NCBI Conserved Domain Search

Fibronectin type 3 domain [General function prediction only];

Pssm-ID: 442628 [Multi-domain] Cd Length: 603 Bit Score: 83.13 E-value: 1.12e-15

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400 1486 TYQFRIQATNDLGPSAFSRESVIVRTLPAAPAVGVGGLKVVPITTTSVRVQWSALETALWNGDASTGGYRILyqqlsdFP 1565
Cdd:COG3401     3 SSYLTSLDAGIAASAAANTAVNALSKAGGSGKTILVYLAVVLSVTTKESPGTLLVAAGLSSGGGLGTGGRAG------TT 76

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400 1566 TALQSTPKTDVHGINENSVVLSDLQQDRNYEIVVLPFNSQGPGPATPPAAVYVGEAVPTgepravdaaPISSTEVRLLWK 1645
Cdd:COG3401    77 SGVAAVAVAAAPPTATGLTTLTGSGSVGGATNTGLTSSDEVPSPAVGTATTATAVAGGA---------ATAGTYALGAGL 147

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400 1646 PPKQSMQNGDILGYKIYYLVTYSPQALEPGRKWEEEIEVVSATATSHSLVFLDKFTEYRIQLLAFNPAGDGPRSAPITVK 1725
Cdd:COG3401   148 YGVDGANASGTTASSVAGAGVVVSPDTSATAAVATTSLTVTSTTLVDGGGDIEPGTTYYYRVAATDTGGESAPSNEVSVT 227

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400 1726 TLPGVPSAPLHLRFSDITMQSLEVTWDPPKflNGEILGYLVtYETTEENEKFSKqVKqKVSNTTLRVQNLEEEVTYTFTV 1805
Cdd:COG3401   228 TPTTPPSAPTGLTATADTPGSVTLSWDPVT--ESDATGYRV-YRSNSGDGPFTK-VA-TVTTTSYTDTGLTNGTTYYYRV 302

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400 1806 RAQTSVDYGPGISENVTTGPQDGSPVAPRDLILTKTLS-SVEMHWinGPSGRGPILGYLIEAKKRDDSRWTKIEQTRKGm 1884
Cdd:COG3401   303 TAVDAAGNESAPSNVVSVTTDLTPPAAPSGLTATAVGSsSITLSW--TASSDADVTGYNVYRSTSGGGTYTKIAETVTT- 379

                         410       420       430
                  ....*....|....*....|....*....|
gi 599137400 1885 mQDFTVSyhILMPSTAYTFRVIAYNRYGIS 1914
Cdd:COG3401   380 -TSYTDT--GLTPGTTYYYKVTAVDAAGNE 406

Fibronectin type 3 domain [General function prediction only];

Pssm-ID: 442628 [Multi-domain] Cd Length: 603 Bit Score: 82.74 E-value: 1.36e-15

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400 1429 IQAHQITFSWTPGRDGFAPLRYYTVEMRENEGRWQPLPERVDPSLSSFTAVGLRPYmTYQFRIQATNDLGPSAFSRESVI 1508
Cdd:COG3401    36 ILVYLAVVLSVTTKESPGTLLVAAGLSSGGGLGTGGRAGTTSGVAAVAVAAAPPTA-TGLTTLTGSGSVGGATNTGLTSS 114

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400 1509 VRTLPAAPAVGVGGLKVVPITTTSVRVQWSALETALWNGDASTGGYRILYQQLSDFPTALQSTPKTDVHGINENSVVLSD 1588
Cdd:COG3401   115 DEVPSPAVGTATTATAVAGGAATAGTYALGAGLYGVDGANASGTTASSVAGAGVVVSPDTSATAAVATTSLTVTSTTLVD 194

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400 1589 ----LQQDRNYEIVVLPFNSQGPGPATPPAAVYVGEAVPTgEPRAVDAAPISSTEVRLLWKPPKqsmqNGDILGYKIYyl 1664
Cdd:COG3401   195 gggdIEPGTTYYYRVAATDTGGESAPSNEVSVTTPTTPPS-APTGLTATADTPGSVTLSWDPVT----ESDATGYRVY-- 267

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400 1665 vtyspQALEPGRKWEEeieVVSATATSHSLVFLDKFTEYRIQLLAFNPAGD-GPRSAPITVKTLPGVPSAPLHLRFSDIT 1743
Cdd:COG3401   268 -----RSNSGDGPFTK---VATVTTTSYTDTGLTNGTTYYYRVTAVDAAGNeSAPSNVVSVTTDLTPPAAPSGLTATAVG 339

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400 1744 MQSLEVTWDPPKflNGEILGYLVtYETTEENEKFSKqVKQKVSNTTLRVQNLEEEVTYTFTVRA---------QTSVDYG 1814
Cdd:COG3401   340 SSSITLSWTASS--DADVTGYNV-YRSTSGGGTYTK-IAETVTTTSYTDTGLTPGTTYYYKVTAvdaagnesaPSEEVSA 415

                         410       420       430       440       450       460
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 599137400 1815 PGISENVTTGPQDGSPVAPRDLILTKTLSSVEMHWINGPSGRGPILGYLIEAKKRDDSRWTKIEQT 1880
Cdd:COG3401   416 TTASAASGESLTASVDAVPLTDVAGATAAASAASNPGVSAAVLADGGDTGNAVPFTTTSSTVTATT 481

Fibronectin type 3 domain [General function prediction only];

Pssm-ID: 442628 [Multi-domain] Cd Length: 603 Bit Score: 82.36 E-value: 1.79e-15

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400  863 PSLIDPLAEQTAILGGLEKFTEYNISVLCFTDPGDGVASSQVAVMTMDDVPDEVTGLHFDDVSDRSVKVLWAPPRASNgi 942
Cdd:COG3401   183 TSLTVTSTTLVDGGGDIEPGTTYYYRVAATDTGGESAPSNEVSVTTPTTPPSAPTGLTATADTPGSVTLSWDPVTESD-- 260

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400  943 LTGYTVRYqvkdRPDTLKSFNL--TADDTELTVNQLQATTHYWFEIVAWTRVGSGIPKTATIQSGVEPVLPHAPTALALS 1020
Cdd:COG3401   261 ATGYRVYR----SNSGDGPFTKvaTVTTTSYTDTGLTNGTTYYYRVTAVDAAGNESAPSNVVSVTTDLTPPAAPSGLTAT 336

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400 1021 NIEAFSVVLQFTPGFDGNssITKWKVEGQTARNMTWFTICEinDPDAETLTVTGLVPFTQYRLRLSASNVVG----SSKP 1096
Cdd:COG3401   337 AVGSSSITLSWTASSDAD--VTGYNVYRSTSGGGTYTKIAE--TVTTTSYTDTGLTPGTTYYYKVTAVDAAGnesaPSEE 412

                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 599137400 1097 SEATKDFQTIQARPKHPPFNVTVRAMSAQQLRVRWIPLQQTEWYGNPRGYNISYKQLVKTPGTIKYVP 1164
Cdd:COG3401   413 VSATTASAASGESLTASVDAVPLTDVAGATAAASAASNPGVSAAVLADGGDTGNAVPFTTTSSTVTAT 480

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: 72.91 E-value: 2.85e-15

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400 1731 PSAPLHLRFSDITMQSLEVTWDPPKFLNGEILGYLVTYETTEENEkFSKQVKQKVSNTTLRVQNLEEEVTYTFTVRAQTS 1810
Cdd:cd00063     1 PSPPTNLRVTDVTSTSVTLSWTPPEDDGGPITGYVVEYREKGSGD-WKEVEVTPGSETSYTLTGLKPGTEYEFRVRAVNG 79

                          90
                  ....*....|....
gi 599137400 1811 VDYG-PGISENVTT 1823
Cdd:cd00063    80 GGESpPSESVTVTT 93

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: 72.53 E-value: 4.87e-15

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400  589 PFPPSNVKVErlpEPQQRSINVSWTPGFDGNSPISKFIIQRREVSELGPvpdpllnwiTELSNVSADQRWILLENLKAAT 668
Cdd:cd00063     1 PSPPTNLRVT---DVTSTSVTLSWTPPEDDGGPITGYVVEYREKGSGDW---------KEVEVTPGSETSYTLTGLKPGT 68

                          90       100
                  ....*....|....*....|....
gi 599137400  669 VYQFRVSAVNRVGEGSPSEPSNVV 692
Cdd:cd00063    69 EYEFRVRAVNGGGESPPSESVTVT 92

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: 72.45 E-value: 5.59e-15

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400  360 PLFFTPMRAETFGEfGGQVQLTCDVVGEPTPQVKWFRNAESVDAHIESGRYTLNTD---NTLVIKKLILDDAAMFQCLAI 436
Cdd:cd20951     1 PEFIIRLQSHTVWE-KSDAKLRVEVQGKPDPEVKWYKNGVPIDPSSIPGKYKIESEygvHVLHIRRVTVEDSAVYSAVAK 79

                          90
                  ....*....|....*
gi 599137400  437 NEAGENSASTWLRVK 451
Cdd:cd20951    80 NIHGEASSSASVVVE 94

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 71.90 E-value: 6.53e-15

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400   495 QIIQPPVDTTVLLGLTATLQCKVSSDPsvPYNIDWYREGQsstPISNSQRIGVQADGQ---LEIQAVRASDVGSYACVVT 571
Cdd:pfam07679    2 KFTQKPKDVEVQEGESARFTCTVTGTP--DPEVSWFKDGQ---PLRSSDRFKVTYEGGtytLTISNVQPDDSGKYTCVAT 76

                           90
                   ....*....|....
gi 599137400   572 SPGGNETRAARLSV 585
Cdd:pfam07679   77 NSAGEAEASAELTV 90

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 70.29 E-value: 1.80e-14

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 599137400    72 PRFTTHPSSSgsIVSEGSTKILQCHALGYPQPTYRWLKDGVPVGDFSSSQFY--------RFHSTRREDAGSYQCIARN 142
Cdd:pfam13927    2 PVITVSPSSV--TVREGETVTLTCEATGSPPPTITWYKNGEPISSGSTRSRSlsgsnstlTISNVTRSDAGTYTCVASN 78

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: 69.06 E-value: 7.08e-14

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400 1416 PQAPSVPQISrsQIQAHQITFSWTPGRDGFAPLRYYTVEMRE-NEGRWQPLpERVDPSLSSFTAVGLRPYMTYQFRIQAT 1494
Cdd:cd00063     1 PSPPTNLRVT--DVTSTSVTLSWTPPEDDGGPITGYVVEYREkGSGDWKEV-EVTPGSETSYTLTGLKPGTEYEFRVRAV 77

                          90
                  ....*....|....*..
gi 599137400 1495 NDLGPSAFSrESVIVRT 1511
Cdd:cd00063    78 NGGGESPPS-ESVTVTT 93

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 68.82 E-value: 7.91e-14

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400    72 PRFTTHPSSSgsIVSEGSTKILQCHALGYPQPTYRWLKDGVPVgdfSSSQFYRFHST-----------RREDAGSYQCIA 140
Cdd:pfam07679    1 PKFTQKPKDV--EVQEGESARFTCTVTGTPDPEVSWFKDGQPL---RSSDRFKVTYEggtytltisnvQPDDSGKYTCVA 75

                           90
                   ....*....|
gi 599137400   141 RNDAGSIFSE 150
Cdd:pfam07679   76 TNSAGEAEAS 85

Fibronectin type III domain;

Pssm-ID: 394996 [Multi-domain] Cd Length: 85 Bit Score: 68.60 E-value: 8.82e-14

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400  1732 SAPLHLRFSDITMQSLEVTWDPPKFLNGEILGYLVTYETTEENEkfsKQVKQKVSNTTLR--VQNLEEEVTYTFTVRAQT 1809
Cdd:pfam00041    1 SAPSNLTVTDVTSTSLTVSWTPPPDGNGPITGYEVEYRPKNSGE---PWNEITVPGTTTSvtLTGLKPGTEYEVRVQAVN 77


                   ....*.
gi 599137400  1810 SVDYGP 1815
Cdd:pfam00041   78 GGGEGP 83

Fibronectin type III domain;

Pssm-ID: 394996 [Multi-domain] Cd Length: 85 Bit Score: 67.44 E-value: 2.16e-13

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400   591 PPSNVKVErlpEPQQRSINVSWTPGFDGNSPISKFIIQRREVSELGPvpdpllnWITElsNVSADQRWILLENLKAATVY 670
Cdd:pfam00041    2 APSNLTVT---DVTSTSLTVSWTPPPDGNGPITGYEVEYRPKNSGEP-------WNEI--TVPGTTTSVTLTGLKPGTEY 69

                           90
                   ....*....|....*.
gi 599137400   671 QFRVSAVNRVGEGSPS 686
Cdd:pfam00041   70 EVRVQAVNGGGEGPPS 85

Fibronectin type III domain;

Pssm-ID: 394996 [Multi-domain] Cd Length: 85 Bit Score: 66.28 E-value: 5.15e-13

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400   914 DEVTGLHFDDVSDRSVKVLWAPPRASNGILTGYTVRYQVKDRPDTLKSFNLTADDTELTVNQLQATTHYWFEIVAWTRVG 993
Cdd:pfam00041    1 SAPSNLTVTDVTSTSLTVSWTPPPDGNGPITGYEVEYRPKNSGEPWNEITVPGTTTSVTLTGLKPGTEYEVRVQAVNGGG 80


                   ....
gi 599137400   994 SGIP 997
Cdd:pfam00041   81 EGPP 84

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: 66.37 E-value: 5.77e-13

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400    500 PVDTTVLLGLTATLQCKVSSDPsvPYNIDWYREGQssTPISNSQRIGVQADGQ---LEIQAVRASDVGSYACVVTSPGGN 576
Cdd:smart00410    1 PPSVTVKEGESVTLSCEASGSP--PPEVTWYKQGG--KLLAESGRFSVSRSGStstLTISNVTPEDSGTYTCAATNSSGS 76


                    ....*....
gi 599137400    577 ETRAARLSV 585
Cdd:smart00410   77 ASSGTTLTV 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: 64.66 E-value: 1.22e-12

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 599137400  378 VQLTCDVVGEPTPQVKWFRNAESVDAHIESGRYTLNTDNTLVIKKLILDDAAMFQCLAINEAGENSAST 446
Cdd:cd00096     1 VTLTCSASGNPPPTITWYKNGKPLPPSSRDSRRSELGNGTLTISNVTLEDSGTYTCVASNSAGGSASAS 69

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: 64.94 E-value: 1.66e-12

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400   1731 PSAPLHLRFSDITMQSLEVTWDPPKFLN--GEILGYLVTYETTEENEkfsKQVKQKVSNTTLRVQNLEEEVTYTFTVRAQ 1808
Cdd:smart00060    1 PSPPSNLRVTDVTSTSVTLSWEPPPDDGitGYIVGYRVEYREEGSEW---KEVNVTPSSTSYTLTGLKPGTEYEFRVRAV 77


                    ....*.
gi 599137400   1809 TSVDYG 1814
Cdd:smart00060   78 NGAGEG 83

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: 1.98e-12

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400 1625 GEPRAVDAAPISSTEVRLLWKPPKQSmqNGDILGYKIYYLVTYSPQAlepgrkweEEIEVVSATATSHSLVFLDKFTEYR 1704
Cdd:cd00063     2 SPPTNLRVTDVTSTSVTLSWTPPEDD--GGPITGYVVEYREKGSGDW--------KEVEVTPGSETSYTLTGLKPGTEYE 71

                          90       100
                  ....*....|....*....|..
gi 599137400 1705 IQLLAFNPAGDGPRSAPITVKT 1726
Cdd:cd00063    72 FRVRAVNGGGESPPSESVTVTT 93

Fibronectin type III domain;

Pssm-ID: 394996 [Multi-domain] Cd Length: 85 Bit Score: 64.36 E-value: 2.65e-12

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400  1220 PLDVQANATSSTTVVVQWGEVPrqHRNGQIDGYKVFYAAADRGQQVLHKTIPNNaTFTTTLTELKKYVVYHVQVLAYTRL 1299
Cdd:pfam00041    3 PSNLTVTDVTSTSLTVSWTPPP--DGNGPITGYEVEYRPKNSGEPWNEITVPGT-TTSVTLTGLKPGTEYEVRVQAVNGG 79


                   ....*.
gi 599137400  1300 GNGALS 1305
Cdd:pfam00041   80 GEGPPS 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: 63.68 E-value: 4.13e-12

                            10        20        30        40        50        60        70
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 599137400    375 GGQVQLTCDVVGEPTPQVKWFRNAESVdaHIESGRYTLNTDN---TLVIKKLILDDAAMFQCLAINEAGENSASTWLRV 450
Cdd:smart00410    9 GESVTLSCEASGSPPPEVTWYKQGGKL--LAESGRFSVSRSGstsTLTISNVTPEDSGTYTCAATNSSGSASSGTTLTV 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: 62.90 E-value: 1.09e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400 1011 PHAPTALALSNIEAFSVVLQFTPGFDGNSSITKWKVEGQTARNMTWFTiCEINDPDAETLTVTGLVPFTQYRLRLSASNV 1090
Cdd:cd00063     1 PSPPTNLRVTDVTSTSVTLSWTPPEDDGGPITGYVVEYREKGSGDWKE-VEVTPGSETSYTLTGLKPGTEYEFRVRAVNG 79

                          90
                  ....*....|....*
gi 599137400 1091 VGSSKPSEaTKDFQT 1105
Cdd:cd00063    80 GGESPPSE-SVTVTT 93

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: 62.51 E-value: 1.17e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400  496 IIQPPVDTTVLLGLTATLQCKVSSDPsVPyNIDWYREGQSsTPISNsQRIGVQADGQLEIQAVRASDVGSYACVVTSPGG 575
Cdd:cd20952     2 ILQGPQNQTVAVGGTVVLNCQATGEP-VP-TISWLKDGVP-LLGKD-ERITTLENGSLQIKGAEKSDTGEYTCVALNLSG 77

                          90
                  ....*....|
gi 599137400  576 NETRAARLSV 585
Cdd:cd20952    78 EATWSAVLDV 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: 62.95 E-value: 1.22e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400   72 PRFTTHPSSSgsIVSEGSTKILQCHALGYPQPTYRWLKDGVPV---GDFSSSQ----------FYRFHSTRR--EDAGSY 136
Cdd:cd07693     1 PRIVEHPSDL--IVSKGDPATLNCKAEGRPTPTIQWLKNGQPLetdKDDPRSHrivlpsgslfFLRVVHGRKgrSDEGVY 78

                          90       100
                  ....*....|....*....|.
gi 599137400  137 QCIARNDAGSIFSEKSDVVVA 157
Cdd:cd07693    79 VCVAHNSLGEAVSRNASLEVA 99

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 61.81 E-value: 1.57e-11

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 599137400   495 QIIQPPVDTTVLLGLTATLQCKVSSDPsvPYNIDWYREGQSSTPISNSQRIGVQADGQLEIQAVRASDVGSYACVVT 571
Cdd:pfam13927    3 VITVSPSSVTVREGETVTLTCEATGSP--PPTITWYKNGEPISSGSTRSRSLSGSNSTLTISNVTRSDAGTYTCVAS 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: 62.13 E-value: 2.00e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400  913 PDEVTGLHFDDVSDRSVKVLWAPPRASNGILTGYTVRYQVKDRPDTLKSFNLTADDTELTVNQLQATTHYWFEIVAWTRV 992
Cdd:cd00063     1 PSPPTNLRVTDVTSTSVTLSWTPPEDDGGPITGYVVEYREKGSGDWKEVEVTPGSETSYTLTGLKPGTEYEFRVRAVNGG 80


                  ....*
gi 599137400  993 GSGIP 997
Cdd:cd00063    81 GESPP 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: 61.64 E-value: 2.60e-11

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 599137400  375 GGQVQLTCDVVGEPTPQVKWFRNAESVDAhiESGRYTLnTDNTLVIKKLILDDAAMFQCLAINEAGENSASTWLRV 450
Cdd:cd20978    16 GQDVTLPCQVTGVPQPKITWLHNGKPLQG--PMERATV-EDGTLTIINVQPEDTGYYGCVATNEIGDIYTETLLHV 88

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: 60.71 E-value: 4.41e-11

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400   1416 PQAPSVPQISrsQIQAHQITFSWTPGRD--GFAPLRYYTVEMRENEGRWQPLPerVDPSLSSFTAVGLRPYMTYQFRIQA 1493
Cdd:smart00060    1 PSPPSNLRVT--DVTSTSVTLSWEPPPDdgITGYIVGYRVEYREEGSEWKEVN--VTPSSTSYTLTGLKPGTEYEFRVRA 76


                    ....*..
gi 599137400   1494 TNDLGPS 1500
Cdd:smart00060   77 VNGAGEG 83

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: 60.49 E-value: 6.23e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400  498 QPPVDTTVLLGLTATLQCKvssdPSVPY---NIDWYREGQssTPISNSQRIGVQADGQLEIQAVRASDVGSYACVVT-SP 573
Cdd:cd05724     2 VEPSDTQVAVGEMAVLECS----PPRGHpepTVSWRKDGQ--PLNLDNERVRIVDDGNLLIAEARKSDEGTYKCVATnMV 75

                          90
                  ....*....|..
gi 599137400  574 GGNETRAARLSV 585
Cdd:cd05724    76 GERESRAARLSV 87

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

Pssm-ID: 464026 [Multi-domain] Cd Length: 79 Bit Score: 60.10 E-value: 6.78e-11

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 599137400    79 SSSGSIVSEGSTKILQCHALGYPQPTYRWLKDGVPVgdfSSSQFYRFHSTRREDAGSYQCIARNDAGSIFSEKSDVVV 156
Cdd:pfam13895    5 TPSPTVVTEGEPVTLTCSAPGNPPPSYTWYKDGSAI---SSSPNFFTLSVSAEDSGTYTCVARNGRGGKVSNPVELTV 79

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: 60.59 E-value: 7.62e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400  375 GGQVQLTCDVVGEPTPQVKWFRNAESV---DAHI----ESGRYTLntdntlVIKKLILDDAAMFQCLAINEAGENSASTW 447
Cdd:cd05744    15 GRLCRFDCKVSGLPTPDLFWQLNGKPVrpdSAHKmlvrENGRHSL------IIEPVTKRDAGIYTCIARNRAGENSFNAE 88


                  ...
gi 599137400  448 LRV 450
Cdd:cd05744    89 LVV 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: 60.20 E-value: 8.87e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400 1830 PVAPRDLILTK-TLSSVEMHWINGPSGRGPILGYLIEAKKRDDSRWTKIEQTRKGmmqdfTVSYHI--LMPSTAYTFRVI 1906
Cdd:cd00063     1 PSPPTNLRVTDvTSTSVTLSWTPPEDDGGPITGYVVEYREKGSGDWKEVEVTPGS-----ETSYTLtgLKPGTEYEFRVR 75

                          90
                  ....*....|...
gi 599137400 1907 AYNRYGISFPVYS 1919
Cdd:cd00063    76 AVNGGGESPPSES 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: 59.95 E-value: 9.18e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400   73 RFTTHPSSSGSIvsEGSTKILQCHALGYPQPTYRWLKDGVPVGDFS-----SSQFYRFHSTRREDAGSYQCIARNDAGSI 147
Cdd:cd20968     1 KITRPPTNVTII--EGLKAVLPCTTMGNPKPSVSWIKGDDLIKENNriavlESGSLRIHNVQKEDAGQYRCVAKNSLGIA 78


                  ....*....
gi 599137400  148 FSEKSDVVV 156
Cdd:cd20968    79 YSKPVTIEV 87

Fibronectin type III domain;

Pssm-ID: 394996 [Multi-domain] Cd Length: 85 Bit Score: 60.12 E-value: 9.42e-11

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400  1419 PSVPQISRSQIQAHQITFSWTPGRDGFAPLRYYTVEMRENEGRWQPLPERVDPSLSSFTAVGLRPYMTYQFRIQATNDLG 1498
Cdd:pfam00041    1 SAPSNLTVTDVTSTSLTVSWTPPPDGNGPITGYEVEYRPKNSGEPWNEITVPGTTTSVTLTGLKPGTEYEVRVQAVNGGG 80


                   ....*
gi 599137400  1499 PSAFS 1503
Cdd:pfam00041   81 EGPPS 85

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: 60.33 E-value: 1.00e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400   77 HPSSSGSIVSEgSTKILQCHALGYPQPTYRWLKDGVPVGD----FSSSQFYR---FHSTRREDAGSYQCIARNDAGSIFS 149
Cdd:cd05760     6 HPASAAEIQPS-SRVTLRCHIDGHPRPTYQWFRDGTPLSDgqgnYSVSSKERtltLRSAGPDDSGLYYCCAHNAFGSVCS 84


                  ...
gi 599137400  150 EKS 152
Cdd:cd05760    85 SQN 87

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: 58.67 E-value: 2.64e-10

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400     80 SSGSIVSEGSTKILQCHALGYPQPTYRWLKDGVPV--------GDFSSSQFY-RFHSTRREDAGSYQCIARNDAGSIFSE 150
Cdd:smart00410    1 PPSVTVKEGESVTLSCEASGSPPPEVTWYKQGGKLlaesgrfsVSRSGSTSTlTISNVTPEDSGTYTCAATNSSGSASSG 80

Fibronectin type 3 domain [General function prediction only];

Pssm-ID: 442628 [Multi-domain] Cd Length: 603 Bit Score: 65.41 E-value: 3.45e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400 1196 NDVGCSKESDTAVERTREAVPSYGPLDVQANATSSTTVVVQWGEVPRQHRNGQIDGYKVFYAAADRGQQVLHKTIPNNAT 1275
Cdd:COG3401   105 GATNTGLTSSDEVPSPAVGTATTATAVAGGAATAGTYALGAGLYGVDGANASGTTASSVAGAGVVVSPDTSATAAVATTS 184

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400 1276 FTTTLTELKKYVV-------YHVQVLAYTRLGNGALStPPIRVQTFEDTPGVPSNVSFPDVSLTMARIIWDvPVDPNGkI 1348
Cdd:COG3401   185 LTVTSTTLVDGGGdiepgttYYYRVAATDTGGESAPS-NEVSVTTPTTPPSAPTGLTATADTPGSVTLSWD-PVTESD-A 261

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400 1349 LAYQVTYTLNGSAmlNYSREFPPSDRTFRATELLPGKYYSFSCTAQTRLGWGKIATALVYTTNNRERPQAPSVPQISRSQ 1428
Cdd:COG3401   262 TGYRVYRSNSGDG--PFTKVATVTTTSYTDTGLTNGTTYYYRVTAVDAAGNESAPSNVVSVTTDLTPPAAPSGLTATAVG 339

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400 1429 IQahQITFSWTPGRDgfAPLRYYTVEmR--ENEGRWQPLPERVDPSlsSFTAVGLRPYMTYQFRIQATNDLGPSAFSRES 1506
Cdd:COG3401   340 SS--SITLSWTASSD--ADVTGYNVY-RstSGGGTYTKIAETVTTT--SYTDTGLTPGTTYYYKVTAVDAAGNESAPSEE 412

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400 1507 VIVRTLPAAPAVGVGGLKVVPITTTSVRVQWSALE------TALWNGDASTGGYRILYQQLSDFPTALQSTPKTDVHGIN 1580
Cdd:COG3401   413 VSATTASAASGESLTASVDAVPLTDVAGATAAASAasnpgvSAAVLADGGDTGNAVPFTTTSSTVTATTTDTTTANLSVT 492

                         410       420       430       440       450
                  ....*....|....*....|....*....|....*....|....*....|..
gi 599137400 1581 ENSVVL-SDLQQDRNYEIVVLPFNSQGPGPATPPAAVYVGEAVPTGEPRAVD 1631
Cdd:COG3401   493 TGSLVGgSGASSVTNSVSVIGASAAAAVGGAPDGTPNVTGASPVTVGASTGD 544

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: 58.18 E-value: 3.91e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400  497 IQPPVDTTVLLGLTATLQCKVSSDPsvPYNIDWYREGqSSTPISnsqRIGVQADGQLEIQAVRASDVGSYACVVTSPGGN 576
Cdd:cd05725     1 VKRPQNQVVLVDDSAEFQCEVGGDP--VPTVRWRKED-GELPKG---RYEILDDHSLKIRKVTAGDMGSYTCVAENMVGK 74


                  ....*....
gi 599137400  577 ETRAARLSV 585
Cdd:cd05725    75 IEASATLTV 83

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: 58.28 E-value: 4.34e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400 1220 PLDVQANATSSTTVVVQWgeVPRQHRNGQIDGYKVFYAAADRGQQVLHKTIPNNATfTTTLTELKKYVVYHVQVLAYTRL 1299
Cdd:cd00063     4 PTNLRVTDVTSTSVTLSW--TPPEDDGGPITGYVVEYREKGSGDWKEVEVTPGSET-SYTLTGLKPGTEYEFRVRAVNGG 80

                          90
                  ....*....|....
gi 599137400 1300 GNGALSTpPIRVQT 1313
Cdd:cd00063    81 GESPPSE-SVTVTT 93

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: 58.28 E-value: 4.47e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400  804 PPTNVKVEAINSTAARCRWTPPNPqqINGINQGYKIQAwqRRLIDGEWRDIERRMKTvppslidplaEQTAILGGLEKFT 883
Cdd:cd00063     3 PPTNLRVTDVTSTSVTLSWTPPED--DGGPITGYVVEY--REKGSGDWKEVEVTPGS----------ETSYTLTGLKPGT 68

                          90       100
                  ....*....|....*....|....*
gi 599137400  884 EYNISVLCFTDPGDGVASSQVAVMT 908
Cdd:cd00063    69 EYEFRVRAVNGGGESPPSESVTVTT 93

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: 57.89 E-value: 5.94e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400 1318 PGVPSNVSFPDVSLTMARIIWDVPVDPNGKILAYQVTYTLNGSAMLNYSREFPPSDRTFRATELLPGKYYSFSCTAQTRL 1397
Cdd:cd00063     1 PSPPTNLRVTDVTSTSVTLSWTPPEDDGGPITGYVVEYREKGSGDWKEVEVTPGSETSYTLTGLKPGTEYEFRVRAVNGG 80

                          90
                  ....*....|...
gi 599137400 1398 GWGKIATALVYTT 1410
Cdd:cd00063    81 GESPPSESVTVTT 93

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: 56.95 E-value: 6.35e-10

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 599137400   93 LQCHALGYPQPTYRWLKDGVPVGDFSSSQFY--------RFHSTRREDAGSYQCIARNDAGSIFS 149
Cdd:cd00096     3 LTCSASGNPPPTITWYKNGKPLPPSSRDSRRselgngtlTISNVTLEDSGTYTCVASNSAGGSAS 67

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: 57.59 E-value: 8.13e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400  359 PPLFFTPMRAETFGEfGGQVQLTCDVVGEPTPQVKWFR------NAESVDAHIESGRYtlntdnTLVIKKLILDDAAMFQ 432
Cdd:cd20972     1 PPQFIQKLRSQEVAE-GSKVRLECRVTGNPTPVVRWFCegkelqNSPDIQIHQEGDLH------SLIIAEAFEEDTGRYS 73

                          90
                  ....*....|...
gi 599137400  433 CLAINEAGENSAS 445
Cdd:cd20972    74 CLATNSVGSDTTS 86

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 57.27 E-value: 8.32e-10

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 599137400   375 GGQVQLTCDVVGEPTPQVKWFRNAESVdahIESGRYTLNTDN---TLVIKKLILDDAAMFQCLAINEAGENSASTWLRV 450
Cdd:pfam07679   15 GESARFTCTVTGTPDPEVSWFKDGQPL---RSSDRFKVTYEGgtyTLTISNVQPDDSGKYTCVATNSAGEAEASAELTV 90

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: 8.56e-10

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 599137400  497 IQPPVDTtVLLGLTATLQCKVSSDPSvpYNIDWYREGQsstPISNSQRIGVQADGQLEIQAVRASDVGSYACVVTSPG 574
Cdd:cd20957     6 IDPPVQT-VDFGRTAVFNCSVTGNPI--HTVLWMKDGK---PLGHSSRVQILSEDVLVIPSVKREDKGMYQCFVRNDG 77

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: 56.85 E-value: 1.07e-09

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400    913 PDEVTGLHFDDVSDRSVKVLWAPPRASNGilTGYTVRYQVKDRP--DTLKSFNLTADDTELTVNQLQATTHYWFEIVAWT 990
Cdd:smart00060    1 PSPPSNLRVTDVTSTSVTLSWEPPPDDGI--TGYIVGYRVEYREegSEWKEVNVTPSSTSYTLTGLKPGTEYEFRVRAVN 78


                    ....*
gi 599137400    991 RVGSG 995
Cdd:smart00060   79 GAGEG 83

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: 56.81 E-value: 1.42e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400  365 PMRAETFGEfGGQVQLTCDVVGEPTPQVKWFRNAESVdahIESGRYTLNTDN----TLVIKKLILDDAAMFQCLAINEAG 440
Cdd:cd20973     3 TLRDKEVVE-GSAARFDCKVEGYPDPEVKWMKDDNPI---VESRRFQIDQDEdglcSLIISDVCGDDSGKYTCKAVNSLG 78

                          90
                  ....*....|
gi 599137400  441 ENSASTWLRV 450
Cdd:cd20973    79 EATCSAELTV 88

Fibronectin type III domain;

Pssm-ID: 394996 [Multi-domain] Cd Length: 85 Bit Score: 56.65 E-value: 1.49e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400  1013 APTALALSNIEAFSVVLQFTPGFDGNSSITKWKVEGQTARNMT-WFTIceINDPDAETLTVTGLVPFTQYRLRLSASNVV 1091
Cdd:pfam00041    2 APSNLTVTDVTSTSLTVSWTPPPDGNGPITGYEVEYRPKNSGEpWNEI--TVPGTTTSVTLTGLKPGTEYEVRVQAVNGG 79


                   ....*.
gi 599137400  1092 GSSKPS 1097
Cdd:pfam00041   80 GEGPPS 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: 56.74 E-value: 1.64e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400 1113 PPFNVTVRAMSAQQLRVRWIPLQqtEWYGNPRGYNISYKQLVKTPgtikyvPRSVVIEDHTANSHVLDSLEEWTLYEVKM 1192
Cdd:cd00063     3 PPTNLRVTDVTSTSVTLSWTPPE--DDGGPITGYVVEYREKGSGD------WKEVEVTPGSETSYTLTGLKPGTEYEFRV 74

                          90
                  ....*....|....*....
gi 599137400 1193 NACNDVGCSKESDTAVERT 1211
Cdd:cd00063    75 RAVNGGGESPPSESVTVTT 93

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: 55.03 E-value: 3.66e-09

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400  511 ATLQCKVSSDPsvPYNIDWYREGQSSTPISNSQRIGVQADGQLEIQAVRASDVGSYACVVTSPGGNETRA 580
Cdd:cd00096     1 VTLTCSASGNP--PPTITWYKNGKPLPPSSRDSRRSELGNGTLTISNVTLEDSGTYTCVASNSAGGSASA 68

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: 55.31 E-value: 4.33e-09

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400    591 PPSNVKVErlpEPQQRSINVSWTPGFDGN--SPISKFIIQRREVSElgpvpdpllNWITElsNVSADQRWILLENLKAAT 668
Cdd:smart00060    3 PPSNLRVT---DVTSTSVTLSWEPPPDDGitGYIVGYRVEYREEGS---------EWKEV--NVTPSSTSYTLTGLKPGT 68

                            90
                    ....*....|....*
gi 599137400    669 VYQFRVSAVNRVGEG 683
Cdd:smart00060   69 EYEFRVRAVNGAGEG 83

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 54.88 E-value: 5.24e-09

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 599137400   359 PPLFFTPMRAETFGEfGGQVQLTCDVVGEPTPQVKWFRNAESVDAHIESGRYTLNTDNTLVIKKLILDDAAMFQCLAIN 437
Cdd:pfam13927    1 KPVITVSPSSVTVRE-GETVTLTCEATGSPPPTITWYKNGEPISSGSTRSRSLSGSNSTLTISNVTRSDAGTYTCVASN 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: 55.20 E-value: 5.40e-09

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 599137400   85 VSEGSTKILQCHALGYPQPTYRWLKDGVPVGDFSSSQF------YRFHSTRREDAGSYQCIARNDAGS 146
Cdd:cd20952    11 VAVGGTVVLNCQATGEPVPTISWLKDGVPLLGKDERITtlengsLQIKGAEKSDTGEYTCVALNLSGE 78

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: 55.26 E-value: 5.49e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400   81 SGSIVSEGSTKILQCHALGYPQPTYRWLKDGVP--------VGDFSSSQ-----FYRFHSTRREDAGSYQCIARNDAGSI 147
Cdd:cd20956     9 SEQTLQPGPSVSLKCVASGNPLPQITWTLDGFPipesprfrVGDYVTSDgdvvsYVNISSVRVEDGGEYTCTATNDVGSV 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: 54.96 E-value: 6.92e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400  495 QIIQPPVDTTVLLGLTATLQCKVSSDPsvPYNIDWYREGQ-----SSTPISNSQRIGVQADGQLEIQAVRASDVGSYACV 569
Cdd:cd05726     1 QFVVKPRDQVVALGRTVTFQCETKGNP--QPAIFWQKEGSqnllfPYQPPQPSSRFSVSPTGDLTITNVQRSDVGYYICQ 78

                          90
                  ....*....|....*.
gi 599137400  570 VTSPGGNETRAARLSV 585
Cdd:cd05726    79 ALNVAGSILAKAQLEV 94

Fibronectin type 3 domain [General function prediction only];

Pssm-ID: 442628 [Multi-domain] Cd Length: 603 Bit Score: 60.79 E-value: 8.00e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400  472 ATISCRAVGSPNPNITWIYNVRTQIIQPPVDTTVLLGLTATLQCKVSSDPSVPYNIDWYREGQSSTPISNSQRIGVQADG 551
Cdd:COG3401   115 DEVPSPAVGTATTATAVAGGAATAGTYALGAGLYGVDGANASGTTASSVAGAGVVVSPDTSATAAVATTSLTVTSTTLVD 194

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400  552 QLEIQAVRASdvGSYACVVTSPGGNETRAARLSVI---ELPFPPSNVKVErlpEPQQRSINVSWTPGfdGNSPISKFIIQ 628
Cdd:COG3401   195 GGGDIEPGTT--YYYRVAATDTGGESAPSNEVSVTtptTPPSAPTGLTAT---ADTPGSVTLSWDPV--TESDATGYRVY 267

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400  629 RREVSelgpvpDPLLNWITELSNVSADQRwilleNLKAATVYQFRVSAVNrvGEGSPSEPSNVVEL-PQEAPSGPPVGFV 707
Cdd:COG3401   268 RSNSG------DGPFTKVATVTTTSYTDT-----GLTNGTTYYYRVTAVD--AAGNESAPSNVVSVtTDLTPPAAPSGLT 334

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400  708 GSARSMSEIITQWQPPLEEHrngqilgyILRYRLFGYNNVPWSYQNITNEAQRNFLIQELITW-KDYIVQIAAYNNMGVG 786
Cdd:COG3401   335 ATAVGSSSITLSWTASSDAD--------VTGYNVYRSTSGGGTYTKIAETVTTTSYTDTGLTPgTTYYYKVTAVDAAGNE 406

                         330       340       350       360       370
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 599137400  787 -----VYTEGSKIKTKEGVPEAPPTNVKVEAINSTAARCRWTPPNPQQINGINQGYKI 839
Cdd:COG3401   407 sapseEVSATTASAASGESLTASVDAVPLTDVAGATAAASAASNPGVSAAVLADGGDT 464

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: 54.14 E-value: 9.80e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400  369 ETFGEFGGQVQLTCDVVGEPTPQVKWFRNAESVDA----HIESGrytlntdnTLVIKKLILDDAAMFQCLAINEAGENSA 444
Cdd:cd05728     8 DTEADIGSSLRWECKASGNPRPAYRWLKNGQPLASenriEVEAG--------DLRITKLSLSDSGMYQCVAENKHGTIYA 79


                  ....*.
gi 599137400  445 STWLRV 450
Cdd:cd05728    80 SAELAV 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: 54.42 E-value: 1.21e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400  701 GPPVGFVGSARSMSEIITQWQPPleEHRNGQILGYILRYRLFGYNNvpWSYQNITNEAQRNFLIQELITWKDYIVQIAAY 780
Cdd:cd00063     2 SPPTNLRVTDVTSTSVTLSWTPP--EDDGGPITGYVVEYREKGSGD--WKEVEVTPGSETSYTLTGLKPGTEYEFRVRAV 77

                          90
                  ....*....|....*.
gi 599137400  781 NNMGVGVYTEGSKIKT 796
Cdd:cd00063    78 NGGGESPPSESVTVTT 93

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: 53.77 E-value: 1.37e-08

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400    804 PPTNVKVEAINSTAARCRWTPPNPQQINGINQGYKIqawQRRLIDGEWRDIERrmktvppslidPLAEQTAILGGLEKFT 883
Cdd:smart00060    3 PPSNLRVTDVTSTSVTLSWEPPPDDGITGYIVGYRV---EYREEGSEWKEVNV-----------TPSSTSYTLTGLKPGT 68

                            90
                    ....*....|....*
gi 599137400    884 EYNISVLCFTDPGDG 898
Cdd:smart00060   69 EYEFRVRAVNGAGEG 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: 53.76 E-value: 1.38e-08

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 599137400   88 GSTKILQCHALGYPQPTYRWLKDGVPVGdfSSSQFY------RFHSTRREDAGSYQCIARNDAGSIFS 149
Cdd:cd05728    14 GSSLRWECKASGNPRPAYRWLKNGQPLA--SENRIEveagdlRITKLSLSDSGMYQCVAENKHGTIYA 79

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: 54.18 E-value: 1.42e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400   86 SEGSTKILQCHALGYPQPTYRWLKDGVPV---GDFSSS----QFYRFHSTRREDAGSYQCIARNDAGSIFSEKSDVVVAY 158
Cdd:cd05848    17 SDEKKVILNCEARGNPVPTYRWLRNGTEIdteSDYRYSlidgNLIISNPSEVKDSGRYQCLATNSIGSILSREALLQFAY 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: 53.73 E-value: 1.58e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400  497 IQPPVDTTVLLGLTATLQCKVSSDPSvpYNIDWYREGQSsTPISNSQRigVQADGQLEIQAV-RASDVGSYACVVTSPGG 575
Cdd:cd20958     4 IRPMGNLTAVAGQTLRLHCPVAGYPI--SSITWEKDGRR-LPLNHRQR--VFPNGTLVIENVqRSSDEGEYTCTARNQQG 78


                  .
gi 599137400  576 N 576
Cdd:cd20958    79 Q 79

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: 53.74 E-value: 1.70e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400   498 QPPVDTTVLLGLTATLQCKVSSDPSVPyNIDWYREGQSSTPISNSQRI-GVQADGQLEIQAVRASDVGSYACVVTSPGGN 576
Cdd:pfam00047    1 SAPPTVTVLEGDSATLTCSASTGSPGP-DVTWSKEGGTLIESLKVKHDnGRTTQSSLLISNVTKEDAGTYTCVVNNPGGS 79


                   ...
gi 599137400   577 ETR 579
Cdd:pfam00047   80 ATL 82

Fibronectin type III domain;

Pssm-ID: 394996 [Multi-domain] Cd Length: 85 Bit Score: 53.57 E-value: 1.80e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400  1625 GEPRAVDAAPISSTEVRLLWKPPKQSmqNGDILGYKIYYLVTYSPQAlepgrkWEEEIevVSATATSHSLVFLDKFTEYR 1704
Cdd:pfam00041    1 SAPSNLTVTDVTSTSLTVSWTPPPDG--NGPITGYEVEYRPKNSGEP------WNEIT--VPGTTTSVTLTGLKPGTEYE 70

                           90
                   ....*....|....*
gi 599137400  1705 IQLLAFNPAGDGPRS 1719
Cdd:pfam00041   71 VRVQAVNGGGEGPPS 85

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: 1.86e-08

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400   1625 GEPRAVDAAPISSTEVRLLWKPPKQSMQNGDILGYKIYYlvtyspqaLEPGRKWEEEIevVSATATSHSLVFLDKFTEYR 1704
Cdd:smart00060    2 SPPSNLRVTDVTSTSVTLSWEPPPDDGITGYIVGYRVEY--------REEGSEWKEVN--VTPSSTSYTLTGLKPGTEYE 71

                            90
                    ....*....|..
gi 599137400   1705 IQLLAFNPAGDG 1716
Cdd:smart00060   72 FRVRAVNGAGEG 83

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: 53.67 E-value: 2.16e-08

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 599137400   76 THPSSSGS-IVSEGSTKILQCHALGYPQPTYRWLKDGVPVGDFSSSQFYRFHST-------RREDAGSYQCIARNDAG 145
Cdd:cd20970     4 STPQPSFTvTAREGENATFMCRAEGSPEPEISWTRNGNLIIEFNTRYIVRENGTtltirniRRSDMGIYLCIASNGVP 81

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: 52.84 E-value: 3.07e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400   73 RFTTHPSSSgsIVSEGSTKILQCHALGYPQPTYRWLKDGVPVGDFSSS-------QFYRFHSTRREDAGSYQCIARNDAG 145
Cdd:cd04978     1 YWIIEPPSL--VLSPGETGELICEAEGNPQPTITWRLNGVPIEPAPEDmrrtvdgRTLIFSNLQPNDTAVYQCNASNVHG 78


                  ...
gi 599137400  146 SIF 148
Cdd:cd04978    79 YLL 81

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: 53.02 E-value: 3.39e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400   72 PRFTTHPSSSgsIVSEGSTK---ILQCHALGYPQPTYRWLKDGVPVgDFSSSQFYRF--------HSTRREDAGSYQCIA 140
Cdd:cd04967     2 PVFEEQPDDT--IFPEDSDEkkvALNCRARANPVPSYRWLMNGTEI-DLESDYRYSLvdgtlvisNPSKAKDAGHYQCLA 78

                          90
                  ....*....|....*...
gi 599137400  141 RNDAGSIFSEKSDVVVAY 158
Cdd:cd04967    79 TNTVGSVLSREATLQFGY 96

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: 53.01 E-value: 3.44e-08

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 599137400  375 GGQVQLTCDVVGEPTPQVKWFRNAESvdahIESG--RYTLNTDNT-LVIKKLILDDAAMFQCLAINEAGENSASTWLRV 450
Cdd:cd05730    18 GQSVTLACDADGFPEPTMTWTKDGEP----IESGeeKYSFNEDGSeMTILDVDKLDEAEYTCIAENKAGEQEAEIHLKV 92

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: 52.23 E-value: 4.18e-08

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400   1220 PLDVQANATSSTTVVVQWGEVPRQHRNGQIDGYKVFYAAADRGQQVLHKTIPNNatfTTTLTELKKYVVYHVQVLAYTRL 1299
Cdd:smart00060    4 PSNLRVTDVTSTSVTLSWEPPPDDGITGYIVGYRVEYREEGSEWKEVNVTPSST---SYTLTGLKPGTEYEFRVRAVNGA 80


                    ...
gi 599137400   1300 GNG 1302
Cdd:smart00060   81 GEG 83

Fibronectin type III domain;

Pssm-ID: 394996 [Multi-domain] Cd Length: 85 Bit Score: 52.42 E-value: 4.68e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400  1520 VGGLKVVPITTTSVRVQWSALETalWNGDAStgGYRILYQQLSDFPTALQSTpktdVHGiNENSVVLSDLQQDRNYEIVV 1599
Cdd:pfam00041    3 PSNLTVTDVTSTSLTVSWTPPPD--GNGPIT--GYEVEYRPKNSGEPWNEIT----VPG-TTTSVTLTGLKPGTEYEVRV 73

                           90
                   ....*....|..
gi 599137400  1600 LPFNSQGPGPAT 1611
Cdd:pfam00041   74 QAVNGGGEGPPS 85

Fibronectin type III domain;

Pssm-ID: 394996 [Multi-domain] Cd Length: 85 Bit Score: 51.65 E-value: 8.17e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400   804 PPTNVKVEAINSTAARCRWTPPNPQqiNGINQGYKIQAWQrrlIDGEWRDIERrmkTVPPSlidplaEQTAILGGLEKFT 883
Cdd:pfam00041    2 APSNLTVTDVTSTSLTVSWTPPPDG--NGPITGYEVEYRP---KNSGEPWNEI---TVPGT------TTSVTLTGLKPGT 67

                           90
                   ....*....|....*...
gi 599137400   884 EYNISVLCFTDPGDGVAS 901
Cdd:pfam00041   68 EYEVRVQAVNGGGEGPPS 85

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: 51.43 E-value: 8.21e-08

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 599137400  378 VQLTCDVVGEPTPQVKWFRNAESVdahIESGRYTLNTDNTLVIKKLILDDAAMFQCLAINEAGENSASTWL 448
Cdd:cd05723    15 IVFECEVTGKPTPTVKWVKNGDVV---IPSDYFKIVKEHNLQVLGLVKSDEGFYQCIAENDVGNAQASAQL 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: 51.74 E-value: 1.02e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400  457 MELPPQNVTALDGKDATISCRAVGSPNPNITWiynvrtqiiqppvdttvllgltatlqckvssdpsvpynidwYREGQSs 536
Cdd:cd20970     5 TPQPSFTVTAREGENATFMCRAEGSPEPEISW-----------------------------------------TRNGNL- 42

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|..
gi 599137400  537 tPISNSQRIGVQADGQ-LEIQAVRASDVGSYACVVTS--PGGNETRAArLSV 585
Cdd:cd20970    43 -IIEFNTRYIVRENGTtLTIRNIRRSDMGIYLCIASNgvPGSVEKRIT-LQV 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: 51.36 E-value: 1.18e-07

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 599137400   85 VSEGSTKILQCHALG-YPQPTYRWLKDG----------VPVGDFSSSQFYRFHSTRREDAGSYQCIARNDAG 145
Cdd:cd05750    11 VQEGSKLVLKCEATSeNPSPRYRWFKDGkelnrkrpknIKIRNKKKNSELQINKAKLEDSGEYTCVVENILG 82

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: 51.48 E-value: 1.22e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400   71 APRFTTHPSSSGSIvsEGSTKILQCHALGYPQPTYRWLKDGVPV---GDFSSSQ----FYRFHSTRREDAGSYQCIARND 143
Cdd:cd20976     1 APSFSSVPKDLEAV--EGQDFVAQCSARGKPVPRITWIRNAQPLqyaADRSTCEagvgELHIQDVLPEDHGTYTCLAKNA 78

                          90
                  ....*....|...
gi 599137400  144 AGSIfSEKSDVVV 156
Cdd:cd20976    79 AGQV-SCSAWVTV 90

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: 51.11 E-value: 1.34e-07

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 599137400   88 GSTKILQCHALGYPQPTYRWLKDGVPVGDFSSSQF--------YRFHSTRREDAGSYQCIARNDAG------SIFSEKS 152
Cdd:cd05736    15 GVEASLRCHAEGIPLPRVQWLKNGMDINPKLSKQLtliangseLHISNVRYEDTGAYTCIAKNEGGvdedisSLFVEDS 93

Immunoglobulin variable domain (IgV); The members here are composed of the immunoglobulin variable domain (IgV). The IgV family contains the standard Ig superfamily V-set AGFCC'C"/DEB domain topology, and are components of immunoglobulin (Ig) and T cell receptors. The basic structure of Ig molecules is a tetramer of two light chains and two heavy chains linked by disulfide bonds. In Ig, each chain is composed of one variable domain (IgV) and one or more constant domains (IgC); these names reflect the fact that the variability in sequences is higher in the variable domain than in the constant domain. Within the variable domain, there are regions of even more variability called the hypervariable or complementarity-determining regions (CDRs) which are responsible for antigen binding. A predominant feature of most Ig domains is the disulfide bridge connecting 2 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" strands in the other.

Pssm-ID: 409355 [Multi-domain] Cd Length: 111 Bit Score: 51.95 E-value: 1.34e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400  496 IIQPPVDTTVLLGLTATLQCKVSSDPSVPYnIDWYREGQSSTPI------SNSQRIGVQADGQ------------LEIQA 557
Cdd:cd00099     1 VTQSPRSLSVQEGESVTLSCEVSSSFSSTY-IYWYRQKPGQGPEfliylsSSKGKTKGGVPGRfsgsrdgtssfsLTISN 79

                          90
                  ....*....|....*....
gi 599137400  558 VRASDVGSYACVVTSPGGN 576
Cdd:cd00099    80 LQPEDSGTYYCAVSESGGT 98

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: 50.87 E-value: 1.34e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400   79 SSSGSIVSEGSTKILQCHALGYPQPTYRWLKDGvpvGDFSSS--QFYRFHSTRR------EDAGSYQCIARNDAGSIFSE 150
Cdd:cd05731     1 SESSTMVLRGGVLLLECIAEGLPTPDIRWIKLG---GELPKGrtKFENFNKTLKienvseADSGEYQCTASNTMGSARHT 77


                  ....*
gi 599137400  151 KSDVV 155
Cdd:cd05731    78 ISVTV 82

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: 51.27 E-value: 1.40e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400   72 PRFTTHPSSSGsiVSEGSTKILQCHALGYPQPTYRWLKDGVPVGDFSSSQFYRFHS--------TRR---EDAGSYQCIA 140
Cdd:cd20951     1 PEFIIRLQSHT--VWEKSDAKLRVEVQGKPDPEVKWYKNGVPIDPSSIPGKYKIESeygvhvlhIRRvtvEDSAVYSAVA 78

                          90
                  ....*....|....*
gi 599137400  141 RNDAGSIFSEKSDVV 155
Cdd:cd20951    79 KNIHGEASSSASVVV 93

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: 1.54e-07

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 599137400  375 GGQVQLTCDVVGEPTPQVKWFRNaesvDAHIESGRYTLNTDNTLVIKKLILDDAAMFQCLAINEAGENSASTWLRV 450
Cdd:cd05725    12 DDSAEFQCEVGGDPVPTVRWRKE----DGELPKGRYEILDDHSLKIRKVTAGDMGSYTCVAENMVGKIEASATLTV 83

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: 50.57 E-value: 1.81e-07

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 599137400  375 GGQVQLTCDVVGEPTPQVKWFRnaesvDAHIESG---RYTLNTDNTLVIKKLILDDAAMFQCLAINEAGENSASTWLRV 450
Cdd:cd20952    14 GGTVVLNCQATGEPVPTISWLK-----DGVPLLGkdeRITTLENGSLQIKGAEKSDTGEYTCVALNLSGEATWSAVLDV 87

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: 50.61 E-value: 2.15e-07

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 599137400   84 IVSEGSTKILQCHALGYPQPTYRWLKDGVPVGDFSSSQFY-----RFHSTRREDAGSYQCIARNDAGSI 147
Cdd:cd20957    12 TVDFGRTAVFNCSVTGNPIHTVLWMKDGKPLGHSSRVQILsedvlVIPSVKREDKGMYQCFVRNDGDSA 80

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: 50.70 E-value: 2.32e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400   74 FTTHPSSSGsiVSEGSTKILQCHALGYPQPTYRWLKDGvpvG-DFSSSQFYRFH-----------STRREDAGSYQCIAR 141
Cdd:cd05763     2 FTKTPHDIT--IRAGSTARLECAATGHPTPQIAWQKDG---GtDFPAARERRMHvmpeddvffivDVKIEDTGVYSCTAQ 76


                  ....*.
gi 599137400  142 NDAGSI 147
Cdd:cd05763    77 NSAGSI 82

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: 50.57 E-value: 2.49e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400 1513 PAAPavgvGGLKVVPITTTSVRVQWSALETALWNGDastgGYRILYQQLSDfptalQSTPKTDVHGINENSVVLSDLQQD 1592
Cdd:cd00063     1 PSPP----TNLRVTDVTSTSVTLSWTPPEDDGGPIT----GYVVEYREKGS-----GDWKEVEVTPGSETSYTLTGLKPG 67

                          90       100
                  ....*....|....*....|....*.
gi 599137400 1593 RNYEIVVLPFNSQGPGPATPPAAVYV 1618
Cdd:cd00063    68 TEYEFRVRAVNGGGESPPSESVTVTT 93

Fibronectin type III domain;

Pssm-ID: 394996 [Multi-domain] Cd Length: 85 Bit Score: 50.11 E-value: 2.61e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400  1832 APRDLILT-KTLSSVEMHWINGPSGRGPILGYLIEAKKRDDSRWTKiEQTRKGMmqdfTVSYHI--LMPSTAYTFRVIAY 1908
Cdd:pfam00041    2 APSNLTVTdVTSTSLTVSWTPPPDGNGPITGYEVEYRPKNSGEPWN-EITVPGT----TTSVTLtgLKPGTEYEVRVQAV 76


                   ....*...
gi 599137400  1909 NRYGISFP 1916
Cdd:pfam00041   77 NGGGEGPP 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: 50.55 E-value: 2.88e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400   73 RFTTHPSSSgsIVSEGSTKILQCHALGYPQPTYRWLKDGVPVGDFSSSQFYRF-----------HS-TRREDAGSYQCIA 140
Cdd:cd05722     3 YFLSEPSDI--VAMRGGPVVLNCSAESDPPPKIEWKKDGVLLNLVSDERRQQLpngsllitsvvHSkHNKPDEGFYQCVA 80

                          90
                  ....*....|....*..
gi 599137400  141 RNDA-GSIFSEKSDVVV 156
Cdd:cd05722    81 QNESlGSIVSRTARVTV 97

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: 3.04e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400  360 PLFFTPMRAETF-GEFGGQVQLTCDVVGEPTPQVKWFRNAESVDAHIEsgRYTLNTDNT-LVIKKLILDDAAMFQCLAIN 437
Cdd:cd20970     1 PVISTPQPSFTVtAREGENATFMCRAEGSPEPEISWTRNGNLIIEFNT--RYIVRENGTtLTIRNIRRSDMGIYLCIASN 78


                  ...
gi 599137400  438 EAG 440
Cdd:cd20970    79 GVP 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: 49.84 E-value: 3.75e-07

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 599137400  373 EFGGQVQLTCDVVGEPTPQVKWFRNAESVDAhieSGRYTLNTDNTLVIKKLILDDAAMFQCLAINEAGENSASTWLRV 450
Cdd:cd20957    14 DFGRTAVFNCSVTGNPIHTVLWMKDGKPLGH---SSRVQILSEDVLVIPSVKREDKGMYQCFVRNDGDSAQATAELKL 88

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: 4.63e-07

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400   1113 PPFNVTVRAMSAQQLRVRWIPLQqtewYGNPRGYNISYKQLVKTPGTikyvPRSVVIEDHTANSHVLDSLEEWTLYEVKM 1192
Cdd:smart00060    3 PPSNLRVTDVTSTSVTLSWEPPP----DDGITGYIVGYRVEYREEGS----EWKEVNVTPSSTSYTLTGLKPGTEYEFRV 74


                    ....*....
gi 599137400   1193 NACNDVGCS 1201
Cdd:smart00060   75 RAVNGAGEG 83

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: 48.72 E-value: 5.16e-07

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 599137400   93 LQCHALGYPQPTYRWLKDGVPV---GDFSSSQ--FYRFHSTRREDAGSYQCIARNDAGS 146
Cdd:cd05746     3 IPCSAQGDPEPTITWNKDGVQVtesGKFHISPegYLAIRDVGVADQGRYECVARNTIGY 61

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: 49.83 E-value: 5.37e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400  364 TPMRAETFGEfGGQVQLTCDVVGEPTPQVKWFR-------NAESVDAHIE-SGRYTLntdNTLVIKKLILDDAAMFQCLA 435
Cdd:cd05732     6 TYLENQTAVE-LEQITLTCEAEGDPIPEITWRRatrgisfEEGDLDGRIVvRGHARV---SSLTLKDVQLTDAGRYDCEA 81

                          90
                  ....*....|....*
gi 599137400  436 INEAGENSASTWLRV 450
Cdd:cd05732    82 SNRIGGDQQSMYLEV 96

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: 49.38 E-value: 5.52e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400  375 GGQVQLTCDVVGEPTPQVKWFRNAESVdaHIESGRYTLNTDNT----LVIKKLILDDAAMFQCLAINEAGENSASTWLRV 450
Cdd:cd05892    15 GDPVRLECQISAIPPPQIFWKKNNEML--QYNTDRISLYQDNCgricLLIQNANKKDAGWYTVSAVNEAGVVSCNARLDV 92

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: 49.66 E-value: 5.53e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400  496 IIQPPVDTTVLLGLTATLQCKVSSDPsVPyNIDWYREGQsstPISNSQRIGV---QADGQLEIQAVRASDVGSYACVVTS 572
Cdd:cd05747     6 ILTKPRSLTVSEGESARFSCDVDGEP-AP-TVTWMREGQ---IIVSSQRHQItstEYKSTFEISKVQMSDEGNYTVVVEN 80


                  ....*
gi 599137400  573 PGGNE 577
Cdd:cd05747    81 SEGKQ 85

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: 48.72 E-value: 5.63e-07

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 599137400  378 VQLTCDVVGEPTPQVKWFRNAESVdahIESGRYTLNTDNTLVIKKLILDDAAMFQCLAINEAGENSASTWL 448
Cdd:cd05746     1 VQIPCSAQGDPEPTITWNKDGVQV---TESGKFHISPEGYLAIRDVGVADQGRYECVARNTIGYASVSMVL 68

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: 49.15 E-value: 6.26e-07

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400   1830 PVAPRDLILTKTLS-SVEMHWI--NGPSGRGPILGYLIEaKKRDDSRWTKIEQTRKgmmqdfTVSYHI--LMPSTAYTFR 1904
Cdd:smart00060    1 PSPPSNLRVTDVTStSVTLSWEppPDDGITGYIVGYRVE-YREEGSEWKEVNVTPS------STSYTLtgLKPGTEYEFR 73

                            90
                    ....*....|
gi 599137400   1905 VIAYNRYGIS 1914
Cdd:smart00060   74 VRAVNGAGEG 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: 49.31 E-value: 6.41e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400  456 IMELPPQNVTALDGKDATISCRAVGSPNPNITWIYNVRTqIIQPPVDTTVllgltatlqckvssdpsvpynidwyregqs 535
Cdd:cd20978     3 FIQKPEKNVVVKGGQDVTLPCQVTGVPQPKITWLHNGKP-LQGPMERATV------------------------------ 51

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 599137400  536 stpisnsqrigvqADGQLEIQAVRASDVGSYACVVTSPGGNETRAARLSV 585
Cdd:cd20978    52 -------------EDGTLTIINVQPEDTGYYGCVATNEIGDIYTETLLHV 88

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: 48.93 E-value: 6.66e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400   72 PRFTTHPSSSgSIVSEGSTKILQCHALGYPQPTYRWLKDGVPV-GDFSSSQFYRFHST----RREDAGSYQCIARNDAGS 146
Cdd:cd20978     1 PKFIQKPEKN-VVVKGGQDVTLPCQVTGVPQPKITWLHNGKPLqGPMERATVEDGTLTiinvQPEDTGYYGCVATNEIGD 79


                  ....
gi 599137400  147 IFSE 150
Cdd:cd20978    80 IYTE 83

Fibronectin type III domain;

Pssm-ID: 394996 [Multi-domain] Cd Length: 85 Bit Score: 48.95 E-value: 7.66e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400  1113 PPFNVTVRAMSAQQLRVRWIPLqqTEWYGNPRGYNISYKQLVKTPGTIKY-VPRsvviedhTANSHVLDSLEEWTLYEVK 1191
Cdd:pfam00041    2 APSNLTVTDVTSTSLTVSWTPP--PDGNGPITGYEVEYRPKNSGEPWNEItVPG-------TTTSVTLTGLKPGTEYEVR 72

                           90
                   ....*....|...
gi 599137400  1192 MNACNDVGCSKES 1204
Cdd:pfam00041   73 VQAVNGGGEGPPS 85

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: 48.85 E-value: 9.01e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400   72 PRFTTHPSSSGsiVSEGSTKILQCHALGYPQPTYRWLKD-GVPVG---DFSSSQFYRFHS--------TRREDAGSYQCI 139
Cdd:cd20954     2 PRWIVEPVDAN--VAAGQDVMLHCQADGFPTPTVTWKKAtGSTPGeykDLLYDPNVRILPngtlvfghVQKENEGHYLCE 79


                  ....*..
gi 599137400  140 ARNDAGS 146
Cdd:cd20954    80 AKNGIGS 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: 48.65 E-value: 1.04e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400   72 PRFTTHPSSSGsiVSEGSTKILQCHALGYPQPTYRWLKDGVPVGDFSSSQFYRFHSTR---------REDAGSYQCIARN 142
Cdd:cd05744     1 PHFLQAPGDLE--VQEGRLCRFDCKVSGLPTPDLFWQLNGKPVRPDSAHKMLVRENGRhsliiepvtKRDAGIYTCIARN 78

                          90       100       110
                  ....*....|....*....|....*....|
gi 599137400  143 DAGsifseksdvvvaymgifENTTEGRLTV 172
Cdd:cd05744    79 RAG-----------------ENSFNAELVV 91

Immunoglobulin V-set domain; This domain is found in antibodies as well as neural protein P0 and CTL4 amongst others.

Pssm-ID: 462230 Cd Length: 109 Bit Score: 48.99 E-value: 1.10e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400   498 QPPVDTTVLLGLTATLQCKVSSDPSVP-YNIDWYREGQSSTP------ISNSQRIGV------------QADGQLEIQAV 558
Cdd:pfam07686    1 QTPREVTVALGGSVTLPCTYSSSMSEAsTSVYWYRQPPGKGPtfliayYSNGSEEGVkkgrfsgrgdpsNGDGSLTIQNL 80

                           90       100
                   ....*....|....*....|....*...
gi 599137400   559 RASDVGSYAC-VVTSPGGNETRAARLSV 585
Cdd:pfam07686   81 TLSDSGTYTCaVIPSGEGVFGKGTRLTV 108

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: 48.17 E-value: 1.24e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400   85 VSEGSTKILQCHA-LGYPQPTYRWLKDGVPVgDFSSSQFYRFHS-------TRREDAGSYQCIARNDAGSIFSEKSDVVV 156
Cdd:cd05724     9 VAVGEMAVLECSPpRGHPEPTVSWRKDGQPL-NLDNERVRIVDDgnlliaeARKSDEGTYKCVATNMVGERESRAARLSV 87

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: 48.40 E-value: 1.25e-06

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 599137400  380 LTCDVVGEPTPQVKWFRNAEsvDAHIESGRYTLNTDNTLV-IKKLILDDAAMFQCLAINEAGENSASTWLRV 450
Cdd:cd20976    21 AQCSARGKPVPRITWIRNAQ--PLQYAADRSTCEAGVGELhIQDVLPEDHGTYTCLAKNAAGQVSCSAWVTV 90

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: 47.99 E-value: 1.36e-06

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400    701 GPPVGFVGSARSMSEIITQWQPPLEEHRNGQILGYILRYRLfgyNNVPWSyQNITNEAQRNFLIQELITWKDYIVQIAAY 780
Cdd:smart00060    2 SPPSNLRVTDVTSTSVTLSWEPPPDDGITGYIVGYRVEYRE---EGSEWK-EVNVTPSSTSYTLTGLKPGTEYEFRVRAV 77


                    ....*.
gi 599137400    781 NNMGVG 786
Cdd:smart00060   78 NGAGEG 83

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: 48.17 E-value: 1.45e-06

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 599137400   92 ILQCHALGYPQPTYRWLKDGVP----------VGDFSSSQFYRFHSTRRED-AGSYQCIARNDAGSIFSEKSDVV 155
Cdd:cd05733    20 TIKCEAKGNPQPTFRWTKDGKFfdpakdprvsMRRRSGTLVIDNHNGGPEDyQGEYQCYASNELGTAISNEIRLV 94

Fibronectin type III domain;

Pssm-ID: 394996 [Multi-domain] Cd Length: 85 Bit Score: 47.79 E-value: 1.63e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400   701 GPPVGFVGSARSMSEIITQWQPPleEHRNGQILGYILRYRLFGyNNVPWSYQNITNEaQRNFLIQELITWKDYIVQIAAY 780
Cdd:pfam00041    1 SAPSNLTVTDVTSTSLTVSWTPP--PDGNGPITGYEVEYRPKN-SGEPWNEITVPGT-TTSVTLTGLKPGTEYEVRVQAV 76


                   ....*....
gi 599137400   781 NNMGVGVYT 789
Cdd:pfam00041   77 NGGGEGPPS 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: 48.03 E-value: 1.69e-06

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 599137400  373 EFGGQVQLTCDVVGEPTPQVKWFRNAESVDaHIESGRYTLNTDNT-LVIKKLILDDAAMFQCLAINEAG 440
Cdd:cd05736    13 EPGVEASLRCHAEGIPLPRVQWLKNGMDIN-PKLSKQLTLIANGSeLHISNVRYEDTGAYTCIAKNEGG 80

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: 48.32 E-value: 1.74e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400  494 TQIIQPPVDTTVLLGLTATLQCKVSSDPSVPYNIDWYREGQS---STPISNSQRIGVQAD-GQLEIQAVRASDVGSYACV 569
Cdd:cd04970     3 TRITLAPSNADITVGENATLQCHASHDPTLDLTFTWSFNGVPidlEKIEGHYRRRYGKDSnGDLEIVNAQLKHAGRYTCT 82

                          90
                  ....*....|....*.
gi 599137400  570 VTSPGGNETRAARLSV 585
Cdd:cd04970    83 AQTVVDSDSASATLVV 98

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: 47.93 E-value: 1.77e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400   88 GSTKILQCHALGYPQPTYRWLK-DGVPVGDF---SSSQFYRFHSTRREDAGSYQCIARNDAGsifseksdvvvaymgifE 163
Cdd:cd04968    16 GQTVTLECFALGNPVPQIKWRKvDGSPSSQWeitTSEPVLEIPNVQFEDEGTYECEAENSRG-----------------K 78


                  ....*....
gi 599137400  164 NTTEGRLTV 172
Cdd:cd04968    79 DTVQGRIIV 87

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: 47.84 E-value: 1.78e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400  365 PMRAETFGEFGGQVQLTCDVVGEPTPQVKWFRNAESVdahIESGRYTLNTDNTLVIKKLILDDAAMFQCLAINEAGENSA 444
Cdd:cd04969     7 PVKKKILAAKGGDVIIECKPKASPKPTISWSKGTELL---TNSSRICILPDGSLKIKNVTKSDEGKYTCFAVNFFGKANS 83


                  ....*.
gi 599137400  445 STWLRV 450
Cdd:cd04969    84 TGSLSV 89

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: 47.77 E-value: 2.25e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400  371 FGEFGGQVQLTCDVVGEPTPQVKWFRNAESVDAHIESGRYTLNTDNTLVIKKLILDDAAMFQCLAINEAGENSASTWLRV 450
Cdd:cd20969    13 FVDEGHTVQFVCRADGDPPPAILWLSPRKHLVSAKSNGRLTVFPDGTLEVRYAQVQDNGTYLCIAANAGGNDSMPAHLHV 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: 47.66 E-value: 2.74e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400   76 THPSSSGSIVSEGSTKILQCHALGYPQPTYRWLKDG----------VPVGDFSSSQFYRFHSTRRED--AGSYQCIARND 143
Cdd:cd05875     4 TKQSAKDYIVDPRDNILIECEAKGNPVPTFHWTRNGkffnvakdprVSMRRRSGTLVIDFRGGGRPEdyEGEYQCFARNK 83


                  ....*...
gi 599137400  144 AGSIFSEK 151
Cdd:cd05875    84 FGTALSNK 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: 47.24 E-value: 2.81e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400  495 QIIQPPVDTTVLLGLTATLQCKVSSDPSVpyNIDWYREgqsSTPISNSQRIGVQADGQLEIQAVRASDVGSYACVV-TSP 573
Cdd:cd20968     1 KITRPPTNVTIIEGLKAVLPCTTMGNPKP--SVSWIKG---DDLIKENNRIAVLESGSLRIHNVQKEDAGQYRCVAkNSL 75

                          90
                  ....*....|..
gi 599137400  574 GGNETRAARLSV 585
Cdd:cd20968    76 GIAYSKPVTIEV 87

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: 47.28 E-value: 2.99e-06

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 599137400  460 PPQNVTALDGKDATISCRAVGSPNPNITWIYNVRTQIIQPP-----VDTTVLL------GLTATLQCKVSSD 520
Cdd:cd05868     5 APTNLVLSPGEDGTLICRANGNPKPSISWLTNGVPIEIAPTdpsrkVDGDTIIfskvqeRSSAVYQCNASNE 76

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: 47.09 E-value: 3.37e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400  505 VLLGLTATLQCKVSSDPSvPyNIDWYreGQSSTPISNSQRIGVQADGQLEIQAVRASDVGSYACVVTSPGGNETRAARLS 584
Cdd:cd05764    12 VLEGQRATLRCKARGDPE-P-AIHWI--SPEGKLISNSSRTLVYDNGTLDILITTVKDTGAFTCIASNPAGEATARVELH 87


                  .
gi 599137400  585 V 585
Cdd:cd05764    88 I 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: 47.31 E-value: 3.60e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400   84 IVSEGSTKILQCHALGYPQPTYRWLKDGVPVGDFSS--------SQFYRFHSTRREDAGSYQCIARNDAGSIFSEKSDVV 155
Cdd:cd05738    10 VVEKARTATMLCAASGNPDPEISWFKDFLPVDTATSngrikqlrSGALQIENSEESDQGKYECVATNSAGTRYSAPANLY 89


                  .
gi 599137400  156 V 156
Cdd:cd05738    90 V 90

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: 48.04 E-value: 3.84e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400  375 GGQVQLTCDVVGEPTPQVKW--------------FRNAESVDAHIESgRYTLNTDNTLVIKKLILDDAAMFQCLAINEAG 440
Cdd:cd20940    15 GDSVELHCEAVGSPIPEIQWwfegqepneicsqlWDGARLDRVHINA-TYHQHATSTISIDNLTEEDTGTYECRASNDPD 93

                          90
                  ....*....|.
gi 599137400  441 ENSASTWLRVK 451
Cdd:cd20940    94 RNHLTRAPKVK 104

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: 47.00 E-value: 3.96e-06

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 599137400  508 GLTATLQCKVSSDPsvPYNIDWYREGQSSTPISNSQRIGVQADGQLEIQAVRASDVGSYACVVTSPGGNETRAARLSV 585
Cdd:cd20969    17 GHTVQFVCRADGDP--PPAILWLSPRKHLVSAKSNGRLTVFPDGTLEVRYAQVQDNGTYLCIAANAGGNDSMPAHLHV 92

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: 46.86 E-value: 4.10e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400  454 APIMELPPQNVTALDGKDATISCRAVGSPNPNITWIYNVRTqiIQPPVDttvllgltatlqcKVSSDPSVpynidwyreg 533
Cdd:cd20976     1 APSFSSVPKDLEAVEGQDFVAQCSARGKPVPRITWIRNAQP--LQYAAD-------------RSTCEAGV---------- 55

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|..
gi 599137400  534 qsstpisnsqrigvqadGQLEIQAVRASDVGSYACVVTSPGGNETRAARLSV 585
Cdd:cd20976    56 -----------------GELHIQDVLPEDHGTYTCLAKNAAGQVSCSAWVTV 90

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: 47.21 E-value: 4.19e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400   72 PRFTT--------HPSSSGSIVSegstkiLQCHALGYPQPTYRWLKDGVPVGDFSSSQFYR---------FHSTRREDAG 134
Cdd:cd05729     1 PRFTDtekmeereHALPAANKVR------LECGAGGNPMPNITWLKDGKEFKKEHRIGGTKveekgwsliIERAIPRDKG 74

                          90
                  ....*....|...
gi 599137400  135 SYQCIARNDAGSI 147
Cdd:cd05729    75 KYTCIVENEYGSI 87

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: 46.84 E-value: 4.39e-06

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400   1011 PHAPTALALSNIEAFSVVLQFTPGFDGNSS--ITKWKVEGQTArNMTWFTIceINDPDAETLTVTGLVPFTQYRLRLSAS 1088
Cdd:smart00060    1 PSPPSNLRVTDVTSTSVTLSWEPPPDDGITgyIVGYRVEYREE-GSEWKEV--NVTPSSTSYTLTGLKPGTEYEFRVRAV 77


                    ....*.
gi 599137400   1089 NVVGSS 1094
Cdd:smart00060   78 NGAGEG 83

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: 46.45 E-value: 4.56e-06

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400   1513 PAAPavgvGGLKVVPITTTSVRVQWSALEtalwngDASTGGYRILYQQLSDFPTALQSTPKTDVhgiNENSVVLSDLQQD 1592
Cdd:smart00060    1 PSPP----SNLRVTDVTSTSVTLSWEPPP------DDGITGYIVGYRVEYREEGSEWKEVNVTP---SSTSYTLTGLKPG 67

                            90
                    ....*....|....*.
gi 599137400   1593 RNYEIVVLPFNSQGPG 1608
Cdd:smart00060   68 TEYEFRVRAVNGAGEG 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: 46.85 E-value: 4.65e-06

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 599137400   88 GSTKILQCHALGYPQPTYRWLKDGVPVGDFSSSQFYRFHSTR-------REDAGSYQCIARNDAG 145
Cdd:cd05730    18 GQSVTLACDADGFPEPTMTWTKDGEPIESGEEKYSFNEDGSEmtildvdKLDEAEYTCIAENKAG 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: 46.42 E-value: 5.62e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400   71 APRFTTHPSSSGsiVSEGSTKILQCHALGYPQPTYRWLKDGVPVG---DFSSSQFYRFHS-----TRREDAGSYQCIARN 142
Cdd:cd20972     1 PPQFIQKLRSQE--VAEGSKVRLECRVTGNPTPVVRWFCEGKELQnspDIQIHQEGDLHSliiaeAFEEDTGRYSCLATN 78


                  ....
gi 599137400  143 DAGS 146
Cdd:cd20972    79 SVGS 82

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: 46.44 E-value: 5.64e-06

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 599137400   79 SSSGSIVSEGSTKILQCHALGYPQPTYRWLKDGVP-----VGDFSSSQFYRFHSTRREDAGSYQCIARNDAGS 146
Cdd:cd05876     1 SSSSLVALRGQSLVLECIAEGLPTPTVKWLRPSGPlppdrVKYQNHNKTLQLLNVGESDDGEYVCLAENSLGS 73

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: 46.84 E-value: 5.97e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400   72 PRFTTHPSSSgsIVSEGSTK---ILQCHALGYPQPTYRWLKDGVPVgDFSSSQFYRF--------HSTRREDAGSYQCIA 140
Cdd:cd05850     3 PVFEEQPSST--LFPEGSAEekvTLACRARASPPATYRWKMNGTEL-KMEPDSRYRLvagnlvisNPVKAKDAGSYQCLA 79

                          90
                  ....*....|....*...
gi 599137400  141 RNDAGSIFSEKSDVVVAY 158
Cdd:cd05850    80 SNRRGTVVSREASLRFGF 97

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: 46.51 E-value: 8.47e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400  364 TPMRAETFGEfGGQVQLTCDVVGEPTPQVKWFRNAE---------SVDAHIE-SGRYtlnTDNTLVIKKLILDDAAMFQC 433
Cdd:cd05870     6 IQLKNETTVE-NGAATLSCKAEGEPIPEITWKRASDghtfsegdkSPDGRIEvKGQH---GESSLHIKDVKLSDSGRYDC 81

                          90
                  ....*....|....*..
gi 599137400  434 LAINEAGENSASTWLRV 450
Cdd:cd05870    82 EAASRIGGHQKSMYLDI 98

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: 45.52 E-value: 1.11e-05

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 599137400  380 LTCDVVGEPTPQVKWFRNAESVDAHIESGRYTLNTDnTLVIKKLILDDAAMFQCLAINEAGENSASTWLRV 450
Cdd:cd04978    19 LICEAEGNPQPTITWRLNGVPIEPAPEDMRRTVDGR-TLIFSNLQPNDTAVYQCNASNVHGYLLANAFLHV 88

Fibronectin type III domain;

Pssm-ID: 394996 [Multi-domain] Cd Length: 85 Bit Score: 45.48 E-value: 1.22e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400  1321 PSNVSFPDVSLTMARIIWDVPVDPNGKILAYQVTY-TLNGSAMLNYSREfPPSDRTFRATELLPGKYYSFSCTAQTRLGW 1399
Cdd:pfam00041    3 PSNLTVTDVTSTSLTVSWTPPPDGNGPITGYEVEYrPKNSGEPWNEITV-PGTTTSVTLTGLKPGTEYEVRVQAVNGGGE 81


                   ..
gi 599137400  1400 GK 1401
Cdd:pfam00041   82 GP 83

Immunoglobulin (Ig) variable (V) domain of T-cell receptor (TCR) alpha chain and similar proteins; The members here are composed of the immunoglobulin (Ig) variable domain of the alpha chain of alpha/beta T-cell antigen receptors (TCRs). TCRs mediate antigen recognition by T lymphocytes, and are composed of alpha and beta, or gamma and delta polypeptide chains with variable (V) and constant (C) regions. This group represents the variable domain of the alpha chain of TCRs and also includes the variable domain of delta chains of TCRs. Alpha/beta TCRs recognize antigen as peptide fragments presented by major histocompatibility complex (MHC) molecules. The variable domain of TCRs is responsible for antigen recognition, and is located at the N-terminus of the receptor. Gamma/delta TCRs recognize intact protein antigens directly without antigen processing and recognize MHC independently of the bound peptide. Members of this group contain standard Ig superfamily V-set AGFCC'C"/DEB domain topology.

Pssm-ID: 409372 [Multi-domain] Cd Length: 109 Bit Score: 46.11 E-value: 1.38e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400  496 IIQPPVDTTVLLGLTATLQCKVSSdpSVPYNIDWYREGQSSTPIS-----------NSQRIGVQAD-----GQLEIQAVR 559
Cdd:cd04983     1 VTQSPQSLSVQEGENVTLNCNYST--STFYYLFWYRQYPGQGPQFliyissdsgnkKKGRFSATLDksrksSSLHISAAQ 78

                          90
                  ....*....|....*...
gi 599137400  560 ASDVGSYACVVTSPGGNE 577
Cdd:cd04983    79 LSDSAVYFCALSESGGTG 96

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: 45.30 E-value: 1.40e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400  500 PVDTTVLLGLTATLQCKVSSDPSvPyNIDWYREGQSSTPISNSQRIGVQA-DGQLEIQAVRASDVGSYACVVTSPGGNET 578
Cdd:cd05763     6 PHDITIRAGSTARLECAATGHPT-P-QIAWQKDGGTDFPAARERRMHVMPeDDVFFIVDVKIEDTGVYSCTAQNSAGSIS 83


                  ....*...
gi 599137400  579 RAARLSVI 586
Cdd:cd05763    84 ANATLTVL 91

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: 45.26 E-value: 1.72e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400  497 IQPPVDTTVLLGLTATLQCKVSSDPSvPyNIDWYREGQsstPISNSQRIGVQADGQ----LEIQAVRASDVGSYACVVTS 572
Cdd:cd20973     1 IQTLRDKEVVEGSAARFDCKVEGYPD-P-EVKWMKDDN---PIVESRRFQIDQDEDglcsLIISDVCGDDSGKYTCKAVN 75

                          90
                  ....*....|...
gi 599137400  573 PGGNETRAARLSV 585
Cdd:cd20973    76 SLGEATCSAELTV 88

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: 45.24 E-value: 1.76e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400   72 PRFTTHPSSSGSIVSE--GSTKILQCHALGYPQPTYRWLKDGVP-----VGDFSSSQF-YRFHSTRREDAGSYQCIARND 143
Cdd:cd05856     1 PRFTQPAKMRRRVIARpvGSSVRLKCVASGNPRPDITWLKDNKPltppeIGENKKKKWtLSLKNLKPEDSGKYTCHVSNR 80


                  ....
gi 599137400  144 AGSI 147
Cdd:cd05856    81 AGEI 84

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: 44.87 E-value: 2.26e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400   83 SIVSeGSTKILQCHALGYPQPTYRWLKDG--VPVGD----FSSSQFYRFHSTRREDAGSYQCIARNDAGSIFSEKSDVVV 156
Cdd:cd20958    11 TAVA-GQTLRLHCPVAGYPISSITWEKDGrrLPLNHrqrvFPNGTLVIENVQRSSDEGEYTCTARNQQGQSASRSVFVKV 89

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: 44.93 E-value: 2.30e-05

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 599137400  377 QVQLTCDVVGEPTPQVKWFRNAESVDahIESG-RYTLnTDNTLVIKKLI-LDDAAMFQCLAINEAG 440
Cdd:cd05848    21 KVILNCEARGNPVPTYRWLRNGTEID--TESDyRYSL-IDGNLIISNPSeVKDSGRYQCLATNSIG 83

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: 44.49 E-value: 2.68e-05

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400   85 VSEGSTKILQCHALGYPQPTYRWLKDGVPVGDFSSSQFYR---------FHSTRREDAGSYQCIARNDAG 145
Cdd:cd20973     9 VVEGSAARFDCKVEGYPDPEVKWMKDDNPIVESRRFQIDQdedglcsliISDVCGDDSGKYTCKAVNSLG 78

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: 44.39 E-value: 2.68e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400   72 PRFTTHpsSSGSIVSEGSTKILQCHALGYPQPTYRWLK-DGVPVGDFSSSQFYRFHS-----TRREDAGSYQCIARNDAG 145
Cdd:cd05764     1 PLITRH--THELRVLEGQRATLRCKARGDPEPAIHWISpEGKLISNSSRTLVYDNGTldiliTTVKDTGAFTCIASNPAG 78

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: 2.75e-05

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 599137400  375 GGQVQLTCDVVGEPTPQVKWFRN-AESVDAHIESGRYTLNTDNTLVIKKLILDDAAMFQCLAINEAGENSASTWLRV 450
Cdd:cd05763    14 GSTARLECAATGHPTPQIAWQKDgGTDFPAARERRMHVMPEDDVFFIVDVKIEDTGVYSCTAQNSAGSISANATLTV 90

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: 44.84 E-value: 2.79e-05

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 599137400   85 VSEGSTKILQCHALGYPQPTYRWLKDGVPVGDFSSSQFYRF---------HSTRREDAGSYQCIARNDAGSI 147
Cdd:cd05857    16 VPAANTVKFRCPAAGNPTPTMRWLKNGKEFKQEHRIGGYKVrnqhwslimESVVPSDKGNYTCVVENEYGSI 87

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: 44.59 E-value: 3.07e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400  364 TPMRAETFGEFGGQVQLTCDVVGEPTPQVKW-------FRNAESVDAHI---ESGRYTlntdnTLVIKKLILDDAAMFQC 433
Cdd:cd05869     6 TYVENQTAMELEEQITLTCEASGDPIPSITWrtstrniSSEEKTLDGHIvvrSHARVS-----SLTLKYIQYTDAGEYLC 80

                          90
                  ....*....|....*..
gi 599137400  434 LAINEAGENSASTWLRV 450
Cdd:cd05869    81 TASNTIGQDSQSMYLEV 97

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: 44.54 E-value: 3.12e-05

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 599137400  376 GQVQLTCDVVGEPTPQVKWFRNAESVDAHIESgRYTLnTDNTLVIKKLI-LDDAAMFQCLAINEAG 440
Cdd:cd04967    20 KKVALNCRARANPVPSYRWLMNGTEIDLESDY-RYSL-VDGTLVISNPSkAKDAGHYQCLATNTVG 83

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: 44.50 E-value: 3.56e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400  495 QIIQPPVDTTVLLGLTATLQCKVSSDPsvPYNIDWYREGQSstpISNSQRIGVQADGQLE---IQAVRASDVGSYACVVT 571
Cdd:cd20972     3 QFIQKLRSQEVAEGSKVRLECRVTGNP--TPVVRWFCEGKE---LQNSPDIQIHQEGDLHsliIAEAFEEDTGRYSCLAT 77

                          90
                  ....*....|....
gi 599137400  572 SPGGNETRAARLSV 585
Cdd:cd20972    78 NSVGSDTTSAEIFV 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: 44.14 E-value: 3.77e-05

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400   1318 PGVPSNVSFPDVSLTMARIIWDVPVDPN--GKILAYQVTYTLNGSAMLNYSRefPPSDRTFRATELLPGKYYSFSCTAQT 1395
Cdd:smart00060    1 PSPPSNLRVTDVTSTSVTLSWEPPPDDGitGYIVGYRVEYREEGSEWKEVNV--TPSSTSYTLTGLKPGTEYEFRVRAVN 78


                    ....*
gi 599137400   1396 RLGWG 1400
Cdd:smart00060   79 GAGEG 83

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: 3.84e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400  496 IIQPPVDTTVLLGLTATLQCKVSSDPsVPyNIDWYREGQSSTPisnsQRIGVQADGQLEIQAVRASDVGSYACVVTSPGG 575
Cdd:cd04968     4 KVRFPADTYALKGQTVTLECFALGNP-VP-QIKWRKVDGSPSS----QWEITTSEPVLEIPNVQFEDEGTYECEAENSRG 77

                          90
                  ....*....|
gi 599137400  576 NETRAARLSV 585
Cdd:cd04968    78 KDTVQGRIIV 87

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: 44.56 E-value: 3.97e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400   73 RFTTHPSSSgsIVSEGSTKILQCHALGYPQPTYRWLKDGV-----------PVGDFSSSQFYRFHST--RREDAGSYQCI 139
Cdd:cd05726     1 QFVVKPRDQ--VVALGRTVTFQCETKGNPQPAIFWQKEGSqnllfpyqppqPSSRFSVSPTGDLTITnvQRSDVGYYICQ 78

                          90       100
                  ....*....|....*....|
gi 599137400  140 ARNDAGSIFS----EKSDVV 155
Cdd:cd05726    79 ALNVAGSILAkaqlEVTDVL 98

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: 4.59e-05

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 599137400  375 GGQVQLTCDVVGEPTPQVKWFRNAESVDAHIES--GRYTLNTDNtlvikkliLDDAAMFQCLAINEAGENSASTWLRVK 451
Cdd:cd05739    12 GGSVNLTCVAVGAPMPYVKWMKGGEELTKEDEMpvGRNVLELTN--------IYESANYTCVAISSLGMIEATAQVTVK 82

Third immunoglobulin (Ig)-like domain of fibroblast growth factor receptor (FGFR); member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig)-like domain of fibroblast growth factor receptor (FGFR). 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. 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: 409363 Cd Length: 102 Bit Score: 44.34 E-value: 5.06e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400  373 EFGGQVQLTCDVVGEPTPQVKWFRNAES------------VDAHIESGRYTLNTDNTLVIKKLILDDAAMFQCLAINEAG 440
Cdd:cd04974    14 VLGSDVEFHCKVYSDAQPHIQWLKHVEVngskygpdglpyVTVLKVAGVNTTGEENTLTISNVTFDDAGEYICLAGNSIG 93


                  ....*...
gi 599137400  441 ENSASTWL 448
Cdd:cd04974    94 LSFHSAWL 101

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: 43.73 E-value: 5.29e-05

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 599137400  375 GGQVQLTCDVVGEPTPQVKWFRNAESVDAHIESGRYTLNTdNTLVIKKLILDDAAMFQCLAINEAGENSASTWLRV 450
Cdd:cd05867    14 GETARLDCQVEGIPTPNITWSINGAPIEGTDPDPRRHVSS-GALILTDVQPSDTAVYQCEARNRHGNLLANAHVHV 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: 44.08 E-value: 5.44e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400  495 QIIQPPVDTTVLLGLTATLQCKVSSDPSvPyNIDWYREGQ---SSTPISNSQRIGVQADGQLEIQAVRA----SDVGSYA 567
Cdd:cd07693     2 RIVEHPSDLIVSKGDPATLNCKAEGRPT-P-TIQWLKNGQpleTDKDDPRSHRIVLPSGSLFFLRVVHGrkgrSDEGVYV 79

                          90
                  ....*....|....*....
gi 599137400  568 CVVTSPGGNET-RAARLSV 585
Cdd:cd07693    80 CVAHNSLGEAVsRNASLEV 98

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: 6.09e-05

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 599137400   92 ILQCHALGYPQPTYRWLKDGVPVGDFSSSQFYRFHSTR-----REDAGSYQCIARNDAGSI 147
Cdd:cd05723    16 VFECEVTGKPTPTVKWVKNGDVVIPSDYFKIVKEHNLQvlglvKSDEGFYQCIAENDVGNA 76

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: 43.69 E-value: 6.20e-05

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 599137400  368 AETFGEFGGQVQLTCDVVGEPTPQVKWFRnaesVDAHIESGRYTLNTDNTLVIKKLILDDAAMFQCLAINEAGENSA 444
Cdd:cd04968     9 ADTYALKGQTVTLECFALGNPVPQIKWRK----VDGSPSSQWEITTSEPVLEIPNVQFEDEGTYECEAENSRGKDTV 81

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: 7.10e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400  364 TPMRAETFGEF----GGQVQLTCDVVGEPTPQVKWFRNAESVDahiESGRYTLNT----DNTLV----IKKLILDDAAMF 431
Cdd:cd20956     1 APVLLETFSEQtlqpGPSVSLKCVASGNPLPQITWTLDGFPIP---ESPRFRVGDyvtsDGDVVsyvnISSVRVEDGGEY 77

                          90
                  ....*....|....*....
gi 599137400  432 QCLAINEAGENSASTWLRV 450
Cdd:cd20956    78 TCTATNDVGSVSHSARINV 96

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: 42.70 E-value: 7.99e-05

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 599137400  280 ELQCIANARPLHELEtlWLKDGLAVETAGVRHTLNDPWNRTLALLQANSSHSGEYTCQVRLRSGG 344
Cdd:cd00096     2 TLTCSASGNPPPTIT--WYKNGKPLPPSSRDSRRSELGNGTLTISNVTLEDSGTYTCVASNSAGG 64

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: 42.96 E-value: 9.60e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400  375 GGQVQLTCDVVGEPTPQVKWFRN----AESVDAHIESGRytlnTDNTLVIKKLILDDAAMFQCLAINEAGENSASTWLRV 450
Cdd:cd05748     7 GESLRLDIPIKGRPTPTVTWSKDgqplKETGRVQIETTA----SSTSLVIKNAKRSDSGKYTLTLKNSAGEKSATINVKV 82

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: 42.68 E-value: 1.13e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400  359 PPLFFTPMRAETFGEFGGQVQLTCDVVGEPTPQVKWFRNAESVdahIESGRYTLNTDNTLVIKKLILDDAAMFQCLAINE 438
Cdd:cd05852     1 PTFEFNPMKKKILAAKGGRVIIECKPKAAPKPKFSWSKGTELL---VNNSRISIWDDGSLEILNITKLDEGSYTCFAENN 77

                          90
                  ....*....|..
gi 599137400  439 AGENSASTWLRV 450
Cdd:cd05852    78 RGKANSTGVLSV 89

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: 42.44 E-value: 1.35e-04

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400  460 PPQNVTALDGKDATISCRAVGSPNPNITWIYNVRTQIIQPP-----VDTTVLL------GLTATLQCKVS 518
Cdd:cd04978     5 EPPSLVLSPGETGELICEAEGNPQPTITWRLNGVPIEPAPEdmrrtVDGRTLIfsnlqpNDTAVYQCNAS 74

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: 42.39 E-value: 1.77e-04

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 599137400  375 GGQVQLTCDVVGEPTPQVKWFRNAESVDAhiESGRYTLNTDN---TLVIKKLILDDAAMFQCLAINEAGENSASTWLRV 450
Cdd:cd20990    15 GKLCRMDCKVSGLPTPDLSWQLDGKPIRP--DSAHKMLVRENgvhSLIIEPVTSRDAGIYTCIATNRAGQNSFNLELVV 91

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: 42.01 E-value: 2.49e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400  495 QIIQPPVDTTVLLGLTATLQCKVSSDPSVpyNIDWYREGQSSTPISnSQRIGVQADG--QLEIQAVRASDVGSYACVVTS 572
Cdd:cd20990     2 HFLQAPGDLTVQEGKLCRMDCKVSGLPTP--DLSWQLDGKPIRPDS-AHKMLVRENGvhSLIIEPVTSRDAGIYTCIATN 78

                          90
                  ....*....|...
gi 599137400  573 PGGNETRAARLSV 585
Cdd:cd20990    79 RAGQNSFNLELVV 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: 41.62 E-value: 2.74e-04

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 599137400  385 VGEPTPQVKWFRNAESVDahIESGRYTLNTDNTLVIKKLILDDAAMFQCLAINEAGE 441
Cdd:cd05724    23 RGHPEPTVSWRKDGQPLN--LDNERVRIVDDGNLLIAEARKSDEGTYKCVATNMVGE 77

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: 2.79e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400  469 GKDATISCRAVGSPNPNITWIYNvrtqiiqppvdttvllglTATLQCkvssdpsvpynidwyregqsstpisnSQRIGVQ 548
Cdd:cd04969    17 GGDVIIECKPKASPKPTISWSKG------------------TELLTN--------------------------SSRICIL 52

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 599137400  549 ADGQLEIQAVRASDVGSYACVVTSPGGNETRAARLSV 585
Cdd:cd04969    53 PDGSLKIKNVTKSDEGKYTCFAVNFFGKANSTGSLSV 89

Third immunoglobulin (Ig)-like domain of fibroblast growth factor receptor (FGFR); member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig)-like domain of fibroblast growth factor receptor (FGFR). 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. 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: 409363 Cd Length: 102 Bit Score: 42.02 E-value: 2.81e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400  496 IIQP--PVDTTVLLGLTATLQCKVSSDPSvPYnIDWYR--------EGQSSTP-ISNSQRIGVQADG---QLEIQAVRAS 561
Cdd:cd04974     2 ILQAglPANQTVVLGSDVEFHCKVYSDAQ-PH-IQWLKhvevngskYGPDGLPyVTVLKVAGVNTTGeenTLTISNVTFD 79


                  ....*...
gi 599137400  562 DVGSYACV 569
Cdd:cd04974    80 DAGEYICL 87

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: 42.08 E-value: 2.92e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400  500 PVDTTVLLGLTATLQCKVSSDPsvPYNIDWYREGqSSTPISNSQRIGVQADGQLEIQAVRAS-----DVGSYACVVT--S 572
Cdd:cd05722     8 PSDIVAMRGGPVVLNCSAESDP--PPKIEWKKDG-VLLNLVSDERRQQLPNGSLLITSVVHSkhnkpDEGFYQCVAQneS 84

                          90
                  ....*....|...
gi 599137400  573 PGGNETRAARLSV 585
Cdd:cd05722    85 LGSIVSRTARVTV 97

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: 41.71 E-value: 3.03e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400  497 IQPPVDTTVLLGLTATLQCKVSSDPsvPYNIDWYREGQSSTPISNSQRIgVQADGQ--LEIQAVRASDVGSYACVVTSPG 574
Cdd:cd05744     4 LQAPGDLEVQEGRLCRFDCKVSGLP--TPDLFWQLNGKPVRPDSAHKML-VRENGRhsLIIEPVTKRDAGIYTCIARNRA 80

                          90
                  ....*....|.
gi 599137400  575 GNETRAARLSV 585
Cdd:cd05744    81 GENSFNAELVV 91

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: 41.34 E-value: 3.15e-04

                            10        20        30        40        50        60        70
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 599137400    280 ELQCIANARPLHELEtlWLKDGLAVETAGVRHTL-NDPWNRTLALLQANSSHSGEYTCQVRLRSGGYpavSASARLQI 356
Cdd:smart00410   13 TLSCEASGSPPPEVT--WYKQGGKLLAESGRFSVsRSGSTSTLTISNVTPEDSGTYTCAATNSSGSA---SSGTTLTV 85

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: 41.57 E-value: 3.28e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400  359 PPLFFTPMRAETFGEfGGQVQLTCDVVGEPTPQVKWFRNAESVdahIESGRYTLNT---DNTLVIKKLILDDAAMFQCLA 435
Cdd:cd05747     3 PATILTKPRSLTVSE-GESARFSCDVDGEPAPTVTWMREGQII---VSSQRHQITSteyKSTFEISKVQMSDEGNYTVVV 78


                  ....*....
gi 599137400  436 INEAGENSA 444
Cdd:cd05747    79 ENSEGKQEA 87

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: 41.51 E-value: 3.51e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400   76 THPSSSGSIVSEGSTKILQCHALGYPQPTYRWLKDG----------VPVGDFSSSQFYRFHSTRREDA--GSYQCIARND 143
Cdd:cd05874     4 THQSPKDYIVDPRENIVIQCEAKGKPPPSFSWTRNGthfdidkdpkVTMKPNTGTLVINIMNGEKAEAyeGVYQCTARNE 83


                  ....*.
gi 599137400  144 AGSIFS 149
Cdd:cd05874    84 RGAAVS 89

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: 41.48 E-value: 4.23e-04

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400  507 LGLTATLQCKVSSDPSvPyNIDWYREGQSSTPiSNSQRIGVQADG-QLEIQAVRASDVGSYACVVTSPGG 575
Cdd:cd05736    14 PGVEASLRCHAEGIPL-P-RVQWLKNGMDINP-KLSKQLTLIANGsELHISNVRYEDTGAYTCIAKNEGG 80

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: 40.92 E-value: 4.61e-04

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 599137400  375 GGQVQLTCDVVGEPTPQVKWFrnaeSVDAHI--ESGRYTLNTDNTLVIKKLILDDAAMFQCLAINEAGENSASTWLRV 450
Cdd:cd05764    15 GQRATLRCKARGDPEPAIHWI----SPEGKLisNSSRTLVYDNGTLDILITTVKDTGAFTCIASNPAGEATARVELHI 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: 41.16 E-value: 5.20e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400   73 RFTTHPSssGSIVSEGSTKILQCHALGYPQPTYRWLKDGVPV-GDFSSSQFYR-------FHSTRREDAGSYQCIARNda 144
Cdd:cd20949     1 TFTENAY--VTTVKEGQSATILCEVKGEPQPNVTWHFNGQPIsASVADMSKYRiladgllINKVTQDDTGEYTCRAYQ-- 76

                          90
                  ....*....|.
gi 599137400  145 gsIFSEKSDVV 155
Cdd:cd20949    77 --VNSIASDMQ 85

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: 40.31 E-value: 5.28e-04

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 599137400   87 EGSTKILQCHALGYPQPTYRWLKDGVPVG-----DFSSSQFYRFHSTRREDAGSYQCIARNDAGS 146
Cdd:cd05745     1 EGQTVDFLCEAQGYPQPVIAWTKGGSQLSvdrrhLVLSSGTLRISRVALHDQGQYECQAVNIVGS 65

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: 5.60e-04

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 599137400   84 IVSEGSTKILQCHALGYPQPTYRWLKDG--VPVGDFS--SSQFYRFHSTRREDAGSYQCIARNDAGSI 147
Cdd:cd05725     8 VVLVDDSAEFQCEVGGDPVPTVRWRKEDgeLPKGRYEilDDHSLKIRKVTAGDMGSYTCVAENMVGKI 75

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: 40.66 E-value: 6.24e-04

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 599137400  375 GGQVQLTCDVVGEPTPQVKWFRNAESVDAH------IESGRYTlntdnTLVIKKLILDDAAMFQCLAINEAG 440
Cdd:cd05891    16 GKTLNLTCTVFGNPDPEVIWFKNDQDIELSehysvkLEQGKYA-----SLTIKGVTSEDSGKYSINVKNKYG 82

Second Ig-like domain of Junctional adhesion molecule-1 (JAM1); a member of the I-set of IgSF domains; The members here are composed of the second Ig-like domain of Junctional adhesion molecule-1 (JAM1). JAM1 is an immunoglobulin superfamily (IgSF) protein with two Ig-like domains in its extracellular region; it plays a role in the formation of endothelial and epithelial tight junction and acts as a receptor for mammalian reovirus sigma-1. The 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 second Ig-like domain of JAM1 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, the A strand of the I-set is discontinuous but lacks 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: 409542 Cd Length: 97 Bit Score: 41.15 E-value: 6.24e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400   78 PSSsgsiVSEGSTKILQCHAL-GYPQPTYRWLKDGVPV-GDFSSSQFYR--------------FHSTRREDAGSYQCIAR 141
Cdd:cd20950     6 PSS----ATIGNRAVLTCSEPdGSPPSEYTWFKDGVVMpTNPKSTRAFSnssysldpttgelvFDPLSASDTGEYSCEAR 81


                  ....*
gi 599137400  142 NDAGS 146
Cdd:cd20950    82 NGYGT 86

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: 41.09 E-value: 6.41e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400  495 QIIQPPVDTTVLLGLTATLQCKVSSdpSVPYNIDWYRegqSSTPISNSQRIGV---QADGQLEIQAVRASDVGSYACVVT 571
Cdd:cd05762     3 QIIQFPEDMKVRAGESVELFCKVTG--TQPITCTWMK---FRKQIQEGEGIKIentENSSKLTITEGQQEHCGCYTLEVE 77

                          90       100
                  ....*....|....*....|..
gi 599137400  572 SPGGNETRAARLSVIELPFPPS 593
Cdd:cd05762    78 NKLGSRQAQVNLTVVDKPDPPA 99

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: 40.78 E-value: 6.77e-04

                          10        20        30
                  ....*....|....*....|....*....|...
gi 599137400  461 PQNVTALDGKDATISCRAVGSPNPNITWIYNVR 493
Cdd:cd20949     6 AYVTTVKEGQSATILCEVKGEPQPNVTWHFNGQ 38

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: 40.51 E-value: 6.87e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400   76 THPSSSGSIVSEGSTKILQCHALGYPQPTYRWLKDG------VPVGDFSSsqfYRFHSTRREDAGSYQCIARNDAGSifS 149
Cdd:cd16082     1 TTGSGYGFTVPQGMRISLQCQAWGSPPISYVWYKEQtnnqepIKVAALST---LLFKPAVVADSGSYFCTAKGRVGS--E 75


                  ....*.
gi 599137400  150 EKSDVV 155
Cdd:cd16082    76 QRSDIV 81

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: 40.47 E-value: 8.25e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400  363 FTPMRAETFGEFGGQ-VQLTCDVVGEPTPQVKWFRNAESVDAhiESGRYTLNTD----NTLVIKKLILDDAAMFQCLAIN 437
Cdd:cd05893     2 FFEMKLKHYKIFEGMpVTFTCRVAGNPKPKIYWFKDGKQISP--KSDHYTIQRDldgtCSLHTTASTLDDDGNYTIMAAN 79

                          90
                  ....*....|...
gi 599137400  438 EAGENSASTWLRV 450
Cdd:cd05893    80 PQGRISCTGRLMV 92

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: 40.62 E-value: 8.37e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400  495 QIIQPpvdttvllGLTATLQCKVSSDPsVPyNIDWYREGQsstPISNSQRIG----VQADGQ----LEIQAVRASDVGSY 566
Cdd:cd20956    11 QTLQP--------GPSVSLKCVASGNP-LP-QITWTLDGF---PIPESPRFRvgdyVTSDGDvvsyVNISSVRVEDGGEY 77

                          90
                  ....*....|....*....
gi 599137400  567 ACVVTSPGGNETRAARLSV 585
Cdd:cd20956    78 TCTATNDVGSVSHSARINV 96

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: 40.61 E-value: 8.64e-04

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 599137400  375 GGQVQLTCDVVGEPTPQVKWFRNAESVDAHIESGRYTLNTDN-TLVIKKLILDDAAMFQCLAINEAG 440
Cdd:cd05857    19 ANTVKFRCPAAGNPTPTMRWLKNGKEFKQEHRIGGYKVRNQHwSLIMESVVPSDKGNYTCVVENEYG 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: 40.20 E-value: 1.01e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400  462 QNVTALDGKDATISCRAVGSPNPNITWIYNVRtqiiqppvdttvllGLTATlqckvssdpsvpynidwyrEGQSSTPISN 541
Cdd:cd05732     9 ENQTAVELEQITLTCEAEGDPIPEITWRRATR--------------GISFE-------------------EGDLDGRIVV 55

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 599137400  542 SQRIGVQAdgqLEIQAVRASDVGSYACVVTSPGGNETRAARLSV 585
Cdd:cd05732    56 RGHARVSS---LTLKDVQLTDAGRYDCEASNRIGGDQQSMYLEV 96

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: 40.38 E-value: 1.04e-03

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 599137400  510 TATLQCKVSSDPSvPyNIDWYREGQSSTPISNSQRIGVQADGQLEIQAVRASDVGSYACVVTSPGG 575
Cdd:cd05738    16 TATMLCAASGNPD-P-EISWFKDFLPVDTATSNGRIKQLRSGALQIENSEESDQGKYECVATNSAG 79

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: 40.31 E-value: 1.08e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400  492 VRTQIIQPPVDTTVllGLTATLQCKVSSDPSvpyNIDWYREgQSSTPISNSQRIGVQADG----QLEIQAVRASDVGSYA 567
Cdd:cd04977     1 LQVKIIPSYAEISV--GESKFFLCKVSGDAK---NINWVSP-NGEKVLTKHGNLKVVNHGsvlsSLTIYNANINDAGIYK 74

                          90
                  ....*....|...
gi 599137400  568 CVVTSPGGNETRA 580
Cdd:cd04977    75 CVATNGKGTESEA 87

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: 40.00 E-value: 1.15e-03

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 599137400  382 CDVVGEPTPQVKWFRNAESVDAHIESGRYTLNTDNTLVIKKLILDDAAMFQCLAINEAGEN-SASTWLRVK 451
Cdd:cd05738    21 CAASGNPDPEISWFKDFLPVDTATSNGRIKQLRSGALQIENSEESDQGKYECVATNSAGTRySAPANLYVR 91

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: 40.09 E-value: 1.27e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400   71 APRFTTHPSSSGSIVSEGSTKIlQCHALGYPQPTYRWLK-DGVPVGD------FSSSQFYRFHSTRRED------AGSYQ 137
Cdd:cd20955     1 GPVFLKEPTNRIDFSNSTGAEI-ECKASGNPMPEIIWIRsDGTAVGDvpglrqISSDGKLVFPPFRAEDyrqevhAQVYA 79

                          90
                  ....*....|....*..
gi 599137400  138 CIARNDAGSIFSEKSDV 154
Cdd:cd20955    80 CLARNQFGSIISRDVHV 96

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: 39.80 E-value: 1.36e-03

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 599137400  281 LQCIANARPlhELETLWLKDGLAVETAGVRHTLNDpWNRTLALLQANSSHSGEYTCqvRLRSGGYPAVSASARLQI 356
Cdd:cd20970    22 FMCRAEGSP--EPEISWTRNGNLIIEFNTRYIVRE-NGTTLTIRNIRRSDMGIYLC--IASNGVPGSVEKRITLQV 92

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: 1.40e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400  494 TQIIQPPVDTTVLLGLTATLQCKVSSDPSVPYNIDWYREGQ---SSTPISNSQRIGVQ-ADGQLEIQAVRASDVGSYACV 569
Cdd:cd05853     3 TRVMVPPSSMDVTVGESIVLPCQVSHDHSLDIVFTWSFNGHlidFQKDGDHFERVGGQdSAGDLMIRSIQLKHAGKYVCM 82

                          90
                  ....*....|....*.
gi 599137400  570 VTSPGGNETRAARLSV 585
Cdd:cd05853    83 VQTSVDKLSAAADLIV 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: 39.49 E-value: 1.53e-03

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 599137400   88 GSTKILQCHALGYPQPTYRWLKDGVPVGDFSSSQFYRFHS-------TRREDAGSYQCIARNDAGSI 147
Cdd:cd05867    14 GETARLDCQVEGIPTPNITWSINGAPIEGTDPDPRRHVSSgaliltdVQPSDTAVYQCEARNRHGNL 80

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

Pssm-ID: 464026 [Multi-domain] Cd Length: 79 Bit Score: 39.30 E-value: 1.64e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400   496 IIQPPvDTTVLLGLTATLQCKVSSDPsvPYNIDWYREGqssTPISNSQRigvqadgqLEIQAVRASDVGSYACVVTSPGG 575
Cdd:pfam13895    3 VLTPS-PTVVTEGEPVTLTCSAPGNP--PPSYTWYKDG---SAISSSPN--------FFTLSVSAEDSGTYTCVARNGRG 68


                   ....*
gi 599137400   576 NETRA 580
Cdd:pfam13895   69 GKVSN 73

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: 39.49 E-value: 1.72e-03

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 599137400    78 PSSSGSIVSEGSTKILQCHA-LGYPQPTYRWLKDG----------VPVGDFSSSQFYrFHSTRREDAGSYQCIARN 142
Cdd:pfam00047    1 SAPPTVTVLEGDSATLTCSAsTGSPGPDVTWSKEGgtlieslkvkHDNGRTTQSSLL-ISNVTKEDAGTYTCVVNN 75

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: 39.37 E-value: 1.84e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400  497 IQPPVDTTVLLGLTATLQCKVSSDPsvPYNIDWYREGQSSTpiSNSQRIGVQADGQ----LEIQAVRASDVGSYACVVTS 572
Cdd:cd05892     4 IQKPQNKKVLEGDPVRLECQISAIP--PPQIFWKKNNEMLQ--YNTDRISLYQDNCgricLLIQNANKKDAGWYTVSAVN 79

                          90
                  ....*....|...
gi 599137400  573 PGGNETRAARLSV 585
Cdd:cd05892    80 EAGVVSCNARLDV 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: 39.30 E-value: 1.91e-03

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 599137400   85 VSEGSTKILQCHALGYPQPTYRWLKDGV-PVGDFSSSQF-------YRFHSTRREDAGSYQCIARNDAG 145
Cdd:cd20969    14 VDEGHTVQFVCRADGDPPPAILWLSPRKhLVSAKSNGRLtvfpdgtLEVRYAQVQDNGTYLCIAANAGG 82

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: 39.94 E-value: 1.94e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400  360 PLFFTPMRAETFGEFGGQVQLTCDVVGEPTPQVKWFRNAES------------VDAHIESGRYTLNTD-NTLVIKKLILD 426
Cdd:cd05858     1 PILQAGLPANTSVVVGTDAEFVCKVYSDAQPHIQWLKHVEKngskygpdglpyVEVLKTAGVNTTDKEiEVLYLRNVTFE 80

                          90       100
                  ....*....|....*....|....
gi 599137400  427 DAAMFQCLAINEAGENSASTWLRV 450
Cdd:cd05858    81 DAGEYTCLAGNSIGISHHSAWLTV 104

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: 39.64 E-value: 2.23e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400  281 LQCIANARPLHELETLWLKDGLAVE---------TAGVRHTLNDpwnrtLALLQANSSHSGEYTC--QVRLRSggypaVS 349
Cdd:cd05854    22 LQCHASHDPTMDLTFTWSLDDFPIDldkpnghyrRMEVKETIGD-----LVIVNAQLSHAGTYTCtaQTVVDS-----AS 91

                          90
                  ....*....|.
gi 599137400  350 ASARLQILEPP 360
Cdd:cd05854    92 ASATLVVRGPP 102

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: 2.32e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400  370 TFGEfGGQVQLTCDVVGEPTPQVKWFRNAESVDAHIESG-RYTLNTDNtLVIKKLILDDAAMFQCLAINEAGENSASTWL 448
Cdd:cd20949    10 TVKE-GQSATILCEVKGEPQPNVTWHFNGQPISASVADMsKYRILADG-LLINKVTQDDTGEYTCRAYQVNSIASDMQER 87


                  ..
gi 599137400  449 RV 450
Cdd:cd20949    88 TV 89

Immunoglobulin (Ig)-like domain of human carcinoembryonic antigen (CEA) related cell adhesion molecule (CEACAM) domains 2, 4, and 6, and similar domains; The members here are composed of the second, fourth, and sixth immunoglobulin (Ig)-like domains in human carcinoembryonic antigen (CEA) related cell adhesion molecule (CEACAM) protein subfamily. 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. This group represents the CEACAM subfamily. CEACAM1 has many important cellular functions; it is a cell adhesion molecule and a signaling molecule that regulates the growth of tumor cells, an angiogenic factor, and a receptor for bacterial and viral pathogens, including mouse hepatitis virus (MHV). In mice, four isoforms of CEACAM1 generated by alternative splicing have either two [D1, D4] or four [D1-D4] Ig-like domains on the cell surface.

Pssm-ID: 409402 [Multi-domain] Cd Length: 89 Bit Score: 38.91 E-value: 2.76e-03

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 599137400  104 TYRWLKDGV--PVGD---FS-SSQFYRFHSTRREDAGSYQCIARNDAGSIFSEKSDVVV 156
Cdd:cd05740    30 SYLWWFNGQslPVTPrltLSnGNRTLTLLNVTREDAGAYQCEISNPVSANRSDPVTLDV 88

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: 38.92 E-value: 2.83e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400  505 VLLGLTATLQCKVSSDPSVpyNIDWYREGQSSTPISNSQRIGVQADG--QLEIQAVRASDVGSYACVVTSPGGNETRAAR 582
Cdd:cd05893    12 IFEGMPVTFTCRVAGNPKP--KIYWFKDGKQISPKSDHYTIQRDLDGtcSLHTTASTLDDDGNYTIMAANPQGRISCTGR 89


                  ...
gi 599137400  583 LSV 585
Cdd:cd05893    90 LMV 92

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 38.70 E-value: 2.83e-03

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 599137400   261 PEIIVRPQDVKVKVGTGVvELQCIANARPLHELEtlWLKDGLAVETAGVRHTLNDPWNRTLALLQANSSHSGEYTCQVR 339
Cdd:pfam13927    2 PVITVSPSSVTVREGETV-TLTCEATGSPPPTIT--WYKNGEPISSGSTRSRSLSGSNSTLTISNVTRSDAGTYTCVAS 77

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: 39.17 E-value: 2.92e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400   70 QAPRFTTHPSSSgsivSEGSTKiLQCHALGYPQPTYRWLKDGVPVgDFSSSQFYRF-------HSTRREDAGSYQCIARN 142
Cdd:cd05849     6 EQPIDTIYPEES----TEGKVS-VNCRARANPFPIYKWRKNNLDI-DLTNDRYSMVggnlvinNPDKYKDAGRYVCIVSN 79

                          90
                  ....*....|....*.
gi 599137400  143 DAGSIFSEKSDVVVAY 158
Cdd:cd05849    80 IYGKVRSREATLSFGY 95

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: 2.99e-03

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 599137400  375 GGQVQLTCDVVGEPTPQVKWFRnaesVDAHIESGRYTL-NTDNTLVIKKLILDDAAMFQCLAINEAGENSASTWLRVK 451
Cdd:cd05731    10 GGVLLLECIAEGLPTPDIRWIK----LGGELPKGRTKFeNFNKTLKIENVSEADSGEYQCTASNTMGSARHTISVTVE 83

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: 39.00 E-value: 3.44e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400  360 PLFFTPMRAETFGEFGGQVQLTCDVVGEPTPQVKWFRNAESVDAHIESGRYTLnTDNTLVIKKLI-----LDDAAMFQCL 434
Cdd:cd05722     1 ELYFLSEPSDIVAMRGGPVVLNCSAESDPPPKIEWKKDGVLLNLVSDERRQQL-PNGSLLITSVVhskhnKPDEGFYQCV 79


                  ....
gi 599137400  435 AINE 438
Cdd:cd05722    80 AQNE 83

Immunoglobulin V-Type;

Pssm-ID: 214650 Cd Length: 81 Bit Score: 38.13 E-value: 4.51e-03

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400    510 TATLQCKVSSDPSVPYNIDWYRE------------GQSSTPISNSQ--------RIGVQADGQLEIQAVRASDVGSYACV 569
Cdd:smart00406    1 SVTLSCKFSGSTFSSYYVSWVRQppgkglewlgyiGSNGSSYYQESykgrftisKDTSKNDVSLTISNLRVEDTGTYYCA 80


                    .
gi 599137400    570 V 570
Cdd:smart00406   81 V 81

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: 38.35 E-value: 5.56e-03

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 599137400  375 GGQVQLTCDVVGEPTPQVKWFRNAESVDAHIESGRYTL-NTDNTLVIKKLILDDAAMFQCLAINEAGENSASTWLRV 450
Cdd:cd05729    19 ANKVRLECGAGGNPMPNITWLKDGKEFKKEHRIGGTKVeEKGWSLIIERAIPRDKGKYTCIVENEYGSINHTYDVDV 95

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 38.01 E-value: 5.59e-03

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 599137400   280 ELQCIANARPLHELEtlWLKDGLAVETAGVRHTLNDPWNRTLALLQANSSHSGEYTCQVRLRSGgypAVSASARLQI 356
Cdd:pfam07679   19 RFTCTVTGTPDPEVS--WFKDGQPLRSSDRFKVTYEGGTYTLTISNVQPDDSGKYTCVATNSAG---EAEASAELTV 90

First immunoglobulin (Ig)-like domain of Tyro3 receptor tyrosine kinase (RTK), and similar domains; The members here are composed of the first immunoglobulin (Ig)-like domain of Tyro3 receptor tyrosine kinase (RTK). Tyro3 together with Axl and Mer form the Axl/Tyro3 family of receptor tyrosine kinases (RTKs). This family includes Axl (also known as Ark, Ufo, and Tyro7), Tyro3 (also known as Sky, Rse, Brt, Dtk, and Tif), and Mer (also known as Nyk, c-Eyk, and Tyro12). Axl/Tyro3 family receptors have an extracellular portion with two Ig-like domains followed by two fibronectin-types III (FNIII) domains, a membrane-spanning single helix, and a cytoplasmic tyrosine kinase domain. Axl, Tyro3 and Mer are widely expressed in adult tissues, though they show higher expression in the brain, in the lymphatic and vascular systems, and in the testis. Axl, Tyro3, and Mer bind the vitamin K dependent protein Gas6 with high affinity, and in doing so activate their tyrosine kinase activity. Axl/Gas6 signaling may play a part in cell adhesion processes, prevention of apoptosis, and cell proliferation.

Pssm-ID: 409553 Cd Length: 87 Bit Score: 37.81 E-value: 5.70e-03

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 599137400   85 VSEGSTKILQCHALGYPQPTYRWLKDG----------VPVGDFSSSQFYRFHSTRREDAGSYQC 138
Cdd:cd20961     5 VSQGQPVKLNCSVEGMEEPDIQWVKDGavvqnldqlyIPVSEQHWIGFLSLKSVERSDAGRYWC 68

Immunoglobulin (Ig)-like domain found in Leukocyte Ig-like receptors, Natural killer inhibitory receptors (KIRs) and similar domains; member of Immunoglobulin Constant-2 set of IgSF domains; The members here are composed of the first and second immunoglobulin (Ig)-like domains found in Leukocyte Ig-like receptors (LILRs), Natural killer inhibitory receptors (KIRs, also known as also known as cluster of differentiation (CD) 158), and similar proteins. This group includes LILRB1 (also known as LIR-1), LILRA5 (also known as LIR9), an activating natural cytotoxicity receptor NKp46, the immune-type receptor glycoprotein VI (GPVI), and the IgA-specific receptor Fc-alphaRI (also known as cluster of differentiation (CD) 89). LILRs are a family of immunoreceptors expressed on expressed on T and B cells, on monocytes, dendritic cells, and subgroups of natural killer (NK) cells. The human LILR family contains nine proteins (LILRA1-3, and 5, and LILRB1-5). From functional assays, and as the cytoplasmic domains of various LILRs, for example LILRB1, LILRB2 (also known as LIR-2), and LILRB3 (also known as LIR-3) contain immunoreceptor tyrosine-based inhibitory motifs (ITIMs), it is thought that LIR proteins are inhibitory receptors. Of the eight LIR family proteins, only LILRB1, and LILRB2, show detectable binding to class I MHC molecules; ligands for the other members have yet to be determined. The extracellular portions of the different LIR proteins contain different numbers of Ig-like domains for example, four in the case of LILRB1, and LILRB2, and two in the case of LILRB4 (also known as LIR-5). The activating natural cytotoxicity receptor NKp46 is expressed in natural killer cells, and is organized as an extracellular portion having two Ig-like extracellular domains, a transmembrane domain, and a small cytoplasmic portion. GPVI, which also contains two Ig-like domains, participates in the processes of collagen-mediated platelet activation and arterial thrombus formation. Fc-alphaRI is expressed on monocytes, eosinophils, neutrophils, and macrophages; it mediates IgA-induced immune effector responses such as phagocytosis, antibody-dependent cell-mediated cytotoxicity and respiratory burst. Killer cell immunoglobulin-like receptors (KIRs; also known as CD158 for human KIR) are transmembrane glycoproteins expressed by natural killer cells and subsets of T cells. KIRs are a family of highly polymorphic activating and inhibitory receptors that serve as key regulators of human NK cell function. The KIR proteins are classified by the number of extracellular immunoglobulin domains (2D or 3D) and by whether they have a long (L) or short (S) cytoplasmic domain. KIR proteins with the long cytoplasmic domain transduce inhibitory signals upon ligand binding via an immune tyrosine-based inhibitory motif (ITIM), while KIR proteins with the short cytoplasmic domain lack the ITIM motif and instead associate with the TYRO protein tyrosine kinase binding protein to transduce activating signals. The major ligands for KIR are MHC class I (HLA-A, -B or -C) molecules.

Pssm-ID: 409518 [Multi-domain] Cd Length: 90 Bit Score: 37.74 E-value: 6.89e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400   80 SSGSIVSEGSTKILQCHAlGYPQPTYRWLKDGVPV--------GDFSSSQFYRFHSTRrEDAGSYQCIARNDAGsiFSEK 151
Cdd:cd16843     7 EPSSVVPLGENVTIRCQG-PPEAVLFQLYKEGNSLsqgtvrekEPQNKAEFYIPHMDR-NHAGRYRCRYRSGTL--WSEP 82


                  ....
gi 599137400  152 SDVV 155
Cdd:cd16843    83 SDPL 86

Phage-related protein, tail protein J [Mobilome: prophages, transposons];

Pssm-ID: 443767 [Multi-domain] Cd Length: 978 Bit Score: 41.47 E-value: 7.01e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400 1204 SDTAVERTreavpsygpldVQANATSSTTVVVQWGEVPrqhrngQIDGYKVFYAAADRGQQVLHKTIPNNATFTTTLTel 1283
Cdd:COG4733   447 DGTSVART-----------VQSVAGRTLTVSTAYSETP------EAGAVWAFGPDELETQLFRVVSIEENEDGTYTIT-- 507

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400 1284 kkyVVYHVQvLAYTRLGNGALSTPPIRVQTFEDTPGVPSNVSFPDVSLTMARIIWDVPVDPNgkilAYQVTYTLNGSAML 1363
Cdd:COG4733   508 ---AVQHAP-EKYAAIDAGAFDDVPPQWPPVNVTTSESLSVVAQGTAVTTLTVSWDAPAGAV----AYEVEWRRDDGNWV 579

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400 1364 NYSREfppSDRTFRATELLPGKYYsFSCTAQTRLGWGKIATALVYTTNNRERPQAPSVPQISRSQIQaHQITFSWTPGRD 1443
Cdd:COG4733   580 SVPRT---SGTSFEVPGIYAGDYE-VRVRAINALGVSSAWAASSETTVTGKTAPPPAPTGLTATGGL-GGITLSWSFPVD 654

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 599137400 1444 gfAPLRYYTVEMRENEGRWQPLPERVDPSLSSFTAVGLRPYMTYQFRIQATNDLG 1498
Cdd:COG4733   655 --ADTLRTEIRYSTTGDWASATVAQALYPGNTYTLAGLKAGQTYYYRARAVDRSG 707

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: 37.99 E-value: 8.64e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 599137400  380 LTCDVVGEPTPQVKWFRNAESVDahIESGRYTLNTDNTLVIKKLIL--------DDAAMFQCLAINEAGENSASTWLrVK 451
Cdd:cd05773    28 LVCQAQGVPRVQFRWAKNGVPLD--LGNPRYEETTEHTGTVHTSILtiinvsaaLDYALFTCTAHNSLGEDSLDIQL-VS 104


                  ....
gi 599137400  452 TSAP 455
Cdd:cd05773   105 TSRP 108