELDGKKIANNDRYQVgqyvtVNGDVVSYLNITSVHANDGGLYKCIAKSKVGvaEHSAKLNV 526
Cdd:cd05748    18 GRPTPTVTWSKDGQPLKETGRVQI-----ETTASSTSLVIKNAKRSDSGKYTLTLKNSAG--EKSATINV 80

Immunoglobulin (Ig)-like domain of human titin C terminus and similar proteins; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the fifth immunoglobulin (Ig)-like domain from the C-terminus of human titin x and similar proteins. Titin (also called connectin) is a fibrous sarcomeric protein specifically found in vertebrate striated muscle. Titin is gigantic; depending on isoform composition it ranges from 2970 to 3700 kDa, and is of a length that spans half a sarcomere. Titin largely consists of multiple repeats of Ig-like and fibronectin type 3 (FN-III)-like domains. Titin connects the ends of myosin thick filaments to Z disks and extends along the thick filament to the H zone and appears to function similar to an elastic band, keeping the myosin filaments centered in the sarcomere during muscle contraction or stretching. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 143224 [Multi-domain] Cd Length: 92 Bit Score: 42.34 E-value: 1.80e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  431 PPVIRQAFQEETMEPGPSVFLKCVAGGNPTPEISWELDGKKIANNDRYQVgqyvtVNGDVVSYLNITSVHANDGGLYKCI 510
Cdd:cd05747     3 PATILTKPRSLTVSEGESARFSCDVDGEPAPTVTWMREGQIIVSSQRHQI-----TSTEYKSTFEISKVQMSDEGNYTVV 77


                  ....*....
gi 386767223  511 AKSKVGVAE 519
Cdd:cd05747    78 VENSEGKQE 86

Immunoglobulin (Ig)-like I-set domain of Neural Cell Adhesion Molecule 1 (NCAM-1); The members here are composed of the fourth Ig domain of Neural Cell Adhesion Molecule 1(NCAM-1). NCAM plays important roles in the development and regeneration of the central nervous system, in synaptogenesis and neural migration. NCAM mediates cell-cell and cell-substratum recognition and adhesion via homophilic (NCAM-NCAM) and heterophilic (NCAM-non-NCAM) interactions. NCAM is expressed as three major isoforms having different intracellular extensions. The extracellular portion of NCAM has five N-terminal Ig-like domains and two fibronectin type III domains. The double zipper adhesion complex model for NCAM homophilic binding involves Ig1, Ig2, and Ig3. By this model, Ig1 and Ig2 mediate dimerization of NCAM molecules situated on the same cell surface (cis interactions), and Ig3 domains mediate interactions between NCAM molecules expressed on the surface of opposing cells (trans interactions), through binding to the Ig1 and Ig2 domains. The adhesive ability of NCAM is modulated by the addition of polysialic acid chains to the fifth Ig-like domain. One of the unique features of I-set domains is the lack of a C" strand. The structures of this group show that the Ig domain lacks this strand and thus is a member of the I-set of Ig domains.

Pssm-ID: 143277 [Multi-domain] Cd Length: 97 Bit Score: 42.27 E-value: 1.86e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  813 APPEFTeKLRNQTARRGEPAV-LQCEAKGEKPIGILWNMN--NMRLDPKN-DNRYTIREEILstgvMSSLSIKRTERSDS 888
Cdd:cd05869     1 AKPKIT-YVENQTAMELEEQItLTCEASGDPIPSITWRTStrNISSEEKTlDGHIVVRSHAR----VSSLTLKYIQYTDA 75

                          90
                  ....*....|....*...
gi 386767223  889 ALFTCVATNAFGSDDASI 906
Cdd:cd05869    76 GEYLCTASNTIGQDSQSM 93

Second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of the Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, and Robo3), and three mammalian Slit homologs (Slit-1,Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit-2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409389 [Multi-domain] Cd Length: 87 Bit Score: 42.00 E-value: 1.94e-04

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 386767223   57 AEIECKAS-GNPMPEIIWIRsDGTAVGDVPGLRQISSDGKLVFPPFRAEDyrqevhAQVYACLARNQFGSIISRD 130
Cdd:cd05724    15 AVLECSPPrGHPEPTVSWRK-DGQPLNLDNERVRIVDDGNLLIAEARKSD------EGTYKCVATNMVGERESRA 82

Immunoglobulin (Ig)-like ectodomain of the LRIG1 (Leucine-rich Repeats And Immunoglobulin-like Domains Protein 1) and similar proteins; member of the I-set of IgSF domains; The members here are composed of subgroup of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. The ectodomain of LRIG1 has two distinct regions: the proposed 15 LRRs and three Ig-like domains closer to the membrane. LRIG1 has been reported to interact with many receptor tyrosine kinases, GDNF/c-Ret, E-cadherin, JAK/STAT, c-Met, and the EGFR family signaling systems. Immunoglobulin Superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The structure of the LRIG1 extracellular Ig domain lacks a C" strand and thus is better described as a member of the I-set of IgSF domains.

Pssm-ID: 409420 [Multi-domain] Cd Length: 91 Bit Score: 42.22 E-value: 1.97e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  352 PPTQTVDFGRPAVFTCQYTGNPIKTVSWMKDG--------KAIGHSEP---VLRIESVKKEDKGMYQCFVRNDQESAEAS 420
Cdd:cd05763     6 PHDITIRAGSTARLECAATGHPTPQIAWQKDGgtdfpaarERRMHVMPeddVFFIVDVKIEDTGVYSCTAQNSAGSISAN 85


                  ...
gi 386767223  421 AEL 423
Cdd:cd05763    86 ATL 88

Immunoglobulin (Ig)-like domain found in neuregulin (NRG)-1; The members here are composed of the immunoglobulin (Ig)-like domain found in neuregulin (NRG)-1. There are many NRG-1 isoforms which arise from the alternative splicing of mRNA. NRG-1 belongs to the neuregulin gene family which is comprised of four genes. This group represents NRG-1. NRGs are signaling molecules which participate in cell-cell interactions in the nervous system, breast, and heart, and other organ systems, and are implicated in the pathology of diseases including schizophrenia, multiple sclerosis, and breast cancer. The NRG-1 protein binds to and activates the tyrosine kinases receptors ErbB3 and ErbB4, initiating signaling cascades. NRG-1 has multiple functions, for example, in the brain it regulates various processes such as radial glia formation and neuronal migration, dendritic development, and expression of neurotransmitters receptors in the peripheral nervous system NRG-1 regulates processes such as target cell differentiation, and Schwann cell survival.

Pssm-ID: 409476 Cd Length: 93 Bit Score: 42.29 E-value: 1.97e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  815 PEFTEkLRNQTARRGEPAVLQCEAKGEKP-IGILWNMNNMRLDPKNDNRYTireEILSTGVMSSLSIKRTERSDSALFTC 893
Cdd:cd05895     1 PKLKE-MKSQEVAAGSKLVLRCETSSEYPsLRFKWFKNGKEINRKNKPENI---KIQKKKKKSELRINKASLADSGEYMC 76

                          90
                  ....*....|....*..
gi 386767223  894 VATNAFGSDDASINMIV 910
Cdd:cd05895    77 KVSSKLGNDSASANVTI 93

First immunoglobulin (Ig)-like domain of neural cell adhesion molecule (NCAM-1); member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the first immunoglobulin (Ig)-like domain of neural cell adhesion molecule (NCAM-1). NCAM-1 plays important roles in the development and regeneration of the central nervous system, in synaptogenesis and neural migration. NCAM mediates cell-cell and cell-substratum recognition and adhesion via homophilic (NCAM-NCAM), and heterophilic (NCAM-nonNCAM), interactions. NCAM is expressed as three major isoforms having different intracellular extensions. The extracellular portion of NCAM has five N-terminal Ig-like domains and two fibronectin type III domains. The double zipper adhesion complex model for NCAM homophilic binding involves the Ig1, Ig2, and Ig3 domains. By this model, Ig1 and Ig2 mediate dimerization of NCAM molecules situated on the same cell surface (cis interactions), and Ig3 domains mediate interactions between NCAM molecules expressed on the surface of opposing cells (trans interactions), through binding to the Ig1 and Ig2 domains. The adhesive ability of NCAM is modulated by the addition of polysialic acid chains to the fifth Ig-like domain. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409451 Cd Length: 97 Bit Score: 42.33 E-value: 2.02e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  446 GPSVFLKC-VAGGNPTPEISW-ELDGKKIANNDryqvgQYVTV--NGDVVSYLNITSVHANDGGLYKCIAKSKVGvAEHS 521
Cdd:cd05865    15 GESKFFLCqVAGEAKDKDISWfSPNGEKLTPNQ-----QRISVvrNDDYSSTLTIYNANIDDAGIYKCVVSNEDE-GESE 88


                  ....*
gi 386767223  522 AKLNV 526
Cdd:cd05865    89 ATVNV 93

Fourth Ig domain of the neural cell adhesion molecule contactin-2, and similar domains; The members here are composed of the fourth Ig domain of the neural cell adhesion molecule contactin-2. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-2 (also called TAG-1, axonin-1) facilitates cell adhesion by homophilic binding between molecules in apposed membranes. The first four Ig domains form the intermolecular binding fragment which arranges as a compact U-shaped module by contacts between Ig domains 1 and 4, and domains 2 and 3. It has been proposed that a linear zipper-like array forms, from contactin-2 molecules alternatively provided by the two apposed membranes.

Pssm-ID: 143205 [Multi-domain] Cd Length: 85 Bit Score: 41.82 E-value: 2.09e-04

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 386767223 1337 CLAVGAPQPEITWKIKGVEFSANDRMRVLpDGSLLIKSVNRQDAGDYSCHAEN 1389
Cdd:cd05728    21 CKASGNPRPAYRWLKNGQPLASENRIEVE-AGDLRITKLSLSDSGMYQCVAEN 72

Fourth Ig-like domain from smooth muscle myosin light chain kinase and similar domains ; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain from smooth muscle myosin light chain kinase (MYLK) and similar domains. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of this group shows that the fourth Ig-like domain from myosin light chain kinase lacks this strand and thus belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409568 [Multi-domain] Cd Length: 90 Bit Score: 41.85 E-value: 2.24e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  539 AIVAGETLIVTCPVAGYPIDSIVWERDNRAL--PINRKQKVFPNGTLIIENVeRNSDQATYTCVAKNQEGySARGSLEVQ 616
Cdd:cd20976    12 EAVEGQDFVAQCSARGKPVPRITWIRNAQPLqyAADRSTCEAGVGELHIQDV-LPEDHGTYTCLAKNAAG-QVSCSAWVT 89


                  .
gi 386767223  617 V 617
Cdd:cd20976    90 V 90

Fourth Ig-like domain from smooth muscle myosin light chain kinase and similar domains ; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain from smooth muscle myosin light chain kinase (MYLK) and similar domains. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of this group shows that the fourth Ig-like domain from myosin light chain kinase lacks this strand and thus belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409568 [Multi-domain] Cd Length: 90 Bit Score: 41.85 E-value: 2.47e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  248 APSFSSDYNSFsyARVVDQSFAMLCQAQAFPLPIMRWYKfiegtTRKQAVVLNDRVKQVSGT--LIIKDAVVEDSGKYLC 325
Cdd:cd20976     1 APSFSSVPKDL--EAVEGQDFVAQCSARGKPVPRITWIR-----NAQPLQYAADRSTCEAGVgeLHIQDVLPEDHGTYTC 73

                          90
                  ....*....|....*..
gi 386767223  326 VVNNSVGGESVETVLTV 342
Cdd:cd20976    74 LAKNAAGQVSCSAWVTV 90

Immunoglobulin (Ig)-like domain of myelin oligodendrocyte glycoprotein (MOG); The members here are composed of the immunoglobulin (Ig)-like domain of myelin oligodendrocyte glycoprotein (MOG). MOG, a minor component of the myelin sheath, is an important CNS-specific autoantigen, linked to the pathogenesis of multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE). It is a transmembrane protein having an extracellular Ig domain. MOG is expressed in the CNS on the outermost lamellae of the myelin sheath, and on the surface of oligodendrocytes, and may participate in the completion, compaction, and/or maintenance of myelin. This group also includes butyrophilin (BTN). BTN is the most abundant protein in bovine milk-fat globule membrane (MFGM).

Pssm-ID: 409378 Cd Length: 114 Bit Score: 42.56 E-value: 2.52e-04

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 386767223  379 WMKDgkAIGHSEPVLRIESVKKEDKGMYQCFVRNDQESAEASAELK 424
Cdd:cd05713    69 LLKD--AIAEGSVALRIHNVRPSDEGQYTCFFRSGSFYEEATLELK 112

Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor; member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor. FGF receptors bind FGF signaling polypeptides. FGFs participate in multiple processes such as morphogenesis, development, and angiogenesis. FGFs bind to four FGF receptor tyrosine kinases (FGFR1, FGFR2, FGFR3, FGFR4). Receptor diversity is controlled by alternative splicing producing splice variants with different ligand binding characteristics and different expression patterns. FGFRs have an extracellular region comprised of three IG-like domains, a single transmembrane helix, and an intracellular tyrosine kinase domain. Ligand binding and specificity reside in the Ig-like domains 2 and 3, and the linker region that connects these two. FGFR activation and signaling depend on FGF-induced dimerization, a process involving cell surface heparin or heparin sulfate proteoglycans.

Pssm-ID: 409443 [Multi-domain] Cd Length: 95 Bit Score: 41.76 E-value: 2.64e-04

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 386767223 1334 KMPCLAVGAPQPEITWKIKGVEFSANDRM---RV-LPDGSLLIKSVNRQDAGDYSCHAENSIAkdSITH 1398
Cdd:cd05857    23 KFRCPAAGNPTPTMRWLKNGKEFKQEHRIggyKVrNQHWSLIMESVVPSDKGNYTCVVENEYG--SINH 89

Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor; member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor. FGF receptors bind FGF signaling polypeptides. FGFs participate in multiple processes such as morphogenesis, development, and angiogenesis. FGFs bind to four FGF receptor tyrosine kinases (FGFR1, FGFR2, FGFR3, FGFR4). Receptor diversity is controlled by alternative splicing producing splice variants with different ligand binding characteristics and different expression patterns. FGFRs have an extracellular region comprised of three IG-like domains, a single transmembrane helix, and an intracellular tyrosine kinase domain. Ligand binding and specificity reside in the Ig-like domains 2 and 3, and the linker region that connects these two. FGFR activation and signaling depend on FGF-induced dimerization, a process involving cell surface heparin or heparin sulfate proteoglycans.

Pssm-ID: 409443 [Multi-domain] Cd Length: 95 Bit Score: 41.76 E-value: 2.77e-04

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  365 FTCQYTGNPIKTVSWMKDGKA------IG-----HSEPVLRIESVKKEDKGMYQCFVRNDQESAEASAEL 423
Cdd:cd05857    24 FRCPAAGNPTPTMRWLKNGKEfkqehrIGgykvrNQHWSLIMESVVPSDKGNYTCVVENEYGSINHTYHL 93

Fifth immunoglobulin (Ig) domain of contactin; The members here are composed of the fifth immunoglobulin (Ig) domain of contactins. Contactins are neural cell adhesion molecules and are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module via contacts between Ig domains 1 and 4, and between Ig domains 2 and 3. Contactin-2 (TAG-1, axonin-1) may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. This group also includes contactin-1 and contactin-5. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-5 is expressed specifically in the rat postnatal nervous system, peaking at about 3 weeks postnatal, and a lack of contactin-5 (NB-2) results in an impairment of neuronal activity in the rat auditory system. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma.

Pssm-ID: 409358 [Multi-domain] Cd Length: 89 Bit Score: 41.68 E-value: 2.80e-04

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 386767223  272 CQAQAFPLPIMRWYKfieGTtrkQAVVLNDRVKQV-SGTLIIKDAVVEDSGKYLCVVNNSVGGESVETVLTV 342
Cdd:cd04969    24 CKPKASPKPTISWSK---GT---ELLTNSSRICILpDGSLKIKNVTKSDEGKYTCFAVNFFGKANSTGSLSV 89

Third immunoglobulin (Ig) domain of contactin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig) domain of contactins. Contactins are neural cell adhesion molecules and are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module via contacts between Ig domains 1 and 4, and between Ig domains 2 and 3. Contactin-2 (TAG-1, axonin-1) may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. This group also includes contactin-1 and contactin-5. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-5 is expressed specifically in the rat postnatal nervous system, peaking at about 3 weeks postnatal, and a lack of contactin-5 (NB-2) results in an impairment of neuronal activity in the rat auditory system. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma. This group belongs to the I-set of IgSF domains.

Pssm-ID: 409357 [Multi-domain] Cd Length: 88 Bit Score: 41.38 E-value: 2.92e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223   59 IECKASGNPMPEIIWIRSDGTAvgdVPGLRQISSDGKLVFPPFRAEDyrqevhAQVYACLARNQFGsiisRDVHVRAVVI 138
Cdd:cd04968    21 LECFALGNPVPQIKWRKVDGSP---SSQWEITTSEPVLEIPNVQFED------EGTYECEAENSRG----KDTVQGRIIV 87


                  .
gi 386767223  139 Q 139
Cdd:cd04968    88 Q 88

Fibronectin type 3 domain [General function prediction only];

Pssm-ID: 442628 [Multi-domain] Cd Length: 603 Bit Score: 45.76 E-value: 2.99e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223 1405 PPQSPH-VTLSATTTDALTVKLKPHEGDTAPlhGYTLHYKP-EFGEWE----TSEVS-VDSqkhnieGLLCGSRYQVYAT 1477
Cdd:COG3401   232 PPSAPTgLTATADTPGSVTLSWDPVTESDAT--GYRVYRSNsGDGPFTkvatVTTTSyTDT------GLTNGTTYYYRVT 303

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223 1478 GFNNIG-AGEASDILNTRTKGQKPKLPEKPRFIEVSSNSVSLhfkAWKD-GGCPMSHFVVESKKRDQIEWNQISNNVKpD 1555
Cdd:COG3401   304 AVDAAGnESAPSNVVSVTTDLTPPAAPSGLTATAVGSSSITL---SWTAsSDADVTGYNVYRSTSGGGTYTKIAETVT-T 379

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 386767223 1556 NNYVVLDLEPATWYNLRITAHNSAGFTVAEydFATLTVTGGTIAPSRDLPELSAEDTIRIILSN 1619
Cdd:COG3401   380 TSYTDTGLTPGTTYYYKVTAVDAAGNESAP--SEEVSATTASAASGESLTASVDAVPLTDVAGA 441

Immunoglobulin domain; Members of the immunoglobulin superfamily are found in hundreds of proteins of different functions. Examples include antibodies, the giant muscle kinase titin and receptor tyrosine kinases. Immunoglobulin-like domains may be involved in protein-protein and protein-ligand interactions.

Pssm-ID: 395002 Cd Length: 86 Bit Score: 41.41 E-value: 3.06e-04

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 386767223   634 NSGETMGIQCTVIKGDLPINITWVLNNHTLNSGDLDVVIGRMSSkSSTLNIDYIAAEHRGVYTCLARNQAGESSYSAEL 712
Cdd:pfam00047    9 LEGDSATLTCSASTGSPGPDVTWSKEGGTLIESLKVKHDNGRTT-QSSLLISNVTKEDAGTYTCVVNNPGGSATLSTSL 86

Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor; member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor. FGF receptors bind FGF signaling polypeptides. FGFs participate in multiple processes such as morphogenesis, development, and angiogenesis. FGFs bind to four FGF receptor tyrosine kinases (FGFR1, FGFR2, FGFR3, FGFR4). Receptor diversity is controlled by alternative splicing producing splice variants with different ligand binding characteristics and different expression patterns. FGFRs have an extracellular region comprised of three IG-like domains, a single transmembrane helix, and an intracellular tyrosine kinase domain. Ligand binding and specificity reside in the Ig-like domains 2 and 3, and the linker region that connects these two. FGFR activation and signaling depend on FGF-induced dimerization, a process involving cell surface heparin or heparin sulfate proteoglycans.

Pssm-ID: 409443 [Multi-domain] Cd Length: 95 Bit Score: 41.76 E-value: 3.31e-04

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 386767223  272 CQAQAFPLPIMRWYKfiEGTTRKQavvlNDR-----VKQVSGTLIIKDAVVEDSGKYLCVVNNSVG 332
Cdd:cd05857    26 CPAAGNPTPTMRWLK--NGKEFKQ----EHRiggykVRNQHWSLIMESVVPSDKGNYTCVVENEYG 85

Immunoglobulin domain I1 of the titin I-band and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin domain I1 of the titin I-band and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. The two sheets are linked together by a conserved disulfide bond between B strand and F strand. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The Ig I1 domain of the titin I-band is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409543 [Multi-domain] Cd Length: 94 Bit Score: 41.64 E-value: 3.42e-04

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 386767223  731 QGSDAKVECKADGFPKPQVTWKK-----AVGDTPGEYKDLKKSDnirveEGTLHVDNIQKTNEGYYLCEAINGIG 800
Cdd:cd20951    14 EKSDAKLRVEVQGKPDPEVKWYKngvpiDPSSIPGKYKIESEYG-----VHVLHIRRVTVEDSAVYSAVAKNIHG 83

First immunoglobulin (Ig) domain of contactin; member of the I-set of (Ig) superfamily domains; The members here are composed of the first immunoglobulin (Ig) domain of contactins. Contactins are neural cell adhesion molecules and are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module via contacts between Ig domains 1 and 4, and between Ig domains 2 and 3. Contactin-2 (TAG-1, axonin-1) may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. This group also includes contactin-1 and contactin-5. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-5 is expressed specifically in the rat postnatal nervous system, peaking at about 3 weeks postnatal, and a lack of contactin-5 (NB-2) results in an impairment of neuronal activity in the rat auditory system. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma. This group belongs to the I-set of IgSF domains.

Pssm-ID: 409356 [Multi-domain] Cd Length: 96 Bit Score: 41.46 E-value: 3.66e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  269 AMLCQAQAFPLPIMRWykFIEGTTRKqaVVLNDRVKQVSGTLIIKDAV-VEDSGKYLCVVNNSVGgesveTVLTVTAPLS 347
Cdd:cd04967    23 ALNCRARANPVPSYRW--LMNGTEID--LESDYRYSLVDGTLVISNPSkAKDAGHYQCLATNTVG-----SVLSREATLQ 93

Third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM), and similar domains; The members here are composed of the third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM). L1 belongs to the L1 subfamily of cell adhesion molecules (CAMs) and is comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region and an intracellular domain. L1 is primarily expressed in the nervous system and is involved in its development and function. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, and spastic paraplegia type 1, that involves abnormalities of axonal growth. This group also contains the chicken neuron-glia cell adhesion molecule, Ng-CAM and human neurofascin.

Pssm-ID: 409394 [Multi-domain] Cd Length: 83 Bit Score: 41.24 E-value: 3.70e-04

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 386767223 1337 CLAVGAPQPEITWKIKGVEfsandrmrvLPDG---------SLLIKSVNRQDAGDYSCHAENSIAKDSITHKLIV 1402
Cdd:cd05731    17 CIAEGLPTPDIRWIKLGGE---------LPKGrtkfenfnkTLKIENVSEADSGEYQCTASNTMGSARHTISVTV 82

First immunoglobulin (Ig)-like domain in neogenin, and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the first immunoglobulin (Ig)-like domain in neogenin and related proteins. Neogenin is a cell surface protein which is expressed in the developing nervous system of vertebrate embryos in the growing nerve cells. It is also expressed in other embryonic tissues and may play a general role in developmental processes such as cell migration, cell-cell recognition, and tissue growth regulation. Included in this group is the tumor suppressor protein DCC which is deleted in colorectal carcinoma. DCC and neogenin each have four Ig-like domains followed by six fibronectin type III domains, a transmembrane domain, and an intracellular domain. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409387 Cd Length: 97 Bit Score: 41.31 E-value: 3.93e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  442 TMEPGPsVFLKCVAGGNPTPEISWELDGKKIA--NNDRYQvgqyVTVNGdvvSYLnITSV-----HANDGGLYKCIAKSK 514
Cdd:cd05722    13 AMRGGP-VVLNCSAESDPPPKIEWKKDGVLLNlvSDERRQ----QLPNG---SLL-ITSVvhskhNKPDEGFYQCVAQNE 83

                          90
                  ....*....|....
gi 386767223  515 -VG-VAEHSAKLNV 526
Cdd:cd05722    84 sLGsIVSRTARVTV 97

Phage-related protein, tail protein J [Mobilome: prophages, transposons];

Pssm-ID: 443767 [Multi-domain] Cd Length: 978 Bit Score: 45.71 E-value: 3.93e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  929 SVQLSWAQPYDGnsplDRYIIEFKRSRASWSEIDRVivpgHTTEAQVQKLsPATTYNIRIVAENAIGTSQ--SSEAVTII 1006
Cdd:COG4733   553 TLTVSWDAPAGA----VAYEVEWRRDDGNWVSVPRT----SGTSFEVPGI-YAGDYEVRVRAINALGVSSawAASSETTV 623

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223 1007 TAEEAPSGKPQNIKVEPVNqTTMRVTWKPPPrtewNGEILGYYVGYklSNTNSsyvFETINFITEEGKEHNLELQNLRVY 1086
Cdd:COG4733   624 TGKTAPPPAPTGLTATGGL-GGITLSWSFPV----DADTLRTEIRY--STTGD---WASATVAQALYPGNTYTLAGLKAG 693

                         170
                  ....*....|....
gi 386767223 1087 TQYSVVIQAFNKIG 1100
Cdd:COG4733   694 QTYYYRARAVDRSG 707

Fourth immunoglobulin (Ig)-like domain of peroxidasin; The members here are composed of the fourth immunoglobulin (Ig)-like domain in peroxidasin. Peroxidasin has a peroxidase domain and interacting extracellular motifs containing four Ig-like domains. It has been suggested that peroxidasin is secreted, and has functions related to the stabilization of the extracellular matrix. It may play a part in various other important processes such as removal and destruction of cells which have undergone programmed cell death and protection of the organism against non-self.

Pssm-ID: 143223 Cd Length: 69 Bit Score: 40.63 E-value: 3.93e-04

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 386767223  366 TCQYTGNPIKTVSWMKDGKAIGHS-------EPVLRIESVKKEDKGMYQCFVRNDQESAEASAEL 423
Cdd:cd05746     4 PCSAQGDPEPTITWNKDGVQVTESgkfhispEGYLAIRDVGVADQGRYECVARNTIGYASVSMVL 68

Sixth immunoglobulin (Ig) domain of contactin-2; The members here are composed of the sixth immunoglobulin (Ig) domain of the neural cell adhesion molecule contactin-2-like. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-2 (TAG-1, axonin-1) facilitates cell adhesion by homophilic binding between molecules in apposed membranes. It may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module by contacts between IG domains 1 and 4, and domains 2 and 3. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-2 is also expressed in retinal amacrine cells (AC) in the developing chick retina, corresponding to the period of formation and maturation of AC processes.

Pssm-ID: 409440 Cd Length: 102 Bit Score: 41.57 E-value: 4.04e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  634 NSGETMGIQCTVIKG-DLPINITWVLNNHTLnsgDLDVVIG---RMSSKSSTLNIDYIAAE--HRGVYTCLARNQAGESS 707
Cdd:cd05854    15 NQGENLTLQCHASHDpTMDLTFTWSLDDFPI---DLDKPNGhyrRMEVKETIGDLVIVNAQlsHAGTYTCTAQTVVDSAS 91

                          90
                  ....*....|.
gi 386767223  708 YSAELKVNVPP 718
Cdd:cd05854    92 ASATLVVRGPP 102

Fourth immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; Members here are composed the fourth immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, Robo3), and three mammalian Slit homologs (Slit-1, Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, and Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409391 [Multi-domain] Cd Length: 98 Bit Score: 41.48 E-value: 4.06e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  350 IDPPTQTVDFGRPAVFTCQYTGNPIKTVSWMKDGKA--IGHSEPV-------------LRIESVKKEDKGMYQCFVRNDQ 414
Cdd:cd05726     4 VKPRDQVVALGRTVTFQCETKGNPQPAIFWQKEGSQnlLFPYQPPqpssrfsvsptgdLTITNVQRSDVGYYICQALNVA 83

                          90
                  ....*....|...
gi 386767223  415 ESAEASAELKLGG 427
Cdd:cd05726    84 GSILAKAQLEVTD 96

Fourth immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; Members here are composed the fourth immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, Robo3), and three mammalian Slit homologs (Slit-1, Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, and Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409391 [Multi-domain] Cd Length: 98 Bit Score: 41.48 E-value: 4.10e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  816 EFTEKLRNQTARRGEPAVLQCEAKGEKPIGILWNMNNMR--LDPKNDNRYTIREEILSTGvmsSLSIKRTERSDSALFTC 893
Cdd:cd05726     1 QFVVKPRDQVVALGRTVTFQCETKGNPQPAIFWQKEGSQnlLFPYQPPQPSSRFSVSPTG---DLTITNVQRSDVGYYIC 77


                  ....*...
gi 386767223  894 VATNAFGS 901
Cdd:cd05726    78 QALNVAGS 85

Immunoglobulin I-set domain of the Leucine-rich repeat and immunoglobin-like domain-containing protein 1 (Lingo-1); The members here are composed of the immunoglobulin I-set (IgI) domain of the Leucine-rich repeat and immunoglobin-like domain-containing protein 1 (Lingo-1). Human Lingo-1 is a central nervous system-specific transmembrane glycoprotein also known as LERN-1, which functions as a negative regulator of neuronal survival, axonal regeneration, and oligodendrocyte differentiation and myelination. Lingo-1 is a key component of the Nogo receptor signaling complex (RTN4R/NGFR) in RhoA activation responsible for some inhibition of axonal regeneration by myelin-associated factors. The ligand-binding ectodomain of human Lingo-1 contains a bimodular, kinked structure composed of leucine-rich repeat (LRR) and immunoglobulin (Ig)-like modules. Diseases associated with Lingo-1 include mental retardation, autosomal recessive 64 and essential tremor. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the Lingo-1 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409561 Cd Length: 92 Bit Score: 41.22 E-value: 4.19e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  260 YARVVDQSFA-------MLCQAQAFPLPIMRWYkfiegTTRKQAVVL--NDRVKQVS-GTLIIKDAVVEDSGKYLCVVNN 329
Cdd:cd20969     5 RDRKAQQVFVdeghtvqFVCRADGDPPPAILWL-----SPRKHLVSAksNGRLTVFPdGTLEVRYAQVQDNGTYLCIAAN 79

                          90
                  ....*....|...
gi 386767223  330 SVGGESVETVLTV 342
Cdd:cd20969    80 AGGNDSMPAHLHV 92

Second immunoglobulin (Ig)-like domain of the receptor protein tyrosine phosphatase (RPTP)-F; member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain found in the receptor protein tyrosine phosphatase (RPTP)-F, also known as LAR. LAR belongs to the RPTP type IIa subfamily. Members of this subfamily are cell adhesion molecule-like proteins involved in central nervous system (CNS) development. They have large extracellular portions comprised of multiple Ig-like domains and two to nine fibronectin type III (FNIII) domains and a cytoplasmic portion having two tandem phosphatase domains.

Pssm-ID: 409400 [Multi-domain] Cd Length: 91 Bit Score: 41.15 E-value: 4.25e-04

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 386767223  453 CVAGGNPTPEISWELDGKKI---ANNDRYQvgqyVTVNGdvvsYLNITSVHANDGGLYKCIAKSKVGvAEHSAKLNVY 527
Cdd:cd05738    21 CAASGNPDPEISWFKDFLPVdtaTSNGRIK----QLRSG----ALQIENSEESDQGKYECVATNSAG-TRYSAPANLY 89

Fifth immunoglobulin (Ig) domain of contactin-1; The members here are composed of the fifth immunoglobulin (Ig) domain of the neural cell adhesion molecule contactin-1. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-1 is differentially expressed in tumor tissues and may through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma.

Pssm-ID: 409438 Cd Length: 89 Bit Score: 41.14 E-value: 4.33e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  535 MEKKAIVA-GETLIVTCPVAGYPIDSIVWERDNRALPINRKQKVFPNGTLIIENVERNsDQATYTCVAKNQEGYS-ARGS 612
Cdd:cd05852     8 MKKKILAAkGGRVIIECKPKAAPKPKFSWSKGTELLVNNSRISIWDDGSLEILNITKL-DEGSYTCFAENNRGKAnSTGV 86


                  ...
gi 386767223  613 LEV 615
Cdd:cd05852    87 LSV 89

Fourth immunoglobulin (Ig)-like domain in neogenin, and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain in neogenin and related proteins. Neogenin is a cell surface protein which is expressed in the developing nervous system of vertebrate embryos in the growing nerve cells. It is also expressed in other embryonic tissues, and may play a general role in developmental processes such as cell migration, cell-cell recognition, and tissue growth regulation. Included in this group is the tumor suppressor protein DCC which is deleted in colorectal carcinoma. DCC and neogenin each have four Ig-like domains followed by six fibronectin type III domains, a transmembrane domain, and an intracellular domain. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409388 Cd Length: 84 Bit Score: 41.03 E-value: 4.56e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  723 EPTDKAFAQGSDAKVECKADGFPKPQVTWKKAvGDT--PGEYKDLkksdnirVEEGTLHVDNIQKTNEGYYLCEAINGIG 800
Cdd:cd05723     3 KPSNIYAHESMDIVFECEVTGKPTPTVKWVKN-GDVviPSDYFKI-------VKEHNLQVLGLVKSDEGFYQCIAENDVG 74


                  ....*....
gi 386767223  801 SGLSAVIMI 809
Cdd:cd05723    75 NAQASAQLI 83

Third immunoglobulin-like domain of the human WFIKKN (WAP, follistatin, immunoglobulin, Kunitz and NTR domain-containing protein), and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin-like domain of the human WFIKKN (WAP, follistatin, immunoglobulin, Kunitz and NTR domain-containing protein) and similar proteins. WFIKKN is a secreted protein that consists of multiple types of protease inhibitory modules, including two tandem Kunitz-type protease inhibitor-domains. The Ig superfamily is a heterogenous group of proteins built on a common fold comprised of a sandwich of two beta sheets. Members of the Ig superfamily are components of immunoglobulin, neuroglia, cell surface glycoproteins, such as T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, such as butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409422 [Multi-domain] Cd Length: 95 Bit Score: 41.00 E-value: 4.87e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  718 PRWILEPTDKAFAQGSDAKVECKADGFPKPQVTWKKAVgdtPGEYKDLKKSDNIR-----VEEGTLHVDNIQKTNEGYYL 792
Cdd:cd05765     1 PALVNSPTHQTVKVGETASFHCDVTGRPQPEITWEKQV---PGKENLIMRPNHVRgnvvvTNIGQLVIYNAQPQDAGLYT 77


                  ....*....
gi 386767223  793 CEAINGIGS 801
Cdd:cd05765    78 CTARNSGGL 86

Third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, Robo3), and three mammalian Slit homologs (Slit-1,Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, and Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409390 [Multi-domain] Cd Length: 83 Bit Score: 40.84 E-value: 4.91e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223   42 LKEPTNRIDFSNSTgAEIECKASGNPMPEIIWIRSDgtavGDVPGLR-QISSDGKLVFPPFRAEDyrqevhAQVYACLAR 120
Cdd:cd05725     1 VKRPQNQVVLVDDS-AEFQCEVGGDPVPTVRWRKED----GELPKGRyEILDDHSLKIRKVTAGD------MGSYTCVAE 69


                  ....*.
gi 386767223  121 NQFGSI 126
Cdd:cd05725    70 NMVGKI 75

Fourth immunoglobulin (Ig)-like domain of NrCAM (NgCAM-related cell adhesion molecule); The members here are composed of the fourth immunoglobulin (Ig)-like domain of NrCAM (NgCAM-related cell adhesion molecule). NrCAM belongs to the L1 subfamily of cell adhesion molecules (CAMs) and is comprised of an extracellular region having six IG-like domains and five fibronectin type III domains, a transmembrane region, and an intracellular domain. NrCAM is primarily expressed in the nervous system.

Pssm-ID: 409454 Cd Length: 89 Bit Score: 41.12 E-value: 4.98e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223   41 FLKEPTNRIDFSNSTGAEIeCKASGNPMPEIIWIrSDGTAVGDVP--GLRQISSDgKLVFPPFraedyrQEVHAQVYACL 118
Cdd:cd05868     2 WITAPTNLVLSPGEDGTLI-CRANGNPKPSISWL-TNGVPIEIAPtdPSRKVDGD-TIIFSKV------QERSSAVYQCN 72

                          90
                  ....*....|
gi 386767223  119 ARNQFGSIIS 128
Cdd:cd05868    73 ASNEYGYLLA 82

Immunoglobulin domain; Members of the immunoglobulin superfamily are found in hundreds of proteins of different functions. Examples include antibodies, the giant muscle kinase titin and receptor tyrosine kinases. Immunoglobulin-like domains may be involved in protein-protein and protein-ligand interactions.

Pssm-ID: 395002 Cd Length: 86 Bit Score: 40.64 E-value: 5.34e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223   722 LEPTDKAFAQGSDAKVECKADGF-PKPQVTWKKAVGDTPGEYKDLKKSDNIRVEegTLHVDNIQKTNEGYYLCEAINGIG 800
Cdd:pfam00047    1 SAPPTVTVLEGDSATLTCSASTGsPGPDVTWSKEGGTLIESLKVKHDNGRTTQS--SLLISNVTKEDAGTYTCVVNNPGG 78


                   ....*...
gi 386767223   801 SGLSAVIM 808
Cdd:pfam00047   79 SATLSTSL 86

Seventh immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the seventh immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.

Pssm-ID: 409546 [Multi-domain] Cd Length: 96 Bit Score: 40.76 E-value: 5.71e-04

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 386767223  261 ARVVDQSFAML-CQAQAFPLPIMRWYKFIeGTT--RKQAVVLNDRVKQVS-GTLIIKDAVVEDSGKYLCVVNNSVG 332
Cdd:cd20954    11 ANVAAGQDVMLhCQADGFPTPTVTWKKAT-GSTpgEYKDLLYDPNVRILPnGTLVFGHVQKENEGHYLCEAKNGIG 85

Sixth immunoglobulin (Ig) domain of contactin; The members here are composed of the sixth immunoglobulin (Ig) domain of contactins. Contactins are neural cell adhesion molecules and are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module via contacts between Ig domains 1 and 4, and between Ig domains 2 and 3. Contactin-2 (TAG-1, axonin-1) may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. This group also includes contactin-1 and contactin-5. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-5 is expressed specifically in the rat postnatal nervous system, peaking at about 3 weeks postnatal, and a lack of contactin-5 (NB-2) results in an impairment of neuronal activity in the rat auditory system. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma.

Pssm-ID: 409359 Cd Length: 102 Bit Score: 41.00 E-value: 5.96e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  634 NSGETMGIQCTVIKGD-LPINITWVLNNHTLNSGDLDVVIGRMSSKSSTLNIDYIAAE--HRGVYTCLARNQAGESSYSA 710
Cdd:cd04970    15 TVGENATLQCHASHDPtLDLTFTWSFNGVPIDLEKIEGHYRRRYGKDSNGDLEIVNAQlkHAGRYTCTAQTVVDSDSASA 94


                  ....*...
gi 386767223  711 ELKVNVPP 718
Cdd:cd04970    95 TLVVRGPP 102

Third immunoglobulin (Ig)-like domain of Neural Cell Adhesion Molecule 1 (NCAM-1); member of the I-set of IgSF domains; The members here are composed of the third immunoglobulin (Ig)-like domain of Neural Cell Adhesion Molecule (NCAM-1). NCAM plays important roles in the development and regeneration of the central nervous system, in synaptogenesis and neural migration. NCAM mediates cell-cell and cell-substratum recognition and adhesion via homophilic (NCAM-NCAM), and heterophilic (NCAM-non-NCAM), interactions. NCAM is expressed as three major isoforms having different intracellular extensions. The extracellular portion of NCAM has five N-terminal Ig-like domains and two fibronectin type III domains. The double zipper adhesion complex model for NCAM homophilic binding involves Ig1, Ig2, and Ig3. By this model, Ig1 and Ig2 mediate dimerization of NCAM molecules situated on the same cell surface (cis interactions), and Ig3 domains mediate interactions between NCAM molecules expressed on the surface of opposing cells (trans interactions) through binding to the Ig1 and Ig2 domains. The adhesive ability of NCAM is modulated by the addition of polysialic acid chains to the fifth Ig-like domain.

Pssm-ID: 143207 [Multi-domain] Cd Length: 95 Bit Score: 40.69 E-value: 7.03e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  620 PPQIRPFDFGDEAS-NSGETMGIQCTVIKGDLPInITWVLNNHTLNSGDLDVVIGRMSSKSSTLNIDyiaAEHRGVYTCL 698
Cdd:cd05730     1 PPTIRARQSEVNATaNLGQSVTLACDADGFPEPT-MTWTKDGEPIESGEEKYSFNEDGSEMTILDVD---KLDEAEYTCI 76

                          90
                  ....*....|....*.
gi 386767223  699 ARNQAGESSYSAELKV 714
Cdd:cd05730    77 AENKAGEQEAEIHLKV 92

First immunoglobulin (Ig) domain of contactin-1; member of the I-set of Ig superfamily domains; The members here are composed of the first immunoglobulin (Ig) domain of the neural cell adhesion molecule contactin-1. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma. This group belongs to the I-set of IgSF domains.

Pssm-ID: 409436 [Multi-domain] Cd Length: 95 Bit Score: 40.71 E-value: 7.06e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223   38 GPVFLKEPTNRIDFSNSTGAEIE--CKASGNPMPEIIWIRSDGTAvgDVPGLRQISSDGKLVFP-PFRAEDyrqevhAQV 114
Cdd:cd05849     1 GPVFEEQPIDTIYPEESTEGKVSvnCRARANPFPIYKWRKNNLDI--DLTNDRYSMVGGNLVINnPDKYKD------AGR 72

                          90
                  ....*....|....*.
gi 386767223  115 YACLARNQFGSIISRD 130
Cdd:cd05849    73 YVCIVSNIYGKVRSRE 88

First immunoglobulin (Ig) domain of contactin-5; member of the I-set of Ig superfamily domains; The members here are composed of the first immunoglobulin (Ig) domain of the neural cell adhesion molecule contactin-5. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains, anchored to the membrane by glycosylphosphatidylinositol. The different contactins show different expression patterns in the central nervous system. In rats, a lack of contactin-5 (NB-2) results in an impairment of the neuronal activity in the auditory system. Contactin-5 is expressed specifically in the postnatal nervous system, peaking at about 3 weeks postnatal. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala; lower levels of expression have been detected in the corpus callosum, caudate nucleus, and spinal cord. This group belongs to the I-set of IgSF domains.

Pssm-ID: 409435 Cd Length: 96 Bit Score: 40.70 E-value: 7.22e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  718 PRWILEPTDKAFAQGSDAK---VECKADGFPKPQVTWKKAvgdtpGEYKDLKKSDNIRVEEGTLHVDNIQKTNE-GYYLC 793
Cdd:cd05848     2 PVFVQEPDDAIFPTDSDEKkviLNCEARGNPVPTYRWLRN-----GTEIDTESDYRYSLIDGNLIISNPSEVKDsGRYQC 76

                          90
                  ....*....|.
gi 386767223  794 EAINGIGSGLS 804
Cdd:cd05848    77 LATNSIGSILS 87

Immunoglobulin domain; Members of the immunoglobulin superfamily are found in hundreds of proteins of different functions. Examples include antibodies, the giant muscle kinase titin and receptor tyrosine kinases. Immunoglobulin-like domains may be involved in protein-protein and protein-ligand interactions.

Pssm-ID: 395002 Cd Length: 86 Bit Score: 40.26 E-value: 8.06e-04

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 386767223   278 PLPIMRWYKfiEGTTRKQAVVLNDRVKQVSG-TLIIKDAVVEDSGKYLCVVNNSVGGESVETVL 340
Cdd:pfam00047   25 PGPDVTWSK--EGGTLIESLKVKHDNGRTTQsSLLISNVTKEDAGTYTCVVNNPGGSATLSTSL 86

C-terminal immunoglobulin (Ig)-like domain of M-protein; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of M-protein (also known as myomesin-2). M-protein is a structural protein localized to the M-band, a transverse structure in the center of the sarcomere, and is a candidate for M-band bridges. M-protein is modular consisting mainly of repetitive IG-like and fibronectin type III (FnIII) domains and has a muscle-type specific expression pattern. M-protein is present in fast fibers.

Pssm-ID: 143299 Cd Length: 92 Bit Score: 40.28 E-value: 8.24e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  266 QSFAMLCQAQAFPLPIMRWYKfiegttRKQAVVLNDR--VKQVSG---TLIIKDAVVEDSGKYLCVVNNSVGGESVETVL 340
Cdd:cd05891    17 KTLNLTCTVFGNPDPEVIWFK------NDQDIELSEHysVKLEQGkyaSLTIKGVTSEDSGKYSINVKNKYGGETVDVTV 90


                  ..
gi 386767223  341 TV 342
Cdd:cd05891    91 SV 92

Immunoglobulin-like domain of human Aortic Preferentially Expressed Protein-1 (APEG-1) and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin I-set (IgI) domain of the Human Aortic Preferentially Expressed Protein-1 (APEG-1) and similar proteins. APEG-1 is a novel specific smooth muscle differentiation marker predicted to play a role in the growth and differentiation of arterial smooth muscle cells (SMCs). The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the human APEG-1 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409567 Cd Length: 91 Bit Score: 40.53 E-value: 8.54e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  815 PEFTEKLRNQTARRGEPAVLQCEAKGE-KPIgILWNMNNMRLDPknDNRYTIREeilSTGVMSSLSIKRTERSDSALFTC 893
Cdd:cd20975     1 PTFKVSLMDQSVREGQDVIMSIRVQGEpKPV-VSWLRNRQPVRP--DQRRFAEE---AEGGLCRLRILAAERGDAGFYTC 74


                  ....*...
gi 386767223  894 VATNAFGS 901
Cdd:cd20975    75 KAVNEYGA 82

C-terminal immunoglobulin (Ig)-like domain of M-protein; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of M-protein (also known as myomesin-2). M-protein is a structural protein localized to the M-band, a transverse structure in the center of the sarcomere, and is a candidate for M-band bridges. M-protein is modular consisting mainly of repetitive IG-like and fibronectin type III (FnIII) domains and has a muscle-type specific expression pattern. M-protein is present in fast fibers.

Pssm-ID: 143299 Cd Length: 92 Bit Score: 40.28 E-value: 8.57e-04

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 386767223  442 TMEPGPSVFLKCVAGGNPTPEISWELDGKKIANNDRYQV----GQYVTvngdvvsyLNITSVHANDGGLYKCIAKSKVG 516
Cdd:cd05891    12 TIMEGKTLNLTCTVFGNPDPEVIWFKNDQDIELSEHYSVkleqGKYAS--------LTIKGVTSEDSGKYSINVKNKYG 82

Third immunoglobulin (Ig)-like domain of the receptor protein tyrosine phosphatase (RPTP)-F (also known as LAR), type IIa; member of the I-set of IgSF domains; The members here are composed of the third immunoglobulin (Ig)-like domain found in the receptor protein tyrosine phosphatase (RPTP)-F, also known as LAR. LAR belongs to the RPTP type IIa subfamily. Members of this subfamily are cell adhesion molecule-like proteins involved in central nervous system (CNS) development. They have large extracellular portions comprised of multiple Ig-like domains and two to nine fibronectin type III (FNIII) domains and a cytoplasmic portion having two tandem phosphatase domains. Included in this group is Drosophila LAR (DLAR).

Pssm-ID: 409401 Cd Length: 82 Bit Score: 39.88 E-value: 8.71e-04

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 386767223 1337 CLAVGAPQPEITWKIKGVEFSANDRMrvlPDGSLLIKSVNRQDAGDYSCHAENSI 1391
Cdd:cd05739    19 CVAVGAPMPYVKWMKGGEELTKEDEM---PVGRNVLELTNIYESANYTCVAISSL 70

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

Pssm-ID: 464026 [Multi-domain] Cd Length: 79 Bit Score: 39.69 E-value: 9.45e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223   432 PVIRQAFQeeTMEPGPSVFLKCVAGGNPTPEISWELDGKKIANNDRYQvgqyvtvngdvvsylnITSVHANDGGLYKCIA 511
Cdd:pfam13895    2 PVLTPSPT--VVTEGEPVTLTCSAPGNPPPSYTWYKDGSAISSSPNFF----------------TLSVSAEDSGTYTCVA 63

                           90
                   ....*....|....*.
gi 386767223   512 K-SKVGVAEHSAKLNV 526
Cdd:pfam13895   64 RnGRGGKVSNPVELTV 79

Immunoglobulin domain of human Synaptic Adhesion-Like Molecule 5 (SALM5) and similar proteins; member of the I-set of IgSF domains; This group contains the immunoglobulin domain of human Synaptic Adhesion-Like Molecule 5 (SALM5) and similar proteins. The SALM (for synaptic adhesion-like molecules; also known as Lrfn for leucine-rich repeat and fibronectin type III domain containing) family of adhesion molecules consists of five known members: SALM1/Lrfn2, SALM2/Lrfn1, SALM3/Lrfn4, SALM4/Lrfn3, and SALM5/Lrfn5. SALMs share a similar domain structure, containing leucine-rich repeats (LRRs), an immunoglobulin (Ig) domain, and a fibronectin III (FNIII) domain, followed by a transmembrane domain and a C-terminal PDZ-binding motif. SALM5 is implicated in autism spectrum disorders (ASDs) and schizophrenia, induces presynaptic differentiation in contacting axons. SALM5 interacts with the Ig domains of LAR (Leukocyte common Antigen-Related) family receptor protein tyrosine phosphatases (LAR-RPTPs; LAR, PTPdelta, and PTPsigma). In addition, PTPdelta is implicated in ASDs, ADHD, bipolar disorder, and restless leg syndrome. Studies have shown that LAR-RPTPs are novel and splicing-dependent presynaptic ligands for SALM5, and that they mediate SALM5-dependent presynaptic differentiation. Furthermore, SALM5 maintains AMPA receptor (AMPAR)-mediated excitatory synaptic transmission through mechanisms involving the interaction of SALM5 with LAR-RPTPs. This group belongs to the I-set of immunoglobulin superfamily (IgSF) domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.

Pssm-ID: 409421 [Multi-domain] Cd Length: 88 Bit Score: 40.15 E-value: 9.46e-04

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 386767223 1333 AKMPCLAVGAPQPEITWKI-KGVEFSANDRMRVLPDGSLLIKSVNRQDAGDYSCHAEN 1389
Cdd:cd05764    18 ATLRCKARGDPEPAIHWISpEGKLISNSSRTLVYDNGTLDILITTVKDTGAFTCIASN 75

Third immunoglobulin domain in Cluster of Differentiation (CD) 22; member of the Constant 2 (C2)-set of IgSF domains; The members here are composed of the third immunoglobulin domain in Cluster of Differentiation (CD) 22 (also known as Siglec-2). CD22, a sialic-acid binding immunoglobulin type-lectin (Siglec) family member, is an inhibitory co-receptor of the B-cell receptor (BCR). The inhibitory function of CD22 and its restricted expression on B cells makes CD22 an attractive target against dysregulated B cells that cause autoimmune diseases and B-cell-derived cancers. CD22 plays a vital role in establishing a baseline level of B-cell inhibition, and thus is an important determinant of homeostasis in humoral immunity. Siglecs are primarily expressed on immune cells and recognize sialic acid-containing glycan ligands. Siglecs are organized as an extracellular module composed of Ig-like domains (an N-terminal variable set of Ig-like carbohydrate recognition domains, and 1 to 16 constant Ig-like domains), followed by transmembrane and short cytoplasmic domains. Human Siglecs are classified into two subgroups, one subgroup is comprised of sialoadhesin (Siglec-1), CD22 (Siglec-2), and MAG (Siglec-4, myelin-associated glycoprotein), the other subgroup is comprised of CD33-related Siglecs which include CD33 (Siglec-3) and human Siglecs 5-11. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. This group belongs to the C2-set of IgSF domains, having A, B, and E strands in one beta-sheet and A', G, F, C' in the other. Unlike other Ig domain sets, the C2-set lacks the D strand.

Pssm-ID: 409531 Cd Length: 88 Bit Score: 40.17 E-value: 9.79e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  346 LSAKIDPPTQTVDFGRPAVFTCQYTG-NPI-KTVSWMKDGKAIGHSEPV-LRIESVKKEDKGMYQCFVRNDQeSAEASAE 422
Cdd:cd20937     3 LEIKVTPSDAIVREGDSVTMTCEVSSsNPEyTTVSWLKDGTSLKKQNTFtLNLREVTKDQSGKYCCQVSNDV-GPGRSEE 81


                  ...
gi 386767223  423 LKL 425
Cdd:cd20937    82 VFL 84

Immunoglobulin (Ig)-like domain at the C-terminus of semaphorins; The members here are composed of the immunoglobulin (Ig)-like domain in semaphorins. Semaphorins are transmembrane protein that have important roles in a variety of tissues. Functionally, semaphorins were initially characterized for their importance in the development of the nervous system and in axonal guidance. Later they have been found to be important for the formation and functioning of the cardiovascular, endocrine, gastrointestinal, hepatic, immune, musculoskeletal, renal, reproductive, and respiratory systems. Semaphorins function through binding to their receptors and transmembrane semaphorins also serves as receptors themselves. Although molecular mechanism of semaphorins is poorly understood, the Ig-like domains may be involved in ligand binding or dimerization.

Pssm-ID: 409368 Cd Length: 88 Bit Score: 40.14 E-value: 9.95e-04

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 386767223 1347 ITWKIKG--VEFSANDRMRVLPDGSLLIKSVNRQDAGDYSCHAENS 1390
Cdd:cd04979    27 VTWIHNGkkVPRYRSPRLVLKTERGLLIRSAQEADAGVYECHSGER 72

Immunoglobulin-like Ig0 domain of basigin-1 (BSG1) and similar proteins; The members here are composed of the immunoglobulin (Ig) domain of the collagenase stimulatory factor, basigin-1 (BSG1; also known as Cluster of Differentiation 147 (CD147) and Extracellular Matrix Metalloproteinase Inducer (EMMPRIN)) and similar proteins. CD147 is a transmembrane glycoprotein that belongs to the immunoglobulin superfamily. It is expressed in nearly all cells including platelets and fibroblasts and is involved in inflammatory diseases, and cancer progression. CD147 is highly expressed in several cancers and used as a prognostic marker. The two primary isoforms of CD147 that are related to cancer progression have been identified: CD147 Ig1-Ig2 (also called Basigin-2) that is ubiquitously expressed in most tissues and CD147 Ig0-Ig1-Ig2 (also called Basigin-1) that is retinal specific and implicated in retinoblastoma. Studies showed that CD147 Ig0 domain is a potent stimulator of interleukin-6 and suggest that the CD147 Ig0 dimer is the functional unit required for activity.

Pssm-ID: 409534 Cd Length: 116 Bit Score: 40.72 E-value: 9.99e-04

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 386767223  446 GPSVFLKCVAGGNPTPEISWELDGKKI----------ANNDRYQVgqYVTVNGDVVSYLNITSVHANDGGLYKCIA 511
Cdd:cd20940    15 GDSVELHCEAVGSPIPEIQWWFEGQEPneicsqlwdgARLDRVHI--NATYHQHATSTISIDNLTEEDTGTYECRA 88

Second immunoglobulin (Ig)-like domain of a Follistatin-related protein 5, and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig)-like domain found in human Follistatin-related protein 5 (FSTL5) and a follistatin-like molecule encoded by the CNS-related Mahya gene. Mahya genes have been retained in certain Bilaterian branches during evolution. They are conserved in Hymenoptera and Deuterostomes, but are absent from other metazoan species such as fruit fly and nematode. Mahya proteins are secretory, with a follistatin-like domain (Kazal-type serine/threonine protease inhibitor domain and EF-hand calcium-binding domain), two Ig-like domains, and a novel C-terminal domain. Mahya may be involved in learning and memory and in processing of sensory information in Hymenoptera and vertebrates. Follistatin is a secreted, multidomain protein that binds activins with high affinity and antagonizes their signaling.

Pssm-ID: 409399 [Multi-domain] Cd Length: 93 Bit Score: 40.32 E-value: 1.01e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  530 PYIRQM-EKKAIVAGETLIVTCPVAGYPIDSIVWERDNRAL--PINRKQKVFPNGT-LIIENVeRNSDQATYTCVAKNQE 605
Cdd:cd05736     1 PVIRVYpEFQAKEPGVEASLRCHAEGIPLPRVQWLKNGMDInpKLSKQLTLIANGSeLHISNV-RYEDTGAYTCIAKNEG 79


                  .
gi 386767223  606 G 606
Cdd:cd05736    80 G 80

Fourth Ig-like domain from smooth muscle myosin light chain kinase and similar domains ; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain from smooth muscle myosin light chain kinase (MYLK) and similar domains. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of this group shows that the fourth Ig-like domain from myosin light chain kinase lacks this strand and thus belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409568 [Multi-domain] Cd Length: 90 Bit Score: 39.93 E-value: 1.06e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  717 PPRWILEPTDKAFAQGSDAKVECKADGFPKPQVTWKKAVgdTPGEYKDLKKSDNIRVeeGTLHVDNIQKTNEGYYLCEAI 796
Cdd:cd20976     1 APSFSSVPKDLEAVEGQDFVAQCSARGKPVPRITWIRNA--QPLQYAADRSTCEAGV--GELHIQDVLPEDHGTYTCLAK 76


                  ....
gi 386767223  797 NGIG 800
Cdd:cd20976    77 NAAG 80

immunoglobulin-like domain of telokin and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig) domain in telokin, the C-terminal domain of myosin light chain kinase which is identical to telokin, and similar proteins. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the telokin Ig domain lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409565 [Multi-domain] Cd Length: 88 Bit Score: 39.87 E-value: 1.06e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  532 IRQMEKKAIVAGETLIVTCPVAGYPIDSIVWERDNRALPINRKQKVFPNG----TLIIENVeRNSDQATYTCVAKNQEGy 607
Cdd:cd20973     1 IQTLRDKEVVEGSAARFDCKVEGYPDPEVKWMKDDNPIVESRRFQIDQDEdglcSLIISDV-CGDDSGKYTCKAVNSLG- 78

                          90
                  ....*....|
gi 386767223  608 SARGSLEVQV 617
Cdd:cd20973    79 EATCSAELTV 88

Immunoglobulin domain I1 of the titin I-band and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin domain I1 of the titin I-band and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. The two sheets are linked together by a conserved disulfide bond between B strand and F strand. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The Ig I1 domain of the titin I-band is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409543 [Multi-domain] Cd Length: 94 Bit Score: 40.10 E-value: 1.10e-03

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 386767223 1330 KEDAKMPCLAVGAPQPEITWKIKGV--EFSANDR-MRVLPDG---SLLIKSVNRQDAGDYSCHAENS 1390
Cdd:cd20951    15 KSDAKLRVEVQGKPDPEVKWYKNGVpiDPSSIPGkYKIESEYgvhVLHIRRVTVEDSAVYSAVAKNI 81

Immunoglobulin I-set domain of the Leucine-rich repeat and immunoglobin-like domain-containing protein 1 (Lingo-1); The members here are composed of the immunoglobulin I-set (IgI) domain of the Leucine-rich repeat and immunoglobin-like domain-containing protein 1 (Lingo-1). Human Lingo-1 is a central nervous system-specific transmembrane glycoprotein also known as LERN-1, which functions as a negative regulator of neuronal survival, axonal regeneration, and oligodendrocyte differentiation and myelination. Lingo-1 is a key component of the Nogo receptor signaling complex (RTN4R/NGFR) in RhoA activation responsible for some inhibition of axonal regeneration by myelin-associated factors. The ligand-binding ectodomain of human Lingo-1 contains a bimodular, kinked structure composed of leucine-rich repeat (LRR) and immunoglobulin (Ig)-like modules. Diseases associated with Lingo-1 include mental retardation, autosomal recessive 64 and essential tremor. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the Lingo-1 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409561 Cd Length: 92 Bit Score: 40.07 E-value: 1.11e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  825 TARRGEPAVLQCEAKGEKPIGILWNMNNMRLDPKNDNRytiREEILSTGvmsSLSIKRTERSDSALFTCVATNAFGSDDA 904
Cdd:cd20969    13 FVDEGHTVQFVCRADGDPPPAILWLSPRKHLVSAKSNG---RLTVFPDG---TLEVRYAQVQDNGTYLCIAANAGGNDSM 86


                  ....*.
gi 386767223  905 SINMIV 910
Cdd:cd20969    87 PAHLHV 92

Third immunoglobulin (Ig)-like domain of hemolin, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the third immunoglobulin (Ig)-like domain of hemolin and similar proteins. Hemolin, an insect immunoglobulin superfamily (IgSF) member containing four Ig-like domains, is a lipopolysaccharide-binding immune protein induced during bacterial infection. Hemolin shares significant sequence similarity with the first four Ig-like domains of the transmembrane cell adhesion molecules (CAMs) of the L1 family. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The third Ig-like domain of hemolin is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules, including vascular (VCAM), intercellular (ICAM), neural (NCAM) and mucosal addressin (MADCAM) cell adhesion molecules, as well as junction adhesion molecules (JAM).

Pssm-ID: 409569 Cd Length: 93 Bit Score: 40.07 E-value: 1.16e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  432 PVIRQAFQEETMEPGPSVFLKCVAGGNPTPEISWELDGKKIANNDRYQVGQYVTVNGDVVSYLNITSVHAndgGLYKCIA 511
Cdd:cd20977     1 PVPQYVSKDMMAKAGDVTMIYCMYGSNPTAHPNYFKNGKDVNGNPEDRITRHNRTSGKRLLFKTTLPEDE---GVYTCEV 77

                          90
                  ....*....|....*.
gi 386767223  512 KSKVG-VAEHSAKLNV 526
Cdd:cd20977    78 DNGVGkPQKHSLKLTV 93

Immunoglobulin (Ig)-like domain of vascular endothelial growth factor receptor (VEGFR); member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig)-like domain of vascular endothelial growth factor receptor (VEGFR). The VEGFRs have an extracellular component with seven Ig-like domains, a transmembrane segment, and an intracellular tyrosine kinase domain interrupted by a kinase-insert domain. The VEGFR family consists of three members, VEGFR-1 (Flt-1), VEGFR-2 (KDR/Flk-1), and VEGFR-3 (Flt-4). VEGFRs bind VEGFs with high affinity at the Ig-like domains. VEGF-A is important to the growth and maintenance of vascular endothelial cells and to the development of new blood- and lymphatic-vessels in physiological and pathological states. VEGFR-2 is a major mediator of the mitogenic, angiogenic, and microvascular permeability-enhancing effects of VEGF-A. VEGFR-1 may play an inhibitory part in these processes by binding VEGF and interfering with its interaction with VEGFR-2. VEGFR-1 has a signaling role in mediating monocyte chemotaxis. VEGFR-1 and VEGFR-2 may mediate a chemotactic and a survival signal in hematopoietic stem cells or leukemia cells. VEGFR-3 has been shown to be involved in tumor angiogenesis and growth. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409365 Cd Length: 90 Bit Score: 39.89 E-value: 1.21e-03

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 386767223 1330 KEDAKMPCLAVGAPQPEITWKIKGVEFSANdrMRVLPDGSLLIKSVNRQDAGDYSCHAENSIA--KDSITHKLIV 1402
Cdd:cd04976    18 KRSVRLPMKVKAYPPPEVVWYKDGLPLTEK--ARYLTRHSLIIKEVTEEDTGNYTILLSNKQSnvFKNLTATLVV 90

Third immunoglobulin (Ig)-like domain of the receptor protein tyrosine phosphatase (RPTP)-F (also known as LAR), type IIa; member of the I-set of IgSF domains; The members here are composed of the third immunoglobulin (Ig)-like domain found in the receptor protein tyrosine phosphatase (RPTP)-F, also known as LAR. LAR belongs to the RPTP type IIa subfamily. Members of this subfamily are cell adhesion molecule-like proteins involved in central nervous system (CNS) development. They have large extracellular portions comprised of multiple Ig-like domains and two to nine fibronectin type III (FNIII) domains and a cytoplasmic portion having two tandem phosphatase domains. Included in this group is Drosophila LAR (DLAR).

Pssm-ID: 409401 Cd Length: 82 Bit Score: 39.50 E-value: 1.29e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  724 PTDKAFAQGSDAKVECKADGFPKPQVTWKKAVgdtpgeyKDLKKSDNIRVEEGTLHVDNIQKTNEgyYLCEAINGIGSgL 803
Cdd:cd05739     4 PSNHEVMPGGSVNLTCVAVGAPMPYVKWMKGG-------EELTKEDEMPVGRNVLELTNIYESAN--YTCVAISSLGM-I 73


                  ....*....
gi 386767223  804 SAVIMISVQ 812
Cdd:cd05739    74 EATAQVTVK 82

Sixth immunoglobulin (Ig) domain of contactin-4; The members here are composed of the sixth immunoglobulin (Ig) domain of the neural cell adhesion molecule contactin-4. Contactins are neural cell adhesion molecules, and are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. The different contactins show different expression patterns in the central nervous system. Highest expression of contactin-4 is in testes, thyroid, small intestine, uterus, and brain. Contactin-4 plays a role in the response of neuroblastoma cells to differentiating agents, such as retinoids. The contactin 4 gene is associated with cerebellar degeneration in spinocerebellar ataxia type 16.

Pssm-ID: 409439 Cd Length: 102 Bit Score: 39.99 E-value: 1.33e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  616 QVMVPPQirPFDFgdeasNSGETMGIQCTVIKG-DLPINITWVLNNHTLN---SGDLDVVIGRMSSkSSTLNIDYIAAEH 691
Cdd:cd05853     4 RVMVPPS--SMDV-----TVGESIVLPCQVSHDhSLDIVFTWSFNGHLIDfqkDGDHFERVGGQDS-AGDLMIRSIQLKH 75

                          90       100
                  ....*....|....*....|....*..
gi 386767223  692 RGVYTCLARNQAGESSYSAELKVNVPP 718
Cdd:cd05853    76 AGKYVCMVQTSVDKLSAAADLIVRGPP 102

Immunoglobulin domain of human Synaptic Adhesion-Like Molecule 5 (SALM5) and similar proteins; member of the I-set of IgSF domains; This group contains the immunoglobulin domain of human Synaptic Adhesion-Like Molecule 5 (SALM5) and similar proteins. The SALM (for synaptic adhesion-like molecules; also known as Lrfn for leucine-rich repeat and fibronectin type III domain containing) family of adhesion molecules consists of five known members: SALM1/Lrfn2, SALM2/Lrfn1, SALM3/Lrfn4, SALM4/Lrfn3, and SALM5/Lrfn5. SALMs share a similar domain structure, containing leucine-rich repeats (LRRs), an immunoglobulin (Ig) domain, and a fibronectin III (FNIII) domain, followed by a transmembrane domain and a C-terminal PDZ-binding motif. SALM5 is implicated in autism spectrum disorders (ASDs) and schizophrenia, induces presynaptic differentiation in contacting axons. SALM5 interacts with the Ig domains of LAR (Leukocyte common Antigen-Related) family receptor protein tyrosine phosphatases (LAR-RPTPs; LAR, PTPdelta, and PTPsigma). In addition, PTPdelta is implicated in ASDs, ADHD, bipolar disorder, and restless leg syndrome. Studies have shown that LAR-RPTPs are novel and splicing-dependent presynaptic ligands for SALM5, and that they mediate SALM5-dependent presynaptic differentiation. Furthermore, SALM5 maintains AMPA receptor (AMPAR)-mediated excitatory synaptic transmission through mechanisms involving the interaction of SALM5 with LAR-RPTPs. This group belongs to the I-set of immunoglobulin superfamily (IgSF) domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.

Pssm-ID: 409421 [Multi-domain] Cd Length: 88 Bit Score: 39.77 E-value: 1.33e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  530 PYI-RQMEKKAIVAGETLIVTCPVAGYPIDSIVW-ERDNRALPINRKQKVFPNGTLIIeNVERNSDQATYTCVAKNQEGy 607
Cdd:cd05764     1 PLItRHTHELRVLEGQRATLRCKARGDPEPAIHWiSPEGKLISNSSRTLVYDNGTLDI-LITTVKDTGAFTCIASNPAG- 78

                          90
                  ....*....|
gi 386767223  608 SARGSLEVQV 617
Cdd:cd05764    79 EATARVELHI 88

C-terminal immunoglobulin (Ig)-like domain of myomesin and M-protein; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of myomesin and M-protein (also known as myomesin-2). Myomesin and M-protein are both structural proteins localized to the M-band, a transverse structure in the center of the sarcomere, and are candidates for M-band bridges. Both proteins are modular, consisting mainly of repetitive Ig-like and fibronectin type III (FnIII) domains. Myomesin is expressed in all types of vertebrate striated muscle; M-protein has a muscle-type specific expression pattern. Myomesin is present in both slow and fast fibers; M-protein is present only in fast fibers. It has been suggested that myomesin acts as a molecular spring with alternative splicing as a means of modifying its elasticity.

Pssm-ID: 319300 Cd Length: 92 Bit Score: 39.88 E-value: 1.38e-03

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 386767223  352 PPTQTVDFGRPAVFTCQYTGNPIKTVSWMKDGKAIGHSE-----------PVLRIESVKKEDKGMYQCFVRN 412
Cdd:cd05737     8 PDVVTIMEGKTLNLTCNVWGDPPPEVSWLKNDQALAFLDhcnlkveagrtVYFTINGVSSEDSGKYGLVVKN 79

Fifth immunoglobulin (Ig) domain of contactin; The members here are composed of the fifth immunoglobulin (Ig) domain of contactins. Contactins are neural cell adhesion molecules and are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module via contacts between Ig domains 1 and 4, and between Ig domains 2 and 3. Contactin-2 (TAG-1, axonin-1) may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. This group also includes contactin-1 and contactin-5. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-5 is expressed specifically in the rat postnatal nervous system, peaking at about 3 weeks postnatal, and a lack of contactin-5 (NB-2) results in an impairment of neuronal activity in the rat auditory system. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma.

Pssm-ID: 409358 [Multi-domain] Cd Length: 89 Bit Score: 39.75 E-value: 1.45e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  446 GPSVFLKCVAGGNPTPEISWELDGKKIANNDRYqvgqYVTVNGDvvsyLNITSVHANDGGLYKCIAKSKVGVAEHSAKLN 525
Cdd:cd04969    17 GGDVIIECKPKASPKPTISWSKGTELLTNSSRI----CILPDGS----LKIKNVTKSDEGKYTCFAVNFFGKANSTGSLS 88


                  .
gi 386767223  526 V 526
Cdd:cd04969    89 V 89

Immunoglobulin (Ig)-like ectodomain of the LRIG1 (Leucine-rich Repeats And Immunoglobulin-like Domains Protein 1) and similar proteins; member of the I-set of IgSF domains; The members here are composed of subgroup of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. The ectodomain of LRIG1 has two distinct regions: the proposed 15 LRRs and three Ig-like domains closer to the membrane. LRIG1 has been reported to interact with many receptor tyrosine kinases, GDNF/c-Ret, E-cadherin, JAK/STAT, c-Met, and the EGFR family signaling systems. Immunoglobulin Superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The structure of the LRIG1 extracellular Ig domain lacks a C" strand and thus is better described as a member of the I-set of IgSF domains.

Pssm-ID: 409420 [Multi-domain] Cd Length: 91 Bit Score: 39.53 E-value: 1.50e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  539 AIVAGETLIVTCPVAGYPIDSIVWERD---NRALPINRKQKVFP-NGTLIIENVeRNSDQATYTCVAKNQEG-YSARGSL 613
Cdd:cd05763    10 TIRAGSTARLECAATGHPTPQIAWQKDggtDFPAARERRMHVMPeDDVFFIVDV-KIEDTGVYSCTAQNSAGsISANATL 88


                  ..
gi 386767223  614 EV 615
Cdd:cd05763    89 TV 90

Third immunoglobulin (Ig) domain of contactin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig) domain of contactins. Contactins are neural cell adhesion molecules and are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module via contacts between Ig domains 1 and 4, and between Ig domains 2 and 3. Contactin-2 (TAG-1, axonin-1) may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. This group also includes contactin-1 and contactin-5. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-5 is expressed specifically in the rat postnatal nervous system, peaking at about 3 weeks postnatal, and a lack of contactin-5 (NB-2) results in an impairment of neuronal activity in the rat auditory system. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma. This group belongs to the I-set of IgSF domains.

Pssm-ID: 409357 [Multi-domain] Cd Length: 88 Bit Score: 39.45 E-value: 1.54e-03

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 386767223  543 GETLIVTCPVAGYPIDSIVWERDNrALPINRKQKVFPNGTLIIENVERnSDQATYTCVAKNQEGYS-ARGSLEVQ 616
Cdd:cd04968    16 GQTVTLECFALGNPVPQIKWRKVD-GSPSSQWEITTSEPVLEIPNVQF-EDEGTYECEAENSRGKDtVQGRIIVQ 88

agrin-responsive second immunoglobulin-like domains (Ig2) of the Muscle-specific kinase (MuSK) ectodomain; a member of the I-set of Ig superfamily domains; The members here are composed of the second immunoglobulin-like (Ig) domains of the Muscle-specific kinase (MuSK) ectodomain. MuSK is a receptor tyrosine kinase specifically expressed in skeletal muscle, where it plays a central role in the formation and maintenance of the neuromuscular junction (NMJ). MuSK is activated by agrin, a neuron-derived heparan sulfate proteoglycan. The activation of MUSK in myotubes regulates the formation of NMJs through the regulation of different processes including the specific expression of genes in subsynaptic nuclei, the reorganization of the actin cytoskeleton and the clustering of the acetylcholine receptors (AChR) in the postsynaptic membrane. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the MuSK lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409560 [Multi-domain] Cd Length: 88 Bit Score: 39.53 E-value: 1.56e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223   43 KEPTNrIDFSNSTGAEIECKASGNPMPEIIWIRSDgTAVGDVPGLRQISSdGKLVFPPFRAEDYRQevhaqvYACLARNQ 122
Cdd:cd20968     4 RPPTN-VTIIEGLKAVLPCTTMGNPKPSVSWIKGD-DLIKENNRIAVLES-GSLRIHNVQKEDAGQ------YRCVAKNS 74

                          90
                  ....*....|.
gi 386767223  123 FGSIISRDVHV 133
Cdd:cd20968    75 LGIAYSKPVTI 85

Fourth Ig domain of the neural cell adhesion molecule contactin-2, and similar domains; The members here are composed of the fourth Ig domain of the neural cell adhesion molecule contactin-2. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-2 (also called TAG-1, axonin-1) facilitates cell adhesion by homophilic binding between molecules in apposed membranes. The first four Ig domains form the intermolecular binding fragment which arranges as a compact U-shaped module by contacts between Ig domains 1 and 4, and domains 2 and 3. It has been proposed that a linear zipper-like array forms, from contactin-2 molecules alternatively provided by the two apposed membranes.

Pssm-ID: 143205 [Multi-domain] Cd Length: 85 Bit Score: 39.51 E-value: 1.58e-03

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 386767223  272 CQAQAFPLPIMRWYKfiegttRKQAVVLNDRVKQVSGTLIIKDAVVEDSGKYLCVVNNSVG 332
Cdd:cd05728    21 CKASGNPRPAYRWLK------NGQPLASENRIEVEAGDLRITKLSLSDSGMYQCVAENKHG 75

Immunoglobulin (Ig)-like domain of myotilin, palladin, and myopalladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig)-like domain in myotilin, palladin, and myopalladin. Myotilin, palladin, and myopalladin function as scaffolds that regulate actin organization. Myotilin and myopalladin are most abundant in skeletal and cardiac muscle; palladin is ubiquitously expressed in the organs of developing vertebrates and plays a key role in cellular morphogenesis. The three family members each interact with specific molecular partners with all three binding to alpha-actinin; In addition, palladin also binds to vasodilator-stimulated phosphoprotein (VASP) and ezrin, myotilin binds to filamin and actin, and myopalladin also binds to nebulin and cardiac ankyrin repeat protein (CARP). This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409405 [Multi-domain] Cd Length: 91 Bit Score: 39.40 E-value: 1.60e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  815 PEFTEKLRNQTARRGEPAVLQCEAKGEKPIGILWNMNNMRLDPKNDNRYTIREeilsTGVMSsLSIKRTERSDSALFTCV 894
Cdd:cd05744     1 PHFLQAPGDLEVQEGRLCRFDCKVSGLPTPDLFWQLNGKPVRPDSAHKMLVRE----NGRHS-LIIEPVTKRDAGIYTCI 75

                          90
                  ....*....|....*.
gi 386767223  895 ATNAFGSDDASINMIV 910
Cdd:cd05744    76 ARNRAGENSFNAELVV 91

First Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin (Ig)-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the titin Z1z2 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409566 [Multi-domain] Cd Length: 93 Bit Score: 39.64 E-value: 1.66e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  432 PVIRQAFQEETMEPGPSVFLKCVAGGNPTPEISWELDGKKIANNDRYQVgQYVTVNGDvvSYLNITSVHANDGGLYKCIA 511
Cdd:cd20974     1 PVFTQPLQSVVVLEGSTATFEAHVSGKPVPEVSWFRDGQVISTSTLPGV-QISFSDGR--AKLSIPAVTKANSGRYSLTA 77

                          90
                  ....*....|....*
gi 386767223  512 KSKVGVAEHSAKLNV 526
Cdd:cd20974    78 TNGSGQATSTAELLV 92

Third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, Robo3), and three mammalian Slit homologs (Slit-1,Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, and Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409390 [Multi-domain] Cd Length: 83 Bit Score: 39.30 E-value: 1.77e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  636 GETMGIQCTViKGDLPINITWvlnnhTLNSGDLDvvIGRMSSKS-STLNIDYIAAEHRGVYTCLARNQAGESSYSAELKV 714
Cdd:cd05725    12 DDSAEFQCEV-GGDPVPTVRW-----RKEDGELP--KGRYEILDdHSLKIRKVTAGDMGSYTCVAENMVGKIEASATLTV 83

Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor_like-1(FGFRL1); member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor like-1(FGFRL1). FGFRL1 is comprised of a signal peptide, three extracellular Ig-like modules, a transmembrane segment, and a short intracellular domain. FGFRL1 is expressed preferentially in skeletal tissues. Similar to FGF receptors, the expressed protein interacts specifically with heparin and with FGF2. FGFRL1 does not have a protein tyrosine kinase domain at its C-terminus; neither does its cytoplasmic domain appear to interact with a signaling partner. It has been suggested that FGFRL1 may not have any direct signaling function, but instead acts as a decoy receptor trapping FGFs and preventing them from binding other receptors.

Pssm-ID: 409442 Cd Length: 92 Bit Score: 39.46 E-value: 1.83e-03

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 386767223  261 ARVVDQSFAMLCQAQAFPLPIMRWYKFIEGTTRKQAvvlnDRVKQVSGTLIIKDAVVEDSGKYLCVVNNSVG 332
Cdd:cd05856    15 ARPVGSSVRLKCVASGNPRPDITWLKDNKPLTPPEI----GENKKKKWTLSLKNLKPEDSGKYTCHVSNRAG 82

Immunoglobulin (Ig)-like domain of Down Syndrome Cell Adhesion molecule (DSCAM); The members here are composed of the immunoglobulin (Ig)-like domain of Down Syndrome Cell Adhesion molecule (DSCAM). DSCAM is a cell adhesion molecule expressed largely in the developing nervous system. The gene encoding DSCAM is located at human chromosome 21q22, the locus associated with the intellectual disability phenotype of Down Syndrome. DSCAM is predicted to be the largest member of the IG superfamily. It has been demonstrated that DSCAM can mediate cation-independent homophilic intercellular adhesion.

Pssm-ID: 409397 [Multi-domain] Cd Length: 97 Bit Score: 39.40 E-value: 1.83e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  543 GETLIVTCPVAGYPIDSIVWERDNRA--------LPINRKQKVFPNGTLIIENVeRNSDQATYTCVAKNQEGYSARGSLE 614
Cdd:cd05734    16 GKAVVLNCSADGYPPPTIVWKHSKGSgvpqfqhiVPLNGRIQLLSNGSLLIKHV-LEEDSGYYLCKVSNDVGADISKSMY 94


                  ...
gi 386767223  615 VQV 617
Cdd:cd05734    95 LTV 97

Immunoglobulin (Ig)-like domain in neuregulins; The members here are composed of the immunoglobulin (Ig)-like domain in neuregulins (NRGs). NRGs are signaling molecules which participate in cell-cell interactions in the nervous system, breast, heart, and other organ systems, and are implicated in the pathology of diseases including schizophrenia, multiple sclerosis, and breast cancer. There are four members of the neuregulin gene family (NRG-1, NRG-2, NRG-3, and NRG-4). The NRG-1 protein, binds to and activates the tyrosine kinases receptors ErbB3 and ErbB4, initiating signaling cascades. The other NRGs proteins bind one or the other or both of these ErbBs. NRG-1 has multiple functions: in the brain it regulates various processes such as radial glia formation and neuronal migration, dendritic development, and expression of neurotransmitters receptors, while in the peripheral nervous system NRG-1 regulates processes such as target cell differentiation, and Schwann cell survival. There are many NRG-1 isoforms which arise from the alternative splicing of mRNA. Less is known of the functions of the other NRGs. NRG-2 and NRG-3 are expressed predominantly in the nervous system. NRG-2 is expressed by motor neurons and terminal Schwann cells, and is concentrated near synaptic sites and may be a signal that regulates synaptic differentiation. NRG-4 has been shown to direct pancreatic islet cell development towards the delta-cell lineage.

Pssm-ID: 409408 [Multi-domain] Cd Length: 92 Bit Score: 39.42 E-value: 1.84e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  441 ETMEPGPSVFLKCVA-GGNPTPEISWELDGKKI----ANNDRYQvgqyvtvNGDVVSYLNITSVHANDGGLYKCIAKSKV 515
Cdd:cd05750     9 QTVQEGSKLVLKCEAtSENPSPRYRWFKDGKELnrkrPKNIKIR-------NKKKNSELQINKAKLEDSGEYTCVVENIL 81

                          90
                  ....*....|.
gi 386767223  516 GVAEHSAKLNV 526
Cdd:cd05750    82 GKDTVTGNVTV 92

Fourth Ig domain of the neural cell adhesion molecule contactin-2, and similar domains; The members here are composed of the fourth Ig domain of the neural cell adhesion molecule contactin-2. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-2 (also called TAG-1, axonin-1) facilitates cell adhesion by homophilic binding between molecules in apposed membranes. The first four Ig domains form the intermolecular binding fragment which arranges as a compact U-shaped module by contacts between Ig domains 1 and 4, and domains 2 and 3. It has been proposed that a linear zipper-like array forms, from contactin-2 molecules alternatively provided by the two apposed membranes.

Pssm-ID: 143205 [Multi-domain] Cd Length: 85 Bit Score: 39.12 E-value: 1.85e-03

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 386767223   60 ECKASGNPMPEIIWIRsDGTAvgdVPGLRQIS-SDGKLVFPPFRAEDyrqevhAQVYACLARNQFGSI 126
Cdd:cd05728    20 ECKASGNPRPAYRWLK-NGQP---LASENRIEvEAGDLRITKLSLSD------SGMYQCVAENKHGTI 77

Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor_like-1(FGFRL1); member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor like-1(FGFRL1). FGFRL1 is comprised of a signal peptide, three extracellular Ig-like modules, a transmembrane segment, and a short intracellular domain. FGFRL1 is expressed preferentially in skeletal tissues. Similar to FGF receptors, the expressed protein interacts specifically with heparin and with FGF2. FGFRL1 does not have a protein tyrosine kinase domain at its C-terminus; neither does its cytoplasmic domain appear to interact with a signaling partner. It has been suggested that FGFRL1 may not have any direct signaling function, but instead acts as a decoy receptor trapping FGFs and preventing them from binding other receptors.

Pssm-ID: 409442 Cd Length: 92 Bit Score: 39.46 E-value: 1.88e-03

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 386767223  732 GSDAKVECKADGFPKPQVTWKK----AVGDTPGEYKDLKksdnirveeGTLHVDNIQKTNEGYYLCEAINGIG 800
Cdd:cd05856    19 GSSVRLKCVASGNPRPDITWLKdnkpLTPPEIGENKKKK---------WTLSLKNLKPEDSGKYTCHVSNRAG 82

Immunoglobulin (Ig)-like domain of the human basement membrane heparan sulfate proteoglycan perlecan and similar proteins; The members here are composed of the immunoglobulin (Ig)-like domain of the human basement membrane heparan sulfate proteoglycan perlecan, also known as HSPG2, and similar proteins. Perlecan consists of five domains: domain I has three putative heparan sulfate attachment sites, domain II has four LDL receptor-like repeats, and one Ig-like repeat, domain III resembles the short arm of laminin chains, domain IV has multiple Ig-like repeats (21 repeats in human perlecan), and domain V resembles the globular G domain of the laminin A chain and internal repeats of EGF. Perlecan may participate in a variety of biological functions including cell binding, LDL-metabolism, basement membrane assembly and selective permeability, calcium binding, and growth- and neurite-promoting activities.

Pssm-ID: 143220 Cd Length: 78 Bit Score: 39.01 E-value: 1.91e-03

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 386767223 1337 CLAVGAPQPEITWKIKGVEFSANDRMRVLPD---GSLLIKSVNRQDAGDYSCHAENS 1390
Cdd:cd05743     8 CVATGVPTPIINWRLNWGHVPDSARVSITSEggyGTLTIRDVKESDQGAYTCEAINT 64

Fifth immunoglobulin (Ig)-like domain of the carcinoembryonic antigen (CEA) related cell adhesion molecule 5 (CEACAM5) and similar domains; member of the C2-set IgSF domains; The members here are composed of the fifth immunoglobulin (Ig)-like domain of the carcinoembryonic antigen (CEA) related cell adhesion molecule 5 (CEACAM5) and similar domains. The CEA family is a group of anchored or secreted glycoproteins, expressed by epithelial cells, leukocytes, endothelial cells and placenta. The CEA family is divided into the CEACAM and pregnancy-specific glycoprotein (PSG) subfamilies. Carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5), also known as CD66e (Cluster of Differentiation 66e), is a cell surface glycoprotein that plays a role in cell adhesion, intracellular signaling and tumor progression. Diseases associated with CEACAM5 include lung cancer and rectum cancer. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. This group belongs to the C2-set of IgSF domains, having A, B, and E strands in one beta-sheet and A', G, F, C' in the other. Unlike other Ig domain sets, the C2-set lacks the D strand.

Pssm-ID: 409540 Cd Length: 76 Bit Score: 38.63 E-value: 1.99e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  255 YNSFSYARVvDQSFAMLCQAQAFPLPIMRWYkfiegttrkqavvLNDRVKQVSGTLIIKDAVVEDSGKYLCVVNNSVGGE 334
Cdd:cd20948     1 SPSDTYYLS-GENLNLSCHAASNPPAQYSWT-------------INGTFQTSSQELFLPAITENNEGTYTCSAHNSLTGK 66


                  ....*....
gi 386767223  335 SVETVLTVT 343
Cdd:cd20948    67 NISLVLSVT 75

Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor_like-1(FGFRL1); member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor like-1(FGFRL1). FGFRL1 is comprised of a signal peptide, three extracellular Ig-like modules, a transmembrane segment, and a short intracellular domain. FGFRL1 is expressed preferentially in skeletal tissues. Similar to FGF receptors, the expressed protein interacts specifically with heparin and with FGF2. FGFRL1 does not have a protein tyrosine kinase domain at its C-terminus; neither does its cytoplasmic domain appear to interact with a signaling partner. It has been suggested that FGFRL1 may not have any direct signaling function, but instead acts as a decoy receptor trapping FGFs and preventing them from binding other receptors.

Pssm-ID: 409442 Cd Length: 92 Bit Score: 39.46 E-value: 2.00e-03

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 386767223  367 CQYTGNPIKTVSWMKDGKAIGHSEP--------VLRIESVKKEDKGMYQCFVRN 412
Cdd:cd05856    26 CVASGNPRPDITWLKDNKPLTPPEIgenkkkkwTLSLKNLKPEDSGKYTCHVSN 79

Third immunoglobulin-like domain of the human WFIKKN (WAP, follistatin, immunoglobulin, Kunitz and NTR domain-containing protein), and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin-like domain of the human WFIKKN (WAP, follistatin, immunoglobulin, Kunitz and NTR domain-containing protein) and similar proteins. WFIKKN is a secreted protein that consists of multiple types of protease inhibitory modules, including two tandem Kunitz-type protease inhibitor-domains. The Ig superfamily is a heterogenous group of proteins built on a common fold comprised of a sandwich of two beta sheets. Members of the Ig superfamily are components of immunoglobulin, neuroglia, cell surface glycoproteins, such as T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, such as butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409422 [Multi-domain] Cd Length: 95 Bit Score: 39.45 E-value: 2.00e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  432 PVIRQAFQEETMEPGPSVFLKCVAGGNPTPEISWE--LDGK-KIANNDRYQVGQYVTVNgdvVSYLNITSVHANDGGLYK 508
Cdd:cd05765     1 PALVNSPTHQTVKVGETASFHCDVTGRPQPEITWEkqVPGKeNLIMRPNHVRGNVVVTN---IGQLVIYNAQPQDAGLYT 77

                          90
                  ....*....|....*...
gi 386767223  509 CIAKSKVGVAEHSAKLNV 526
Cdd:cd05765    78 CTARNSGGLLRANFPLSV 95

Immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM) and similar proteins; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the first immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM). L1 belongs to the L1 subfamily of cell adhesion molecules (CAMs) and is comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region and an intracellular domain. L1 is primarily expressed in the nervous system and is involved in its development and function. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, or spastic paraplegia type 1, that involves abnormalities of axonal growth. This group also contains NrCAM [Ng(neuronglia)CAM-related cell adhesion molecule], which is primarily expressed in the nervous system, and human neurofascin. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lacks a C" strand.

Pssm-ID: 409396 [Multi-domain] Cd Length: 94 Bit Score: 39.31 E-value: 2.02e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  717 PPRWILEPTDkafaqgsDAKVECKADGFPKPQVTWKKAvgdtpGEYKDLKKSDNIRVEE--GTLHVDN---IQKTNEGYY 791
Cdd:cd05733     8 PKDYIVDPRD-------NITIKCEAKGNPQPTFRWTKD-----GKFFDPAKDPRVSMRRrsGTLVIDNhngGPEDYQGEY 75

                          90
                  ....*....|....*...
gi 386767223  792 LCEAINGIGSGLSAVIMI 809
Cdd:cd05733    76 QCYASNELGTAISNEIRL 93

Third immunoglobulin-like domain of the human WFIKKN (WAP, follistatin, immunoglobulin, Kunitz and NTR domain-containing protein), and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin-like domain of the human WFIKKN (WAP, follistatin, immunoglobulin, Kunitz and NTR domain-containing protein) and similar proteins. WFIKKN is a secreted protein that consists of multiple types of protease inhibitory modules, including two tandem Kunitz-type protease inhibitor-domains. The Ig superfamily is a heterogenous group of proteins built on a common fold comprised of a sandwich of two beta sheets. Members of the Ig superfamily are components of immunoglobulin, neuroglia, cell surface glycoproteins, such as T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, such as butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409422 [Multi-domain] Cd Length: 95 Bit Score: 39.45 E-value: 2.04e-03

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 386767223  538 KAIVAGETLIVTCPVAGYPIDSIVWER--DNRALPINRKQKVFPN------GTLIIENVeRNSDQATYTCVAKNQEG 606
Cdd:cd05765    10 QTVKVGETASFHCDVTGRPQPEITWEKqvPGKENLIMRPNHVRGNvvvtniGQLVIYNA-QPQDAGLYTCTARNSGG 85

C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin, and similar domains; member of the I-set IgSF domains; The members here are composed of the C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin and similar proteins, including Caenorhabditis elegans and Aplysia californica Twitchin, Drosophila melanogaster Projectin, and similar proteins. These are very large muscle proteins containing multiple immunoglobulin (Ig)-like and fibronectin type III (FN3) domains and a single kinase domain near the C-terminus. In humans these proteins are called Titin. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The Ig-like domain of the Twitchin is a member of the I-set IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins (titin, telokin, and twitchin), the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D.

Pssm-ID: 409541 [Multi-domain] Cd Length: 89 Bit Score: 39.24 E-value: 2.14e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  442 TMEPGPSVFLKCVAGGNPTPEISWELDGKKIANNDRYQVGQYVTVNGdvvsyLNITSVHANDGGLYKCIAKSKVGVAEHS 521
Cdd:cd20949    10 TVKEGQSATILCEVKGEPQPNVTWHFNGQPISASVADMSKYRILADG-----LLINKVTQDDTGEYTCRAYQVNSIASDM 84


                  ....*
gi 386767223  522 AKLNV 526
Cdd:cd20949    85 QERTV 89

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

Pssm-ID: 464026 [Multi-domain] Cd Length: 79 Bit Score: 38.92 E-value: 2.15e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223   636 GETMGIQCTvIKGDLPINITWVLNNHTLNSgdldvvigrmSSKSSTLNIdyiAAEHRGVYTCLARNQAG-ESSYSAELKV 714
Cdd:pfam13895   14 GEPVTLTCS-APGNPPPSYTWYKDGSAISS----------SPNFFTLSV---SAEDSGTYTCVARNGRGgKVSNPVELTV 79

Third immunoglobulin (Ig)-like domain of peroxidasin; The members here are composed of the third immunoglobulin (Ig)-like domain in peroxidasin. Peroxidasin has a peroxidase domain and interacting extracellular motifs containing four Ig-like domains. It has been suggested that peroxidasin is secreted and has functions related to the stabilization of the extracellular matrix. It may play a part in various other important processes such as removal and destruction of cells which have undergone programmed cell death and protection of the organism against non-self.

Pssm-ID: 143222 [Multi-domain] Cd Length: 74 Bit Score: 38.77 E-value: 2.19e-03

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 386767223  355 QTVDFgrpavfTCQYTGNPIKTVSWMKDGKAIG----H---SEPVLRIESVKKEDKGMYQCFVRNDQESAEASAEL 423
Cdd:cd05745     3 QTVDF------LCEAQGYPQPVIAWTKGGSQLSvdrrHlvlSSGTLRISRVALHDQGQYECQAVNIVGSQRTVAQL 72

Third immunoglobulin-like domain of the human WFIKKN (WAP, follistatin, immunoglobulin, Kunitz and NTR domain-containing protein), and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin-like domain of the human WFIKKN (WAP, follistatin, immunoglobulin, Kunitz and NTR domain-containing protein) and similar proteins. WFIKKN is a secreted protein that consists of multiple types of protease inhibitory modules, including two tandem Kunitz-type protease inhibitor-domains. The Ig superfamily is a heterogenous group of proteins built on a common fold comprised of a sandwich of two beta sheets. Members of the Ig superfamily are components of immunoglobulin, neuroglia, cell surface glycoproteins, such as T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, such as butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409422 [Multi-domain] Cd Length: 95 Bit Score: 39.45 E-value: 2.19e-03

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 386767223 1331 EDAKMPCLAVGAPQPEITWKiKGVEFSANDRMR---------VLPDGSLLIKSVNRQDAGDYSCHAENS 1390
Cdd:cd05765    16 ETASFHCDVTGRPQPEITWE-KQVPGKENLIMRpnhvrgnvvVTNIGQLVIYNAQPQDAGLYTCTARNS 83

Immunoglobulin domain of human Synaptic Adhesion-Like Molecule 5 (SALM5) and similar proteins; member of the I-set of IgSF domains; This group contains the immunoglobulin domain of human Synaptic Adhesion-Like Molecule 5 (SALM5) and similar proteins. The SALM (for synaptic adhesion-like molecules; also known as Lrfn for leucine-rich repeat and fibronectin type III domain containing) family of adhesion molecules consists of five known members: SALM1/Lrfn2, SALM2/Lrfn1, SALM3/Lrfn4, SALM4/Lrfn3, and SALM5/Lrfn5. SALMs share a similar domain structure, containing leucine-rich repeats (LRRs), an immunoglobulin (Ig) domain, and a fibronectin III (FNIII) domain, followed by a transmembrane domain and a C-terminal PDZ-binding motif. SALM5 is implicated in autism spectrum disorders (ASDs) and schizophrenia, induces presynaptic differentiation in contacting axons. SALM5 interacts with the Ig domains of LAR (Leukocyte common Antigen-Related) family receptor protein tyrosine phosphatases (LAR-RPTPs; LAR, PTPdelta, and PTPsigma). In addition, PTPdelta is implicated in ASDs, ADHD, bipolar disorder, and restless leg syndrome. Studies have shown that LAR-RPTPs are novel and splicing-dependent presynaptic ligands for SALM5, and that they mediate SALM5-dependent presynaptic differentiation. Furthermore, SALM5 maintains AMPA receptor (AMPAR)-mediated excitatory synaptic transmission through mechanisms involving the interaction of SALM5 with LAR-RPTPs. This group belongs to the I-set of immunoglobulin superfamily (IgSF) domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.

Pssm-ID: 409421 [Multi-domain] Cd Length: 88 Bit Score: 39.00 E-value: 2.21e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  815 PEFTEKLRNQTARRGEPAVLQCEAKGEKPIGILWNMNNMRLDPkNDNRYTIREEilstgvmSSLSIKRTERSDSALFTCV 894
Cdd:cd05764     1 PLITRHTHELRVLEGQRATLRCKARGDPEPAIHWISPEGKLIS-NSSRTLVYDN-------GTLDILITTVKDTGAFTCI 72

                          90
                  ....*....|....*.
gi 386767223  895 ATNAFGSDDASINMIV 910
Cdd:cd05764    73 ASNPAGEATARVELHI 88

Second immunoglobulin (Ig)-like domain of the receptor protein tyrosine phosphatase (RPTP)-F; member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain found in the receptor protein tyrosine phosphatase (RPTP)-F, also known as LAR. LAR belongs to the RPTP type IIa subfamily. Members of this subfamily are cell adhesion molecule-like proteins involved in central nervous system (CNS) development. They have large extracellular portions comprised of multiple Ig-like domains and two to nine fibronectin type III (FNIII) domains and a cytoplasmic portion having two tandem phosphatase domains.

Pssm-ID: 409400 [Multi-domain] Cd Length: 91 Bit Score: 39.22 E-value: 2.31e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  352 PPTQTVDFGRPAVFTCQYTGNPIKTVSWMKD----------GKAIGHSEPVLRIESVKKEDKGMYQCFVRND---QESAE 418
Cdd:cd05738     6 PQLKVVEKARTATMLCAASGNPDPEISWFKDflpvdtatsnGRIKQLRSGALQIENSEESDQGKYECVATNSagtRYSAP 85


                  ....*.
gi 386767223  419 ASAELK 424
Cdd:cd05738    86 ANLYVR 91

First immunoglobulin (Ig) domain of contactin; member of the I-set of (Ig) superfamily domains; The members here are composed of the first immunoglobulin (Ig) domain of contactins. Contactins are neural cell adhesion molecules and are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module via contacts between Ig domains 1 and 4, and between Ig domains 2 and 3. Contactin-2 (TAG-1, axonin-1) may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. This group also includes contactin-1 and contactin-5. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-5 is expressed specifically in the rat postnatal nervous system, peaking at about 3 weeks postnatal, and a lack of contactin-5 (NB-2) results in an impairment of neuronal activity in the rat auditory system. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma. This group belongs to the I-set of IgSF domains.

Pssm-ID: 409356 [Multi-domain] Cd Length: 96 Bit Score: 39.15 E-value: 2.31e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  438 FQEETMEPgpSVFLKCVAGGNPTPEISWELDGK--KIANNDRYQVgqyvtVNGDVVsylnITS-VHANDGGLYKCIAKSK 514
Cdd:cd04967    13 FPEDSDEK--KVALNCRARANPVPSYRWLMNGTeiDLESDYRYSL-----VDGTLV----ISNpSKAKDAGHYQCLATNT 81


                  ..
gi 386767223  515 VG 516
Cdd:cd04967    82 VG 83

Immunoglobulin (Ig)-like domain of titin and similar proteins; The members here are composed of the immunoglobulin (Ig)-like domain found in titin-like proteins and similar proteins. Titin (also called connectin) is a fibrous sarcomeric protein specifically found in vertebrate striated muscle. Titin is a giant protein; depending on isoform composition, it ranges from 2970 to 3700 kDa, and is of a length that spans half a sarcomere. Titin largely consists of multiple repeats of Ig-like and fibronectin type 3 (FN-III)-like domains. Titin connects the ends of myosin thick filaments to Z disks and extends along the thick filament to the H zone. It appears to function similarly to an elastic band, keeping the myosin filaments centered in the sarcomere during muscle contraction or stretching. Within the sarcomere, titin is also attached to or is associated with myosin binding protein C (MyBP-C). MyBP-C appears to contribute to the generation of passive tension by titin and like titin has repeated Ig-like and FN-III domains. Also included in this group are worm twitchin and insect projectin, thick filament proteins of invertebrate muscle which also have repeated Ig-like and FN-III domains.

Pssm-ID: 409406 [Multi-domain] Cd Length: 82 Bit Score: 38.72 E-value: 2.42e-03

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 386767223  369 YTGNPIKTVSWMKDGKAIGHSEPV----------LRIESVKKEDKGMYQCFVRNDQESAEASAELK 424
Cdd:cd05748    16 IKGRPTPTVTWSKDGQPLKETGRVqiettasstsLVIKNAKRSDSGKYTLTLKNSAGEKSATINVK 81

C5 immunoglobulin (Ig) domain of cardiac myosin binding protein C (MyBP-C); The members here are composed of the C5 immunoglobulin (Ig) domain of cardiac myosin binding protein C (MyBP-C). MyBP-C consists of repeated domains, Ig and fibronectin type 3, and various linkers. Three isoforms of MYBP-C exist: slow-skeletal (ssMyBP-C), fast-skeletal (fsMyBP-C), and cardiac (cMyBP-C). cMYBP-C has insertions between and inside domains and an additional cardiac-specific Ig domain at the N-terminus. For cMYBP_C an interaction has been demonstrated between this C5 domain and the Ig C8 domain.

Pssm-ID: 409475 Cd Length: 86 Bit Score: 38.67 E-value: 2.49e-03

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 386767223  370 TGNPIKTVSWMKDGKAIGHSEPVLRIESVK-----------KEDKGMYQCFVRNdqESAEASAELKL 425
Cdd:cd05894    20 SGEPAPTVTWSRGDKAFTATEGRVRVESYKdlssfviegaeREDEGVYTITVTN--PVGEDHASLFV 84

Fourth immunoglobulin (Ig)-like domain of L1, Ng-CAM (Neuron-glia CAM cell adhesion molecule), and NrCAM (Ng-CAM-related); The members here are composed of the fourth immunoglobulin (Ig)-like domain of L1, Ng-CAM (Neuron-glia CAM cell adhesion molecule), and NrCAM (Ng-CAM-related). These proteins belong to the L1 subfamily of cell adhesion molecules (CAMs) and are comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region and an intracellular domain. These molecules are primarily expressed in the nervous system. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, or spastic paraplegia type 1, that involves abnormalities of axonal growth.

Pssm-ID: 409367 [Multi-domain] Cd Length: 89 Bit Score: 38.58 E-value: 2.92e-03

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 386767223  829 GEPAVLQCEAKGE-KPIgILWNMNNMRLDP------KNDNRYTIREEILStgvmsslsikrteRSDSALFTCVATNAFG 900
Cdd:cd04978    14 GETGELICEAEGNpQPT-ITWRLNGVPIEPapedmrRTVDGRTLIFSNLQ-------------PNDTAVYQCNASNVHG 78

agrin-responsive first immunoglobulin-like domains (Ig1) of the MuSK ectodomain; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin-like domains (Ig1) of the Muscle-specific kinase (MuSK). MuSK is a receptor tyrosine kinase specifically expressed in skeletal muscle, where it plays a central role in the formation and maintenance of the neuromuscular junction (NMJ). MuSK is activated by agrin, a neuron-derived heparan sulfate proteoglycan. The activation of MUSK in myotubes regulates the formation of NMJs through the regulation of different processes including the specific expression of genes in subsynaptic nuclei, the reorganization of the actin cytoskeleton and the clustering of the acetylcholine receptors (AChR) in the postsynaptic membrane. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the MuSK lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409562 [Multi-domain] Cd Length: 92 Bit Score: 38.64 E-value: 2.95e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  342 VTAPLSakidPPTQTVDFGRPAVFTCQYTGNPIKTVSWMKDGKAI-----GHS----EPVLRIESVKKEDKGMYQCFVRN 412
Cdd:cd20970     3 ISTPQP----SFTVTAREGENATFMCRAEGSPEPEISWTRNGNLIiefntRYIvrenGTTLTIRNIRRSDMGIYLCIASN 78

Second Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the titin Z1z2 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409564 [Multi-domain] Cd Length: 91 Bit Score: 38.72 E-value: 2.96e-03

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 386767223  272 CQAQAFPLPIMRWYKfiEGTTRKQAvvLNDRVKQVSG--TLIIKDAVVEDSGKYLCVVNNSVGGES 335
Cdd:cd20972    23 CRVTGNPTPVVRWFC--EGKELQNS--PDIQIHQEGDlhSLIIAEAFEEDTGRYSCLATNSVGSDT 84

Immunoglobulin domain; Members of the immunoglobulin superfamily are found in hundreds of proteins of different functions. Examples include antibodies, the giant muscle kinase titin and receptor tyrosine kinases. Immunoglobulin-like domains may be involved in protein-protein and protein-ligand interactions.

Pssm-ID: 395002 Cd Length: 86 Bit Score: 38.72 E-value: 3.05e-03

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 386767223  1331 EDAKMPCLAV-GAPQPEITWKIKG-------VEFSANDRMRVLpdgSLLIKSVNRQDAGDYSCHAENSIAKDSIT 1397
Cdd:pfam00047   12 DSATLTCSAStGSPGPDVTWSKEGgtlieslKVKHDNGRTTQS---SLLISNVTKEDAGTYTCVVNNPGGSATLS 83

Fifth immunoglobulin (Ig) domain of contactin; The members here are composed of the fifth immunoglobulin (Ig) domain of contactins. Contactins are neural cell adhesion molecules and are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module via contacts between Ig domains 1 and 4, and between Ig domains 2 and 3. Contactin-2 (TAG-1, axonin-1) may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. This group also includes contactin-1 and contactin-5. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-5 is expressed specifically in the rat postnatal nervous system, peaking at about 3 weeks postnatal, and a lack of contactin-5 (NB-2) results in an impairment of neuronal activity in the rat auditory system. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma.

Pssm-ID: 409358 [Multi-domain] Cd Length: 89 Bit Score: 38.60 E-value: 3.17e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  826 ARRGEPAVLQCEAKGEKPIGILWNMNNMRLdpKNDNRYTIREEilstgvmSSLSIKRTERSDSALFTCVATNAFGSDDAS 905
Cdd:cd04969    14 AAKGGDVIIECKPKASPKPTISWSKGTELL--TNSSRICILPD-------GSLKIKNVTKSDEGKYTCFAVNFFGKANST 84


                  ....*
gi 386767223  906 INMIV 910
Cdd:cd04969    85 GSLSV 89

Second C-terminal immunoglobulin (Ig)-like domain of palladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of palladin. Palladin belongs to the palladin-myotilin-myopalladin family. Proteins belonging to this family contain multiple Ig-like domains and function as scaffolds, modulating actin cytoskeleton. Palladin binds to alpha-actinin ezrin, vasodilator-stimulated phosphoprotein VASP, SPIN90 (also known as DIP or mDia interacting protein), and Src. Palladin also binds F-actin directly, via its Ig3 domain. Palladin is expressed as several alternatively spliced isoforms, having various combinations of Ig-like domains, in a cell-type-specific manner. It has been suggested that palladin's different Ig-like domains may be specialized for distinct functions. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409582 Cd Length: 91 Bit Score: 38.93 E-value: 3.17e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  629 GDEASNSGETMGIQCTVIKGDLPiNITWVLNNHTLNSGDLDVVIGRMSSKSStLNIDYIAAEHRGVYTCLARNQAGESSY 708
Cdd:cd20990     8 GDLTVQEGKLCRMDCKVSGLPTP-DLSWQLDGKPIRPDSAHKMLVRENGVHS-LIIEPVTSRDAGIYTCIATNRAGQNSF 85


                  ....*.
gi 386767223  709 SAELKV 714
Cdd:cd20990    86 NLELVV 91

Third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM), and similar domains; The members here are composed of the third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM). L1 belongs to the L1 subfamily of cell adhesion molecules (CAMs) and is comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region and an intracellular domain. L1 is primarily expressed in the nervous system and is involved in its development and function. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, and spastic paraplegia type 1, that involves abnormalities of axonal growth. This group also contains the chicken neuron-glia cell adhesion molecule, Ng-CAM and human neurofascin.

Pssm-ID: 409394 [Multi-domain] Cd Length: 83 Bit Score: 38.54 E-value: 3.22e-03

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 386767223  354 TQTVDFGRPAVFTCQYTGNPIKTVSWMKDGKAIGHSEP-------VLRIESVKKEDKGMYQCFVRNDQESA 417
Cdd:cd05731     4 STMVLRGGVLLLECIAEGLPTPDIRWIKLGGELPKGRTkfenfnkTLKIENVSEADSGEYQCTASNTMGSA 74

Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor_like-1(FGFRL1); member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor like-1(FGFRL1). FGFRL1 is comprised of a signal peptide, three extracellular Ig-like modules, a transmembrane segment, and a short intracellular domain. FGFRL1 is expressed preferentially in skeletal tissues. Similar to FGF receptors, the expressed protein interacts specifically with heparin and with FGF2. FGFRL1 does not have a protein tyrosine kinase domain at its C-terminus; neither does its cytoplasmic domain appear to interact with a signaling partner. It has been suggested that FGFRL1 may not have any direct signaling function, but instead acts as a decoy receptor trapping FGFs and preventing them from binding other receptors.

Pssm-ID: 409442 Cd Length: 92 Bit Score: 38.69 E-value: 3.28e-03

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 386767223 1334 KMPCLAVGAPQPEITWKIKG---VEFSANDRMRvlPDGSLLIKSVNRQDAGDYSCHAENSIAKDSITHKLIV 1402
Cdd:cd05856    23 RLKCVASGNPRPDITWLKDNkplTPPEIGENKK--KKWTLSLKNLKPEDSGKYTCHVSNRAGEINATYKVDV 92

Third immunoglobulin (Ig)-like domain of fibroblast growth factor receptor 2 (FGFR2); member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig)-like domain of human fibroblast growth factor receptor 2 (FGFR2). Fibroblast growth factors (FGFs) participate in morphogenesis, development, angiogenesis, and wound healing. These FGF-stimulated processes are mediated by four FGFR tyrosine kinases (FGRF1-4). FGFRs are comprised of an extracellular portion consisting of three Ig-like domains, a transmembrane helix, and a cytoplasmic portion having protein tyrosine kinase activity. The highly conserved Ig-like domains 2 and 3, and the linker region between D2 and D3 define a general binding site for FGFs. FGFR2 is required for male sex determination. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409444 Cd Length: 105 Bit Score: 39.17 E-value: 3.32e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223 1326 TATFKEDAKMPCLAVGAPQPEITWkIKGVEFSANdrmRVLPDGS--------------------LLIKSVNRQDAGDYSC 1385
Cdd:cd05858    12 SVVVGTDAEFVCKVYSDAQPHIQW-LKHVEKNGS---KYGPDGLpyvevlktagvnttdkeievLYLRNVTFEDAGEYTC 87

                          90
                  ....*....|....*...
gi 386767223 1386 HAENSIAKDSITHKLIVL 1403
Cdd:cd05858    88 LAGNSIGISHHSAWLTVL 105

Immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM) and similar proteins; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the first immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM). L1 belongs to the L1 subfamily of cell adhesion molecules (CAMs) and is comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region and an intracellular domain. L1 is primarily expressed in the nervous system and is involved in its development and function. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, or spastic paraplegia type 1, that involves abnormalities of axonal growth. This group also contains NrCAM [Ng(neuronglia)CAM-related cell adhesion molecule], which is primarily expressed in the nervous system, and human neurofascin. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lacks a C" strand.

Pssm-ID: 409396 [Multi-domain] Cd Length: 94 Bit Score: 38.54 E-value: 3.63e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  432 PVI-RQAFQEETMEPGPSVFLKCVAGGNPTPEISWELDGK--KIANNDRyqvgqyVTVNGDVVSYlnitSVHANDG---- 504
Cdd:cd05733     1 PTItEQSPKDYIVDPRDNITIKCEAKGNPQPTFRWTKDGKffDPAKDPR------VSMRRRSGTL----VIDNHNGgped 70

                          90
                  ....*....|....*.
gi 386767223  505 --GLYKCIAKSKVGVA 518
Cdd:cd05733    71 yqGEYQCYASNELGTA 86

Fourth immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM); The members here are composed of the fourth immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM). L1 is comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region, and an intracellular domain. L1 is primarily expressed in the nervous system and is involved in its development and function. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, and spastic paraplegia type 1, that involves abnormalities of axonal growth. This group also contains the chicken neuron-glia cell adhesion molecule, Ng-CAM.

Pssm-ID: 409453 [Multi-domain] Cd Length: 89 Bit Score: 38.34 E-value: 4.08e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223   41 FLKEPTNRIdFSNSTGAEIECKASGNPMPEIIWiRSDGTAV-GDVPGLRQISSDGKLVFPPFRAEDyrqevhAQVYACLA 119
Cdd:cd05867     2 WTRRPQSHL-YGPGETARLDCQVEGIPTPNITW-SINGAPIeGTDPDPRRHVSSGALILTDVQPSD------TAVYQCEA 73

                          90
                  ....*....|....*
gi 386767223  120 RNQFGSI-ISRDVHV 133
Cdd:cd05867    74 RNRHGNLlANAHVHV 88

C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin, and similar domains; member of the I-set IgSF domains; The members here are composed of the C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin and similar proteins, including Caenorhabditis elegans and Aplysia californica Twitchin, Drosophila melanogaster Projectin, and similar proteins. These are very large muscle proteins containing multiple immunoglobulin (Ig)-like and fibronectin type III (FN3) domains and a single kinase domain near the C-terminus. In humans these proteins are called Titin. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The Ig-like domain of the Twitchin is a member of the I-set IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins (titin, telokin, and twitchin), the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D.

Pssm-ID: 409541 [Multi-domain] Cd Length: 89 Bit Score: 38.47 E-value: 4.12e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  719 RWILEPTDKAFAQGSDAKVECKADGFPKPQVTWKKAVGDTPGEYKDLKKsdnIRVEEGTLHVDNIQKTNEGYYLCEA--I 796
Cdd:cd20949     1 TFTENAYVTTVKEGQSATILCEVKGEPQPNVTWHFNGQPISASVADMSK---YRILADGLLINKVTQDDTGEYTCRAyqV 77


                  ....*
gi 386767223  797 NGIGS 801
Cdd:cd20949    78 NSIAS 82

Immunoglobulin (Ig)-like domain of titin and similar proteins; The members here are composed of the immunoglobulin (Ig)-like domain found in titin-like proteins and similar proteins. Titin (also called connectin) is a fibrous sarcomeric protein specifically found in vertebrate striated muscle. Titin is a giant protein; depending on isoform composition, it ranges from 2970 to 3700 kDa, and is of a length that spans half a sarcomere. Titin largely consists of multiple repeats of Ig-like and fibronectin type 3 (FN-III)-like domains. Titin connects the ends of myosin thick filaments to Z disks and extends along the thick filament to the H zone. It appears to function similarly to an elastic band, keeping the myosin filaments centered in the sarcomere during muscle contraction or stretching. Within the sarcomere, titin is also attached to or is associated with myosin binding protein C (MyBP-C). MyBP-C appears to contribute to the generation of passive tension by titin and like titin has repeated Ig-like and FN-III domains. Also included in this group are worm twitchin and insect projectin, thick filament proteins of invertebrate muscle which also have repeated Ig-like and FN-III domains.

Pssm-ID: 409406 [Multi-domain] Cd Length: 82 Bit Score: 37.95 E-value: 4.41e-03

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 386767223  275 QAFPLPIMRWYKfiEGTTRKQAVVLNDRVKQVSGTLIIKDAVVEDSGKY-LCVVNNSvgGESVETV 339
Cdd:cd05748    17 KGRPTPTVTWSK--DGQPLKETGRVQIETTASSTSLVIKNAKRSDSGKYtLTLKNSA--GEKSATI 78

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

Pssm-ID: 464026 [Multi-domain] Cd Length: 79 Bit Score: 37.76 E-value: 4.54e-03

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 386767223  1330 KEDAKMPCLAVGAPQPEITWKIKGVEFSandrmrvlPDGSLLIKSVNRQDAGDYSCHAENS-IAKDSITHKLIV 1402
Cdd:pfam13895   14 GEPVTLTCSAPGNPPPSYTWYKDGSAIS--------SSPNFFTLSVSAEDSGTYTCVARNGrGGKVSNPVELTV 79

Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor_like-1(FGFRL1); member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor like-1(FGFRL1). FGFRL1 is comprised of a signal peptide, three extracellular Ig-like modules, a transmembrane segment, and a short intracellular domain. FGFRL1 is expressed preferentially in skeletal tissues. Similar to FGF receptors, the expressed protein interacts specifically with heparin and with FGF2. FGFRL1 does not have a protein tyrosine kinase domain at its C-terminus; neither does its cytoplasmic domain appear to interact with a signaling partner. It has been suggested that FGFRL1 may not have any direct signaling function, but instead acts as a decoy receptor trapping FGFs and preventing them from binding other receptors.

Pssm-ID: 409442 Cd Length: 92 Bit Score: 38.30 E-value: 4.58e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  534 QMEKKAIV--AGETLIVTCPVAGYPIDSIVWERDNRALPI-----NRKQKVfpngTLIIENVeRNSDQATYTCVAKNQEG 606
Cdd:cd05856     8 KMRRRVIArpVGSSVRLKCVASGNPRPDITWLKDNKPLTPpeigeNKKKKW----TLSLKNL-KPEDSGKYTCHVSNRAG 82

Third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM), and similar domains; The members here are composed of the third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM). L1 belongs to the L1 subfamily of cell adhesion molecules (CAMs) and is comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region and an intracellular domain. L1 is primarily expressed in the nervous system and is involved in its development and function. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, and spastic paraplegia type 1, that involves abnormalities of axonal growth. This group also contains the chicken neuron-glia cell adhesion molecule, Ng-CAM and human neurofascin.

Pssm-ID: 409394 [Multi-domain] Cd Length: 83 Bit Score: 37.77 E-value: 4.77e-03

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 386767223  272 CQAQAFPLPIMRWYKfIEGTTRKQAVVLNDRVKqvsgTLIIKDAVVEDSGKYLCVVNNSVGgeSVETVLTVT 343
Cdd:cd05731    17 CIAEGLPTPDIRWIK-LGGELPKGRTKFENFNK----TLKIENVSEADSGEYQCTASNTMG--SARHTISVT 81

C-terminal immunoglobulin (Ig)-like domain of M-protein; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of M-protein (also known as myomesin-2). M-protein is a structural protein localized to the M-band, a transverse structure in the center of the sarcomere, and is a candidate for M-band bridges. M-protein is modular consisting mainly of repetitive IG-like and fibronectin type III (FnIII) domains and has a muscle-type specific expression pattern. M-protein is present in fast fibers.

Pssm-ID: 143299 Cd Length: 92 Bit Score: 37.97 E-value: 5.17e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223 1318 IASFDDTFTATFKEDAKMPCLAVGAPQPEITWKIKGVEFSANDRMRVLPD----GSLLIKSVNRQDAGDYSCHAENSIAK 1393
Cdd:cd05891     4 IGGLPDVVTIMEGKTLNLTCTVFGNPDPEVIWFKNDQDIELSEHYSVKLEqgkyASLTIKGVTSEDSGKYSINVKNKYGG 83


                  ...
gi 386767223 1394 DSI 1396
Cdd:cd05891    84 ETV 86

Second immunoglobulin (Ig)-like domain of a Follistatin-related protein 5, and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig)-like domain found in human Follistatin-related protein 5 (FSTL5) and a follistatin-like molecule encoded by the CNS-related Mahya gene. Mahya genes have been retained in certain Bilaterian branches during evolution. They are conserved in Hymenoptera and Deuterostomes, but are absent from other metazoan species such as fruit fly and nematode. Mahya proteins are secretory, with a follistatin-like domain (Kazal-type serine/threonine protease inhibitor domain and EF-hand calcium-binding domain), two Ig-like domains, and a novel C-terminal domain. Mahya may be involved in learning and memory and in processing of sensory information in Hymenoptera and vertebrates. Follistatin is a secreted, multidomain protein that binds activins with high affinity and antagonizes their signaling.

Pssm-ID: 409399 [Multi-domain] Cd Length: 93 Bit Score: 38.01 E-value: 5.39e-03

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 386767223  259 SYARVVDQSFAMLCQAQAFPLPIMRWYKFIEGTTRKQAVVLNdrvKQVSGT-LIIKDAVVEDSGKYLCVVNNSVG 332
Cdd:cd05736     9 FQAKEPGVEASLRCHAEGIPLPRVQWLKNGMDINPKLSKQLT---LIANGSeLHISNVRYEDTGAYTCIAKNEGG 80

First immunoglobulin (Ig) domain of contactin-2; member of the I-set of Ig superfamily domains; The members here are composed of the first immunoglobulin (Ig) domain of the neural cell adhesion molecule contactin-2-like. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-2 (TAG-1, axonin-1) facilitates cell adhesion by homophilic binding between molecules in apposed membranes. It may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module by contacts between IG domains 1 and 4, and domains 2 and 3. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-2 is also expressed in retinal amacrine cells in the developing chick retina, corresponding to the period of formation and maturation of AC processes. This group belongs to the I-set of IgSF domains.

Pssm-ID: 409437 [Multi-domain] Cd Length: 97 Bit Score: 38.37 E-value: 5.47e-03

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 386767223  272 CQAQAFPLPIMRWYkfIEGTTRKQAVvlNDRVKQVSGTLIIKDAV-VEDSGKYLCVVNNSVG 332
Cdd:cd05850    27 CRARASPPATYRWK--MNGTELKMEP--DSRYRLVAGNLVISNPVkAKDAGSYQCLASNRRG 84

Third immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the Constant 2 (C2)-set of IgSF domains; The members here are composed of the third immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. This group belongs to the C2-set of IgSF domains, having A, B, and E strands in one beta-sheet and A', G, F, C, and C' in the other. Unlike other Ig domain sets, the C2-set lacks the D strand.

Pssm-ID: 409549 [Multi-domain] Cd Length: 88 Bit Score: 37.90 E-value: 5.50e-03

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 386767223   57 AEIECKASGNPMPEIIWiRSDGTAVGDvPGLRQISSDGKLVFPPFRAEDyrqevhAQVYACLARN 121
Cdd:cd20957    19 AVFNCSVTGNPIHTVLW-MKDGKPLGH-SSRVQILSEDVLVIPSVKRED------KGMYQCFVRN 75

C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin, and similar domains; member of the I-set IgSF domains; The members here are composed of the C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin and similar proteins, including Caenorhabditis elegans and Aplysia californica Twitchin, Drosophila melanogaster Projectin, and similar proteins. These are very large muscle proteins containing multiple immunoglobulin (Ig)-like and fibronectin type III (FN3) domains and a single kinase domain near the C-terminus. In humans these proteins are called Titin. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The Ig-like domain of the Twitchin is a member of the I-set IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins (titin, telokin, and twitchin), the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D.

Pssm-ID: 409541 [Multi-domain] Cd Length: 89 Bit Score: 38.08 E-value: 5.63e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  350 IDPPTQTVDFGRPAVFTCQYTGNPIKTVSWMKDGKAIGHSEPV----------LRIESVKKEDKGMYQCFVRNDQESAEA 419
Cdd:cd20949     4 ENAYVTTVKEGQSATILCEVKGEPQPNVTWHFNGQPISASVADmskyriladgLLINKVTQDDTGEYTCRAYQVNSIASD 83


                  ....
gi 386767223  420 SAEL 423
Cdd:cd20949    84 MQER 87

Eighth immunoglobulin (Ig)-like domain of human myosin light-chain kinase (MLCK) and similar protein; member of the I-set of IgSF domains; The members here are composed of the eighth immunoglobulin (Ig)-like domain of human myosin light-chain kinase (MLCK) and similar proteins. Myosin light-chain kinase (MLCK) is a key regulator of different forms of cell motility involving actin and myosin II. Agonist stimulation of smooth muscle cells increases cytosolic Ca2+ which binds calmodulin. This Ca2+-calmodulin complex in turn binds to and activates MLCK. Activated MLCK leads to the phosphorylation of the 20 kDa myosin regulatory light chain (RLC) of myosin II and the stimulation of actin-activated myosin MgATPase activity. MLCK is widely present in vertebrate tissues; it phosphorylates the 20 kDa RLC of both smooth and nonmuscle myosin II. Phosphorylation leads to the activation of the myosin motor domain and altered structural properties of myosin II. In smooth muscle MLCK it is involved in initiating contraction. In nonmuscle cells, MLCK may participate in cell division and cell motility; it has been suggested MLCK plays a role in cardiomyocyte differentiation and contraction through regulation of nonmuscle myosin II.

Pssm-ID: 409419 Cd Length: 99 Bit Score: 38.40 E-value: 5.66e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  620 PPQIRPFDfGDEASNSGETMGIQCTVIkGDLPINITWVLNNHTLNSGDLDVVIGrmSSKSSTLNIDYIAAEHRGVYTCLA 699
Cdd:cd05762     1 PPQIIQFP-EDMKVRAGESVELFCKVT-GTQPITCTWMKFRKQIQEGEGIKIEN--TENSSKLTITEGQQEHCGCYTLEV 76

                          90
                  ....*....|....*
gi 386767223  700 RNQAGESSYSAELKV 714
Cdd:cd05762    77 ENKLGSRQAQVNLTV 91

Immunoglobulin I-set domain of the Leucine-rich repeat and immunoglobin-like domain-containing protein 1 (Lingo-1); The members here are composed of the immunoglobulin I-set (IgI) domain of the Leucine-rich repeat and immunoglobin-like domain-containing protein 1 (Lingo-1). Human Lingo-1 is a central nervous system-specific transmembrane glycoprotein also known as LERN-1, which functions as a negative regulator of neuronal survival, axonal regeneration, and oligodendrocyte differentiation and myelination. Lingo-1 is a key component of the Nogo receptor signaling complex (RTN4R/NGFR) in RhoA activation responsible for some inhibition of axonal regeneration by myelin-associated factors. The ligand-binding ectodomain of human Lingo-1 contains a bimodular, kinked structure composed of leucine-rich repeat (LRR) and immunoglobulin (Ig)-like modules. Diseases associated with Lingo-1 include mental retardation, autosomal recessive 64 and essential tremor. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the Lingo-1 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409561 Cd Length: 92 Bit Score: 38.14 E-value: 6.15e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  439 QEETMEPGPSVFLKCVAGGNPTPEISWELDGK---KIANNDRYQVGQYVTvngdvvsyLNITSVHANDGGLYKCIAKSKV 515
Cdd:cd20969    10 QQVFVDEGHTVQFVCRADGDPPPAILWLSPRKhlvSAKSNGRLTVFPDGT--------LEVRYAQVQDNGTYLCIAANAG 81

                          90
                  ....*....|.
gi 386767223  516 GVAEHSAKLNV 526
Cdd:cd20969    82 GNDSMPAHLHV 92

First C-terminal immunoglobulin (Ig)-like domain of palladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of palladin. Palladin belongs to the palladin-myotilin-myopalladin family. Proteins belonging to this family contain multiple Ig-like domains and function as scaffolds, modulating actin cytoskeleton. Palladin binds to alpha-actinin ezrin, vasodilator-stimulated phosphoprotein VASP, SPIN90 (also known as DIP or mDia interacting protein), and Src. Palladin also binds F-actin directly, via its Ig3 domain. Palladin is expressed as several alternatively spliced isoforms, having various combinations of Ig-like domains, in a cell-type-specific manner. It has been suggested that palladin's different Ig-like domains may be specialized for distinct functions. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409474 Cd Length: 92 Bit Score: 37.77 E-value: 6.39e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  432 PVIRQAFQEETMEPGPSVFLKCVAGGNPTPEISWELDGKKIA-NNDRYQVGQYVtvngDVVSYLNITSVHANDGGLYKCI 510
Cdd:cd05893     1 PFFEMKLKHYKIFEGMPVTFTCRVAGNPKPKIYWFKDGKQISpKSDHYTIQRDL----DGTCSLHTTASTLDDDGNYTIM 76

                          90
                  ....*....|....*.
gi 386767223  511 AKSKVGVAEHSAKLNV 526
Cdd:cd05893    77 AANPQGRISCTGRLMV 92

Immunoglobulin (Ig)-like domain of titin and similar proteins; The members here are composed of the immunoglobulin (Ig)-like domain found in titin-like proteins and similar proteins. Titin (also called connectin) is a fibrous sarcomeric protein specifically found in vertebrate striated muscle. Titin is a giant protein; depending on isoform composition, it ranges from 2970 to 3700 kDa, and is of a length that spans half a sarcomere. Titin largely consists of multiple repeats of Ig-like and fibronectin type 3 (FN-III)-like domains. Titin connects the ends of myosin thick filaments to Z disks and extends along the thick filament to the H zone. It appears to function similarly to an elastic band, keeping the myosin filaments centered in the sarcomere during muscle contraction or stretching. Within the sarcomere, titin is also attached to or is associated with myosin binding protein C (MyBP-C). MyBP-C appears to contribute to the generation of passive tension by titin and like titin has repeated Ig-like and FN-III domains. Also included in this group are worm twitchin and insect projectin, thick filament proteins of invertebrate muscle which also have repeated Ig-like and FN-III domains.

Pssm-ID: 409406 [Multi-domain] Cd Length: 82 Bit Score: 37.18 E-value: 7.26e-03

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 386767223  743 GFPKPQVTWKKavGDTPgeykdLKKSDNIRVEEG----TLHVDNIQKTNEGYYLCEAINGIGS 801
Cdd:cd05748    18 GRPTPTVTWSK--DGQP-----LKETGRVQIETTasstSLVIKNAKRSDSGKYTLTLKNSAGE 73

Immunoglobulin domain I1 of the titin I-band and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin domain I1 of the titin I-band and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. The two sheets are linked together by a conserved disulfide bond between B strand and F strand. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The Ig I1 domain of the titin I-band is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409543 [Multi-domain] Cd Length: 94 Bit Score: 37.79 E-value: 7.69e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  531 YIRQMEKKAIVAGETLIVTCPVAGYPIDSIVWERDNRAL---PINRKQKVFPNG---TLIIENVERNsDQATYTCVAKNQ 604
Cdd:cd20951     3 FIIRLQSHTVWEKSDAKLRVEVQGKPDPEVKWYKNGVPIdpsSIPGKYKIESEYgvhVLHIRRVTVE-DSAVYSAVAKNI 81

                          90
                  ....*....|...
gi 386767223  605 EGY-SARGSLEVQ 616
Cdd:cd20951    82 HGEaSSSASVVVE 94

T-cell surface glycoprotein CD3 delta chain; This is an immunoglobulin-like domain. It is found on the T-cell surface glycoprotein CD3 delta chain. CD3delta and CD3epsilon complex together as part of the T-cell receptor complex.

Pssm-ID: 465231 Cd Length: 63 Bit Score: 36.84 E-value: 7.79e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 386767223   364 VF-TCQYTGNPIKtvsWMKDGKAI-GHSEPVLRIESVKKEDKGMYQCFVRNDQES 416
Cdd:pfam16680    4 VLlTCNSSSKSIT---WLKDGKGIkSTNTKTLDLGKFSEDPRGLYQCQGEKKKSS 55

First C-terminal immunoglobulin (Ig)-like domain of palladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of palladin. Palladin belongs to the palladin-myotilin-myopalladin family. Proteins belonging to this family contain multiple Ig-like domains and function as scaffolds, modulating actin cytoskeleton. Palladin binds to alpha-actinin ezrin, vasodilator-stimulated phosphoprotein VASP, SPIN90 (also known as DIP or mDia interacting protein), and Src. Palladin also binds F-actin directly, via its Ig3 domain. Palladin is expressed as several alternatively spliced isoforms, having various combinations of Ig-like domains, in a cell-type-specific manner. It has been suggested that palladin's different Ig-like domains may be specialized for distinct functions. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409474 Cd Length: 92 Bit Score: 37.38 E-value: 8.57e-03

                          10        20
                  ....*....|....*....|....*..
gi 386767223  360 GRPAVFTCQYTGNPIKTVSWMKDGKAI 386
Cdd:cd05893    15 GMPVTFTCRVAGNPKPKIYWFKDGKQI 41

Immunoglobulin (Ig)-like I-set domain of Neural Cell Adhesion Molecule 2 (NCAM-2); The members here are composed of the fourth Ig domain of Neural Cell Adhesion Molecule NCAM-2 (also known as OCAM/mamFas II and RNCAM). NCAM-2 is organized similarly to NCAM, including five N-terminal Ig-like domains and two fibronectin type III domains. NCAM-2 is differentially expressed in the developing and mature olfactory epithelium (OE), and may function like NCAM, as an adhesion molecule. One of the unique features of I-set domains is the lack of a C" strand. The structures of this group show that the Ig domain lacks this strand and thus is a member of the I-set of Ig domains.

Pssm-ID: 143278 [Multi-domain] Cd Length: 98 Bit Score: 37.65 E-value: 8.78e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767223  820 KLRNQTARRGEPAVLQCEAKGEKPIGILWN-----MNNMRLDPKNDNRYTIREEILStgvmSSLSIKRTERSDSALFTCV 894
Cdd:cd05870     7 QLKNETTVENGAATLSCKAEGEPIPEITWKrasdgHTFSEGDKSPDGRIEVKGQHGE----SSLHIKDVKLSDSGRYDCE 82

                          90
                  ....*....|..
gi 386767223  895 ATNAFGSDDASI 906
Cdd:cd05870    83 AASRIGGHQKSM 94

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

Pssm-ID: 464026 [Multi-domain] Cd Length: 79 Bit Score: 36.99 E-value: 9.75e-03

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 386767223   266 QSFAMLCQAQAFPLPIMRWYKfiegttrkqavvlNDRVKQVSGTLIIKDAVVEDSGKYLCVVNNSVGGEsVETVLTVT 343
Cdd:pfam13895   15 EPVTLTCSAPGNPPPSYTWYK-------------DGSAISSSPNFFTLSVSAEDSGTYTCVARNGRGGK-VSNPVELT 78