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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2178167339  66 KFAMEPQDQTAVVGSRVTLPCRVE-NKAGQLQWTKDDfglglhRELSGYDRYKMigSDEEGDYSLDIREVTLDDDAKYQC 144
Cdd:pfam07679   2 KFTQKPKDVEVQEGESARFTCTVTgTPDPEVSWFKDG------QPLRSSDRFKV--TYEGGTYTLTISNVQPDDSGKYTC 73

                  ...
gi 2178167339 145 QVS 147
Cdd:pfam07679  74 VAT 76

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2178167339 444 PPKI-ISNHTQFGSQGDTVNIECAAFSIPRiDTIIWTYEDKEIDTVHDHDYLFredlqagGIVNSTLTIRESQSRHFGVY 522
Cdd:pfam13927   1 KPVItVSPSSVTVREGETVTLTCEATGSPP-PTITWYKNGEPISSGSTRSRSL-------SGSNSTLTISNVTRSDAGTY 72

                  ....*.
gi 2178167339 523 KCNVSN 528
Cdd:pfam13927  73 TCVASN 78

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2178167339 190 LECVSVGGKPPAEITWVDSnaGVLTQGVTTTVEPLSDGQRFTTRSIIRMAPKQEHNNQTFTCQAQNTADRAYRAASILIE 269
Cdd:cd05759    20 LTCRARGAKPAAEIIWFRD--GEQLEGAVYSKELLKDGKRETTVSTLLITPSDLDTGRTFTCRARNEAIPNGKETSITLD 97

                  .
gi 2178167339 270 V 270
Cdd:cd05759    98 V 98

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 2178167339 358 PPSFRSYPKDVEAEVGKQVTLSCDVDGFPAPEIRWLH-----YEEDTNIRVGRTPNLTLT---VDTHTSGRYLCKAS 426
Cdd:pfam13927   1 KPVITVSPSSVTVREGETVTLTCEATGSPPPTITWYKngepiSSGSTRSRSLSGSNSTLTisnVTRSDAGTYTCVAS 77

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2178167339 444 PPKI-ISNHTQFGSQGDTVNIECAAFSIPRiDTIIWTYEDKEIDTVHDHDYLFredlqagGIVNSTLTIRESQSRHFGVY 522
Cdd:pfam13927   1 KPVItVSPSSVTVREGETVTLTCEATGSPP-PTITWYKNGEPISSGSTRSRSL-------SGSNSTLTISNVTRSDAGTY 72

                  ....*.
gi 2178167339 523 KCNVSN 528
Cdd:pfam13927  73 TCVASN 78

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2178167339 443 GPPKIISNHTQFGSQGDTVNIECAAFSIPRIDTIIWTYEDKEIDTVHDHDYLFREDLQAGGIVnSTLTIRESQSRHFG-V 521
Cdd:cd05758     1 GPPIITAEATQPAILGEKARLECLVFSSPPPDRIVWSWDEGFLESGSSGRFSVETFPTEPGVI-SVLHISGTQRSDFQtS 79

                          90
                  ....*....|....*....
gi 2178167339 522 YKCNVSNDYGSDTLEIVLR 540
Cdd:cd05758    80 FNCSAWNRFGEGTAIVSLG 98

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2178167339  455 GSQGDTVNIECAAFSIPRiDTIIWTYEDKEIDTVHDHDYLFREDLqaggivNSTLTIRESQSRHFGVYKCNVSNDYGSDT 534
Cdd:smart00410   6 VKEGESVTLSCEASGSPP-PEVTWYKQGGKLLAESGRFSVSRSGS------TSTLTISNVTPEDSGTYTCAATNSSGSAS 78

                   ....*.
gi 2178167339  535 LEIVLR 540
Cdd:smart00410  79 SGTTLT 84

Immunoglobulin (Ig)-like domain found in neuregulin (NRG)-1; The members here are composed of the immunoglobulin (Ig)-like domain found in neuregulin (NRG)-1. There are many NRG-1 isoforms which arise from the alternative splicing of mRNA. NRG-1 belongs to the neuregulin gene family which is comprised of four genes. This group represents NRG-1. NRGs are signaling molecules which participate in cell-cell interactions in the nervous system, breast, and heart, and other organ systems, and are implicated in the pathology of diseases including schizophrenia, multiple sclerosis, and breast cancer. The NRG-1 protein binds to and activates the tyrosine kinases receptors ErbB3 and ErbB4, initiating signaling cascades. NRG-1 has multiple functions, for example, in the brain it regulates various processes such as radial glia formation and neuronal migration, dendritic development, and expression of neurotransmitters receptors in the peripheral nervous system NRG-1 regulates processes such as target cell differentiation, and Schwann cell survival.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2178167339 274 PKVKiRIKSgRRIPEGQDVVISCTADANPGNLTFRWVMNESIIG--------------NSSELKITNISRAYNGAvLKCM 339
Cdd:cd05895     1 PKLK-EMKS-QEVAAGSKLVLRCETSSEYPSLRFKWFKNGKEINrknkpenikiqkkkKKSELRINKASLADSGE-YMCK 77

                  ....*.
gi 2178167339 340 VFNEVG 345
Cdd:cd05895    78 VSSKLG 83

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2178167339 190 LECVSVGGKPPAEITWVDSnaGVLTQGVTTTVEPLSDGQRFTTRSIIRMAPKQEHNNQTFTCQAQNTADRAYRAASILIE 269
Cdd:cd05759    20 LTCRARGAKPAAEIIWFRD--GEQLEGAVYSKELLKDGKRETTVSTLLITPSDLDTGRTFTCRARNEAIPNGKETSITLD 97

                  .
gi 2178167339 270 V 270
Cdd:cd05759    98 V 98

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 2178167339 358 PPSFRSYPKDVEAEVGKQVTLSCDVDGFPAPEIRWLH-----YEEDTNIRVGRTPNLTLT---VDTHTSGRYLCKAS 426
Cdd:pfam13927   1 KPVITVSPSSVTVREGETVTLTCEATGSPPPTITWYKngepiSSGSTRSRSLSGSNSTLTisnVTRSDAGTYTCVAS 77

Second immunoglobulin (Ig) domain of Nectin-2 and Nectin-like protein 5, and similar domains; member of the C1-set of the Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig) domain of nectin-2 (also known as poliovirus receptor related protein 2 or Cluster of Differentiation 112 (CD112)), nectin-like protein 5 (CD155), and similar proteins. Nectins and Nectin-like molecules are a family of Ca(2+)-independent immunoglobulin-like transmembrane glycoproteins belonging to the class of adhesion receptors, consisting of nine members (nectins 1 through 4 and nectin-like proteins 1 through 5). Nectins are synaptic cell adhesion molecules (CAMs) which facilitate adhesion and signaling at various intracellular junctions. Nectins form homophilic cis-dimers, followed by homophilic and heterophilic trans-dimers involved in cell-cell adhesion. Nectin-2 and nectin-3 localize at Sertoli-spermatid junctions where they form heterophilic trans-interactions between the cells that are essential for the formation and maintenance of the junctions and for spermatid development. CD155 is the fifth member in the nectin-like molecule family, and functions as the receptor of poliovirus; therefore, CD155 is also referred to as Necl-5, or PVR. In contrast to all other family members, CD155 lacks self-adhesion capacity, yet it shares with nectins the feature to interact with other nectins. For instance, CD155 heterophilically trans-interacts with nectin-3, thereby contributing significantly to the establishment of adherens junctions between epithelial cells. This group belongs to the Constant 1 (C1)-set of IgSF domains, which has one beta-sheet that is formed by strands A-B-E-D and the other strands by G-F-C-C'.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 2178167339 192 CVSVGGKPPAEITWVDSnagvLTQGVTTTVEPLSDGQRFTTRSIIRMAPKQEHNNQTFTC 251
Cdd:cd07703    22 CVSANGRPPARISWSST----LNGNANTTQVPGPDSGTVTVTSEYSLVPTPEANGKEVTC 77

Immunoglobulin I-set domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2178167339 359 PSFRSYPKDVEAEVGKQVTLSCDVDGFPAPEIRWLHYEEDTN----IRVGRTPNL-TLT---VDTHTSGRYLCKASVEgY 430
Cdd:pfam07679   1 PKFTQKPKDVEVQEGESARFTCTVTGTPDPEVSWFKDGQPLRssdrFKVTYEGGTyTLTisnVQPDDSGKYTCVATNS-A 79

                          90
                  ....*....|.
gi 2178167339 431 PEIETEASIFI 441
Cdd:pfam07679  80 GEAEASAELTV 90

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2178167339 443 GPPKIISNHTQFGSQGDTVNIECAAFSIPRIDTIIWTYEDKEIDTVHDHDYLFREDLQAGGIVnSTLTIRESQSRHFG-V 521
Cdd:cd05758     1 GPPIITAEATQPAILGEKARLECLVFSSPPPDRIVWSWDEGFLESGSSGRFSVETFPTEPGVI-SVLHISGTQRSDFQtS 79

                          90
                  ....*....|....*....
gi 2178167339 522 YKCNVSNDYGSDTLEIVLR 540
Cdd:cd05758    80 FNCSAWNRFGEGTAIVSLG 98

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2178167339  67 FAMEPQDQTAVVGSRVTLPCRVE-NKAGQLQWTKDdfglGLHRELSGYDRYKMIgsdeeGDYSLDIREVT-----LDDDA 140
Cdd:cd05722     4 FLSEPSDIVAMRGGPVVLNCSAEsDPPPKIEWKKD----GVLLNLVSDERRQQL-----PNGSLLITSVVhskhnKPDEG 74

                          90       100
                  ....*....|....*....|....*
gi 2178167339 141 KYQCQVSSGSRGepAIRSRYARLTV 165
Cdd:cd05722    75 FYQCVAQNESLG--SIVSRTARVTV 97

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2178167339 359 PSFRSYP-KDVEAEVGKQVTLSCDVDGFPAPEIRWLHyeedtNIRVGRTPNLTLTVDTHT----------SGRYLCKASV 427
Cdd:cd20978     1 PKFIQKPeKNVVVKGGQDVTLPCQVTGVPQPKITWLH-----NGKPLQGPMERATVEDGTltiinvqpedTGYYGCVATN 75

                          90
                  ....*....|..
gi 2178167339 428 EgYPEIETEASI 439
Cdd:cd20978    76 E-IGDIYTETLL 86

Immunoglobulin I-set domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2178167339 458 GDTVNIECAAFSIPRIdTIIWTYEDKEIDTVHDHDYLFREDlqaggivNSTLTIRESQSRHFGVYKCNVSNDYGSDTLEI 537
Cdd:pfam07679  15 GESARFTCTVTGTPDP-EVSWFKDGQPLRSSDRFKVTYEGG-------TYTLTISNVQPDDSGKYTCVATNSAGEAEASA 86

                  ..
gi 2178167339 538 VL 539
Cdd:pfam07679  87 EL 88

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2178167339  455 GSQGDTVNIECAAFSIPRiDTIIWTYEDKEIDTVHDHDYLFREDLqaggivNSTLTIRESQSRHFGVYKCNVSNDYGSDT 534
Cdd:smart00410   6 VKEGESVTLSCEASGSPP-PEVTWYKQGGKLLAESGRFSVSRSGS------TSTLTISNVTPEDSGTYTCAATNSSGSAS 78

                   ....*.
gi 2178167339  535 LEIVLR 540
Cdd:smart00410  79 SGTTLT 84

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2178167339 358 PPSFRSYPKDVEAEVGKQVTLSCDVDGFPAPEIRW-------------LHYEEDTNIrvgrTPNLTLTVDtHTS----GR 420
Cdd:cd20954     1 PPRWIVEPVDANVAAGQDVMLHCQADGFPTPTVTWkkatgstpgeykdLLYDPNVRI----LPNGTLVFG-HVQkeneGH 75

                  ....*.
gi 2178167339 421 YLCKAS 426
Cdd:cd20954    76 YLCEAK 81

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 2178167339  70 EPQDQTAVVGSRVTLPCRVE-NKAGQLQWTKDDfglglHRELSGYDRYKMIGSDEegdYSLDIREVTLDDDAKYQCQVS 147
Cdd:pfam13927   7 SPSSVTVREGETVTLTCEATgSPPPTITWYKNG-----EPISSGSTRSRSLSGSN---STLTISNVTRSDAGTYTCVAS 77

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'.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2178167339 162 RLTVLVPPEPPKilqgnfystpEDRIIKLECVSVGGKPP-AEITWVDSNAGVLTQGVTTTVEPLSDGqRFTTRSIIRMAP 240
Cdd:cd00098     1 TVTLLPPSPEEK----------GGGKVTLVCLVSGFYPKdITVTWLKNGVPLTSGVSTSSPVEPNDG-TYSVTSSLTVPP 69

                          90
                  ....*....|....*..
gi 2178167339 241 KQEHNNQTFTCQAQNTA 257
Cdd:cd00098    70 SDWDEGATYTCVVTHES 86

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2178167339 358 PPSFRSYPKDVEA--EVGKQVTLSCDVDGFPAPEIRW------LHYEEDTNIRVGRTPNLT-LTVDTHTSGRYLCKASVE 428
Cdd:cd05730     1 PPTIRARQSEVNAtaNLGQSVTLACDADGFPEPTMTWtkdgepIESGEEKYSFNEDGSEMTiLDVDKLDEAEYTCIAENK 80

                          90
                  ....*....|....
gi 2178167339 429 GYpeiETEASIFIK 442
Cdd:cd05730    81 AG---EQEAEIHLK 91

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

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 2178167339  70 EPQDQTAVVGSRVTLPCRVE-NKAGQLQWTKDDFGLGLhrelsgyDRYKMIgsdeeGDYSLDIREVTLDDDAKYQCQ 145
Cdd:cd05725     3 RPQNQVVLVDDSAEFQCEVGgDPVPTVRWRKEDGELPK-------GRYEIL-----DDHSLKIRKVTAGDMGSYTCV 67

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 2178167339 376 VTLSCDVDGFPAPEIRWLH-----YEEDTNIRVGRTPNLTLTVDTHT---SGRYLCKAS 426
Cdd:cd00096     1 VTLTCSASGNPPPTITWYKngkplPPSSRDSRRSELGNGTLTISNVTledSGTYTCVAS 59

Immunoglobulin (Ig)-like domain found in neuregulin (NRG)-1; The members here are composed of the immunoglobulin (Ig)-like domain found in neuregulin (NRG)-1. There are many NRG-1 isoforms which arise from the alternative splicing of mRNA. NRG-1 belongs to the neuregulin gene family which is comprised of four genes. This group represents NRG-1. NRGs are signaling molecules which participate in cell-cell interactions in the nervous system, breast, and heart, and other organ systems, and are implicated in the pathology of diseases including schizophrenia, multiple sclerosis, and breast cancer. The NRG-1 protein binds to and activates the tyrosine kinases receptors ErbB3 and ErbB4, initiating signaling cascades. NRG-1 has multiple functions, for example, in the brain it regulates various processes such as radial glia formation and neuronal migration, dendritic development, and expression of neurotransmitters receptors in the peripheral nervous system NRG-1 regulates processes such as target cell differentiation, and Schwann cell survival.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2178167339 274 PKVKiRIKSgRRIPEGQDVVISCTADANPGNLTFRWVMNESIIG--------------NSSELKITNISRAYNGAvLKCM 339
Cdd:cd05895     1 PKLK-EMKS-QEVAAGSKLVLRCETSSEYPSLRFKWFKNGKEINrknkpenikiqkkkKKSELRINKASLADSGE-YMCK 77

                  ....*.
gi 2178167339 340 VFNEVG 345
Cdd:cd05895    78 VSSKLG 83

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

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2178167339 458 GDTVNIECAAFSIPRiDTIIWTYEDKEIDTVhDHDYLFREDlqaggivNSTLTIRESQSRHFGVYKCNVSND-YGSDTLE 536
Cdd:cd20970    17 GENATFMCRAEGSPE-PEISWTRNGNLIIEF-NTRYIVREN-------GTTLTIRNIRRSDMGIYLCIASNGvPGSVEKR 87

                  ...
gi 2178167339 537 IVL 539
Cdd:cd20970    88 ITL 90

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 2178167339 363 SYPKDVEAEVGKQVTLSCDVDGFPAPEIRW------LHYEE---DTNIRV---GRTPNLTLTVDTHT-SGRYLCKAS 426
Cdd:cd05732     6 TYLENQTAVELEQITLTCEAEGDPIPEITWrratrgISFEEgdlDGRIVVrghARVSSLTLKDVQLTdAGRYDCEAS 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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2178167339  70 EPQDQTAVVGSRVTLPCR--VENKAGQLQWTKDDFGLGLHRElsgydRYKMIgsdeeGDYSLDIREVTLDDDAKYQCqVS 147
Cdd:cd05724     3 EPSDTQVAVGEMAVLECSppRGHPEPTVSWRKDGQPLNLDNE-----RVRIV-----DDGNLLIAEARKSDEGTYKC-VA 71

                          90
                  ....*....|....*...
gi 2178167339 148 SGSRGEPaiRSRYARLTV 165
Cdd:cd05724    72 TNMVGER--ESRAARLSV 87

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.

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                  ....*....|....*....|....*....|....*...
gi 2178167339 356 TYPPSFRSYPKDVEAEVGKQVTLSCDVDGFPAPEIRWL 393
Cdd:cd05747     1 TLPATILTKPRSLTVSEGESARFSCDVDGEPAPTVTWM 38

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2178167339 362 RSYPKDVEAEVGKQVTLSCDVD-GFPAPEIRWLH-----YEEDTNIRVGRTPNLTLT-VDTHTSGRYLCKAS 426
Cdd:cd05724     1 RVEPSDTQVAVGEMAVLECSPPrGHPEPTVSWRKdgqplNLDNERVRIVDDGNLLIAeARKSDEGTYKCVAT 72

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.

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                  ....*....|....*....|....*....|....*....|
gi 2178167339 358 PPSFRSYPKDVEAEVGKQVTLSCDVDGFPAPEIRWLHYEE 397
Cdd:cd05851     1 PADINVKFKDTYALKGQNVTLECFALGNPVPVIRWRKILE 40

Immunoglobulin Variable (V) domain of the Coxsackievirus and Adenovirus Receptor (CAR), and similar proteins; The members here are composed of the Variable (V) domain of the Coxsackievirus and Adenovirus Receptor (CAR), and similar proteins. CAR, which is encoded by human CXADR gene, is a cell adhesion molecule of the Immunoglobulin (Ig) superfamily. The CAR acts as a type I membrane receptor for group B1-B6 coxsackie viruses and subgroup C adenoviruses. For instance, adenovirus interacts with the coxsackievirus and adenovirus receptor to enter epithelial airway cells. The CAR is also shown to be involved in physiological processes such as neuronal and heart development, epithelial tight junction integrity, and tumor suppression. The CAR is a component of the epithelial apical junction complex that may function as a homophilic cell adhesion molecule and is essential for tight junction integrity. The CAR is also involved in transepithelial migration of leukocytes through adhesive interactions with JAML a transmembrane protein of the plasma membrane of leukocytes. The interaction between both receptors also mediates the activation of gamma-delta T-cells, a subpopulation of T-cells residing in epithelia and involved in tissue homeostasis and repair. The CAR is composed of one V-set and one C2-set Ig module, a single transmembrane helix, and an intracellular domain. This group belongs to the V-set of IgSF domains, having A, B, E and D strands in one beta-sheet and A', G, F, C, C' and C" in the other

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2178167339  77 VVGSRVTLPCRVE---NKAGQL--QW--TKDDFGL-------------GLHRELSGydRYKMIGSDEEGDYSLDIREVTL 136
Cdd:cd20960    13 VAGENVTLPCHHQlglEDQGTLdiEWllLPSDKVEkvvitysgdrvynHYYPALKG--RVAFTSNDLSGDASLNISNLKL 90

                          90       100
                  ....*....|....*....|....*...
gi 2178167339 137 DDDAKYQCQVSSGsrgePAIRSRYARLT 164
Cdd:cd20960    91 SDTGTYQCKVKKA----PGYAWSKITLI 114