NCBI Conserved Domain Search

Neogenin C-terminus; This family represents the C-terminus of eukaryotic neogenin precursor proteins, which contains several potential phosphorylation sites. Neogenin is a member of the N-CAM family of cell adhesion molecules (and therefore contains multiple copies of pfam00047 and pfam00041) and is closely related to the DCC tumour suppressor gene product - these proteins may play an integral role in regulating differentiation programmes and/or cell migration events within many adult and embryonic tissues.

Pssm-ID: 461954 [Multi-domain] Cd Length: 289 Bit Score: 363.46 E-value: 2.67e-115

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340   1125 LRPPDLWIHHEEMELKNMEKPSGSAPSGRDSPI-QSCQEIPPVSHSQSESQMGSKS-SHSGADADESSSSistlersLAA 1202
Cdd:pfam06583    1 LKPPDLWIHHEQMELKNIEKSPSPNPSGTDSPIgQSSQDLPPVDHSQSESQIHQKSnSYSGNDSDEKSST-------LAG 73

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340   1203 RRATRTKMMIPMDSQPSNTPVVSAIPVPTLDSSQ---YPGILPSPSCGFTaHPKFSLrpmPFSTLTVERSYTsAMSAEGA 1279
Cdd:pfam06583   74 RRGTRPKMMLPMDSQPSNQPVVSAIPIPSLDSSHqyaHPGILPSPTCGYL-HNQFSL---PFPGTPVPRSDT-APSAESV 148

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340   1280 TPMAPQPQPALIPTAQSE----PQVSEEIPSRSIPTACVRPTHPLRSFTNTLLPPPMGTIEPkvFSPVTGGSLPKPQVKT 1355
Cdd:pfam06583  149 ENTPLQSQLPYQPSSQSEsgslSSAVEEEPNRSIPTAKVRPGHPLKSFSVPAPPPQSAPSTP--LQQQHRPTLSKSPVKT 226

                          250       260       270       280       290       300
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 77993340   1356 ASLGQAGKARSPLlPVSVPTAPESAEDGQKPPEDPSSVYEQDDLSEQMASLEGLMKQLNAITGS 1419
Cdd:pfam06583  227 ASLGTAGKARSPL-PVSVPNAPDTSEETERLLEDAAPSYETDELSEEMANLEGLMKDLNAITAS 289

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: 150.04 E-value: 1.49e-42

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340  330 LNYPSNTYAYESSDIEMECAVTGNPQPVVRWVKNGEVVVPSDYFQIVDGGHLQILGLVRSDEGFYQCIAENEAGNSQAMA 409
Cdd:cd05723    1 LKKPSNIYAHESMDIVFECEVTGKPTPTVKWVKNGDVVIPSDYFKIVKEHNLQVLGLVKSDEGFYQCIAENDVGNAQASA 80


                 ....
gi 77993340  410 QLIL 413
Cdd:cd05723   81 QLII 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: 149.55 E-value: 3.43e-42

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340   35 LRFVLQPQDVVTVRGGVLQLDCDALSDQgVPSISWKKDGVLLSAVVDERRRQLSNGSLLVQNVMHSRHHRPDEGSYQCLA 114
Cdd:cd05722    2 LYFLSEPSDIVAMRGGPVVLNCSAESDP-PPKIEWKKDGVLLNLVSDERRQQLPNGSLLITSVVHSKHNKPDEGFYQCVA 80

                         90
                 ....*....|....*..
gi 77993340  115 SLEGIGAIVSRTARVTV 131
Cdd:cd05722   81 QNESLGSIVSRTARVTV 97

Fibronectin type 3 domain [General function prediction only];

Pssm-ID: 442628 [Multi-domain] Cd Length: 603 Bit Score: 100.08 E-value: 2.96e-21

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340  533 EAVSPTSIQASWDPPAPANGPVQSYRLLWTETSSGKEQNVEVVGQSYRMEGLKKFTEYSLRVLAVNRHGPGVSDKDTLIT 612
Cdd:COG3401  148 YGVDGANASGTTASSVAGAGVVVSPDTSATAAVATTSLTVTSTTLVDGGGDIEPGTTYYYRVAATDTGGESAPSNEVSVT 227

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340  613 TLSDVPSsPPQNVSLEVVYSRSIKVSWQPPPANTqngfITGYKIrYRKTGRRGEQEAI-EPNNLWYLFTGLEKGSQYSFQ 691
Cdd:COG3401  228 TPTTPPS-APTGLTATADTPGSVTLSWDPVTESD----ATGYRV-YRSNSGDGPFTKVaTVTTTSYTDTGLTNGTTYYYR 301

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340  692 VSGMTVNGT-GPSSEWLTAETpendldESQVPHQPSSLHV-RPLPNSIIMSWTPplNPNTLIRGYTI--GYGVGSPYAQT 767
Cdd:COG3401  302 VTAVDAAGNeSAPSNVVSVTT------DLTPPAAPSGLTAtAVGSSSITLSWTA--SSDADVTGYNVyrSTSGGGTYTKI 373

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340  768 VRVdSKQRYYSIENLEPSSHYVISLKAFNNAG-EGVPLYESAVTRSMTDSSSAPMIPPVGVQAVALTSDSVRVSWADNsi 846
Cdd:COG3401  374 AET-VTTTSYTDTGLTPGTTYYYKVTAVDAAGnESAPSEEVSATTASAASGESLTASVDAVPLTDVAGATAAASAASN-- 450

                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340  847 PKNQKSSEVRYYSVKWRTSHSTSGKHKSADTTALSHTVTGLKPNtmyefSVMVTKGRKSSTWSMTAHATTYEAAPSSAPK 926
Cdd:COG3401  451 PGVSAAVLADGGDTGNAVPFTTTSSTVTATTTDTTTANLSVTTG-----SLVGGSGASSVTNSVSVIGASAAAAVGGAPD 525


                 ....*
gi 77993340  927 DLTVI 931
Cdd:COG3401  526 GTPNV 530

Fibronectin type 3 domain [General function prediction only];

Pssm-ID: 442628 [Multi-domain] Cd Length: 603 Bit Score: 97.77 E-value: 1.47e-20

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340  609 TLITTLSDVPSSPPQNVSLEVVYSRSIKVSWQPPPANTQNGFITGYKIRYRKTGRRGEqeAIEPNNLWYLFTGLEKGSQY 688
Cdd:COG3401   22 AVNALSKAGGSGKTILVYLAVVLSVTTKESPGTLLVAAGLSSGGGLGTGGRAGTTSGV--AAVAVAAAPPTATGLTTLTG 99

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340  689 SFQVSGMTVNGTGPSSEWLTAETPEN-DLDESQVPHQPSSLHVRPLPNSIIMSWTPPLNPNTLIRGYTIGYGVGSPYAQT 767
Cdd:COG3401  100 SGSVGGATNTGLTSSDEVPSPAVGTAtTATAVAGGAATAGTYALGAGLYGVDGANASGTTASSVAGAGVVVSPDTSATAA 179

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340  768 V-----RVDSKQRYYSIENLEPSSHYVISLKAFNNAGEGVPlyesAVTRSMTDSSSAPMiPPVGVQAVALTSDSVRVSWA 842
Cdd:COG3401  180 VattslTVTSTTLVDGGGDIEPGTTYYYRVAATDTGGESAP----SNEVSVTTPTTPPS-APTGLTATADTPGSVTLSWD 254

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340  843 DNSipknqkSSEVRYYSVKWRTSHSTSGKhKSADTTALSHTVTGLKPNTMYEFSVM-VTKGRKSSTWSMTAHATTYEAAP 921
Cdd:COG3401  255 PVT------ESDATGYRVYRSNSGDGPFT-KVATVTTTSYTDTGLTNGTTYYYRVTaVDAAGNESAPSNVVSVTTDLTPP 327

                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340  922 sSAPKDLTVIGREgrPRAILISWQPPLEANgrITGFILYYTLEKNLPIdDWVMEPISGdrLTHQVLDLNLDTVYYFRIQA 1001
Cdd:COG3401  328 -AAPSGLTATAVG--SSSITLSWTASSDAD--VTGYNVYRSTSGGGTY-TKIAETVTT--TSYTDTGLTPGTTYYYKVTA 399

                        410       420
                 ....*....|....*....|.
gi 77993340 1002 KNAKGV-GPLSDPVQYRTSKV 1021
Cdd:COG3401  400 VDAAGNeSAPSEEVSATTASA 420

Fibronectin type 3 domain [General function prediction only];

Pssm-ID: 442628 [Multi-domain] Cd Length: 603 Bit Score: 97.38 E-value: 2.03e-20

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340  393 FYQCIAENEAGNSQAMAQLILLQPVTPrsavsPSAPRDVAPVLVSSRFVRLSWRPPEEPRgpILTYGVFYSEEGInrERS 472
Cdd:COG3401  206 YYRVAATDTGGESAPSNEVSVTTPTTP-----PSAPTGLTATADTPGSVTLSWDPVTESD--ATGYRVYRSNSGD--GPF 276

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340  473 VNVTEAESLQLTVSNLRPEASYSFRVLAYNEQG-PGESSEAIrlSTQAELLVPGPVENLQAEAVSPTSIQASWDPpaPAN 551
Cdd:COG3401  277 TKVATVTTTSYTDTGLTNGTTYYYRVTAVDAAGnESAPSNVV--SVTTDLTPPAAPSGLTATAVGSSSITLSWTA--SSD 352

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340  552 GPVQSYRLLWTETSSGKEQNV--EVVGQSYRMEGLKKFTEYSLRVLAVNRHG-----PGVSDKDTLITTLSDVPSSPPQN 624
Cdd:COG3401  353 ADVTGYNVYRSTSGGGTYTKIaeTVTTTSYTDTGLTPGTTYYYKVTAVDAAGnesapSEEVSATTASAASGESLTASVDA 432

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340  625 VSLEVVYSRSIKVSWQPPPANTQNGFITGYKIRYRKT-GRRGEQEAIEPNNLWYLFTGLEKGSQYSFQVSGMTVNGTGPS 703
Cdd:COG3401  433 VPLTDVAGATAAASAASNPGVSAAVLADGGDTGNAVPfTTTSSTVTATTTDTTTANLSVTTGSLVGGSGASSVTNSVSVI 512

                        330       340       350       360       370       380       390
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 77993340  704 SEWLTAETPeNDLDESQVPHQPSSLHVRPLPNSIIMSWTPPLNPNTLIRGYTIGYGVGSPYAQTVRVDSKQRY 776
Cdd:COG3401  513 GASAAAAVG-GAPDGTPNVTGASPVTVGASTGDVLITDLVSLTTSASSSVSGAGLGSGNLYLITTLGGSLLTT 584

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: 85.24 E-value: 1.13e-19

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340  425 PSAPRDVAPVLVSSRFVRLSWRPPEEPRGPILTYGVFYSEEGINRERSVNVTEAESLQLTVSNLRPEASYSFRVLAYNEQ 504
Cdd:cd00063    1 PSPPTNLRVTDVTSTSVTLSWTPPEDDGGPITGYVVEYREKGSGDWKEVEVTPGSETSYTLTGLKPGTEYEFRVRAVNGG 80

                         90
                 ....*....|...
gi 77993340  505 GPGESSEAIRLST 517
Cdd:cd00063   81 GESPPSESVTVTT 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: 79.46 E-value: 1.13e-17

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340  524 PGPVENLQAEAVSPTSIQASWDPPAPANGPVQSYRLLWTETSSGKEQNVEVV---GQSYRMEGLKKFTEYSLRVLAVNRH 600
Cdd:cd00063    1 PSPPTNLRVTDVTSTSVTLSWTPPEDDGGPITGYVVEYREKGSGDWKEVEVTpgsETSYTLTGLKPGTEYEFRVRAVNGG 80

                         90
                 ....*....|...
gi 77993340  601 GPGVSDKDTLITT 613
Cdd:cd00063   81 GESPPSESVTVTT 93

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

Pssm-ID: 143205 [Multi-domain] Cd Length: 85 Bit Score: 78.41 E-value: 1.94e-17

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340  328 QFLNYPSNTYAYESSDIEMECAVTGNPQPVVRWVKNGEVVVPSDYFQiVDGGHLQILGLVRSDEGFYQCIAENEAGNSQA 407
Cdd:cd05728    1 EWLKVISDTEADIGSSLRWECKASGNPRPAYRWLKNGQPLASENRIE-VEAGDLRITKLSLSDSGMYQCVAENKHGTIYA 79


                 ....
gi 77993340  408 MAQL 411
Cdd:cd05728   80 SAEL 83

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 76.53 E-value: 1.19e-16

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340    327 PQFLNYPSNTYAYESSDIEMECAVTGNPQPVVRWVKNGEVVVPSDYFQIV-DGGH--LQILGLVRSDEGFYQCIAENEAG 403
Cdd:pfam07679    1 PKFTQKPKDVEVQEGESARFTCTVTGTPDPEVSWFKDGQPLRSSDRFKVTyEGGTytLTISNVQPDDSGKYTCVATNSAG 80


                   ....*....
gi 77993340    404 NSQAMAQLI 412
Cdd:pfam07679   81 EAEASAELT 89

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 76.14 E-value: 1.39e-16

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340    237 VFLQRPQKVSVLQGRDAVLECSASGFPNPAFYWLRGNELIQSrSKKYSLL---SGSNLLISSVTDDDSGIYTCIAHNKQQ 313
Cdd:pfam07679    2 KFTQKPKDVEVQEGESARFTCTVTGTPDPEVSWFKDGQPLRS-SDRFKVTyegGTYTLTISNVQPDDSGKYTCVATNSAG 80

                           90
                   ....*....|
gi 77993340    314 NISASCELAV 323
Cdd:pfam07679   81 EAEASAELTV 90

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: 76.00 E-value: 1.60e-16

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340  620 SPPQNVSLEVVYSRSIKVSWQPPPANtqNGFITGYKIRYRKTGRRGEQEA--IEPNNLWYLFTGLEKGSQYSFQVSGMTV 697
Cdd:cd00063    2 SPPTNLRVTDVTSTSVTLSWTPPEDD--GGPITGYVVEYREKGSGDWKEVevTPGSETSYTLTGLKPGTEYEFRVRAVNG 79

                         90
                 ....*....|....
gi 77993340  698 NGTGPSSEWLTAET 711
Cdd:cd00063   80 GGESPPSESVTVTT 93

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: 74.84 E-value: 3.71e-16

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340  238 FLQRPQKVSVLQGRDAVLECSASGFPNPAFYWLRGNELIQ--SRSKKYSLLSGS-NLLISSVTDDDSGIYTCIAHNKQQN 314
Cdd:cd05744    3 FLQAPGDLEVQEGRLCRFDCKVSGLPTPDLFWQLNGKPVRpdSAHKMLVRENGRhSLIIEPVTKRDAGIYTCIARNRAGE 82


                 ....*....
gi 77993340  315 ISASCELAV 323
Cdd:cd05744   83 NSFNAELVV 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: 73.42 E-value: 1.02e-15

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340     620 SPPQNVSLEVVYSRSIKVSWQPPPANTQNGFITGYKIRYRKTGRRGEQEAIEPNNLWYLFTGLEKGSQYSFQVSGMTVNG 699
Cdd:smart00060    2 SPPSNLRVTDVTSTSVTLSWEPPPDDGITGYIVGYRVEYREEGSEWKEVNVTPSSTSYTLTGLKPGTEYEFRVRAVNGAG 81


                    ..
gi 77993340     700 TG 701
Cdd:smart00060   82 EG 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: 72.63 E-value: 2.48e-15

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340  238 FLQRPQKVSVLQGRDAVLECSASGFPNPAFYWLRGNELIQSRSKKYslLSGSNLLISSVTDDDSGIYTCIAHNKQQNISA 317
Cdd:cd05728    2 WLKVISDTEADIGSSLRWECKASGNPRPAYRWLKNGQPLASENRIE--VEAGDLRITKLSLSDSGMYQCVAENKHGTIYA 79


                 ....*.
gi 77993340  318 SCELAV 323
Cdd:cd05728   80 SAELAV 85

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 71.83 E-value: 3.53e-15

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 77993340    237 VFLQRPQKVSVLQGRDAVLECSASGFPNPAFYWLRGNELIQS--RSKKYSLLSGSNLLISSVTDDDSGIYTCIAHN 310
Cdd:pfam13927    3 VITVSPSSVTVREGETVTLTCEATGSPPPTITWYKNGEPISSgsTRSRSLSGSNSTLTISNVTRSDAGTYTCVASN 78

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: 71.77 E-value: 4.44e-15

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340     242 PQKVSVLQGRDAVLECSASGFPNPAFYWLRGNELIQSRSKKYSLLSGSN---LLISSVTDDDSGIYTCIAHNKQQNISAS 318
Cdd:smart00410    1 PPSVTVKEGESVTLSCEASGSPPPEVTWYKQGGKLLAESGRFSVSRSGStstLTISNVTPEDSGTYTCAATNSSGSASSG 80


                    ....*
gi 77993340     319 CELAV 323
Cdd:smart00410   81 TTLTV 85

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 71.44 E-value: 4.87e-15

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 77993340    326 PPQFLNYPSNTYAYESSDIEMECAVTGNPQPVVRWVKNGEVVVP---SDYFQIVDGGHLQILGLVRSDEGFYQCIAEN 400
Cdd:pfam13927    1 KPVITVSPSSVTVREGETVTLTCEATGSPPPTITWYKNGEPISSgstRSRSLSGSNSTLTISNVTRSDAGTYTCVASN 78

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: 70.89 E-value: 8.21e-15

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340  143 SVSAHLGDTALLRCEVTGDPMPVVRWQKNREDLpltfdPDSRVVILPSGSLQVSRVQPPDSATYRCLAEN 212
Cdd:cd05725    6 NQVVLVDDSAEFQCEVGGDPVPTVRWRKEDGEL-----PKGRYEILDDHSLKIRKVTAGDMGSYTCVAEN 70

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

Pssm-ID: 214495 [Multi-domain] Cd Length: 83 Bit Score: 70.34 E-value: 1.42e-14

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340     524 PGPVENLQAEAVSPTSIQASWDPPAPAN--GPVQSYRLLWTETSSG-KEQNVEVVGQSYRMEGLKKFTEYSLRVLAVNRH 600
Cdd:smart00060    1 PSPPSNLRVTDVTSTSVTLSWEPPPDDGitGYIVGYRVEYREEGSEwKEVNVTPSSTSYTLTGLKPGTEYEFRVRAVNGA 80


                    ...
gi 77993340     601 GPG 603
Cdd:smart00060   81 GEG 83

Fibronectin type III domain;

Pssm-ID: 394996 [Multi-domain] Cd Length: 85 Bit Score: 69.75 E-value: 2.00e-14

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340    525 GPVENLQAEAVSPTSIQASWDPPAPANGPVQSYRLLWTETSSGKEQNVEVVG---QSYRMEGLKKFTEYSLRVLAVNRHG 601
Cdd:pfam00041    1 SAPSNLTVTDVTSTSLTVSWTPPPDGNGPITGYEVEYRPKNSGEPWNEITVPgttTSVTLTGLKPGTEYEVRVQAVNGGG 80


                   ..
gi 77993340    602 PG 603
Cdd:pfam00041   81 EG 82

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

Pssm-ID: 409570 [Multi-domain] Cd Length: 88 Bit Score: 69.34 E-value: 2.88e-14

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 77993340  327 PQFLNYP-SNTYAYESSDIEMECAVTGNPQPVVRWVKNGEVVVPSDYFQIVDGGHLQILGLVRSDEGFYQCIAENEAG 403
Cdd:cd20978    1 PKFIQKPeKNVVVKGGQDVTLPCQVTGVPQPKITWLHNGKPLQGPMERATVEDGTLTIINVQPEDTGYYGCVATNEIG 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: 69.83 E-value: 2.97e-14

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340  923 SAPKDLTVigREGRPRAILISWQPPLEANGRITGFILYYTLEKNlpiDDWV-MEPISGDRLTHQVLDLNLDTVYYFRIQA 1001
Cdd:cd00063    2 SPPTNLRV--TDVTSTSVTLSWTPPEDDGGPITGYVVEYREKGS---GDWKeVEVTPGSETSYTLTGLKPGTEYEFRVRA 76

                         90
                 ....*....|....*..
gi 77993340 1002 KNAKGVGPLSDPVQYRT 1018
Cdd:cd00063   77 VNGGGESPPSESVTVTT 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: 69.06 E-value: 4.20e-14

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340  237 VFLQRPQKVSVLQGRDAVLECSASGFPNPAFYWLRGNELIQSRSKKYSLLSGSNLLISSVTDDDSGIYTCIAHNKQQNIS 316
Cdd:cd20952    1 IILQGPQNQTVAVGGTVVLNCQATGEPVPTISWLKDGVPLLGKDERITTLENGSLQIKGAEKSDTGEYTCVALNLSGEAT 80


                 ....*..
gi 77993340  317 ASCELAV 323
Cdd:cd20952   81 WSAVLDV 87

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

Pssm-ID: 409562 [Multi-domain] Cd Length: 92 Bit Score: 69.07 E-value: 4.79e-14

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 77993340  240 QRPQKVSVLQGRDAVLECSASGFPNPAFYWLRGNELIQSRSKKYSLLS-GSNLLISSVTDDDSGIYTCIAHNK 311
Cdd:cd20970    7 QPSFTVTAREGENATFMCRAEGSPEPEISWTRNGNLIIEFNTRYIVREnGTTLTIRNIRRSDMGIYLCIASNG 79

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: 68.12 E-value: 5.29e-14

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 77993340  152 ALLRCEVTGDPMPVVRWQKNREDLPLTfDPDSRVVILPSGSLQVSRVQPPDSATYRCLAENP 213
Cdd:cd00096    1 VTLTCSASGNPPPTITWYKNGKPLPPS-SRDSRRSELGNGTLTISNVTLEDSGTYTCVASNS 61

Fibronectin type III domain;

Pssm-ID: 394996 [Multi-domain] Cd Length: 85 Bit Score: 67.44 E-value: 1.34e-13

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340    620 SPPQNVSLEVVYSRSIKVSWQPPPanTQNGFITGYKIRYRKTGR-RGEQEAIEPNNLW-YLFTGLEKGSQYSFQVSGMTV 697
Cdd:pfam00041    1 SAPSNLTVTDVTSTSLTVSWTPPP--DGNGPITGYEVEYRPKNSgEPWNEITVPGTTTsVTLTGLKPGTEYEVRVQAVNG 78


                   ....*..
gi 77993340    698 NGTGPSS 704
Cdd:pfam00041   79 GGEGPPS 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: 67.25 E-value: 1.57e-13

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340     425 PSAPRDVAPVLVSSRFVRLSWRPPEEP--RGPILTYGVFYSEEGiNRERSVNVTEAESlQLTVSNLRPEASYSFRVLAYN 502
Cdd:smart00060    1 PSPPSNLRVTDVTSTSVTLSWEPPPDDgiTGYIVGYRVEYREEG-SEWKEVNVTPSST-SYTLTGLKPGTEYEFRVRAVN 78


                    ....*
gi 77993340     503 EQGPG 507
Cdd:smart00060   79 GAGEG 83

Fibronectin type III domain;

Pssm-ID: 394996 [Multi-domain] Cd Length: 85 Bit Score: 67.05 E-value: 1.71e-13

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340    426 SAPRDVAPVLVSSRFVRLSWRPPEEPRGPILTYGVFYSEEG-INRERSVNVTEAESlQLTVSNLRPEASYSFRVLAYNEQ 504
Cdd:pfam00041    1 SAPSNLTVTDVTSTSLTVSWTPPPDGNGPITGYEVEYRPKNsGEPWNEITVPGTTT-SVTLTGLKPGTEYEVRVQAVNGG 79


                   ....*.
gi 77993340    505 GPGESS 510
Cdd:pfam00041   80 GEGPPS 85

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 66.90 E-value: 2.69e-13

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340    143 SVSAHLGDTALLRCEVTGDPMPVVRWQKNREDLPltfdPDSRVVILPSG---SLQVSRVQPPDSATYRCLAENPGSARTg 219
Cdd:pfam07679    9 DVEVQEGESARFTCTVTGTPDPEVSWFKDGQPLR----SSDRFKVTYEGgtyTLTISNVQPDDSGKYTCVATNSAGEAE- 83


                   ....*..
gi 77993340    220 TDADLRV 226
Cdd:pfam07679   84 ASAELTV 90

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

Pssm-ID: 409353 [Multi-domain] Cd Length: 70 Bit Score: 65.81 E-value: 3.19e-13

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 77993340  253 AVLECSASGFPNPAFYWLRGNELIQS--RSKKYSLLSGSNLLISSVTDDDSGIYTCIAHNK 311
Cdd:cd00096    1 VTLTCSASGNPPPTITWYKNGKPLPPssRDSRRSELGNGTLTISNVTLEDSGTYTCVASNS 61

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 66.05 E-value: 3.32e-13

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 77993340    134 PLRVLVSTESVSAHLGDTALLRCEVTGDPMPVVRWQKNREDLPLTFDPDSRVVIlPSGSLQVSRVQPPDSATYRCLAEN 212
Cdd:pfam13927    1 KPVITVSPSSVTVREGETVTLTCEATGSPPPTITWYKNGEPISSGSTRSRSLSG-SNSTLTISNVTRSDAGTYTCVASN 78

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

Pssm-ID: 409389 [Multi-domain] Cd Length: 87 Bit Score: 65.88 E-value: 5.88e-13

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340   39 LQPQDVVTVRGGVLQLDCDALSDQGVPSISWKKDGVLLsAVVDERRRQLSNGSLLVQNVMHSrhhrpDEGSYQCLASlEG 118
Cdd:cd05724    2 VEPSDTQVAVGEMAVLECSPPRGHPEPTVSWRKDGQPL-NLDNERVRIVDDGNLLIAEARKS-----DEGTYKCVAT-NM 74

                         90
                 ....*....|...
gi 77993340  119 IGAIVSRTARVTV 131
Cdd:cd05724   75 VGERESRAARLSV 87

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: 65.04 E-value: 7.45e-13

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 77993340  344 IEMECAVTGNPQPVVRWVKNGEVVVPSDYFQIV---DGGHLQILGLVRSDEGFYQCIAENEAGNSQA 407
Cdd:cd00096    1 VTLTCSASGNPPPTITWYKNGKPLPPSSRDSRRselGNGTLTISNVTLEDSGTYTCVASNSAGGSAS 67

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: 65.22 E-value: 8.10e-13

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340     333 PSNTYAYESSDIEMECAVTGNPQPVVRWVKNG-EVVVPSDYFQIVDGG---HLQILGLVRSDEGFYQCIAENEAGNSQAM 408
Cdd:smart00410    1 PPSVTVKEGESVTLSCEASGSPPPEVTWYKQGgKLLAESGRFSVSRSGstsTLTISNVTPEDSGTYTCAATNSSGSASSG 80


                    ....
gi 77993340     409 AQLI 412
Cdd:smart00410   81 TTLT 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: 64.45 E-value: 1.67e-12

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340     142 ESVSAHLGDTALLRCEVTGDPMPVVRWQKNREDLPLtfdPDSRVVILPSG---SLQVSRVQPPDSATYRCLAENPGSART 218
Cdd:smart00410    2 PSVTVKEGESVTLSCEASGSPPPEVTWYKQGGKLLA---ESGRFSVSRSGstsTLTISNVTPEDSGTYTCAATNSSGSAS 78


                    ....*...
gi 77993340     219 GTdADLRV 226
Cdd:smart00410   79 SG-TTLTV 85

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: 64.34 E-value: 1.72e-12

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 77993340  240 QRPQKVSVLQGRDAVLECSAS-GFPNPAFYWLRGNELIQSRSKKYSLLSGSNLLISSVTDDDSGIYTCIAHN 310
Cdd:cd05724    2 VEPSDTQVAVGEMAVLECSPPrGHPEPTVSWRKDGQPLNLDNERVRIVDDGNLLIAEARKSDEGTYKCVATN 73

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: 64.09 E-value: 2.20e-12

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340  134 PLRVLVSTESVSAHLGDTALLRCEVTGDPMPVVRWQKNREDLPltfdPDSRVVILPSGSLQVSRVQPPDSATYRCLAENP 213
Cdd:cd20957    1 PLSATIDPPVQTVDFGRTAVFNCSVTGNPIHTVLWMKDGKPLG----HSSRVQILSEDVLVIPSVKREDKGMYQCFVRND 76

                         90
                 ....*....|...
gi 77993340  214 GSARTGTdADLRV 226
Cdd:cd20957   77 GDSAQAT-AELKL 88

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: 64.05 E-value: 2.70e-12

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340  823 PPVGVQAVALTSDSVRVSWAdnsiPKNQKSSEVRYYSVKWRTSHSTSGKH-KSADTTALSHTVTGLKPNTMYEFSVMVTK 901
Cdd:cd00063    3 PPTNLRVTDVTSTSVTLSWT----PPEDDGGPITGYVVEYREKGSGDWKEvEVTPGSETSYTLTGLKPGTEYEFRVRAVN 78

                         90
                 ....*....|....*
gi 77993340  902 GRKSSTWSMTAHATT 916
Cdd:cd00063   79 GGGESPPSESVTVTT 93

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: 63.98 E-value: 3.01e-12

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340  236 LVFLQRPQKVSVLQGRDAVLECSASGFPNPAFYWLRGNELIQSRSK--KYSLLSGSN---LLISSVTDDDSGIYTCIAHN 310
Cdd:cd20951    1 PEFIIRLQSHTVWEKSDAKLRVEVQGKPDPEVKWYKNGVPIDPSSIpgKYKIESEYGvhvLHIRRVTVEDSAVYSAVAKN 80

                         90
                 ....*....|...
gi 77993340  311 KQQNISASCELAV 323
Cdd:cd20951   81 IHGEASSSASVVV 93

Fibronectin type III domain;

Pssm-ID: 394996 [Multi-domain] Cd Length: 85 Bit Score: 63.20 E-value: 4.03e-12

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340    923 SAPKDLTVIGRegRPRAILISWQPPLEANGRITGFILYYTlEKNLPiDDWVMEPISGDRLTHQVLDLNLDTVYYFRIQAK 1002
Cdd:pfam00041    1 SAPSNLTVTDV--TSTSLTVSWTPPPDGNGPITGYEVEYR-PKNSG-EPWNEITVPGTTTSVTLTGLKPGTEYEVRVQAV 76


                   ....*....
gi 77993340   1003 NAKGVGPLS 1011
Cdd:pfam00041   77 NGGGEGPPS 85

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: 63.28 E-value: 5.05e-12

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340  327 PQFLNYPSNTYAYESSDIEMECAVTGNPQPVVRWVKNGEVVVPSDYFQIV---DGGH-LQILGLVRSDEGFYQCIAENEA 402
Cdd:cd05744    1 PHFLQAPGDLEVQEGRLCRFDCKVSGLPTPDLFWQLNGKPVRPDSAHKMLvreNGRHsLIIEPVTKRDAGIYTCIARNRA 80


                 ....*....
gi 77993340  403 GNSQAMAQL 411
Cdd:cd05744   81 GENSFNAEL 89

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: 63.41 E-value: 5.58e-12

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 77993340  250 GRDAVLECSASGFPNPAFYWLRGNELIQSRSKKYSL-LSGSNLLISSVTDDDSGIYTCIAHNKQQNISASCELAVLV 325
Cdd:cd05730   18 GQSVTLACDADGFPEPTMTWTKDGEPIESGEEKYSFnEDGSEMTILDVDKLDEAEYTCIAENKAGEQEAEIHLKVFA 94

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

Pssm-ID: 409564 [Multi-domain] Cd Length: 91 Bit Score: 61.83 E-value: 1.58e-11

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340  326 PPQFLNYPSNTYAYESSDIEMECAVTGNPQPVVRWVKNGEVVVPSDYFQIVDGGHLQILGLVRS---DEGFYQCIAENEA 402
Cdd:cd20972    1 PPQFIQKLRSQEVAEGSKVRLECRVTGNPTPVVRWFCEGKELQNSPDIQIHQEGDLHSLIIAEAfeeDTGRYSCLATNSV 80

                         90
                 ....*....|.
gi 77993340  403 GNSQAMAQLIL 413
Cdd:cd20972   81 GSDTTSAEIFV 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: 61.48 E-value: 1.66e-11

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340     722 PHQPSSLHVRPL-PNSIIMSWTPPLNPNTL--IRGYTIGYGVGSPYAQTVRVDSKQRYYSIENLEPSSHYVISLKAFNNA 798
Cdd:smart00060    1 PSPPSNLRVTDVtSTSVTLSWEPPPDDGITgyIVGYRVEYREEGSEWKEVNVTPSSTSYTLTGLKPGTEYEFRVRAVNGA 80


                    ...
gi 77993340     799 GEG 801
Cdd:smart00060   81 GEG 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: 61.74 E-value: 1.69e-11

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340  722 PHQPSSLHVRPL-PNSIIMSWTPPLNPNTLIRGYTIGY-GVGSPYAQTVRV-DSKQRYYSIENLEPSSHYVISLKAFNNA 798
Cdd:cd00063    1 PSPPTNLRVTDVtSTSVTLSWTPPEDDGGPITGYVVEYrEKGSGDWKEVEVtPGSETSYTLTGLKPGTEYEFRVRAVNGG 80

                         90
                 ....*....|..
gi 77993340  799 GEGVPLYESAVT 810
Cdd:cd00063   81 GESPPSESVTVT 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: 61.48 E-value: 1.72e-11

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340     923 SAPKDLTVIGREgrPRAILISWQPPLEANGriTGFILYYTLEKNLPIDDWVMEPISGDRLTHQVLDLNLDTVYYFRIQAK 1002
Cdd:smart00060    2 SPPSNLRVTDVT--STSVTLSWEPPPDDGI--TGYIVGYRVEYREEGSEWKEVNVTPSSTSYTLTGLKPGTEYEFRVRAV 77


                    ....*.
gi 77993340    1003 NAKGVG 1008
Cdd:smart00060   78 NGAGEG 83

Fibronectin type III domain;

Pssm-ID: 394996 [Multi-domain] Cd Length: 85 Bit Score: 61.28 E-value: 1.81e-11

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340    724 QPSSLHVRPL-PNSIIMSWTPPLNPNTLIRGYTIGYGV--GSPYAQTVRVDSKQRYYSIENLEPSSHYVISLKAFNNAGE 800
Cdd:pfam00041    2 APSNLTVTDVtSTSLTVSWTPPPDGNGPITGYEVEYRPknSGEPWNEITVPGTTTSVTLTGLKPGTEYEVRVQAVNGGGE 81


                   ...
gi 77993340    801 GVP 803
Cdd:pfam00041   82 GPP 84

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: 61.48 E-value: 2.06e-11

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340  238 FLQRPQKVSVLQGRDAVLECSASGFPNPAFYWLR--GNELIQSRSKKYSLLSGSNLL-ISSVTDDDSGIYTCIAHNKQQN 314
Cdd:cd05763    2 FTKTPHDITIRAGSTARLECAATGHPTPQIAWQKdgGTDFPAARERRMHVMPEDDVFfIVDVKIEDTGVYSCTAQNSAGS 81

                         90
                 ....*....|
gi 77993340  315 ISASCELAVL 324
Cdd:cd05763   82 ISANATLTVL 91

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: 61.36 E-value: 2.15e-11

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340  129 VTVSGPLRVLVSTesvsahlGDTALLRCEVTGDPMPVVRWQKNREDLPLTfdpDSRVVILPSGSLQVSRVQPPDSATYRC 208
Cdd:cd20952    1 IILQGPQNQTVAV-------GGTVVLNCQATGEPVPTISWLKDGVPLLGK---DERITTLENGSLQIKGAEKSDTGEYTC 70


                 ....*....
gi 77993340  209 LAENP-GSA 216
Cdd:cd20952   71 VALNLsGEA 79

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: 60.73 E-value: 3.59e-11

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340  242 PQKVSVLQGRDAVLECSASGFPNPAFYWLRGNELIQSRSKKYSLLSGSNLL-ISSVTDDDSGIYTCIAHNKQQNISASCE 320
Cdd:cd20976    8 PKDLEAVEGQDFVAQCSARGKPVPRITWIRNAQPLQYAADRSTCEAGVGELhIQDVLPEDHGTYTCLAKNAAGQVSCSAW 87


                 ...
gi 77993340  321 LAV 323
Cdd:cd20976   88 VTV 90

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: 60.55 E-value: 3.62e-11

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340  327 PQFLNYP--SNTYAYESSDIEMECAVTGNPQPVVRWVKNGEVVVPSDYFQIVDGGHLQILGLVRSDEGFYQCIAENEAGN 404
Cdd:cd04969    1 PDFELNPvkKKILAAKGGDVIIECKPKASPKPTISWSKGTELLTNSSRICILPDGSLKIKNVTKSDEGKYTCFAVNFFGK 80


                 ....*....
gi 77993340  405 SQAMAQLIL 413
Cdd:cd04969   81 ANSTGSLSV 89

Fibronectin type III domain;

Pssm-ID: 394996 [Multi-domain] Cd Length: 85 Bit Score: 60.51 E-value: 3.72e-11

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340    823 PPVGVQAVALTSDSVRVSWadnsIPKNQKSSEVRYYSVKWRTSHSTSG-KHKSADTTALSHTVTGLKPNTMYEFSVMVTK 901
Cdd:pfam00041    2 APSNLTVTDVTSTSLTVSW----TPPPDGNGPITGYEVEYRPKNSGEPwNEITVPGTTTSVTLTGLKPGTEYEVRVQAVN 77


                   ....*...
gi 77993340    902 GRKSSTWS 909
Cdd:pfam00041   78 GGGEGPPS 85

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

Pssm-ID: 409549 [Multi-domain] Cd Length: 88 Bit Score: 60.62 E-value: 4.44e-11

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 77993340  343 DIEMECAVTGNPQPVVRWVKNGEVVVPSDYFQIVDGGHLQILGLVRSDEGFYQCIAENEAGNSQAMAQLIL 413
Cdd:cd20957   18 TAVFNCSVTGNPIHTVLWMKDGKPLGHSSRVQILSEDVLVIPSVKREDKGMYQCFVRNDGDSAQATAELKL 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: 60.64 E-value: 5.69e-11

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340   36 RFVLQPQDVVTVRGGVLQLDCDAlSDQGVPSISWKKDGVLLSAVVDERRRQ---LSNGSLLVQNVMHSRHHRPDEGSYQC 112
Cdd:cd07693    2 RIVEHPSDLIVSKGDPATLNCKA-EGRPTPTIQWLKNGQPLETDKDDPRSHrivLPSGSLFFLRVVHGRKGRSDEGVYVC 80

                         90       100
                 ....*....|....*....|
gi 77993340  113 LASLEgIGAIVSRTARVTVS 132
Cdd:cd07693   81 VAHNS-LGEAVSRNASLEVA 99

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: 59.72 E-value: 7.42e-11

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340  239 LQRPQKVSVLQGRDAVLECSASGFPNPAFYWLR-GNELIQSRskkYSLLSGSNLLISSVTDDDSGIYTCIAHNKQQNISA 317
Cdd:cd05725    1 VKRPQNQVVLVDDSAEFQCEVGGDPVPTVRWRKeDGELPKGR---YEILDDHSLKIRKVTAGDMGSYTCVAENMVGKIEA 77


                 ....*.
gi 77993340  318 SCELAV 323
Cdd:cd05725   78 SATLTV 83

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

Pssm-ID: 409398 Cd Length: 101 Bit Score: 59.81 E-value: 1.09e-10

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340  325 VPPQFLNYPSNTYAYESSDIEMECAVTGNPQPVVRWVKNGEVVVPSDYFQIV----DGGH-----LQILGLVRSDEGFYQ 395
Cdd:cd05735    2 IPAMITSYPNTTLATKGQKKEMSCTAHGEKPIIVRWEKEDTIINPSEMSRYLvttkEVGDevistLQILPTVREDSGFFS 81

                         90
                 ....*....|....*...
gi 77993340  396 CIAENEAGNSQAMAQLIL 413
Cdd:cd05735   82 CHAINSYGEDRGIIQLTV 99

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: 59.05 E-value: 1.32e-10

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340   37 FVLQPQDVVTVRGGVLQLDCDALSDQgVPSISWKKDGVLLsAVVDERRRQLSNGSLLVQNVMHSrhhrpDEGSYQCLA-S 115
Cdd:cd20952    2 ILQGPQNQTVAVGGTVVLNCQATGEP-VPTISWLKDGVPL-LGKDERITTLENGSLQIKGAEKS-----DTGEYTCVAlN 74


                 ...
gi 77993340  116 LEG 118
Cdd:cd20952   75 LSG 77

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: 58.59 E-value: 2.15e-10

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340  327 PQFLNYPSNTYAYESSDIEMECAVTGNPQPVVRWVKNGEVV----VPSDY-FQIVDGGH-LQILGLVRSDEGFYQCIAEN 400
Cdd:cd20951    1 PEFIIRLQSHTVWEKSDAKLRVEVQGKPDPEVKWYKNGVPIdpssIPGKYkIESEYGVHvLHIRRVTVEDSAVYSAVAKN 80

                         90
                 ....*....|..
gi 77993340  401 EAGNSQAMAQLI 412
Cdd:cd20951   81 IHGEASSSASVV 92

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

Pssm-ID: 143223 Cd Length: 69 Bit Score: 57.19 E-value: 3.97e-10

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 77993340  344 IEMECAVTGNPQPVVRWVKNGEVVVPSDYFQIVDGGHLQILGLVRSDEGFYQCIAENEAGNSQAMAQL 411
Cdd:cd05746    1 VQIPCSAQGDPEPTITWNKDGVQVTESGKFHISPEGYLAIRDVGVADQGRYECVARNTIGYASVSMVL 68

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: 57.56 E-value: 4.23e-10

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340  332 YPSNTYAYESSDIEMECAVTGNPQPVVRWVKNGEVVVPSdYFQIVDGGHLQILGLVRSDEGFYQCIAENEAGNSQAMAQL 411
Cdd:cd04968    7 FPADTYALKGQTVTLECFALGNPVPQIKWRKVDGSPSSQ-WEITTSEPVLEIPNVQFEDEGTYECEAENSRGKDTVQGRI 85


                 .
gi 77993340  412 I 412
Cdd:cd04968   86 I 86

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: 57.42 E-value: 4.47e-10

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340  245 VSVLQGRDAVLECSASGFPNPAFYWLR-GNELIQSRSKKYSLlsGSNLLISSVTDDDSGIYTCIAHNKQQniSASCELAV 323
Cdd:cd05731    5 TMVLRGGVLLLECIAEGLPTPDIRWIKlGGELPKGRTKFENF--NKTLKIENVSEADSGEYQCTASNTMG--SARHTISV 80


                 ..
gi 77993340  324 LV 325
Cdd:cd05731   81 TV 82

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: 57.47 E-value: 5.51e-10

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340  237 VFLQRPQKVSVLQGRDAVLECSASGFPNPAFYWLRGNELIQSRSKKYSLLSGSN----LLISSVTDDDSGIYTCIAHNKQ 312
Cdd:cd05892    2 MFIQKPQNKKVLEGDPVRLECQISAIPPPQIFWKKNNEMLQYNTDRISLYQDNCgricLLIQNANKKDAGWYTVSAVNEA 81

                         90
                 ....*....|.
gi 77993340  313 QNISASCELAV 323
Cdd:cd05892   82 GVVSCNARLDV 92

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: 57.08 E-value: 6.12e-10

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340  243 QKVSVLQGRDAVLECSASGFPNPAFYWLRGNELIQSrSKKYSLLSGSNLLISSVTDDDSGIYTCIAHNKQQNISASCELA 322
Cdd:cd04969   10 KKILAAKGGDVIIECKPKASPKPTISWSKGTELLTN-SSRICILPDGSLKIKNVTKSDEGKYTCFAVNFFGKANSTGSLS 88


                 .
gi 77993340  323 V 323
Cdd:cd04969   89 V 89

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: 57.49 E-value: 6.67e-10

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340  134 PLRVLVSTESVSAHLGDTALLRCEVTGDPMPVVRWQKNreDLPLTFDPDSRVVILPSGSLQVSRVQ-----PPDSATYRC 208
Cdd:cd05722    1 ELYFLSEPSDIVAMRGGPVVLNCSAESDPPPKIEWKKD--GVLLNLVSDERRQQLPNGSLLITSVVhskhnKPDEGFYQC 78


                 ....
gi 77993340  209 LAEN 212
Cdd:cd05722   79 VAQN 82

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: 56.25 E-value: 1.30e-09

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340  330 LNYPSNTYAYESSDIEMECAVTGNPQPVVRWVKN-GEVvvPSDYFQIVDGGHLQILGLVRSDEGFYQCIAENEAGNSQAM 408
Cdd:cd05725    1 VKRPQNQVVLVDDSAEFQCEVGGDPVPTVRWRKEdGEL--PKGRYEILDDHSLKIRKVTAGDMGSYTCVAENMVGKIEAS 78


                 ....
gi 77993340  409 AQLI 412
Cdd:cd05725   79 ATLT 82

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: 56.25 E-value: 1.38e-09

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340  143 SVSAHLGDTALLRCEV-TGDPMPVVRWQKNreDLPLTFDpDSRVVILPSGSLQVSRVQPPDSATYRCLAENPGSARTGTD 221
Cdd:cd05724    6 DTQVAVGEMAVLECSPpRGHPEPTVSWRKD--GQPLNLD-NERVRIVDDGNLLIAEARKSDEGTYKCVATNMVGERESRA 82


                 ....*
gi 77993340  222 ADLRV 226
Cdd:cd05724   83 ARLSV 87

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: 56.50 E-value: 1.43e-09

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 77993340  250 GRDAVLECSASGFPNPAFYWLR-GNELIQSRSKKYSLLS-GSNLLISSVTDDDSGIYTCIAHN 310
Cdd:cd05736   15 GVEASLRCHAEGIPLPRVQWLKnGMDINPKLSKQLTLIAnGSELHISNVRYEDTGAYTCIAKN 77

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: 56.41 E-value: 1.50e-09

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340  149 GDTALLRCEVTGDPMPVVRWQKNREDLPL-TFDPDSRVVILPSGSLQVSRVQP-----PDSATYRCLAENPGSARTGTDA 222
Cdd:cd07693   15 GDPATLNCKAEGRPTPTIQWLKNGQPLETdKDDPRSHRIVLPSGSLFFLRVVHgrkgrSDEGVYVCVAHNSLGEAVSRNA 94


                 ....
gi 77993340  223 DLRV 226
Cdd:cd07693   95 SLEV 98

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: 55.87 E-value: 1.53e-09

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 77993340  333 PSNTYAYESSDIEMEC-AVTGNPQPVVRWVKNGEVVVPSD-YFQIVDGGHLQILGLVRSDEGFYQCIAENEAG 403
Cdd:cd05724    4 PSDTQVAVGEMAVLECsPPRGHPEPTVSWRKDGQPLNLDNeRVRIVDDGNLLIAEARKSDEGTYKCVATNMVG 76

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

Pssm-ID: 409568 [Multi-domain] Cd Length: 90 Bit Score: 56.10 E-value: 1.60e-09

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340  326 PPQFLNYPSNTYAYESSDIEMECAVTGNPQPVVRWVKNG-EVVVPSDYFQIVDG-GHLQILGLVRSDEGFYQCIAENEAG 403
Cdd:cd20976    1 APSFSSVPKDLEAVEGQDFVAQCSARGKPVPRITWIRNAqPLQYAADRSTCEAGvGELHIQDVLPEDHGTYTCLAKNAAG 80


                 ....*...
gi 77993340  404 NSQAMAQL 411
Cdd:cd20976   81 QVSCSAWV 88

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: 55.71 E-value: 1.66e-09

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 77993340  149 GDTALLRCEVTGDPMPVVRWQKNREDLPLtfdpDSRVVILPSGSLQVSRVQPPDSATYRCLAENP-GSART 218
Cdd:cd05745    2 GQTVDFLCEAQGYPQPVIAWTKGGSQLSV----DRRHLVLSSGTLRISRVALHDQGQYECQAVNIvGSQRT 68

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

Pssm-ID: 409570 [Multi-domain] Cd Length: 88 Bit Score: 55.48 E-value: 2.29e-09

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 77993340  238 FLQRPQK-VSVLQGRDAVLECSASGFPNPAFYWLRGNELIQSRSKKYSLLSGSnLLISSVTDDDSGIYTCIAHN 310
Cdd:cd20978    3 FIQKPEKnVVVKGGQDVTLPCQVTGVPQPKITWLHNGKPLQGPMERATVEDGT-LTIINVQPEDTGYYGCVATN 75

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: 55.59 E-value: 2.33e-09

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 77993340  333 PSNTYAYESSDIEMECAVTGNPQPVVRWVKNGEVVVPSDYFQIV--DGGHLQILGLVRSDEGFYQCIAENEAGNS 405
Cdd:cd20970    9 SFTVTAREGENATFMCRAEGSPEPEISWTRNGNLIIEFNTRYIVreNGTTLTIRNIRRSDMGIYLCIASNGVPGS 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: 55.31 E-value: 2.84e-09

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340     823 PPVGVQAVALTSDSVRVSWadNSIPKNQKSSEVRYYSVKWRTShSTSGKHKSADTTALSHTVTGLKPNTMYEFSVMVTKG 902
Cdd:smart00060    3 PPSNLRVTDVTSTSVTLSW--EPPPDDGITGYIVGYRVEYREE-GSEWKEVNVTPSSTSYTLTGLKPGTEYEFRVRAVNG 79


                    ....
gi 77993340     903 RKSS 906
Cdd:smart00060   80 AGEG 83

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: 55.49 E-value: 2.91e-09

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340  238 FLQRPQKVSVLQGRDAVLECSASGFPNPAFYWLRGNELIQSRSKKYSLLSGS---NLLISSVTDDDSGIYTCIAHNKQQN 314
Cdd:cd20990    3 FLQAPGDLTVQEGKLCRMDCKVSGLPTPDLSWQLDGKPIRPDSAHKMLVRENgvhSLIIEPVTSRDAGIYTCIATNRAGQ 82


                 ....*....
gi 77993340  315 ISASCELAV 323
Cdd:cd20990   83 NSFNLELVV 91

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

Pssm-ID: 409564 [Multi-domain] Cd Length: 91 Bit Score: 54.90 E-value: 4.30e-09

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340  238 FLQRPQKVSVLQGRDAVLECSASGFPNPAFYWLRGNELIQSrSKKYSLLSGSN---LLISSVTDDDSGIYTCIAHNKQQN 314
Cdd:cd20972    4 FIQKLRSQEVAEGSKVRLECRVTGNPTPVVRWFCEGKELQN-SPDIQIHQEGDlhsLIIAEAFEEDTGRYSCLATNSVGS 82


                 ....*....
gi 77993340  315 ISASCELAV 323
Cdd:cd20972   83 DTTSAEIFV 91

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: 55.18 E-value: 4.68e-09

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340  329 FLNYPSNTYAYESSDIEMECAVTGNPQPVVRWVKNGEVV--VPSDYFQIVDGGHLQILGLV-----RSDEGFYQCIAENE 401
Cdd:cd05722    4 FLSEPSDIVAMRGGPVVLNCSAESDPPPKIEWKKDGVLLnlVSDERRQQLPNGSLLITSVVhskhnKPDEGFYQCVAQNE 83

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

Pssm-ID: 143259 Cd Length: 88 Bit Score: 54.64 E-value: 4.81e-09

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 77993340  335 NTYAYESSDIEMECAVTGNPQPVVRWVKNGEvVVPSDYFQIVDGGHLQILGLVRSDEGFYQCIAENEAGNSQAMAQL 411
Cdd:cd05851   10 DTYALKGQNVTLECFALGNPVPVIRWRKILE-PMPATAEISMSGAVLKIFNIQPEDEGTYECEAENIKGKDKHQARV 85

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

Pssm-ID: 409560 [Multi-domain] Cd Length: 88 Bit Score: 54.56 E-value: 5.68e-09

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 77993340  242 PQKVSVLQGRDAVLECSASGFPNPAFYWLRGNELIQSRSKKYSLLSGSnLLISSVTDDDSGIYTCIAHN 310
Cdd:cd20968    6 PTNVTIIEGLKAVLPCTTMGNPKPSVSWIKGDDLIKENNRIAVLESGS-LRIHNVQKEDAGQYRCVAKN 73

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: 54.07 E-value: 8.30e-09

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340  242 PQKVSVLQGRDAVLECSASGFPNPAFYWLRGNELIQSRSKKYsLLSGSNLLISSVTDDDSGIYTCIAHNKQQNISASCEL 321
Cdd:cd20957    8 PPVQTVDFGRTAVFNCSVTGNPIHTVLWMKDGKPLGHSSRVQ-ILSEDVLVIPSVKREDKGMYQCFVRNDGDSAQATAEL 86

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

Pssm-ID: 143222 [Multi-domain] Cd Length: 74 Bit Score: 53.02 E-value: 1.23e-08

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 77993340  340 ESSDIEMECAVTGNPQPVVRWVKNGEVVVPSDYFQIVDGGHLQILGLVRSDEGFYQCIAENEAGNSQAMAQLIL 413
Cdd:cd05745    1 EGQTVDFLCEAQGYPQPVIAWTKGGSQLSVDRRHLVLSSGTLRISRVALHDQGQYECQAVNIVGSQRTVAQLTV 74

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: 53.35 E-value: 1.23e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340  239 LQRPQKVSVLQGRDAVLECSASGFPNPAFYWLRGNELIQSrSKKYSLLSGSNLLISSVTDDDSGIYTCIAHNKQQNISAS 318
Cdd:cd05723    1 LKKPSNIYAHESMDIVFECEVTGKPTPTVKWVKNGDVVIP-SDYFKIVKEHNLQVLGLVKSDEGFYQCIAENDVGNAQAS 79


                 ....*
gi 77993340  319 CELAV 323
Cdd:cd05723   80 AQLII 84

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: 53.46 E-value: 1.28e-08

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 77993340  346 MECAVTGNPQPVVRWVKNGEVVVPSDYFQIVDGGHLQILGLVRSDEGFYQCIAENEAGNSQAMAQLIL 413
Cdd:cd05852   22 IECKPKAAPKPKFSWSKGTELLVNNSRISIWDDGSLEILNITKLDEGSYTCFAENNRGKANSTGVLSV 89

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

Pssm-ID: 409394 [Multi-domain] Cd Length: 83 Bit Score: 53.18 E-value: 1.29e-08

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 77993340  334 SNTYAYESSDIEMECAVTGNPQPVVRWVK-NGEVvvPSDYFQIVD-GGHLQILGLVRSDEGFYQCIAENEAGNSQ 406
Cdd:cd05731    3 SSTMVLRGGVLLLECIAEGLPTPDIRWIKlGGEL--PKGRTKFENfNKTLKIENVSEADSGEYQCTASNTMGSAR 75

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: 53.51 E-value: 1.49e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340  325 VPPQFLNYPSNTYAYESSDIEMECAVTGNPQPVVRWVKNGEVVVPSDYFQIVDGGH---LQILGLVRSDEGFYQCIAENE 401
Cdd:cd05747    2 LPATILTKPRSLTVSEGESARFSCDVDGEPAPTVTWMREGQIIVSSQRHQITSTEYkstFEISKVQMSDEGNYTVVVENS 81


                 ....*.
gi 77993340  402 AGNSQA 407
Cdd:cd05747   82 EGKQEA 87

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

Pssm-ID: 409567 Cd Length: 91 Bit Score: 53.24 E-value: 1.65e-08

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 77993340  340 ESSDIEMECAVTGNPQPVVRWVKNGEVVVPSD--YFQIVDGG--HLQILGLVRSDEGFYQCIAENEAGNSQAMAQL 411
Cdd:cd20975   14 EGQDVIMSIRVQGEPKPVVSWLRNRQPVRPDQrrFAEEAEGGlcRLRILAAERGDAGFYTCKAVNEYGARQCEARL 89

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

Pssm-ID: 464026 [Multi-domain] Cd Length: 79 Bit Score: 52.78 E-value: 1.74e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340    241 RPQKVSVLQGRDAVLECSASGFPNPAFYWLRGNELIQSrskkysllsGSNLLISSVTDDDSGIYTCIAHNKQQNI-SASC 319
Cdd:pfam13895    5 TPSPTVVTEGEPVTLTCSAPGNPPPSYTWYKDGSAISS---------SPNFFTLSVSAEDSGTYTCVARNGRGGKvSNPV 75


                   ....
gi 77993340    320 ELAV 323
Cdd:pfam13895   76 ELTV 79

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: 53.40 E-value: 1.75e-08

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 77993340  335 NTYAYESSDIEMECAVTGNPQPVVRWVKNGEVVVPSD--YFQIVDGGHLQILGLVRSDEGFYQCIAENEAGNSQAMAQL 411
Cdd:cd05730   12 NATANLGQSVTLACDADGFPEPTMTWTKDGEPIESGEekYSFNEDGSEMTILDVDKLDEAEYTCIAENKAGEQEAEIHL 90

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

Pssm-ID: 143259 Cd Length: 88 Bit Score: 53.10 E-value: 1.78e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340  134 PLRVLVSTESVSAHLGDTALLRCEVTGDPMPVVRWQKNREDLPLTFDpdsrvvILPSGS-LQVSRVQPPDSATYRCLAEN 212
Cdd:cd05851    1 PADINVKFKDTYALKGQNVTLECFALGNPVPVIRWRKILEPMPATAE------ISMSGAvLKIFNIQPEDEGTYECEAEN 74

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: 52.88 E-value: 1.92e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340  329 FLNYPSNTYAYESSDIEMECAVTGNPQPVVRWVKNG-EVVVPSDYFQIVDGGHLQILGLVRSDEGFYQCIAENEAGNSQA 407
Cdd:cd20952    2 ILQGPQNQTVAVGGTVVLNCQATGEPVPTISWLKDGvPLLGKDERITTLENGSLQIKGAEKSDTGEYTCVALNLSGEATW 81


                 ....
gi 77993340  408 MAQL 411
Cdd:cd20952   82 SAVL 85

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: 53.04 E-value: 2.59e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340  328 QFLNYPSNTYAYESSDIEMECAVTGNPQPVVRWVKNGEVVV--------PSDYFQIVDGGHLQILGLVRSDEGFYQCIAE 399
Cdd:cd05726    1 QFVVKPRDQVVALGRTVTFQCETKGNPQPAIFWQKEGSQNLlfpyqppqPSSRFSVSPTGDLTITNVQRSDVGYYICQAL 80

                         90
                 ....*....|..
gi 77993340  400 NEAGNSQAMAQL 411
Cdd:cd05726   81 NVAGSILAKAQL 92

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: 52.94 E-value: 2.87e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340  327 PQFLNYPSNTYAYESSDIEMECAVTGNPQPVVRWVKNGEVVV-----PSDYFQIVDGGHLQILGLV-----RSDEGFYQC 396
Cdd:cd07693    1 PRIVEHPSDLIVSKGDPATLNCKAEGRPTPTIQWLKNGQPLEtdkddPRSHRIVLPSGSLFFLRVVhgrkgRSDEGVYVC 80


                 ....*....
gi 77993340  397 IAENEAGNS 405
Cdd:cd07693   81 VAHNSLGEA 89

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: 52.02 E-value: 4.20e-08

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 77993340  343 DIEMECAVTGNPQPVVRWVKNGEVVVPSDYFQIV---DGGHLQIL---GLVRSDEGFYQCIAENEAGNsqAMAQLILLQ 415
Cdd:cd05733   18 NITIKCEAKGNPQPTFRWTKDGKFFDPAKDPRVSmrrRSGTLVIDnhnGGPEDYQGEYQCYASNELGT--AISNEIRLV 94

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: 51.81 E-value: 4.46e-08

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 77993340    242 PQKVSVLQGRDAVLECSASGF-PNPAFYWLR-GNELIQSR--SKKYSLLSGSNLLISSVTDDDSGIYTCIAHN 310
Cdd:pfam00047    3 PPTVTVLEGDSATLTCSASTGsPGPDVTWSKeGGTLIESLkvKHDNGRTTQSSLLISNVTKEDAGTYTCVVNN 75

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: 51.81 E-value: 4.86e-08

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 77993340  340 ESSDIEMECAVTGNPQPVVRWVKNGEVVVPSDYFQIVDGG----HLQILGLVRSDEGFYQCIAENEAGNSQAMAQLIL 413
Cdd:cd20973   11 EGSAARFDCKVEGYPDPEVKWMKDDNPIVESRRFQIDQDEdglcSLIISDVCGDDSGKYTCKAVNSLGEATCSAELTV 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: 51.47 E-value: 5.64e-08

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 77993340  328 QFLNYPSNTYAYESSDIEMECAVTGNPQPVVRWVKNGEVVVPSDYFQIVDGGHLQILGLVRSDEGFYQCIAENEAG 403
Cdd:cd20968    1 KITRPPTNVTIIEGLKAVLPCTTMGNPKPSVSWIKGDDLIKENNRIAVLESGSLRIHNVQKEDAGQYRCVAKNSLG 76

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: 51.43 E-value: 6.98e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340    139 VSTESVSAHLGDTALLRCEV-TGDPMPVVRWQKN--REDLPLTFDPDSRVVIlpSGSLQVSRVQPPDSATYRCLAENPGS 215
Cdd:pfam00047    1 SAPPTVTVLEGDSATLTCSAsTGSPGPDVTWSKEggTLIESLKVKHDNGRTT--QSSLLISNVTKEDAGTYTCVVNNPGG 78

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: 51.71 E-value: 7.75e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340  236 LVFLQRPQKVSVLQGRDAVLECSASGFPNPAFYWLRGNELIQ--SRSKKYSLLSGSnLLISSVT-----DDDSGIYTCIA 308
Cdd:cd05722    2 LYFLSEPSDIVAMRGGPVVLNCSAESDPPPKIEWKKDGVLLNlvSDERRQQLPNGS-LLITSVVhskhnKPDEGFYQCVA 80


                 ...
gi 77993340  309 HNK 311
Cdd:cd05722   81 QNE 83

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

Pssm-ID: 409421 [Multi-domain] Cd Length: 88 Bit Score: 51.32 E-value: 8.15e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340  240 QRPQKVSVLQGRDAVLECSASGFPNPAFYWLRGNELIQSRSKKYSLLSGSNLLISSVTDDDSGIYTCIAHNKQQNISASC 319
Cdd:cd05764    5 RHTHELRVLEGQRATLRCKARGDPEPAIHWISPEGKLISNSSRTLVYDNGTLDILITTVKDTGAFTCIASNPAGEATARV 84


                 ....
gi 77993340  320 ELAV 323
Cdd:cd05764   85 ELHI 88

Purple acid Phosphatase, N-terminal domain; This domain is found at the N-terminus of Purple acid phosphatase proteins.

Pssm-ID: 465220 [Multi-domain] Cd Length: 93 Bit Score: 51.26 E-value: 8.73e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340    824 PVGVQaVALTSD--SVRVSWADNSipkNQKSSEVRY---YSVKWRTSHSTSGKHKSAD-TTALSHTV--TGLKPNTMYEF 895
Cdd:pfam16656    1 PEQVH-LSLTGDstSMTVSWVTPS---AVTSPVVQYgtsSSALTSTATATSSTYTTGDgGTGYIHRAtlTGLEPGTTYYY 76

                           90       100
                   ....*....|....*....|.
gi 77993340    896 SVmvtkGRKSSTWSMTAHATT 916
Cdd:pfam16656   77 RV----GDDNGGWSEVYSFTT 93

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: 50.91 E-value: 9.04e-08

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 77993340  333 PSNTYAYESSDIEMECAVTGNPQPVVRWVKNGEVV--VPSDYFQIVDGGHLQILGLVRSDEGFYQCIAENEAG 403
Cdd:cd04978    6 PPSLVLSPGETGELICEAEGNPQPTITWRLNGVPIepAPEDMRRTVDGRTLIFSNLQPNDTAVYQCNASNVHG 78

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

Pssm-ID: 443767 [Multi-domain] Cd Length: 978 Bit Score: 56.88 E-value: 9.76e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340  436 VSSRFVRLSWRPPEEPR-GPILTYGVfySEEGINRERSVNVTEAEslqltvsnlrpEASYSFRVLAYNEqgpgESSEAIR 514
Cdd:COG4733  458 VAGRTLTVSTAYSETPEaGAVWAFGP--DELETQLFRVVSIEENE-----------DGTYTITAVQHAP----EKYAAID 520

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340  515 LSTQAELLVPGPVENL--------QAEAVSPTSIQASWDPPAPANgpvqSYRLLWTeTSSGKEQNV-EVVGQSYRMEGLK 585
Cdd:COG4733  521 AGAFDDVPPQWPPVNVttseslsvVAQGTAVTTLTVSWDAPAGAV----AYEVEWR-RDDGNWVSVpRTSGTSFEVPGIY 595

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340  586 KfTEYSLRVLAVNRHGPGVSDKDTLITTLSDVPSSPPQNVSLEVVYS-RSIKVSWQPPPantqNGFITGYKIRYRKTGRR 664
Cdd:COG4733  596 A-GDYEVRVRAINALGVSSAWAASSETTVTGKTAPPPAPTGLTATGGlGGITLSWSFPV----DADTLRTEIRYSTTGDW 670

                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|....
gi 77993340  665 GEQEAIE---PNNLWYLfTGLEKGSQYSFQVSgmTVNGTGPSSEWLTAETPEND 715
Cdd:COG4733  671 ASATVAQalyPGNTYTL-AGLKAGQTYYYRAR--AVDRSGNVSAWWVSGQASAD 721

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: 51.10 E-value: 1.09e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340  327 PQFLNYPSNTYAYESSD---IEMECAVTGNPQPVVRWVKNG-EVVVPSDY-FQIVDGGHLQILGLVRSDEGFYQCIAENE 401
Cdd:cd05848    2 PVFVQEPDDAIFPTDSDekkVILNCEARGNPVPTYRWLRNGtEIDTESDYrYSLIDGNLIISNPSEVKDSGRYQCLATNS 81


                 ..
gi 77993340  402 AG 403
Cdd:cd05848   82 IG 83

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: 1.13e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340  137 VLVSTESVSAHLGDTALLRCEVTGDPMPVVRWQKNREDlpLTFDPDSRVVILPSGS-LQVSRVQPPDSATYRCLAENPGs 215
Cdd:cd05736    3 IRVYPEFQAKEPGVEASLRCHAEGIPLPRVQWLKNGMD--INPKLSKQLTLIANGSeLHISNVRYEDTGAYTCIAKNEG- 79

                         90
                 ....*....|..
gi 77993340  216 artGTDADLRVL 227
Cdd:cd05736   80 ---GVDEDISSL 88

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

Pssm-ID: 409408 [Multi-domain] Cd Length: 92 Bit Score: 50.59 E-value: 1.41e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340  239 LQRPQKVSVLQGRDAVLECSA-SGFPNPAFYWLR-GNELIQSRSKKYSLLSG---SNLLISSVTDDDSGIYTCIAHNKQQ 313
Cdd:cd05750    3 LKEMKSQTVQEGSKLVLKCEAtSENPSPRYRWFKdGKELNRKRPKNIKIRNKkknSELQINKAKLEDSGEYTCVVENILG 82

                         90
                 ....*....|
gi 77993340  314 NISASCELAV 323
Cdd:cd05750   83 KDTVTGNVTV 92

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: 50.38 E-value: 1.65e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340  243 QKVSVLQGRDAVLECSASGFPNPAFYWLRGNELIQSRSKKYSLLSGSnLLISSVTDDDSGIYTCIAHNKQQNISASCELA 322
Cdd:cd05852   10 KKILAAKGGRVIIECKPKAAPKPKFSWSKGTELLVNNSRISIWDDGS-LEILNITKLDEGSYTCFAENNRGKANSTGVLS 88


                 .
gi 77993340  323 V 323
Cdd:cd05852   89 V 89

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: 50.32 E-value: 1.73e-07

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340  148 LGDTALLRCEVTGDPMPVVRWQKNrEDLpltFDPDSRVVILPSGSLQVSRVQPPDSATYRCLAENP-GSA 216
Cdd:cd20968   13 EGLKAVLPCTTMGNPKPSVSWIKG-DDL---IKENNRIAVLESGSLRIHNVQKEDAGQYRCVAKNSlGIA 78

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

Pssm-ID: 409460 [Multi-domain] Cd Length: 83 Bit Score: 49.91 E-value: 2.07e-07

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 77993340  247 VLQGRDAVLECSASGFPNPAFYWLRGNELIQSRSKKYsLLSGSNLLISSVTDDDSGIYTCIAHN 310
Cdd:cd05876    7 ALRGQSLVLECIAEGLPTPTVKWLRPSGPLPPDRVKY-QNHNKTLQLLNVGESDDGEYVCLAEN 69

Third immunoglobulin-like domain of the human WFIKKN (WAP, follistatin, immunoglobulin, Kunitz and NTR domain-containing protein), and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin-like domain of the human WFIKKN (WAP, follistatin, immunoglobulin, Kunitz and NTR domain-containing protein) and similar proteins. WFIKKN is a secreted protein that consists of multiple types of protease inhibitory modules, including two tandem Kunitz-type protease inhibitor-domains. The Ig superfamily is a heterogenous group of proteins built on a common fold comprised of a sandwich of two beta sheets. Members of the Ig superfamily are components of immunoglobulin, neuroglia, cell surface glycoproteins, such as T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, such as butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409422 [Multi-domain] Cd Length: 95 Bit Score: 50.24 E-value: 2.15e-07

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 77993340  145 SAHLGDTALLRCEVTGDPMPVVRWQK---NREDLPLTfdPD---SRVVILPSGSLQVSRVQPPDSATYRCLAENPG 214
Cdd:cd05765   11 TVKVGETASFHCDVTGRPQPEITWEKqvpGKENLIMR--PNhvrGNVVVTNIGQLVIYNAQPQDAGLYTCTARNSG 84

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: 49.88 E-value: 2.66e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340  247 VLQGRDAVLECSASGFPNPAFYWLR-GNELIQSRSKKYSLLSGSN--LLISSVTDDDSGIYTCIAHNKQQNISASCELAV 323
Cdd:cd20973    9 VVEGSAARFDCKVEGYPDPEVKWMKdDNPIVESRRFQIDQDEDGLcsLIISDVCGDDSGKYTCKAVNSLGEATCSAELTV 88

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

Pssm-ID: 443767 [Multi-domain] Cd Length: 978 Bit Score: 55.34 E-value: 2.77e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340  534 AVSPTSIQASW-DPPAPANGPVqsyrllWTETSSgkeqnvEVVGQSYRMEGLKKFTEYSLRVLAVNrHGPgvsDKDTLIT 612
Cdd:COG4733  457 SVAGRTLTVSTaYSETPEAGAV------WAFGPD------ELETQLFRVVSIEENEDGTYTITAVQ-HAP---EKYAAID 520

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340  613 T--LSDV-PSSPPQNVSLEVVYSR--------SIKVSWQPPPANTqngfitGYKIRYRKTGrrGE-QEAIEPNNLWYLFT 680
Cdd:COG4733  521 AgaFDDVpPQWPPVNVTTSESLSVvaqgtavtTLTVSWDAPAGAV------AYEVEWRRDD--GNwVSVPRTSGTSFEVP 592

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340  681 GLEKGsQYSFQVSGmtVNGTGPSSEWLTAETPENDLDESqVPHQPSSLHVRPLPNSIIMSWTPPLNPNTLirGYTIGYGV 760
Cdd:COG4733  593 GIYAG-DYEVRVRA--INALGVSSAWAASSETTVTGKTA-PPPAPTGLTATGGLGGITLSWSFPVDADTL--RTEIRYST 666

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340  761 GSPYAQTVRVDS--KQRYYSIENLEPSSHYVISLKAFNNAG------------EGVPLYESAVTRSMTDSSSAPMIPPVG 826
Cdd:COG4733  667 TGDWASATVAQAlyPGNTYTLAGLKAGQTYYYRARAVDRSGnvsawwvsgqasADAAGILDAITGQILETELGQELDAII 746

                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340  827 VQAVALTSDSVRVSWADNSIPKNqkssevryYSVKWRTSHSTSGKHKSADTTALSHTVTGLKPNTmyeFSVMVTKGRKSS 906
Cdd:COG4733  747 QNATVAEVVAATVTDVTAQIDTA--------VLFAGVATAAAIGAEARVAATVAESATAAAATGT---AADAAGDASGGV 815

                        410
                 ....*....|....*..
gi 77993340  907 TWSMTAHATTYEAAPSS 923
Cdd:COG4733  816 TAGTSGTTGAGDTAAST 832

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: 49.70 E-value: 2.91e-07

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 77993340  149 GDTALLRCEVTGDPMPVVRWQKNREDlPLTFDPDSRVVILPSGSLQVSRVQPPDSATYRCLAENPGS 215
Cdd:cd20969   17 GHTVQFVCRADGDPPPAILWLSPRKH-LVSAKSNGRLTVFPDGTLEVRYAQVQDNGTYLCIAANAGG 82

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: 49.85 E-value: 3.31e-07

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 77993340  344 IEMECAVTGNPQPVVRWVKNGEVVVPSDYFqivdGG------HLQIL--GLVRSDEGFYQCIAENEAGN 404
Cdd:cd05857   22 VKFRCPAAGNPTPTMRWLKNGKEFKQEHRI----GGykvrnqHWSLImeSVVPSDKGNYTCVVENEYGS 86

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: 49.33 E-value: 3.54e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340  327 PQFLNYPSNTYAYESSDIEMECAVTGNPQPVVRWVKNGEVVVPSDYFQIV---DGGHLQILGLVRS-DEGFYQCIAENEA 402
Cdd:cd20990    1 PHFLQAPGDLTVQEGKLCRMDCKVSGLPTPDLSWQLDGKPIRPDSAHKMLvreNGVHSLIIEPVTSrDAGIYTCIATNRA 80

                         90
                 ....*....|.
gi 77993340  403 GNSQAMAQLIL 413
Cdd:cd20990   81 GQNSFNLELVV 91

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 48.72 E-value: 4.11e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340     36 RFVLQPQDVVTVRGGVLQLDCDALSDQgVPSISWKKDG-VLLSAVVDERRRQLSNGSLLVQNVMHSrhhrpDEGSYQCLA 114
Cdd:pfam13927    3 VITVSPSSVTVREGETVTLTCEATGSP-PPTITWYKNGePISSGSTRSRSLSGSNSTLTISNVTRS-----DAGTYTCVA 76


                   .
gi 77993340    115 S 115
Cdd:pfam13927   77 S 77

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: 48.94 E-value: 4.38e-07

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 77993340  140 STESVSAHLGDTALLRCEVTGDPMPVVRWQKNREDLPltfdPDSRVVILPSGSLQVSRVQPPDSATYRCLAENP-GSAR 217
Cdd:cd05731    1 SESSTMVLRGGVLLLECIAEGLPTPDIRWIKLGGELP----KGRTKFENFNKTLKIENVSEADSGEYQCTASNTmGSAR 75

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

Pssm-ID: 409400 [Multi-domain] Cd Length: 91 Bit Score: 49.24 E-value: 5.05e-07

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 77993340  346 MECAVTGNPQPVVRWVKNG---EVVVPSDYFQIVDGGHLQILGLVRSDEGFYQCIAENEAG 403
Cdd:cd05738   19 MLCAASGNPDPEISWFKDFlpvDTATSNGRIKQLRSGALQIENSEESDQGKYECVATNSAG 79

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

Pssm-ID: 409570 [Multi-domain] Cd Length: 88 Bit Score: 48.93 E-value: 5.80e-07

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 77993340  144 VSAHLGDTALLRCEVTGDPMPVVRWQKNREdlplTFDPDSRVVILPSGSLQVSRVQPPDSATYRCLAEN 212
Cdd:cd20978   11 VVVKGGQDVTLPCQVTGVPQPKITWLHNGK----PLQGPMERATVEDGTLTIINVQPEDTGYYGCVATN 75

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

Pssm-ID: 143205 [Multi-domain] Cd Length: 85 Bit Score: 48.75 E-value: 5.81e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340  146 AHLGDTALLRCEVTGDPMPVVRWQKNREDLPltfdPDSRVVILpSGSLQVSRVQPPDSATYRCLAENpgsaRTGT---DA 222
Cdd:cd05728   11 ADIGSSLRWECKASGNPRPAYRWLKNGQPLA----SENRIEVE-AGDLRITKLSLSDSGMYQCVAEN----KHGTiyaSA 81


                 ....
gi 77993340  223 DLRV 226
Cdd:cd05728   82 ELAV 85

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: 49.16 E-value: 6.05e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340  327 PQFLNYPSNTYAYESSD---IEMECAVTGNPQPVVRWVKNG-EVVVPSDYFQIVDGGHLQILGLVRS-DEGFYQCIAENE 401
Cdd:cd04967    2 PVFEEQPDDTIFPEDSDekkVALNCRARANPVPSYRWLMNGtEIDLESDYRYSLVDGTLVISNPSKAkDAGHYQCLATNT 81


                 ..
gi 77993340  402 AG 403
Cdd:cd04967   82 VG 83

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

Pssm-ID: 409420 [Multi-domain] Cd Length: 91 Bit Score: 48.77 E-value: 6.08e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340  345 EMECAVTGNPQPVVRWVKNGEVVVPS------------DYFQIVDgghLQIlglvrSDEGFYQCIAENEAGNSQAMAQLI 412
Cdd:cd05763   18 RLECAATGHPTPQIAWQKDGGTDFPAarerrmhvmpedDVFFIVD---VKI-----EDTGVYSCTAQNSAGSISANATLT 89


                 ..
gi 77993340  413 LL 414
Cdd:cd05763   90 VL 91

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: 48.57 E-value: 7.04e-07

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 77993340  149 GDTALLRCEVTGDPMPVVRWQKNREdlPLTFDPDSRVVILPSGS----LQVSRVQPPDSATYRCLAEN 212
Cdd:cd20951   15 KSDAKLRVEVQGKPDPEVKWYKNGV--PIDPSSIPGKYKIESEYgvhvLHIRRVTVEDSAVYSAVAKN 80

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

Pssm-ID: 409353 [Multi-domain] Cd Length: 70 Bit Score: 47.71 E-value: 7.99e-07

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 77993340   52 LQLDCDALSDQgVPSISWKKDGV-LLSAVVDERRRQLSNGSLLVQNVMHSrhhrpDEGSYQCLASLEGIGAIVSRT 126
Cdd:cd00096    1 VTLTCSASGNP-PPTITWYKNGKpLPPSSRDSRRSELGNGTLTISNVTLE-----DSGTYTCVASNSAGGSASASV 70

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: 48.40 E-value: 8.47e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340  235 GLVFLQRPQKVSVLQGRD---AVLECSASGFPNPAFYWLR-GNELIQSRSKKYSLLSGsNLLISSVTD-DDSGIYTCIAH 309
Cdd:cd05848    1 GPVFVQEPDDAIFPTDSDekkVILNCEARGNPVPTYRWLRnGTEIDTESDYRYSLIDG-NLIISNPSEvKDSGRYQCLAT 79


                 .
gi 77993340  310 N 310
Cdd:cd05848   80 N 80

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: 48.23 E-value: 9.51e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340  327 PQFLNYPSNTYAYESSDIEMECAVTGNPQPVVRWVKNGEVV-VPSDYFQIVDGGH----LQILGLVRSDEGFYQCIAENE 401
Cdd:cd05892    1 PMFIQKPQNKKVLEGDPVRLECQISAIPPPQIFWKKNNEMLqYNTDRISLYQDNCgricLLIQNANKKDAGWYTVSAVNE 80

                         90
                 ....*....|
gi 77993340  402 AGNSQAMAQL 411
Cdd:cd05892   81 AGVVSCNARL 90

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

Pssm-ID: 409357 [Multi-domain] Cd Length: 88 Bit Score: 47.93 E-value: 1.19e-06

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 77993340  142 ESVSAHLGDTALLRCEVTGDPMPVVRWQKNREDLPltfdpdSRVVILPS-GSLQVSRVQPPDSATYRCLAEN 212
Cdd:cd04968    9 ADTYALKGQTVTLECFALGNPVPQIKWRKVDGSPS------SQWEITTSePVLEIPNVQFEDEGTYECEAEN 74

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

Pssm-ID: 409399 [Multi-domain] Cd Length: 93 Bit Score: 48.03 E-value: 1.27e-06

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 77993340  346 MECAVTGNPQPVVRWVKNGEVV---VPSDYFQIVDGGHLQILGLVRSDEGFYQCIAENEAGNSQAMAQLIL 413
Cdd:cd05736   20 LRCHAEGIPLPRVQWLKNGMDInpkLSKQLTLIANGSELHISNVRYEDTGAYTCIAKNEGGVDEDISSLFV 90

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

Pssm-ID: 409546 [Multi-domain] Cd Length: 96 Bit Score: 48.08 E-value: 1.38e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340   36 RFVLQPQDVVTVRGGVLQLDCDAlsdQGV--PSISWKKD-----GVLLSAVVDERRRQLSNGSLLVQNVMHSrhhrpDEG 108
Cdd:cd20954    3 RWIVEPVDANVAAGQDVMLHCQA---DGFptPTVTWKKAtgstpGEYKDLLYDPNVRILPNGTLVFGHVQKE-----NEG 74

                         90       100
                 ....*....|....*....|...
gi 77993340  109 SYQCLASlEGIGAIVSRTARVTV 131
Cdd:cd20954   75 HYLCEAK-NGIGSGLSKVIFLKV 96

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: 47.71 E-value: 1.48e-06

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 77993340  238 FLQRPQKVSVLQGRDAVLECSASGFPNPAFYW-LRGNELIQSRS--KKYSLLSgSNLLISSVTDDDSGIYTCIAHN 310
Cdd:cd20949    2 FTENAYVTTVKEGQSATILCEVKGEPQPNVTWhFNGQPISASVAdmSKYRILA-DGLLINKVTQDDTGEYTCRAYQ 76

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: 47.44 E-value: 1.50e-06

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 77993340  149 GDTALLRCEVTGDPMPVVRWQKNREdlPLTFDPDSRVVILPSGSLQVSRVQPPDSATYRCLAENPG 214
Cdd:cd04978   14 GETGELICEAEGNPQPTITWRLNGV--PIEPAPEDMRRTVDGRTLIFSNLQPNDTAVYQCNASNVH 77

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: 47.50 E-value: 1.68e-06

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340      41 PQDVVTVRGGVLQLDCDAlSDQGVPSISWKKDGVLLSAVVD--ERRRQLSNGSLLVQNVMHSrhhrpDEGSYQCLASLEG 118
Cdd:smart00410    1 PPSVTVKEGESVTLSCEA-SGSPPPEVTWYKQGGKLLAESGrfSVSRSGSTSTLTISNVTPE-----DSGTYTCAATNSS 74

                            90
                    ....*....|...
gi 77993340     119 IgaIVSRTARVTV 131
Cdd:smart00410   75 G--SASSGTTLTV 85

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: 47.17 E-value: 2.26e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340  326 PPQFLN-YPSNTYAyESSDIEMECAVTGNPQPVVRWVKNGEVVVPSDYFQI-----VDG---GHLQILGLVRSDEGFYQC 396
Cdd:cd20956    1 APVLLEtFSEQTLQ-PGPSVSLKCVASGNPLPQITWTLDGFPIPESPRFRVgdyvtSDGdvvSYVNISSVRVEDGGEYTC 79

                         90
                 ....*....|....*
gi 77993340  397 IAENEAGNSQAMAQL 411
Cdd:cd20956   80 TATNDVGSVSHSARI 94

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: 47.01 E-value: 2.69e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340  238 FLQRPQKVSVLQGRDAVLECSASGFPNPAFYWLRGNELIQSRSKKYSL---LSGS-NLLISSVTDDDSGIYTCIAHNKQQ 313
Cdd:cd05893    3 FEMKLKHYKIFEGMPVTFTCRVAGNPKPKIYWFKDGKQISPKSDHYTIqrdLDGTcSLHTTASTLDDDGNYTIMAANPQG 82

                         90
                 ....*....|
gi 77993340  314 NISASCELAV 323
Cdd:cd05893   83 RISCTGRLMV 92

First immunoglobulin-like domains A168 within the A-band segment of human cardiac titin, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin-like domain A168 within the A-band segment of human cardiac titin. 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 structures of the titin-A168169 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: 409563 Cd Length: 93 Bit Score: 47.08 E-value: 2.75e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340  327 PQFLNYPSNTYAYESSDIEMECAVTGNPQPVVRWVKNGeVVVPSDYFQIVDGG-----HLQILGL-VRSDEGFYQCIAEN 400
Cdd:cd20971    2 PHFKEELRNLNVRYQSNATLVCKVTGHPKPIVKWYRQG-KEIIADGLKYRIQEfkggyHQLIIASvTDDDATVYQVRATN 80


                 ....*....
gi 77993340  401 EAGNSQAMA 409
Cdd:cd20971   81 QGGSVSGTA 89

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: 46.92 E-value: 3.04e-06

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 77993340  242 PQKVSVLQGRDAVLECSASGFPNPAFYWLR--GNELIQSRSKKY----SLLSGSNLLISSVTDDDSGIYTCIAHN 310
Cdd:cd20954    8 PVDANVAAGQDVMLHCQADGFPTPTVTWKKatGSTPGEYKDLLYdpnvRILPNGTLVFGHVQKENEGHYLCEAKN 82

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

Pssm-ID: 409436 [Multi-domain] Cd Length: 95 Bit Score: 46.87 E-value: 3.54e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340  327 PQFLNYPSNT-YAYESSD--IEMECAVTGNPQPVVRWVK-NGEVVVPSDYFQIVdGGHLQILGLVRS-DEGFYQCIAENE 401
Cdd:cd05849    2 PVFEEQPIDTiYPEESTEgkVSVNCRARANPFPIYKWRKnNLDIDLTNDRYSMV-GGNLVINNPDKYkDAGRYVCIVSNI 80


                 ..
gi 77993340  402 AG 403
Cdd:cd05849   81 YG 82

Immunoglobulin domain; Members of the immunoglobulin superfamily are found in hundreds of proteins of different functions. Examples include antibodies, the giant muscle kinase titin and receptor tyrosine kinases. Immunoglobulin-like domains may be involved in protein-protein and protein-ligand interactions.

Pssm-ID: 395002 Cd Length: 86 Bit Score: 46.42 E-value: 3.69e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340    333 PSNTYAYESSDIEMEC-AVTGNPQPVVRWVKNGEVVVPSDYFQIVDGGH----LQILGLVRSDEGFYQCIAENEAGNSQA 407
Cdd:pfam00047    3 PPTVTVLEGDSATLTCsASTGSPGPDVTWSKEGGTLIESLKVKHDNGRTtqssLLISNVTKEDAGTYTCVVNNPGGSATL 82

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

Pssm-ID: 409453 [Multi-domain] Cd Length: 89 Bit Score: 46.43 E-value: 4.04e-06

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 77993340  149 GDTALLRCEVTGDPMPVVRWQKNREDLPLTfDPDSRVVIlPSGSLQVSRVQPPDSATYRCLAEN 212
Cdd:cd05867   14 GETARLDCQVEGIPTPNITWSINGAPIEGT-DPDPRRHV-SSGALILTDVQPSDTAVYQCEARN 75

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: 46.39 E-value: 4.25e-06

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 77993340  240 QRPQKVSVLQGRDAVLECSASGFPNPAFYWLRGNELIQSRskKYSLLSGSNLLISSVTDDDSGIYTCIAHN 310
Cdd:cd04968    6 RFPADTYALKGQTVTLECFALGNPVPQIKWRKVDGSPSSQ--WEITTSEPVLEIPNVQFEDEGTYECEAEN 74

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

Pssm-ID: 409391 [Multi-domain] Cd Length: 98 Bit Score: 46.49 E-value: 4.90e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340  238 FLQRPQKVSVLQGRDAVLECSASGFPNPAFYWLR-GNELI------QSRSKKYSLLSGSNLLISSVTDDDSGIYTCIAHN 310
Cdd:cd05726    2 FVVKPRDQVVALGRTVTFQCETKGNPQPAIFWQKeGSQNLlfpyqpPQPSSRFSVSPTGDLTITNVQRSDVGYYICQALN 81

                         90
                 ....*....|...
gi 77993340  311 KQQNISASCELAV 323
Cdd:cd05726   82 VAGSILAKAQLEV 94

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: 46.09 E-value: 5.07e-06

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 77993340  154 LRCEVTGDPMPVVRWQKNREdlPLTFDPDSRVVILPSGSLQVSRVQPPDSATYRCLAEN 212
Cdd:cd20976   21 AQCSARGKPVPRITWIRNAQ--PLQYAADRSTCEAGVGELHIQDVLPEDHGTYTCLAKN 77

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: 45.93 E-value: 5.23e-06

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 77993340  149 GDTALLRCEVTGDPMPVVRWQKNREDLpltFDPDSRVVILPSGSLQVSRVQPPDSATYRCLAENPGSARTGTdADLRV 226
Cdd:cd05764   15 GQRATLRCKARGDPEPAIHWISPEGKL---ISNSSRTLVYDNGTLDILITTVKDTGAFTCIASNPAGEATAR-VELHI 88

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 46.10 E-value: 5.42e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340     36 RFVLQPQDVVTVRGGVLQLDCDAlSDQGVPSISWKKDGVLLSAvvDERRRQLSNG---SLLVQNVMHSrhhrpDEGSYQC 112
Cdd:pfam07679    2 KFTQKPKDVEVQEGESARFTCTV-TGTPDPEVSWFKDGQPLRS--SDRFKVTYEGgtyTLTISNVQPD-----DSGKYTC 73

                           90
                   ....*....|....*....
gi 77993340    113 LASLEGiGAiVSRTARVTV 131
Cdd:pfam07679   74 VATNSA-GE-AEASAELTV 90

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: 46.08 E-value: 5.92e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340  235 GLVFLQRPQKVSVLQGRD---AVLECSASGFPNPAFYWLR-GNELIQSRSKKYSLLSGsNLLISS-VTDDDSGIYTCIAH 309
Cdd:cd04967    1 GPVFEEQPDDTIFPEDSDekkVALNCRARANPVPSYRWLMnGTEIDLESDYRYSLVDG-TLVISNpSKAKDAGHYQCLAT 79


                 .
gi 77993340  310 N 310
Cdd:cd04967   80 N 80

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: 46.06 E-value: 6.35e-06

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 77993340  342 SDIEMECAVTGNPQPVVRWVKNGEVVVPSDYFQIVD----GGHLQILGLVRSDEGFYQCIAENEAG 403
Cdd:cd05729   20 NKVRLECGAGGNPMPNITWLKDGKEFKKEHRIGGTKveekGWSLIIERAIPRDKGKYTCIVENEYG 85

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: 45.64 E-value: 6.38e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340  241 RP-QKVSVLQGRDAVLECSASGFPNPAFYWLR-GNELIQSRSKKysLLSGSNLLISSVT-DDDSGIYTCIAHNKQQNiSA 317
Cdd:cd20958    5 RPmGNLTAVAGQTLRLHCPVAGYPISSITWEKdGRRLPLNHRQR--VFPNGTLVIENVQrSSDEGEYTCTARNQQGQ-SA 81


                 ....*...
gi 77993340  318 SCELAVLV 325
Cdd:cd20958   82 SRSVFVKV 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: 45.84 E-value: 6.49e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340  243 QKVSVLQGRDAVLECSASGFPNPAFYWL-RGNELIQSRSK-KYSLLSGSNLLISSVTDDDSGIYTCIAHNKQQNISASCE 320
Cdd:cd20969   10 QQVFVDEGHTVQFVCRADGDPPPAILWLsPRKHLVSAKSNgRLTVFPDGTLEVRYAQVQDNGTYLCIAANAGGNDSMPAH 89


                 ...
gi 77993340  321 LAV 323
Cdd:cd20969   90 LHV 92

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: 45.64 E-value: 6.70e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340   37 FVLQPQDVVTVRGGVLQLDCDALsdqGVP--SISWKKDGVLLSavVDERRRQLSNGSLLVQNVmhsrHHRPDEGSYQCLA 114
Cdd:cd20958    3 FIRPMGNLTAVAGQTLRLHCPVA---GYPisSITWEKDGRRLP--LNHRQRVFPNGTLVIENV----QRSSDEGEYTCTA 73

                         90
                 ....*....|....*..
gi 77993340  115 SLEGiGAIVSRTARVTV 131
Cdd:cd20958   74 RNQQ-GQSASRSVFVKV 89

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

Pssm-ID: 409443 [Multi-domain] Cd Length: 95 Bit Score: 46.00 E-value: 7.44e-06

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 77993340  149 GDTALLRCEVTGDPMPVVRWQKNREDlpltFDPDSRV----VILPSGSLQVSRVQPPDSATYRCLAEN 212
Cdd:cd05857   19 ANTVKFRCPAAGNPTPTMRWLKNGKE----FKQEHRIggykVRNQHWSLIMESVVPSDKGNYTCVVEN 82

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

Pssm-ID: 409358 [Multi-domain] Cd Length: 89 Bit Score: 45.53 E-value: 7.71e-06

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340  153 LLRCEVTGDPMPVVRWQKNREDLPLTfdpdSRVVILPSGSLQVSRVQPPDSATYRCLAEN 212
Cdd:cd04969   21 IIECKPKASPKPTISWSKGTELLTNS----SRICILPDGSLKIKNVTKSDEGKYTCFAVN 76

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: 45.62 E-value: 8.85e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340  241 RPQKVSVLQGRDAVLECSASGFPNPAFYWLRGNELI------QSRSKKYSLLsgsnllISSVTDDDSGIYTCIAHNKQQN 314
Cdd:cd05856   10 RRRVIARPVGSSVRLKCVASGNPRPDITWLKDNKPLtppeigENKKKKWTLS------LKNLKPEDSGKYTCHVSNRAGE 83


                 ....*....
gi 77993340  315 ISASCELAV 323
Cdd:cd05856   84 INATYKVDV 92

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: 46.17 E-value: 9.00e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340  240 QRPQKVSVLQGRDAVLECSASG-FPNPAFYWLRGNE------LIQSRSKKYSLLSGSN--------------LLISSVTD 298
Cdd:cd00099    3 QSPRSLSVQEGESVTLSCEVSSsFSSTYIYWYRQKPgqgpefLIYLSSSKGKTKGGVPgrfsgsrdgtssfsLTISNLQP 82

                         90
                 ....*....|
gi 77993340  299 DDSGIYTCIA 308
Cdd:cd00099   83 EDSGTYYCAV 92

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: 45.70 E-value: 9.55e-06

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 77993340  154 LRCEVTGDPMPVVRWQKNREDLPLTfdPDSRVVILpSGSLQVSR-VQPPDSATYRCLAENPGSARTGTDADLR 225
Cdd:cd04967   24 LNCRARANPVPSYRWLMNGTEIDLE--SDYRYSLV-DGTLVISNpSKAKDAGHYQCLATNTVGSVLSREATLQ 93

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: 45.27 E-value: 9.69e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340  149 GDTALLRCEVTGDPMPVVRWQknREDLPLTFDPDsrVVILPSG---SLQVSRVQPPDSATYRCLAENPgSARTGTDADLR 225
Cdd:cd20972   16 GSKVRLECRVTGNPTPVVRWF--CEGKELQNSPD--IQIHQEGdlhSLIIAEAFEEDTGRYSCLATNS-VGSDTTSAEIF 90


                 .
gi 77993340  226 V 226
Cdd:cd20972   91 V 91

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: 45.69 E-value: 9.93e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340  237 VFLQRPQKVSVLQGRDAV-LECSASGFPNPAFYWLR-GNELIQSRSKkYSLLSGS-NLLISSVTDDDSGIYTCIAHN--- 310
Cdd:cd05760    2 VVLKHPASAAEIQPSSRVtLRCHIDGHPRPTYQWFRdGTPLSDGQGN-YSVSSKErTLTLRSAGPDDSGLYYCCAHNafg 80

                         90
                 ....*....|.
gi 77993340  311 ---KQQNISAS 318
Cdd:cd05760   81 svcSSQNFTLS 91

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: 45.40 E-value: 1.00e-05

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 77993340  149 GDTALLRCEVTGDPMPVVRWQKNREDLPLTFDPDSRVVILPSGsLQVSRVQPPDSATYRCLAEN 212
Cdd:cd20949   14 GQSATILCEVKGEPQPNVTWHFNGQPISASVADMSKYRILADG-LLINKVTQDDTGEYTCRAYQ 76

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: 45.42 E-value: 1.10e-05

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 77993340  239 LQRPQKVSVLQGRDAVLECSASGFPNPAFYWLRGNELIQSrSKKYSLLS---GSNLLISSVTDDDSGIYTCIAHNKQ 312
Cdd:cd05747    7 LTKPRSLTVSEGESARFSCDVDGEPAPTVTWMREGQIIVS-SQRHQITSteyKSTFEISKVQMSDEGNYTVVVENSE 82

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

Pssm-ID: 409367 [Multi-domain] Cd Length: 89 Bit Score: 45.13 E-value: 1.16e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340  241 RPQKVSVLQGRDAVLECSASGFPNPAFYWLRGNELIQSRSKKYSLL-SGSNLLISSVTDDDSGIYTCIAHNKQQNISASC 319
Cdd:cd04978    5 EPPSLVLSPGETGELICEAEGNPQPTITWRLNGVPIEPAPEDMRRTvDGRTLIFSNLQPNDTAVYQCNASNVHGYLLANA 84


                 ....*
gi 77993340  320 ELAVL 324
Cdd:cd04978   85 FLHVL 89

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: 45.21 E-value: 1.17e-05

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 77993340  142 ESVSAHLGDTALLRCEVTGDPMPVVRWQKNREDlpLTF---DPDSRVVI---LPSGSLQVSRVQPPDSATYRCLAENP 213
Cdd:cd05732    9 ENQTAVELEQITLTCEAEGDPIPEITWRRATRG--ISFeegDLDGRIVVrghARVSSLTLKDVQLTDAGRYDCEASNR 84

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: 45.33 E-value: 1.17e-05

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 77993340  148 LGDTALLRCEVTGDPMPVVRWQKNREDLPL----TFDPDSRVVILPSGSLQVSRVQPPDSATYRCLAEN 212
Cdd:cd05726   13 LGRTVTFQCETKGNPQPAIFWQKEGSQNLLfpyqPPQPSSRFSVSPTGDLTITNVQRSDVGYYICQALN 81

First 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 first 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 first Ig-like domain of hemolin is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules, including vascular (VCAM), intercellular (ICAM), neural (NCAM) and mucosal addressin (MADCAM) cell adhesion molecules, as well as junction adhesion molecules (JAM).

Pssm-ID: 409571 Cd Length: 91 Bit Score: 45.25 E-value: 1.22e-05

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 77993340  333 PSNTYAYESSDIEMECAVTGNPQPV-VRWVKNGE--VVVPSDYFQIVDGGHLQILGLVRSDEGFYQCIAENEAG 403
Cdd:cd20979    7 PAEVLFREGQPTVLECVTEGGDQGVkYSWLKDGKsfNWQEHNVAQRKDEGSLVFLKPQASDEGQYQCFAETPAG 80

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

Pssm-ID: 409490 [Multi-domain] Cd Length: 99 Bit Score: 45.24 E-value: 1.41e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340  239 LQRPQKVSVLQGRDAVLECSASGFPNPAFYWLRGNELIQS-----RSKKYSLLSGSNLLISSV----TDDDSGIYTCIAH 309
Cdd:cd07693    4 VEHPSDLIVSKGDPATLNCKAEGRPTPTIQWLKNGQPLETdkddpRSHRIVLPSGSLFFLRVVhgrkGRSDEGVYVCVAH 83


                 .
gi 77993340  310 N 310
Cdd:cd07693   84 N 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: 1.44e-05

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 77993340  144 VSAHLGDTALLRCEVTGDPMPVVRWQKNREDLPLtfdpDSRVVILPSGSLQVSRVQPP-DSATYRCLAENP 213
Cdd:cd20958   10 LTAVAGQTLRLHCPVAGYPISSITWEKDGRRLPL----NHRQRVFPNGTLVIENVQRSsDEGEYTCTARNQ 76

Interferon-alpha/beta receptor, fibronectin type III; Members of this family adopt a secondary structure consisting of seven beta-strands arranged in an immunoglobulin-like beta-sandwich, in a Greek-key topology. They are required for binding to interferon-alpha.

Pssm-ID: 462746 Cd Length: 103 Bit Score: 45.03 E-value: 1.68e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340    620 SPPQnVSLEVVySRSIKVSWQPPPANTQNGFIT-------GYKIRYRKTGRRGEQEAIEPNNLWYLFTGLEKGSQYSFQV 692
Cdd:pfam09294    4 GPPE-VELEVE-GGSLNVTVKDPETREGKNLSLrdlygslQYRVSYWKNSSNGEKKNTTSTNSFVVLSDLEPGTTYCVSV 81

                           90       100
                   ....*....|....*....|..
gi 77993340    693 SG--MTVNGTGPSSEWLTAETP 712
Cdd:pfam09294   82 QAfsPLDNKSSQRSPPQCIRTT 103

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: 1.97e-05

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 77993340  336 TYAYESSDIEMECAVTGNPQPVVRWVK-NGEVVVPSDYFQIVDGGHLQILGLVRSDEGFYQCIAENEAGNSQAMAQL 411
Cdd:cd05764   10 LRVLEGQRATLRCKARGDPEPAIHWISpEGKLISNSSRTLVYDNGTLDILITTVKDTGAFTCIASNPAGEATARVEL 86

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: 44.11 E-value: 2.12e-05

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 77993340  138 LVSTESVSAHLGDTALLRCEVTGDPMPVVRWQKNREdlplTFDPDSRVVILPSGSLQVSRVQPPDSATYRCLAEN 212
Cdd:cd05723    1 LKKPSNIYAHESMDIVFECEVTGKPTPTVKWVKNGD----VVIPSDYFKIVKEHNLQVLGLVKSDEGFYQCIAEN 71

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: 43.84 E-value: 3.25e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340  134 PLRVLVSTESVSAHLGDTALLRCEVTGDPMPVVRWQKNREDLPLT---FDPDSRVVILPSGSLQVSRVQPPDSATYRCLA 210
Cdd:cd20954    1 PPRWIVEPVDANVAAGQDVMLHCQADGFPTPTVTWKKATGSTPGEykdLLYDPNVRILPNGTLVFGHVQKENEGHYLCEA 80


                 ..
gi 77993340  211 EN 212
Cdd:cd20954   81 KN 82

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

Pssm-ID: 409397 [Multi-domain] Cd Length: 97 Bit Score: 44.02 E-value: 3.57e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340  238 FLQRPQKVSVLQGRDAVLECSASGFPNPAFYWL----RGNELIQS---RSKKYSLLSGSNLLISSVTDDDSGIYTCIAHN 310
Cdd:cd05734    4 FVVQPNDQDGIYGKAVVLNCSADGYPPPTIVWKhskgSGVPQFQHivpLNGRIQLLSNGSLLIKHVLEEDSGYYLCKVSN 83

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: 43.74 E-value: 3.70e-05

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 77993340  340 ESSDIEMECAVTGNPQPVVRWVKNGEVVVPSDYFQI-VDGGH---LQILGLVRSDEGFYQCIAENEAG 403
Cdd:cd05891   15 EGKTLNLTCTVFGNPDPEVIWFKNDQDIELSEHYSVkLEQGKyasLTIKGVTSEDSGKYSINVKNKYG 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: 43.36 E-value: 3.77e-05

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 77993340  334 SNTYAYESSDIEMECAVTGNPQPVVRWVKNGEVVVPSDYFQIVDGGHLQILGLVRSDEGFYQCIAENEAGNSQ 406
Cdd:cd05876    3 SSLVALRGQSLVLECIAEGLPTPTVKWLRPSGPLPPDRVKYQNHNKTLQLLNVGESDDGEYVCLAENSLGSAR 75

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: 43.32 E-value: 4.59e-05

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 77993340  335 NTYAYESSDIEMECAVTGNPQPVVRWVKNGEVVvPSDYFQIV-DGGHLQILGLVR-SDEGFYQCIAENEAGNS 405
Cdd:cd20958    9 NLTAVAGQTLRLHCPVAGYPISSITWEKDGRRL-PLNHRQRVfPNGTLVIENVQRsSDEGEYTCTARNQQGQS 80

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: 43.46 E-value: 4.97e-05

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 77993340  151 TALLRCEVTGDPMPVVRWQKnrEDLPL-TFDPDSRVVILPSGSLQVSRVQPPDSATYRCLAENPGSARTGTDADLRV 226
Cdd:cd05738   16 TATMLCAASGNPDPEISWFK--DFLPVdTATSNGRIKQLRSGALQIENSEESDQGKYECVATNSAGTRYSAPANLYV 90

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: 43.60 E-value: 5.72e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340    142 ESVSAHLGDTALLRCEVTGDPM---PVVRWQKNREDLPLTFD------------PDSRVVIL-----PSGSLQVSRVQPP 201
Cdd:pfam07686    4 REVTVALGGSVTLPCTYSSSMSeasTSVYWYRQPPGKGPTFLiayysngseegvKKGRFSGRgdpsnGDGSLTIQNLTLS 83

                           90       100
                   ....*....|....*....|....*.
gi 77993340    202 DSATYRCLAENPGSARTGTDADLRVL 227
Cdd:pfam07686   84 DSGTYTCAVIPSGEGVFGKGTRLTVL 109

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

Pssm-ID: 143207 [Multi-domain] Cd Length: 95 Bit Score: 43.38 E-value: 5.73e-05

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 77993340  135 LRVLVSTESVSAHLGDTALLRCEVTGDPMPVVRWQKNREDLPltfDPDSRVVILPSGS-LQVSRVQPPDSATYRCLAEN 212
Cdd:cd05730    4 IRARQSEVNATANLGQSVTLACDADGFPEPTMTWTKDGEPIE---SGEEKYSFNEDGSeMTILDVDKLDEAEYTCIAEN 79

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: 42.77 E-value: 6.76e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340   41 PQDVVTVRGGVLQLDCDALSDQgVPSISWKKDGVLLSavvDERRRQLSNGSLLVQNVMHSrhhrpDEGSYQCLASlEGIG 120
Cdd:cd05725    4 PQNQVVLVDDSAEFQCEVGGDP-VPTVRWRKEDGELP---KGRYEILDDHSLKIRKVTAG-----DMGSYTCVAE-NMVG 73

                         90
                 ....*....|.
gi 77993340  121 AIvSRTARVTV 131
Cdd:cd05725   74 KI-EASATLTV 83

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: 43.07 E-value: 7.08e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340  326 PPQFLNYPSNTYAYESSDIEMECAVTGNPQPVVRWVKN-----GEV--VVPSDYFQIVDGGHLQILGLVRSDEGFYQCIA 398
Cdd:cd20954    1 PPRWIVEPVDANVAAGQDVMLHCQADGFPTPTVTWKKAtgstpGEYkdLLYDPNVRILPNGTLVFGHVQKENEGHYLCEA 80


                 ....*
gi 77993340  399 ENEAG 403
Cdd:cd20954   81 KNGIG 85

First 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 first 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 all FGFs.

Pssm-ID: 409362 Cd Length: 94 Bit Score: 42.96 E-value: 7.48e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340  134 PLRVLVSTESVSAHLGDTALLRCEVTgDPMPVVRWQKNREDLPltfdPDSRVVILPSgSLQVSRVQPPDSATYRCLAENP 213
Cdd:cd04973    9 PTYQISEVESYSAHPGDLLQLRCRLR-DDVQSINWTKDGVQLG----ENNRTRITGE-EVQIKDAVPRDSGLYACVTSSP 82


                 ....*
gi 77993340  214 GSART 218
Cdd:cd04973   83 SGSDT 87

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: 42.87 E-value: 7.55e-05

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 77993340  149 GDTALLRCEVTGDPMPVVRWQKNREdlPLTFDPDSRVVILPSG--SLQVSRVQPPDSATYRCLAEN 212
Cdd:cd05744   15 GRLCRFDCKVSGLPTPDLFWQLNGK--PVRPDSAHKMLVRENGrhSLIIEPVTKRDAGIYTCIARN 78

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: 42.92 E-value: 8.28e-05

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 77993340  255 LECSASGFPNPAFYWLR-GNELIQS-RSKKYSL-LSGSNLLISSVTDDDSGIYTCIAHNKQQNISASCELAV 323
Cdd:cd05857   24 FRCPAAGNPTPTMRWLKnGKEFKQEhRIGGYKVrNQHWSLIMESVVPSDKGNYTCVVENEYGSINHTYHLDV 95

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

Pssm-ID: 409420 [Multi-domain] Cd Length: 91 Bit Score: 42.61 E-value: 8.93e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340  144 VSAHLGDTALLRCEVTGDPMPVVRWQKN-REDLPLTfdPDSRVVILPSGS-LQVSRVQPPDSATYRCLAENpgSART-GT 220
Cdd:cd05763    9 ITIRAGSTARLECAATGHPTPQIAWQKDgGTDFPAA--RERRMHVMPEDDvFFIVDVKIEDTGVYSCTAQN--SAGSiSA 84


                 ....*..
gi 77993340  221 DADLRVL 227
Cdd:cd05763   85 NATLTVL 91

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

Pssm-ID: 409566 [Multi-domain] Cd Length: 93 Bit Score: 42.73 E-value: 9.34e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340  237 VFLQRPQKVSVLQGRDAVLECSASGFPNPAFYWLRGNELIQ-SRSK--KYSLLSG-SNLLISSVTDDDSGIYTCIAHNKQ 312
Cdd:cd20974    2 VFTQPLQSVVVLEGSTATFEAHVSGKPVPEVSWFRDGQVIStSTLPgvQISFSDGrAKLSIPAVTKANSGRYSLTATNGS 81

                         90
                 ....*....|..
gi 77993340  313 QNISASCELAVL 324
Cdd:cd20974   82 GQATSTAELLVL 93

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: 42.55 E-value: 9.56e-05

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 77993340  255 LECSASGFPNPAFYWLRGNELIQS----RSKKYSLLSG---SNLLISSVTDDDSGIYTCIAHNK 311
Cdd:cd20956   21 LKCVASGNPLPQITWTLDGFPIPEsprfRVGDYVTSDGdvvSYVNISSVRVEDGGEYTCTATND 84

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: 42.78 E-value: 9.60e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340  339 YESSDIEMECAVTGNPQPVVRWVKNGEVVVP-SDYFQI---VDGG-HLQILGLVRSDEGFYQCIAENEAGNSQAMAQLIL 413
Cdd:cd05893   13 FEGMPVTFTCRVAGNPKPKIYWFKDGKQISPkSDHYTIqrdLDGTcSLHTTASTLDDDGNYTIMAANPQGRISCTGRLMV 92

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

Pssm-ID: 409393 [Multi-domain] Cd Length: 95 Bit Score: 42.59 E-value: 9.75e-05

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 77993340  255 LECSASGFPNPAFYWLRGN---------ELIQSRSKKYSLLsgsnllISSVTDDDSGIYTCIAHNKQQNISASCELAV 323
Cdd:cd05729   24 LECGAGGNPMPNITWLKDGkefkkehriGGTKVEEKGWSLI------IERAIPRDKGKYTCIVENEYGSINHTYDVDV 95

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

Pssm-ID: 409454 Cd Length: 89 Bit Score: 42.28 E-value: 1.02e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340  242 PQKVSVLQGRDAVLECSASGFPNPAFYWLRGNELIQSRSKKYSL-LSGSNLLISSVTDDDSGIYTCIAHNKQQNISASCE 320
Cdd:cd05868    6 PTNLVLSPGEDGTLICRANGNPKPSISWLTNGVPIEIAPTDPSRkVDGDTIIFSKVQERSSAVYQCNASNEYGYLLANAF 85


                 ....
gi 77993340  321 LAVL 324
Cdd:cd05868   86 VNVL 89

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

Pssm-ID: 443767 [Multi-domain] Cd Length: 978 Bit Score: 46.86 E-value: 1.06e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340  827 VQAVALTSDSVRVSWAdnsIPKNQKSSEVRYY--SVKWRTShstsgkhksADTTALSHTVTGLKPNTmYEFSVM-VTKGR 903
Cdd:COG4733  544 VVAQGTAVTTLTVSWD---APAGAVAYEVEWRrdDGNWVSV---------PRTSGTSFEVPGIYAGD-YEVRVRaINALG 610

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340  904 KSSTWSMTAHAT-TYEAAPSSAPKDLTVigrEGRPRAILISWQPPleANGRITGFILYYTleknlPIDDW---VMEPISG 979
Cdd:COG4733  611 VSSAWAASSETTvTGKTAPPPAPTGLTA---TGGLGGITLSWSFP--VDADTLRTEIRYS-----TTGDWasaTVAQALY 680

                        170       180
                 ....*....|....*....|....*..
gi 77993340  980 DRLTHQVLDLNLDTVYYFRIQAKNAKG 1006
Cdd:COG4733  681 PGNTYTLAGLKAGQTYYYRARAVDRSG 707

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

Pssm-ID: 409454 Cd Length: 89 Bit Score: 42.28 E-value: 1.07e-04

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 77993340  333 PSNTYAYESSDIEMECAVTGNPQPVVRWVKNGE--VVVPSDYFQIVDGGHLQILGLVRSDEGFYQCIAENEAG 403
Cdd:cd05868    6 PTNLVLSPGEDGTLICRANGNPKPSISWLTNGVpiEIAPTDPSRKVDGDTIIFSKVQERSSAVYQCNASNEYG 78

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: 42.32 E-value: 1.21e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340  329 FLNYPSNTYAYESSDIEMECAVTGNPQPVVRWVKNGEVVVPS----DYFQIVDGGhLQILGLVRSDEGFYQCIAENEAGN 404
Cdd:cd20949    2 FTENAYVTTVKEGQSATILCEVKGEPQPNVTWHFNGQPISASvadmSKYRILADG-LLINKVTQDDTGEYTCRAYQVNSI 80


                 ....*..
gi 77993340  405 SQAMAQL 411
Cdd:cd20949   81 ASDMQER 87

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

Pssm-ID: 409397 [Multi-domain] Cd Length: 97 Bit Score: 42.48 E-value: 1.32e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340   36 RFVLQPQDVVTVRGGVLQLDCDAlSDQGVPSISWKKD---GVLL---SAVVDERRRQLSNGSLLVQNVMHSrhhrpDEGS 109
Cdd:cd05734    3 RFVVQPNDQDGIYGKAVVLNCSA-DGYPPPTIVWKHSkgsGVPQfqhIVPLNGRIQLLSNGSLLIKHVLEE-----DSGY 76

                         90       100
                 ....*....|....*....|..
gi 77993340  110 YQCLASlEGIGAIVSRTARVTV 131
Cdd:cd05734   77 YLCKVS-NDVGADISKSMYLTV 97

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

Pssm-ID: 143259 Cd Length: 88 Bit Score: 41.93 E-value: 1.50e-04

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 77993340  243 QKVSVLQGRDAVLECSASGFPNPAFYWLRGNELIQSrSKKYSlLSGSNLLISSVTDDDSGIYTCIAHN 310
Cdd:cd05851    9 KDTYALKGQNVTLECFALGNPVPVIRWRKILEPMPA-TAEIS-MSGAVLKIFNIQPEDEGTYECEAEN 74

Immunoglobulin (Ig)-like domain at the C-terminus of semaphorins; The members here are composed of the immunoglobulin (Ig)-like domain in semaphorins. Semaphorins are transmembrane protein that have important roles in a variety of tissues. Functionally, semaphorins were initially characterized for their importance in the development of the nervous system and in axonal guidance. Later they have been found to be important for the formation and functioning of the cardiovascular, endocrine, gastrointestinal, hepatic, immune, musculoskeletal, renal, reproductive, and respiratory systems. Semaphorins function through binding to their receptors and transmembrane semaphorins also serves as receptors themselves. Although molecular mechanism of semaphorins is poorly understood, the Ig-like domains may be involved in ligand binding or dimerization.

Pssm-ID: 409368 Cd Length: 88 Bit Score: 42.06 E-value: 1.50e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340  149 GDTALLRCEVTGDPMPVVrWQKNREDLPLTFDPDSRVVIlpSGSLQVSRVQPPDSATYRCLAENPGSARTGTDADLRVLP 228
Cdd:cd04979   11 GDTVILSCSVKSNNAPVT-WIHNGKKVPRYRSPRLVLKT--ERGLLIRSAQEADAGVYECHSGERVLGSTLRSVTLHVLE 87

Second immunoglobulin (Ig)-like domain of interleukin-1 receptor-2 (IL1R2), and similar domains; The members here are composed of the second immunoglobulin (Ig)-like domain of interleukin-1 receptor-2 (IL1R2). IL-1 alpha and IL-1 beta are cytokines which participate in the regulation of inflammation, immune responses, and hematopoiesis. These cytokines bind to the IL-1 receptor type 1 (IL1R1), which is activated on additional association with interleukin-1 receptor accessory protein (IL1RAP). IL-1 also binds the IL-1 receptor, type II (IL1R2) represented in this group. Mature IL1R2 consists of three IG-like domains, a transmembrane domain, and a short cytoplasmic domain. It lacks the large cytoplasmic domain of mature IL1R1 and does not initiate signal transduction. A naturally occurring cytokine IL-1RA (IL-1 receptor antagonist) is widely expressed and binds to IL-1 receptors, inhibiting the binding of IL-1 alpha and IL-1 beta.

Pssm-ID: 409478 Cd Length: 95 Bit Score: 42.05 E-value: 1.54e-04

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 77993340  269 WLRGNELIQSRSKKYSLLSGS-NLLISSVTDDDSGIYTC---IAH-NKQQNISASCELAVL 324
Cdd:cd05897   34 WYKDSLLLDKDNEKFLSVKGStHLLIHDVSLNDSGYYTCkltFTHeGKKYNITRSIELRIV 94

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

Pssm-ID: 409562 [Multi-domain] Cd Length: 92 Bit Score: 42.11 E-value: 1.60e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340  140 STESVSAHLGDTALLRCEVTGDPMPVVRWQKNrEDLPLTFdpDSRVVILPSGS-LQVSRVQPPDSATYRCLAEN--PGSA 216
Cdd:cd20970    8 PSFTVTAREGENATFMCRAEGSPEPEISWTRN-GNLIIEF--NTRYIVRENGTtLTIRNIRRSDMGIYLCIASNgvPGSV 84

Immunoglobulin (Ig)-like domain of vascular endothelial growth factor receptor 1 (VEGFR-1); member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig)-like domain of vascular endothelial growth factor receptor 1 (VEGFR-1). VEGFRs have an extracellular component with seven Ig-like domains, a transmembrane segment, and an intracellular tyrosine kinase domain interrupted by a kinase-insert domain. VEGFRs bind VEGFs with high affinity at the Ig-like domains. VEGFR-1 binds VEGF-A strongly; VEGF-A is important to the growth and maintenance of vascular endothelial cells and to the development of new blood- and lymphatic-vessels in physiological and pathological states. VEGFR-1 may play an inhibitory role in the function of VEGFR-2 by binding VEGF-A and interfering with its interaction with VEGFR-2. VEGFR-1 has a signaling role in mediating monocyte chemotaxis and may mediate a chemotactic and a survival signal in hematopoietic stem cells or leukemia cells. 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: 409499 Cd Length: 92 Bit Score: 41.79 E-value: 1.60e-04

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 77993340  262 FPNPAFYWLRGNELIQSRSKKYSLlSGSNLLISSVTDDDSGIYTCIAHNKQQNISASCELAVLV 325
Cdd:cd07702   30 FPSPEVIWLKDGLPATEKCARYLT-RGYSLIIKDVTEEDAGNYTILLSIKQSNLFKNLTATLIV 92

Immunoglobulin (Ig)-like domain at the C-terminus of semaphorins; The members here are composed of the immunoglobulin (Ig)-like domain in semaphorins. Semaphorins are transmembrane protein that have important roles in a variety of tissues. Functionally, semaphorins were initially characterized for their importance in the development of the nervous system and in axonal guidance. Later they have been found to be important for the formation and functioning of the cardiovascular, endocrine, gastrointestinal, hepatic, immune, musculoskeletal, renal, reproductive, and respiratory systems. Semaphorins function through binding to their receptors and transmembrane semaphorins also serves as receptors themselves. Although molecular mechanism of semaphorins is poorly understood, the Ig-like domains may be involved in ligand binding or dimerization.

Pssm-ID: 409368 Cd Length: 88 Bit Score: 41.68 E-value: 1.86e-04

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340  242 PQKVSVLQGRDAVLECSASGFPNPAFYWLRGNELIQSRSKKYSLLSGSNLLISSVTDDDSGIYTCIAHNK 311
Cdd:cd04979    3 FKQISVKEGDTVILSCSVKSNNAPVTWIHNGKKVPRYRSPRLVLKTERGLLIRSAQEADAGVYECHSGER 72

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: 41.48 E-value: 2.35e-04

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 77993340  255 LECSASGFPNPAFYWLRGNELIQSRSKKYSLLSGsNLLISSV-TDDDSGIYTCIAHN 310
Cdd:cd05849   24 VNCRARANPFPIYKWRKNNLDIDLTNDRYSMVGG-NLVINNPdKYKDAGRYVCIVSN 79

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: 2.37e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340  134 PLRVLVSTESVSAHLGDTALLRCEVTGDPMPVVRWQknREDLPLTFDPDSRVVILPSGS-LQVSRVQPPDSATYRCLAEN 212
Cdd:cd05747    3 PATILTKPRSLTVSEGESARFSCDVDGEPAPTVTWM--REGQIIVSSQRHQITSTEYKStFEISKVQMSDEGNYTVVVEN 80

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

Pssm-ID: 409356 [Multi-domain] Cd Length: 96 Bit Score: 41.46 E-value: 2.51e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340   37 FVLQPQDVVTVRG---GVLQLDCDALSDQgVPSISWKKDGVLLSAVVDERRRqLSNGSLLVQNVMHSRhhrpDEGSYQCL 113
Cdd:cd04967    4 FEEQPDDTIFPEDsdeKKVALNCRARANP-VPSYRWLMNGTEIDLESDYRYS-LVDGTLVISNPSKAK----DAGHYQCL 77

                         90
                 ....*....|....
gi 77993340  114 ASlEGIGAIVSRTA 127
Cdd:cd04967   78 AT-NTVGSVLSREA 90

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

Pssm-ID: 409561 Cd Length: 92 Bit Score: 41.22 E-value: 2.70e-04

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 77993340  340 ESSDIEMECAVTGNPQPVVRWVKNGEVVVPS---DYFQIVDGGHLQILGLVRSDEGFYQCIAENEAGNSQAMAQL 411
Cdd:cd20969   16 EGHTVQFVCRADGDPPPAILWLSPRKHLVSAksnGRLTVFPDGTLEVRYAQVQDNGTYLCIAANAGGNDSMPAHL 90

Immunoglobulin Variable (IgV) domain of B7-H4; The members here are composed of the immunoglobulin variable (IgV) domain of B7-H4 (also known as B7-S1, B7x, or Vtcn1). B7-H4 is one of the B7 family of immune-regulatory ligands that act as negative regulators of T cell function; it contains one IgV domain and one IgC domain. The B7-family consists of structurally related cell-surface protein ligands, which bind to receptors on lymphocytes that regulate immune responses. The binding of B7-H4 to unidentified receptors results in the inhibition of TCR-mediated T cell proliferation, cell-cycle progression and IL-2 production. As a co-inhibitory molecule, B7-H4 is widely expressed in tumor tissues and its expression is significantly associated with poor prognosis in human cancers such as glioma, pancreatic cancer, oral squamous cell carcinoma, renal cell carcinoma, and lung cancer.

Pssm-ID: 409576 Cd Length: 110 Bit Score: 41.82 E-value: 2.71e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340  139 VSTESVSAHLGDTALLRCEVTGDPMP---VVRWQKnREDLPLTF------------DPDSR--------VVILPSGSLQV 195
Cdd:cd20984    2 VTAKHLAGNIGEDGILSCTFTPDIKLsdiVIQWLK-EGDSGLVHefkegkdelsrqSPMFRgrtslfadQVHVGNASLRL 80

                         90
                 ....*....|....*..
gi 77993340  196 SRVQPPDSATYRCLAEN 212
Cdd:cd20984   81 KNVQLTDAGTYLCIISN 97

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: 41.05 E-value: 3.03e-04

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340  149 GDTALLRCEVTGDPMPVVRWQKNREDLPltfdPDSRVVILPSGSLQVSRVQPPDSATYRCLAENP-GSAR 217
Cdd:cd05876   10 GQSLVLECIAEGLPTPTVKWLRPSGPLP----PDRVKYQNHNKTLQLLNVGESDDGEYVCLAENSlGSAR 75

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

Pssm-ID: 143223 Cd Length: 69 Bit Score: 40.24 E-value: 3.81e-04

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 77993340  255 LECSASGFPNPAFYWLRgnELIQ-SRSKKYSLLSGSNLLISSVTDDDSGIYTCIAHNKQQNISASCELA 322
Cdd:cd05746    3 IPCSAQGDPEPTITWNK--DGVQvTESGKFHISPEGYLAIRDVGVADQGRYECVARNTIGYASVSMVLS 69

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: 41.10 E-value: 4.04e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340  240 QRPQKVSVLQGRDAVLECSASGFPNPAFYWLR-----GNELIQSRSKKYSLLSG-------------SNLLISSVTDDDS 301
Cdd:cd04983    3 QSPQSLSVQEGENVTLNCNYSTSTFYYLFWYRqypgqGPQFLIYISSDSGNKKKgrfsatldksrksSSLHISAAQLSDS 82


                 ....*..
gi 77993340  302 GIYTCIA 308
Cdd:cd04983   83 AVYFCAL 89

Herpes virus major outer envelope glycoprotein (BLLF1); This family consists of the BLLF1 viral late glycoprotein, also termed gp350/220. It is the most abundantly expressed glycoprotein in the viral envelope of the Herpesviruses and is the major antigen responsible for stimulating the production of neutralising antibodies in vivo.

Pssm-ID: 282904 [Multi-domain] Cd Length: 886 Bit Score: 44.91 E-value: 4.06e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340   1187 DESSSSISTLERSL----AARRATRTKMMIPMDSQPSNTPVVsaipvPTLDSSQYPGilPSPSCGF--TAHPKFSLRPMP 1260
Cdd:pfam05109  390 DITVSGLGTAPKTLiitrTATNATTTTHKVIFSKAPESTTTS-----PTLNTTGFAA--PNTTTGLpsSTHVPTNLTAPA 462

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340   1261 FSTLTVER----SYTSAMSAEGATPMAPQPQPALIPTAQSEPQVSEEIPSRSIPTA-CVRPTHPLRSFTNTLLPPPMGTI 1335
Cdd:pfam05109  463 STGPTVSTadvtSPTPAGTTSGASPVTPSPSPRDNGTESKAPDMTSPTSAVTTPTPnATSPTPAVTTPTPNATSPTLGKT 542

                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340   1336 EPK--VFSPVTGGSLPKPQVKT----ASLGQAGKArSPLLPVSVPTAPESAED-GQKPPE 1388
Cdd:pfam05109  543 SPTsaVTTPTPNATSPTPAVTTptpnATIPTLGKT-SPTSAVTTPTPNATSPTvGETSPQ 601

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: 4.14e-04

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 77993340  249 QGRDAVLECSASGFPNPAFYWLRGNELIqSRSKKYSLLSGSNLLISSVTDDDSGIYTCIAHNKQQNISASCELAV 323
Cdd:cd05745    1 EGQTVDFLCEAQGYPQPVIAWTKGGSQL-SVDRRHLVLSSGTLRISRVALHDQGQYECQAVNIVGSQRTVAQLTV 74

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: 41.25 E-value: 4.16e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340  331 NYPSNTYAYESSDIEMECAVTGNPQPVVRWVK----NGEVVVPSDY-----FQIVDGGH------LQILGLVRSDEGFYQ 395
Cdd:cd04974    6 GLPANQTVVLGSDVEFHCKVYSDAQPHIQWLKhvevNGSKYGPDGLpyvtvLKVAGVNTtgeentLTISNVTFDDAGEYI 85

                         90
                 ....*....|....*.
gi 77993340  396 CIAENEAGNSQAMAQL 411
Cdd:cd04974   86 CLAGNSIGLSFHSAWL 101

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

Pssm-ID: 464026 [Multi-domain] Cd Length: 79 Bit Score: 40.46 E-value: 4.38e-04

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 77993340    149 GDTALLRCEVTGDPMPVVRWQKNREDLPltfdpdsrvvilPSGSLQVSRVQPPDSATYRCLAENPG 214
Cdd:pfam13895   14 GEPVTLTCSAPGNPPPSYTWYKDGSAIS------------SSPNFFTLSVSAEDSGTYTCVARNGR 67

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

Pssm-ID: 464026 [Multi-domain] Cd Length: 79 Bit Score: 40.07 E-value: 4.88e-04

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 77993340    333 PSNTYAYESSDIEMECAVTGNPQPVVRWVKNGEVVVPSdyfqivdgGHLQILGLVRSDEGFYQCIAENEAG 403
Cdd:pfam13895    6 PSPTVVTEGEPVTLTCSAPGNPPPSYTWYKDGSAISSS--------PNFFTLSVSAEDSGTYTCVARNGRG 68

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: 40.51 E-value: 4.90e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340   36 RFVLQPQDVVTVRGGVLQLDCDAlsdQGVP--SISWKKDGVLLSAVVDERRRQLSNGSLLVQNVMHSrhhrpDEGSYQCL 113
Cdd:cd04978    1 YWIIEPPSLVLSPGETGELICEA---EGNPqpTITWRLNGVPIEPAPEDMRRTVDGRTLIFSNLQPN-----DTAVYQCN 72


                 ..
gi 77993340  114 AS 115
Cdd:cd04978   73 AS 74

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

Pssm-ID: 409394 [Multi-domain] Cd Length: 83 Bit Score: 40.09 E-value: 6.00e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340   44 VVTVRGGVLQLDCDAlsdQGVPS--ISW-KKDGVLLSAvvderRRQLSN--GSLLVQNVMHSrhhrpDEGSYQCLASlEG 118
Cdd:cd05731    5 TMVLRGGVLLLECIA---EGLPTpdIRWiKLGGELPKG-----RTKFENfnKTLKIENVSEA-----DSGEYQCTAS-NT 70

                         90
                 ....*....|...
gi 77993340  119 IGAIvSRTARVTV 131
Cdd:cd05731   71 MGSA-RHTISVTV 82

C-terminal immunoglobulin (Ig)-like domain of M-protein; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of M-protein (also known as myomesin-2). M-protein is a structural protein localized to the M-band, a transverse structure in the center of the sarcomere, and is a candidate for M-band bridges. M-protein is modular consisting mainly of repetitive IG-like and fibronectin type III (FnIII) domains and has a muscle-type specific expression pattern. M-protein is present in fast fibers.

Pssm-ID: 143299 Cd Length: 92 Bit Score: 40.28 E-value: 6.04e-04

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 77993340  242 PQKVSVLQGRDAVLECSASGFPNPAFYWLRGNELIQ-SRSKKYSLLSG--SNLLISSVTDDDSGIYTCIAHNK 311
Cdd:cd05891    8 PDVVTIMEGKTLNLTCTVFGNPDPEVIWFKNDQDIElSEHYSVKLEQGkyASLTIKGVTSEDSGKYSINVKNK 80

Fifth immunoglobulin (Ig)-like domain of the carcinoembryonic antigen (CEA) related cell adhesion molecule 5 (CEACAM5) and similar domains; member of the C2-set IgSF domains; The members here are composed of the fifth immunoglobulin (Ig)-like domain of the carcinoembryonic antigen (CEA) related cell adhesion molecule 5 (CEACAM5) and similar domains. The CEA family is a group of anchored or secreted glycoproteins, expressed by epithelial cells, leukocytes, endothelial cells and placenta. The CEA family is divided into the CEACAM and pregnancy-specific glycoprotein (PSG) subfamilies. Carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5), also known as CD66e (Cluster of Differentiation 66e), is a cell surface glycoprotein that plays a role in cell adhesion, intracellular signaling and tumor progression. Diseases associated with CEACAM5 include lung cancer and rectum cancer. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. This group belongs to the C2-set of IgSF domains, having A, B, and E strands in one beta-sheet and A', G, F, C' in the other. Unlike other Ig domain sets, the C2-set lacks the D strand.

Pssm-ID: 409540 Cd Length: 76 Bit Score: 39.79 E-value: 6.05e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340  242 PQKVSVLQGRDAVLECSASGFPNPAFYWLRGNELIQSRSKkysllsgsnLLISSVTDDDSGIYTCIAHNKQQNISASCEL 321
Cdd:cd20948    2 PSDTYYLSGENLNLSCHAASNPPAQYSWTINGTFQTSSQE---------LFLPAITENNEGTYTCSAHNSLTGKNISLVL 72


                 ....
gi 77993340  322 AVLV 325
Cdd:cd20948   73 SVTV 76

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: 40.07 E-value: 6.35e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340   37 FVLQPQDVVTVRGG-VLQLDCDAlsdQGVPS--ISWKKDGVLLSAvvDERRRQLSNGSLLVQNVMHSrhhrpDEGSYQCL 113
Cdd:cd20978    3 FIQKPEKNVVVKGGqDVTLPCQV---TGVPQpkITWLHNGKPLQG--PMERATVEDGTLTIINVQPE-----DTGYYGCV 72

                         90
                 ....*....|....
gi 77993340  114 ASLEgIGAIVSRTA 127
Cdd:cd20978   73 ATNE-IGDIYTETL 85

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: 40.18 E-value: 6.70e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340   39 LQPQDVVTVRGGVLQLDCDAlSDQGVPSISWKKDGVLLSAvVDERRRQLSNGSLL-VQNVmhsrhHRPDEGSYQCLASLE 117
Cdd:cd20970    7 QPSFTVTAREGENATFMCRA-EGSPEPEISWTRNGNLIIE-FNTRYIVRENGTTLtIRNI-----RRSDMGIYLCIASNG 79


                 ....*...
gi 77993340  118 GIGAIVSR 125
Cdd:cd20970   80 VPGSVEKR 87

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

Pssm-ID: 409397 [Multi-domain] Cd Length: 97 Bit Score: 40.17 E-value: 8.40e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340  326 PPQFLNYPSNTYAYESSDIEMECAVTGNPQPVVRWVKNGEVVVPSDYFQIVDGGHLQILG--------LVRSDEGFYQCI 397
Cdd:cd05734    1 PPRFVVQPNDQDGIYGKAVVLNCSADGYPPPTIVWKHSKGSGVPQFQHIVPLNGRIQLLSngsllikhVLEEDSGYYLCK 80

                         90
                 ....*....|...
gi 77993340  398 AENEAGN--SQAM 408
Cdd:cd05734   81 VSNDVGAdiSKSM 93

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: 39.09 E-value: 8.53e-04

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 77993340  154 LRCEVTGDPMPVVRWqkNREDLPLTfdPDSRVVILPSGSLQVSRVQPPDSATYRCLAENP-GSART 218
Cdd:cd05746    3 IPCSAQGDPEPTITW--NKDGVQVT--ESGKFHISPEGYLAIRDVGVADQGRYECVARNTiGYASV 64

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: 39.93 E-value: 9.04e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340   37 FVLQPQDVV---TVRGGVLQLDCDALSDQgVPSISWKKDGVLLSAVVDeRRRQLSNGSLLVQNVMHSRhhrpDEGSYQCL 113
Cdd:cd05848    4 FVQEPDDAIfptDSDEKKVILNCEARGNP-VPTYRWLRNGTEIDTESD-YRYSLIDGNLIISNPSEVK----DSGRYQCL 77

                         90
                 ....*....|....
gi 77993340  114 ASlEGIGAIVSRTA 127
Cdd:cd05848   78 AT-NSIGSILSREA 90

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

Pssm-ID: 409396 [Multi-domain] Cd Length: 94 Bit Score: 39.70 E-value: 9.35e-04

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 77993340  150 DTALLRCEVTGDPMPVVRWQKNREdlplTFDP--DSRVVILP-SGSLQVS-RVQPPDS--ATYRCLAEN 212
Cdd:cd05733   17 DNITIKCEAKGNPQPTFRWTKDGK----FFDPakDPRVSMRRrSGTLVIDnHNGGPEDyqGEYQCYASN 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: 39.44 E-value: 1.20e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340   39 LQPQDVVTVRGGVLQLDCdALSDQGVPSISWKKDGVLLSAvvDERRRQLSNGSLLVQNVmhsrhHRPDEGSYQCLASLEG 118
Cdd:cd20957    6 IDPPVQTVDFGRTAVFNC-SVTGNPIHTVLWMKDGKPLGH--SSRVQILSEDVLVIPSV-----KREDKGMYQCFVRNDG 77


                 ...
gi 77993340  119 IGA 121
Cdd:cd20957   78 DSA 80

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: 39.11 E-value: 1.28e-03

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 77993340  342 SDIEMECAVTGNPQPVVRWVKNGEVVVPSDYFQI---VDGGHLQILGLVRSDEGFYQCIAENEAG 403
Cdd:cd05748    8 ESLRLDIPIKGRPTPTVTWSKDGQPLKETGRVQIettASSTSLVIKNAKRSDSGKYTLTLKNSAG 72

Fifth domain (immunoglobulin-like) of Trk receptor TrkB; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the fifth domain of Trk receptor, TrkB, an immunoglobulin (Ig)-like domain which binds to neurotrophin. The Trk family of receptors are tyrosine kinase receptors, which mediate the trophic effects of the neurotrophin Nerve Growth Factor (NGF) family. Trks are activated by dimerization, leading to autophosphorylation of intracellular tyrosine residues, and triggering the signal transduction pathway. TrkB shares significant sequence homology and domain organization with TrkA and TrkC. The first three domains are leucine-rich domains while the fourth and fifth domains are Ig-like domains playing a part in ligand binding. TrKB is recognized by brain-derived neurotrophic factor (BDNF) and neurotrophin (NT)-4. In some cell systems NT-3 can activate TrkA and TrkB receptors. TrKB transcripts are found throughout multiple structures of the central and peripheral nervous systems. This group belongs to the I-set of IgSF domains

Pssm-ID: 409441 Cd Length: 94 Bit Score: 39.45 E-value: 1.28e-03

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 77993340  350 VTGNPQPVVRWVKNGEVVVPSDYF--QIVDGGHLQILGLVRSD------EGFYQCIAENEAG 403
Cdd:cd05855   22 VKGNPKPTLQWFHEGAILNESEYIctKIHVINNTEYHGCLQLDnpthlnNGIYTLVAKNEYG 83

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

Pssm-ID: 143220 Cd Length: 78 Bit Score: 39.01 E-value: 1.28e-03

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 77993340  149 GDTALLRCEVTGDPMPVVRWQKNREDLPltfdpDSRVVILPS----GSLQVSRVQPPDSATYRCLAEN 212
Cdd:cd05743    1 GETVEFTCVATGVPTPIINWRLNWGHVP-----DSARVSITSeggyGTLTIRDVKESDQGAYTCEAIN 63

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: 1.29e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340  238 FLQRPQKVSVLQGRDAVLECSASGFPNPAFYW-LRGNELIQSRSKKYSLLSGSNLLISSVTDDDSGIYTCIAHNKQQNIS 316
Cdd:cd05867    2 WTRRPQSHLYGPGETARLDCQVEGIPTPNITWsINGAPIEGTDPDPRRHVSSGALILTDVQPSDTAVYQCEARNRHGNLL 81


                 ....*...
gi 77993340  317 ASCELAVL 324
Cdd:cd05867   82 ANAHVHVV 89

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: 39.57 E-value: 1.34e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340  343 DIEMECAVTGNPQPVVRWVKNGEvvvpsdYFQIVD---------GGHLQIL----GLVRSDEGFYQCIAENEAGNsqAMA 409
Cdd:cd05875   18 NILIECEAKGNPVPTFHWTRNGK------FFNVAKdprvsmrrrSGTLVIDfrggGRPEDYEGEYQCFARNKFGT--ALS 89


                 ....*.
gi 77993340  410 QLILLQ 415
Cdd:cd05875   90 NKIRLQ 95

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: 38.73 E-value: 1.67e-03

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 77993340  333 PSNTYAYESSDIEMECAVTGNPQPVVRWVKNGEVVVPSDYFQIVDGGhLQILGLVRSDEgfYQCIAENEAGNSQAMAQL 411
Cdd:cd05739    4 PSNHEVMPGGSVNLTCVAVGAPMPYVKWMKGGEELTKEDEMPVGRNV-LELTNIYESAN--YTCVAISSLGMIEATAQV 79

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: 39.46 E-value: 1.69e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340  242 PQKVSVLQGRDAVLECSASGFP--NPAFYW-LRGNELIQSRS-----KKYSLLSGSNLLISSVTDDDSGIYTCIAHNKQQ 313
Cdd:cd04970    9 PSNADITVGENATLQCHASHDPtlDLTFTWsFNGVPIDLEKIeghyrRRYGKDSNGDLEIVNAQLKHAGRYTCTAQTVVD 88

                         90
                 ....*....|....
gi 77993340  314 NISASCELAVLVPP 327
Cdd:cd04970   89 SDSASATLVVRGPP 102

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

Pssm-ID: 409397 [Multi-domain] Cd Length: 97 Bit Score: 39.01 E-value: 1.69e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340  134 PLRVLVSTESVSAHLGDTALLRCEVTGDPMPVVRWQKNREDLPLTFDP----DSRVVILPSGSLQVSRVQPPDSATYRCL 209
Cdd:cd05734    1 PPRFVVQPNDQDGIYGKAVVLNCSADGYPPPTIVWKHSKGSGVPQFQHivplNGRIQLLSNGSLLIKHVLEEDSGYYLCK 80


                 ...
gi 77993340  210 AEN 212
Cdd:cd05734   81 VSN 83

Immunoglobulin Constant-1 (C1)-set domain; The members here are composed of C1-set domains, classical Ig-like domains resembling the antibody constant domain. Members of the IgC1 family are components of immunoglobulin, T-cell receptors, CD1 cell surface glycoproteins, secretory glycoproteins A/C, and major histocompatibility complex (MHC) class I/II molecules. In immunoglobulins, each chain is composed of one variable domain (IgV) and one or more IgC domains. These names reflect the fact that the variability in sequences is higher in the variable domain than in the constant domain. The IgV domain is responsible for antigen binding, while the IgC domain is involved in oligomerization and molecular interactions. 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 strands by G, F, C, and C'.

Pssm-ID: 409354 Cd Length: 95 Bit Score: 38.98 E-value: 1.72e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340  136 RVLVSTESVSAHLGDTALLRCEVTG--DPMPVVRWQKNREDLPLTFDPDSrVVILPSGS------LQVSRVQPPDSATYR 207
Cdd:cd00098    1 TVTLLPPSPEEKGGGKVTLVCLVSGfyPKDITVTWLKNGVPLTSGVSTSS-PVEPNDGTysvtssLTVPPSDWDEGATYT 79


                 ....*...
gi 77993340  208 CLAENPGS 215
Cdd:cd00098   80 CVVTHESL 87

Immunoglobulin (Ig)-like domain of vascular endothelial growth factor receptor (VEGFR); member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig)-like domain of vascular endothelial growth factor receptor (VEGFR). The VEGFRs have an extracellular component with seven Ig-like domains, a transmembrane segment, and an intracellular tyrosine kinase domain interrupted by a kinase-insert domain. The VEGFR family consists of three members, VEGFR-1 (Flt-1), VEGFR-2 (KDR/Flk-1), and VEGFR-3 (Flt-4). VEGFRs bind VEGFs with high affinity at the Ig-like domains. VEGF-A is important to the growth and maintenance of vascular endothelial cells and to the development of new blood- and lymphatic-vessels in physiological and pathological states. VEGFR-2 is a major mediator of the mitogenic, angiogenic, and microvascular permeability-enhancing effects of VEGF-A. VEGFR-1 may play an inhibitory part in these processes by binding VEGF and interfering with its interaction with VEGFR-2. VEGFR-1 has a signaling role in mediating monocyte chemotaxis. VEGFR-1 and VEGFR-2 may mediate a chemotactic and a survival signal in hematopoietic stem cells or leukemia cells. VEGFR-3 has been shown to be involved in tumor angiogenesis and growth. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409365 Cd Length: 90 Bit Score: 38.73 E-value: 1.98e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340  245 VSVLQGRDAVLECSA-----------SGFPNPAFYWLRGNELIQSrskKYSLLSGSNLLISSVTDDDSGIYTCIAHNKQQ 313
Cdd:cd04976    2 ITVKHRKQQVLEATAgkrsvrlpmkvKAYPPPEVVWYKDGLPLTE---KARYLTRHSLIIKEVTEEDTGNYTILLSNKQS 78

                         90
                 ....*....|..
gi 77993340  314 NISASCELAVLV 325
Cdd:cd04976   79 NVFKNLTATLVV 90

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

Pssm-ID: 464026 [Multi-domain] Cd Length: 79 Bit Score: 38.53 E-value: 1.98e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340     36 RFVLQPQDVVTVRGGVLQLDCDALSDQgVPSISWKKDGVLLSavvderrrqlSNGSLLVQNVmhsrhHRPDEGSYQCLAS 115
Cdd:pfam13895    1 KPVLTPSPTVVTEGEPVTLTCSAPGNP-PPSYTWYKDGSAIS----------SSPNFFTLSV-----SAEDSGTYTCVAR 64

                           90
                   ....*....|....*.
gi 77993340    116 LEGIGaIVSRTARVTV 131
Cdd:pfam13895   65 NGRGG-KVSNPVELTV 79

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: 39.56 E-value: 2.09e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340  238 FLQRPQKVSVLQGRDAVLECSASGFPNPAF-YWLRGNELIQSRSK--------------KYSLLSGSNLLISSVTDDDSG 302
Cdd:cd20940    3 FIKSPLSQQRLVGDSVELHCEAVGSPIPEIqWWFEGQEPNEICSQlwdgarldrvhinaTYHQHATSTISIDNLTEEDTG 82


                 ....*...
gi 77993340  303 IYTCIAHN 310
Cdd:cd20940   83 TYECRASN 90

Purple acid Phosphatase, N-terminal domain; This domain is found at the N-terminus of Purple acid phosphatase proteins.

Pssm-ID: 465220 [Multi-domain] Cd Length: 93 Bit Score: 38.93 E-value: 2.13e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340    622 PQNVSLEVV-YSRSIKVSWQPPPANTqngfitGYKIRYRKTGRRGEQEA------------IEPNNLWYLFTGLEKGSQY 688
Cdd:pfam16656    1 PEQVHLSLTgDSTSMTVSWVTPSAVT------SPVVQYGTSSSALTSTAtatsstyttgdgGTGYIHRATLTGLEPGTTY 74

                           90       100
                   ....*....|....*....|...
gi 77993340    689 SFQVsgmtVNGTGPSSEWLTAET 711
Cdd:pfam16656   75 YYRV----GDDNGGWSEVYSFTT 93

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: 39.36 E-value: 2.16e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340    242 PQKVSVLQGRDAVLECSASGF---PNPAFYWLRGN------ELI---------QSRSKKYSLLSGSN-----LLISSVTD 298
Cdd:pfam07686    3 PREVTVALGGSVTLPCTYSSSmseASTSVYWYRQPpgkgptFLIayysngseeGVKKGRFSGRGDPSngdgsLTIQNLTL 82


                   ....*...
gi 77993340    299 DDSGIYTC 306
Cdd:pfam07686   83 SDSGTYTC 90

Third immunoglobulin (Ig)-like domain of fibroblast growth factor receptor 2 (FGFR2); member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig)-like domain of human fibroblast growth factor receptor 2 (FGFR2). Fibroblast growth factors (FGFs) participate in morphogenesis, development, angiogenesis, and wound healing. These FGF-stimulated processes are mediated by four FGFR tyrosine kinases (FGRF1-4). FGFRs are comprised of an extracellular portion consisting of three Ig-like domains, a transmembrane helix, and a cytoplasmic portion having protein tyrosine kinase activity. The highly conserved Ig-like domains 2 and 3, and the linker region between D2 and D3 define a general binding site for FGFs. FGFR2 is required for male sex determination. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409444 Cd Length: 105 Bit Score: 39.17 E-value: 2.31e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340  333 PSNTYAYESSDIEMECAVTGNPQPVVRWVK----NGEVVVPSD--YFQIVDGG-------HLQILGL---VRSDEGFYQC 396
Cdd:cd05858    8 PANTSVVVGTDAEFVCKVYSDAQPHIQWLKhvekNGSKYGPDGlpYVEVLKTAgvnttdkEIEVLYLrnvTFEDAGEYTC 87

                         90
                 ....*....|....*...
gi 77993340  397 IAENEAGNSQAMAQLILL 414
Cdd:cd05858   88 LAGNSIGISHHSAWLTVL 105

Immunoglobulin domain; Members of the immunoglobulin superfamily are found in hundreds of proteins of different functions. Examples include antibodies, the giant muscle kinase titin and receptor tyrosine kinases. Immunoglobulin-like domains may be involved in protein-protein and protein-ligand interactions.

Pssm-ID: 395002 Cd Length: 86 Bit Score: 38.33 E-value: 2.37e-03

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 77993340     41 PQDVVTVRGGVLQLDCDALSDQGVPSISWKKDG--VLLSAVVDERRRQLSNGSLLVQNVMhsrhhRPDEGSYQCLAS 115
Cdd:pfam00047    3 PPTVTVLEGDSATLTCSASTGSPGPDVTWSKEGgtLIESLKVKHDNGRTTQSSLLISNVT-----KEDAGTYTCVVN 74

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: 38.71 E-value: 2.38e-03

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 77993340  149 GDTALLRCEVTGDPMPVVRWQKnrEDLPLTfdPDSRVVILPSG----SLQVSRVQPPDSATYRCLAEN 212
Cdd:cd20973   12 GSAARFDCKVEGYPDPEVKWMK--DDNPIV--ESRRFQIDQDEdglcSLIISDVCGDDSGKYTCKAVN 75

First immunoglobulin (Ig) domain of contactin-2; member of the I-set of Ig superfamily domains; The members here are composed of the first immunoglobulin (Ig) domain of the neural cell adhesion molecule contactin-2-like. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-2 (TAG-1, axonin-1) facilitates cell adhesion by homophilic binding between molecules in apposed membranes. It may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module by contacts between IG domains 1 and 4, and domains 2 and 3. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-2 is also expressed in retinal amacrine cells in the developing chick retina, corresponding to the period of formation and maturation of AC processes. This group belongs to the I-set of IgSF domains.

Pssm-ID: 409437 [Multi-domain] Cd Length: 97 Bit Score: 38.75 E-value: 2.58e-03

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 77993340   69 WKKDGVLLSAVVDERRRQLSnGSLLVQNVMHSRhhrpDEGSYQCLASlEGIGAIVSRTA 127
Cdd:cd05850   39 WKMNGTELKMEPDSRYRLVA-GNLVISNPVKAK----DAGSYQCLAS-NRRGTVVSREA 91

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

Pssm-ID: 143277 [Multi-domain] Cd Length: 97 Bit Score: 38.81 E-value: 2.63e-03

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340  148 LGDTALLRCEVTGDPMPVVRWQKNREDLPLTFDP-DSRVVILPS---GSLQVSRVQPPDSATYRCLAENP 213
Cdd:cd05869   16 LEEQITLTCEASGDPIPSITWRTSTRNISSEEKTlDGHIVVRSHarvSSLTLKYIQYTDAGEYLCTASNT 85

Immunoglobulin (Ig)-like domain found in Perlecan and similar proteins; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig)-like domain found in Perlecan. Perlecan is a large multi-domain heparin sulfate proteoglycan, important in tissue development and organogenesis. Perlecan can be represented as 5 major portions; its fourth major portion (domain IV) is a tandem repeat of immunoglobulin-like domains (Ig2-Ig15) which can vary in size due to alternative splicing. Perlecan binds many cellular and extracellular ligands. Its domain IV region has many binding sites. Some of these have been mapped at the level of individual Ig-like domains, including a site restricted to the Ig5 domain for heparin/sulfatide, a site restricted to the Ig3 domain for nidogen-1 and nidogen-2, a site restricted to Ig4-5 for fibronectin, and sites restricted to Ig2 and to Ig13-15 for fibulin-2. 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: 409412 Cd Length: 85 Bit Score: 38.31 E-value: 2.67e-03

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 77993340  237 VFLQRPQKVSVLQGRDAVLECSA-SGFPNPAFYWLRGNELIQSRSKKysllSGSNLLISSVTDDDSGIYTCIAHN 310
Cdd:cd05754    3 VTVEEPRSQEVRPGADVSFICRAkSKSPAYTLVWTRVNGTLPSRAMD----FNGILTIRNVQLSDAGTYVCTGSN 73

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: 38.26 E-value: 2.78e-03

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340  145 SAHLGDTALLRCEVTGD-PMPVVRWQKNREDLPLTFDPDSRVVILPSGS-LQVSRVQPPDSATYRCLAEN 212
Cdd:cd05750   10 TVQEGSKLVLKCEATSEnPSPRYRWFKDGKELNRKRPKNIKIRNKKKNSeLQINKAKLEDSGEYTCVVEN 79

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: 38.44 E-value: 2.87e-03

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 77993340  142 ESVSAHLGDTALLRCEVTGDPMPVVRWQKNREDLPltfdPDSRVVILPSGSLQVSRVQPPDSATYRCLAENPGSARTGT 220
Cdd:cd05852   10 KKILAAKGGRVIIECKPKAAPKPKFSWSKGTELLV----NNSRISIWDDGSLEILNITKLDEGSYTCFAENNRGKANST 84

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: 38.35 E-value: 3.00e-03

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 77993340  149 GDTALLRCEVTGDPMPVVRWQKNREDLPLTfdpDSRVVILPSG---SLQVSRVQPPDSATYRCLAEN 212
Cdd:cd05891   16 GKTLNLTCTVFGNPDPEVIWFKNDQDIELS---EHYSVKLEQGkyaSLTIKGVTSEDSGKYSINVKN 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: 38.39 E-value: 3.12e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340  129 VTVSGPLRVLVSTESVSAHLgdtaLLRCEVTGDPMPVVRWQKNREDLPLtfDPDSRVVILpSGSLQVSRV-QPPDSATYR 207
Cdd:cd05848    3 VFVQEPDDAIFPTDSDEKKV----ILNCEARGNPVPTYRWLRNGTEIDT--ESDYRYSLI-DGNLIISNPsEVKDSGRYQ 75


                 ....*
gi 77993340  208 CLAEN 212
Cdd:cd05848   76 CLATN 80

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: 38.54 E-value: 3.14e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340  327 PQFLNYPSNTYAYE-SSDIEMECAVTGNPQPVVRWVK-----------------NGEVVVP----SDYFQIVdggHLQIl 384
Cdd:cd20955    2 PVFLKEPTNRIDFSnSTGAEIECKASGNPMPEIIWIRsdgtavgdvpglrqissDGKLVFPpfraEDYRQEV---HAQV- 77

                         90       100
                 ....*....|....*....|
gi 77993340  385 glvrsdegfYQCIAENEAGN 404
Cdd:cd20955   78 ---------YACLARNQFGS 88

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

Pssm-ID: 409396 [Multi-domain] Cd Length: 94 Bit Score: 38.16 E-value: 3.42e-03

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 77993340  240 QRPQKVSVLQGRDAVLECSASGFPNPAFYWLR-GNELIQSRSKKYSLLSGSNLLI----SSVTDDDSGIYTCIAHNK 311
Cdd:cd05733    6 QSPKDYIVDPRDNITIKCEAKGNPQPTFRWTKdGKFFDPAKDPRVSMRRRSGTLVidnhNGGPEDYQGEYQCYASNE 82

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

Pssm-ID: 319300 Cd Length: 92 Bit Score: 38.34 E-value: 3.46e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340  232 VSRGLvflqrPQKVSVLQGRDAVLECSASGFPNPAFYWLRGNELIQSR---SKKYSLLSGSNLLISSVTDDDSGIYTCIA 308
Cdd:cd05737    3 VLGGL-----PDVVTIMEGKTLNLTCNVWGDPPPEVSWLKNDQALAFLdhcNLKVEAGRTVYFTINGVSSEDSGKYGLVV 77


                 ...
gi 77993340  309 HNK 311
Cdd:cd05737   78 KNK 80

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

Pssm-ID: 409566 [Multi-domain] Cd Length: 93 Bit Score: 38.10 E-value: 3.74e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340  327 PQFLNYPSNTYAYESSDIEMECAVTGNPQPVVRWVKNGEVV----VPSDYFQIVDG-GHLQILGLVRSDEGFYQCIAENE 401
Cdd:cd20974    1 PVFTQPLQSVVVLEGSTATFEAHVSGKPVPEVSWFRDGQVIststLPGVQISFSDGrAKLSIPAVTKANSGRYSLTATNG 80

                         90
                 ....*....|...
gi 77993340  402 AGNSQAMAQLILL 414
Cdd:cd20974   81 SGQATSTAELLVL 93

Second immunoglobulin (Ig)-like domain of interleukin-1 receptor (IL1R), and similar domains; The members here are composed of the second immunoglobulin (Ig)-like domain of interleukin-1 receptor (IL1R; also known as cluster of differentiation (CD) 121). IL-1 alpha and IL-1 beta are cytokines which participate in the regulation of inflammation, immune responses, and hematopoiesis. These cytokines bind to the IL-1 receptor type 1 (IL1R1), which is activated on additional association with interleukin-1 receptor accessory protein (IL1RAP). IL-1 also binds a second receptor designated type II (IL1R2). Mature IL1R1 consists of three IG-like domains, a transmembrane domain, and a large cytoplasmic domain. Mature IL1R2 is organized similarly except that it has a short cytoplasmic domain. The latter does not initiate signal transduction. A naturally occurring cytokine IL-1RA (IL-1 receptor antagonist) is widely expressed and binds to IL-1 receptors, inhibiting the binding of IL-1 alpha and IL-1 beta. This group also contains ILIR-like 1 (IL1R1L) which maps to the same chromosomal location as IL1R1 and IL1R2.

Pssm-ID: 409415 Cd Length: 92 Bit Score: 38.07 E-value: 4.01e-03

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 77993340   65 PSISWKKDGVLLsavvDERRRQLSNGS-LLVQNVMHSrhhrpDEGSYQCLASLEGIGAI--VSRTARVTVSG 133
Cdd:cd05757   30 PPIQWYKDCKPL----QGDKRFIPKGSkLLIQNVTEE-----DAGNYTCKFTYTHNGKQynVTRTISLTVTE 92

Fifth domain (immunoglobulin-like) of Trk receptors TrkA, TrkB, and TrkC; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the fifth domain of Trk receptors TrkA, TrkB, and TrkC, an immunoglobulin (Ig)-like domain which binds to neurotrophin. The Trk family of receptors are tyrosine kinase receptors. They are activated by dimerization, leading to autophosphorylation of intracellular tyrosine residues, and triggering the signal transduction pathway. TrkA, TrkB, and TrkC share significant sequence homology and domain organization. The first three domains are leucine-rich domains while the fourth and fifth domains are Ig-like domains playing a part in ligand binding. TrkA, TrkB, and TrkC mediate the trophic effects of the neurotrophin Nerve Growth Factor (NGF) family. TrkA is recognized by NGF. TrkB is recognized by brain-derived neurotrophic factor (BDNF) and neurotrophin (NT)-4. TrkC is recognized by NT-3. NT-3 is promiscuous as in some cell systems it activates TrkA and TrkB receptors. TrkA is a receptor found in all major NGF targets, including the sympathetic, trigeminal, and dorsal root ganglia, cholinergic neurons of the basal forebrain, and the striatum. TrKB transcripts are found throughout multiple structures of the central and peripheral nervous systems. The TrkC gene is expressed throughout the mammalian nervous system. This group belongs to the I-set of IgSF domains.

Pssm-ID: 409360 Cd Length: 96 Bit Score: 38.15 E-value: 4.36e-03

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 77993340  350 VTGNPQPVVRWVKNGEVVVPSDY----------FQIVDGGHLQILGLVRSDEGFYQCIAENEAG 403
Cdd:cd04971   22 VRGNPKPTLTWYHNGAVLNESDYirteihyeaaTPTEYHGCLKFDNPTHVNNGNYTLVASNEYG 85

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: 4.77e-03

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 77993340  344 IEMECAVTGNPQPVVRWVKNGEVVVPSD--YFQIVDG---GHLQILGLVRSDEGFYQCIAEN 400
Cdd:cd20961   11 VKLNCSVEGMEEPDIQWVKDGAVVQNLDqlYIPVSEQhwiGFLSLKSVERSDAGRYWCQVED 72

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: 37.82 E-value: 4.83e-03

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 77993340   65 PSISWKKDGVLLSAvvDERRRQLSNGSLLVQNVMHSrhhrpDEGSYQCLAS 115
Cdd:cd04969   32 PTISWSKGTELLTN--SSRICILPDGSLKIKNVTKS-----DEGKYTCFAV 75

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: 37.57 E-value: 4.88e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340   37 FVLQPQDVVTVRGGVLQLDCDAlsdQGVPS--ISWKKDGVLLSAVVDERRRQLSNGSLLVQNVMHSrhhrpDEGSYQCLA 114
Cdd:cd05867    2 WTRRPQSHLYGPGETARLDCQV---EGIPTpnITWSINGAPIEGTDPDPRRHVSSGALILTDVQPS-----DTAVYQCEA 73

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

Pssm-ID: 319300 Cd Length: 92 Bit Score: 37.57 E-value: 4.92e-03

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 77993340  149 GDTALLRCEVTGDPMPVVRWQKNREDLPLTFDPDSRVVILPSGSLQVSRVQPPDSATYRCLAENPGSARTG 219
Cdd:cd05737   16 GKTLNLTCNVWGDPPPEVSWLKNDQALAFLDHCNLKVEAGRTVYFTINGVSSEDSGKYGLVVKNKYGSETS 86

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: 37.98 E-value: 5.16e-03

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 77993340  153 LLRCEVTGDPMPVVRWQKNREDlpLTFDPDSRVViLPSGSLQVSR-VQPPDSATYRCLAENPGSARTGTDADLR 225
Cdd:cd05850   24 TLACRARASPPATYRWKMNGTE--LKMEPDSRYR-LVAGNLVISNpVKAKDAGSYQCLASNRRGTVVSREASLR 94

large tegument protein UL36; Provisional

Pssm-ID: 223021 [Multi-domain] Cd Length: 3151 Bit Score: 41.46 E-value: 5.23e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340  1145 PSGSAPSGRDSPIQSCQEIPPVSHSQ-----SESQMGSKSSHSG-----ADADESSSSISTLERSLAARRATRTKMMiPM 1214
Cdd:PHA03247 2722 PPGPAAARQASPALPAAPAPPAVPAGpatpgGPARPARPPTTAGppapaPPAAPAAGPPRRLTRPAVASLSESRESL-PS 2800

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340  1215 DSQPSNTPVVSAIPVPTLDSSQYP-GILPSPSCGFTAHPKFSLRPMPfSTLTVE-----------RSYTSAMSAEGATPM 1282
Cdd:PHA03247 2801 PWDPADPPAAVLAPAAALPPAASPaGPLPPPTSAQPTAPPPPPGPPP-PSLPLGgsvapggdvrrRPPSRSPAAKPAAPA 2879

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340  1283 AP----------------QPQPALIPTAQSEPQVSEEIPSRSIPTACVRPTHPLRsftntllPPPMGTIEPKVFSPVTGG 1346
Cdd:PHA03247 2880 RPpvrrlarpavsrstesFALPPDQPERPPQPQAPPPPQPQPQPPPPPQPQPPPP-------PPPRPQPPLAPTTDPAGA 2952

                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....*.
gi 77993340  1347 SLPKPQVKTASLGQAGKARSPLLPVSVPTAPESAEDGQKPPEDPSS 1392
Cdd:PHA03247 2953 GEPSGAVPQPWLGALVPGRVAVPRFRVPQPAPSREAPASSTPPLTG 2998

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

Pssm-ID: 319300 Cd Length: 92 Bit Score: 37.57 E-value: 5.59e-03

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 77993340  340 ESSDIEMECAVTGNPQPVVRWVKNGEVVVPSDYFQI-VDGG---HLQILGLVRSDEGFYQCIAENEAG 403
Cdd:cd05737   15 EGKTLNLTCNVWGDPPPEVSWLKNDQALAFLDHCNLkVEAGrtvYFTINGVSSEDSGKYGLVVKNKYG 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: 37.61 E-value: 6.17e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340   41 PQDVVTVRGGVLQLDCDAlSDQGVPSISWKKDGVLLSAVVDERRRQLSNGSLLVQNVmhsrhhRP-DEGSYQCLAslEGI 119
Cdd:cd20976    8 PKDLEAVEGQDFVAQCSA-RGKPVPRITWIRNAQPLQYAADRSTCEAGVGELHIQDV------LPeDHGTYTCLA--KNA 78

                         90
                 ....*....|..
gi 77993340  120 GAIVSRTARVTV 131
Cdd:cd20976   79 AGQVSCSAWVTV 90

Immunoglobulin (Ig)-like domain of vascular endothelial growth factor receptor 2 (VEGFR-2); member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig)-like domain of vascular endothelial growth factor receptor 2 (VEGFR-2). The VEGFRs have an extracellular component with seven Ig-like domains, a transmembrane segment, and an intracellular tyrosine kinase domain interrupted by a kinase-insert domain. VEGFRs bind VEGFs with high affinity at the Ig-like domains. VEGFR-2 (KDR/Flk-1) is a major mediator of the mitogenic, angiogenic and microvascular permeability-enhancing effects of VEGF-A; VEGF-A is important to the growth and maintenance of vascular endothelial cells and to the development of new blood- and lymphatic-vessels in physiological and pathological states. VEGF-A also interacts with VEGFR-1, which it binds more strongly than VEGFR-2. VEGFR-1 and VEGFR-2 may mediate a chemotactic and a survival signal in hematopoietic stem cells or leukemia cells. 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: 409450 Cd Length: 89 Bit Score: 37.21 E-value: 6.58e-03

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 77993340  261 GFPNPAFYWLRGNELIQSRSKKYSllsGSNLLISSVTDDDSGIYTCIAHNK 311
Cdd:cd05864   28 GYPPPEIKWYKNGIPIESNHTIKA---GHVLTIMEVTEKDAGNYTVVLTNP 75

Immunoglobulin (Ig)-like domain of semaphorin 4D (Sema4D) and similar proteins; The members here are composed of the immunoglobulin (Ig)-like domain of semaphorin 4D (Sema4D) and similar proteins. Sema4D is a Class IV semaphorin. Semaphorins are classified based on structural features additional to the Sema domain. Sema4D has extracellular Sema and Ig domains, a transmembrane domain, and a short cytoplasmic domain. Sema4D plays a part in the development of GABAergic synapses. Sema4D in addition is an immune semaphorin. It is abundant on resting T cells; its expression is weak on resting B cells and antigen presenting cells (APCs), but is upregulated by various stimuli. The receptor used by Sema4D in the immune system is CD72. Sem4D enhances the activation of B cells and DCs through binding CD72, perhaps by reducing CD72s inhibitory signals. The receptor used by Sema4D in the non-lymphatic tissues is plexin-B1. Sem4D is anchored to the cell surface but its extracellular domain can be released from the cell surface by a metalloprotease-dependent process. Sem4D may mediate its effects in its membrane-bound form and/or its cleaved form.

Pssm-ID: 409457 Cd Length: 87 Bit Score: 37.10 E-value: 6.67e-03

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*.
gi 77993340  269 WLRGNELIQSRSKKYSLLSGsNLLISSVTDDDSGIYTCIAHNKQQN 314
Cdd:cd05873   29 WKFQGKVLKAESPKYGLYGD-GLLIFNASEADAGRYQCLSVEKSKA 73

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: 37.15 E-value: 6.98e-03

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 77993340  148 LGDTALLRCEVTGDPMPVVRWQKNREDLPLTFDPDSRvviLPSGSLQVSRVQPPDSATYRCLAEN 212
Cdd:cd05856   18 VGSSVRLKCVASGNPRPDITWLKDNKPLTPPEIGENK---KKKWTLSLKNLKPEDSGKYTCHVSN 79

Second immunoglobulin (Ig)-like domain of interleukin-1 receptor (IL1R), and similar domains; The members here are composed of the second immunoglobulin (Ig)-like domain of interleukin-1 receptor (IL1R; also known as cluster of differentiation (CD) 121). IL-1 alpha and IL-1 beta are cytokines which participate in the regulation of inflammation, immune responses, and hematopoiesis. These cytokines bind to the IL-1 receptor type 1 (IL1R1), which is activated on additional association with interleukin-1 receptor accessory protein (IL1RAP). IL-1 also binds a second receptor designated type II (IL1R2). Mature IL1R1 consists of three IG-like domains, a transmembrane domain, and a large cytoplasmic domain. Mature IL1R2 is organized similarly except that it has a short cytoplasmic domain. The latter does not initiate signal transduction. A naturally occurring cytokine IL-1RA (IL-1 receptor antagonist) is widely expressed and binds to IL-1 receptors, inhibiting the binding of IL-1 alpha and IL-1 beta. This group also contains ILIR-like 1 (IL1R1L) which maps to the same chromosomal location as IL1R1 and IL1R2.

Pssm-ID: 409415 Cd Length: 92 Bit Score: 36.92 E-value: 8.09e-03

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 77993340  269 WLRGNELIQSRsKKYSLLsGSNLLISSVTDDDSGIYTCI---AHN-KQQNISASCELAVLV 325
Cdd:cd05757   34 WYKDCKPLQGD-KRFIPK-GSKLLIQNVTEEDAGNYTCKftyTHNgKQYNVTRTISLTVTE 92

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: 36.80 E-value: 8.17e-03

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 77993340  148 LGDTALLRCEVTGDPMPVVRWQKNREDLpltfDPDSRvviLPSGS--LQVSRVQppDSATYRCLA 210
Cdd:cd05739   11 PGGSVNLTCVAVGAPMPYVKWMKGGEEL----TKEDE---MPVGRnvLELTNIY--ESANYTCVA 66

large tegument protein UL36; Provisional

Pssm-ID: 223021 [Multi-domain] Cd Length: 3151 Bit Score: 41.08 E-value: 8.37e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340  1100 RRSSAQQRKKRAthSAGKRKGSQKDLRPPdlwihheEMELKNMEKP--SGSAPSGRDSPIQSCQEIPPVSHSQSESQMGS 1177
Cdd:PHA03247 2665 RRARRLGRAAQA--SSPPQRPRRRAARPT-------VGSLTSLADPppPPPTPEPAPHALVSATPLPPGPAAARQASPAL 2735

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340  1178 KSSHSgADADESSSSISTLERSLAARRATRTKMMIPMDSQPSNTPVVSAIPVPTLDSSQYPGILPSPscgftahPKFSLR 1257
Cdd:PHA03247 2736 PAAPA-PPAVPAGPATPGGPARPARPPTTAGPPAPAPPAAPAAGPPRRLTRPAVASLSESRESLPSP-------WDPADP 2807

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340  1258 PMPFSTLTVERSYTSAMSAEGATPMAPQPQPALIPTAQSEPQ------------VSEEIPSRSIPTACVRPTHP-LRSFT 1324
Cdd:PHA03247 2808 PAAVLAPAAALPPAASPAGPLPPPTSAQPTAPPPPPGPPPPSlplggsvapggdVRRRPPSRSPAAKPAAPARPpVRRLA 2887

                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 77993340  1325 NTLLPPPMGtiepkvfspvtggSLPKPQVKTASLGQAGKARSPLLPVSVPTAPESAEDGQKPPEDPSSVYEQDD 1398
Cdd:PHA03247 2888 RPAVSRSTE-------------SFALPPDQPERPPQPQAPPPPQPQPQPPPPPQPQPPPPPPPRPQPPLAPTTD 2948

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: 37.20 E-value: 9.28e-03

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 77993340  149 GDTALLRCEVTGDPMPVVRWQKNREDLPLTFDPDSRVVILPSGSLQVSRVQPPDSATYRCLAEN 212
Cdd:cd05729   19 ANKVRLECGAGGNPMPNITWLKDGKEFKKEHRIGGTKVEEKGWSLIIERAIPRDKGKYTCIVEN 82

Immunoglobulin V-Type;

Pssm-ID: 214650 Cd Length: 81 Bit Score: 36.59 E-value: 9.51e-03

                            10        20        30        40        50        60        70
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 77993340     252 DAVLECSASGFPNP--AFYWLR-----GNELIQSRSKKYSLLSGS-----------------NLLISSVTDDDSGIYTC 306
Cdd:smart00406    1 SVTLSCKFSGSTFSsyYVSWVRqppgkGLEWLGYIGSNGSSYYQEsykgrftiskdtskndvSLTISNLRVEDTGTYYC 79

First immunoglobulin-like domains A168 within the A-band segment of human cardiac titin, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin-like domain A168 within the A-band segment of human cardiac titin. 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 structures of the titin-A168169 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: 409563 Cd Length: 93 Bit Score: 37.06 E-value: 1.00e-02

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77993340  146 AHLGDTALLRCEVTGDPMPVVRWQKNREDLpltfdPDSRVVILPSGSLQVSRV------QPPDSATYRCLAENP-GSART 218
Cdd:cd20971   13 VRYQSNATLVCKVTGHPKPIVKWYRQGKEI-----IADGLKYRIQEFKGGYHQliiasvTDDDATVYQVRATNQgGSVSG 87