Immunoglobulin domain; This domain contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24650621   442 EGQNVTFKCRADARPPVtSYSWFKNGMRMSgeSTEIMHLTQLERESAGAYACGATNTEGETRSSSLTLKV 511
Cdd:pfam13895  13 EGEPVTLTCSAPGNPPP-SYTWYKDGSAIS--SSPNFFTLSVSAEDSGTYTCVARNGRGGKVSNPVELTV 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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24650621 211 VPPEEPrifdaqgkEISQMAGPFREGYELFLCCQVRGGRPPPKVTWWRDDTELIGTShtSVEE---GATVMVNQLLIGTT 287
Cdd:cd05761   2 GVPEKP--------VITGFTSPVVEGDEITLTCTTSGSKPAADIRWFKNDKELKGVK--EVQEsgaGKTFTVTSTLRFRV 71

                        90
                ....*....|....
gi 24650621 288 TRDFYGIRIECRAQ 301
Cdd:cd05761  72 DRDDDGVAVICRVD 85

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24650621   442 EGQNVTFKCRADARPPVtSYSWFKNGMRMSgeSTEIMHLTQLERESAGAYACGATNTEGETRSSSLTLKV 511
Cdd:pfam13895  13 EGEPVTLTCSAPGNPPP-SYTWYKDGSAIS--SSPNFFTLSVSAEDSGTYTCVARNGRGGKVSNPVELTV 79

Third immunoglobulin domain in Cluster of Differentiation (CD) 22; member of the Constant 2 (C2)-set of IgSF domains; The members here are composed of the third immunoglobulin domain in Cluster of Differentiation (CD) 22 (also known as Siglec-2). CD22, a sialic-acid binding immunoglobulin type-lectin (Siglec) family member, is an inhibitory co-receptor of the B-cell receptor (BCR). The inhibitory function of CD22 and its restricted expression on B cells makes CD22 an attractive target against dysregulated B cells that cause autoimmune diseases and B-cell-derived cancers. CD22 plays a vital role in establishing a baseline level of B-cell inhibition, and thus is an important determinant of homeostasis in humoral immunity. Siglecs are primarily expressed on immune cells and recognize sialic acid-containing glycan ligands. Siglecs are organized as an extracellular module composed of Ig-like domains (an N-terminal variable set of Ig-like carbohydrate recognition domains, and 1 to 16 constant Ig-like domains), followed by transmembrane and short cytoplasmic domains. Human Siglecs are classified into two subgroups, one subgroup is comprised of sialoadhesin (Siglec-1), CD22 (Siglec-2), and MAG (Siglec-4, myelin-associated glycoprotein), the other subgroup is comprised of CD33-related Siglecs which include CD33 (Siglec-3) and human Siglecs 5-11. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. This group belongs to the C2-set of IgSF domains, having A, B, and E strands in one beta-sheet and A', G, F, C' in the other. Unlike other Ig domain sets, the C2-set lacks the D strand.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24650621 434 PSRLVTRaEGQNVTFKCR-ADARPPVTSYSWFKNGMRMSGESTEIMHLTQLERESAGAYACGATNTEGETRSSSLTLKVQ 512
Cdd:cd20937   9 PSDAIVR-EGDSVTMTCEvSSSNPEYTTVSWLKDGTSLKKQNTFTLNLREVTKDQSGKYCCQVSNDVGPGRSEEVFLQVQ 87

                .
gi 24650621 513 F 513
Cdd:cd20937  88 Y 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 24650621    435 SRLVTRAEGQNVTFKCRADARPPVTsYSWFKNGMRMSGESTEI----------MHLTQLERESAGAYACGATNTEGETrS 504
Cdd:smart00410   1 PPSVTVKEGESVTLSCEASGSPPPE-VTWYKQGGKLLAESGRFsvsrsgststLTISNVTPEDSGTYTCAATNSSGSA-S 78

                   ....*..
gi 24650621    505 SSLTLKV 511
Cdd:smart00410  79 SGTTLTV 85

CD80-like C2-set immunoglobulin domain; These domains belong to the immunoglobulin superfamily.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 24650621   235 EGYELFLCCQVRGGRPPPKVTWWRDDTELIG--TSHTSVEEGATVMVNQLLIGTTTRDFYGIRIECRAQ 301
Cdd:pfam08205  13 EGPEVVATCSSAGGKPAPRITWYLDGKPLEAaeTSSEQDPESGLVTVTSELKLVPSRSDHGQSLTCQVS 81

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24650621    100 VWAALGKTVELPCdltpPTSQDSVKLLLWFKDTTGIPLYSLDsrggnvklaphaaiasdlgqrlfFSIGDNPKDSRLQIN 179
Cdd:smart00410   4 VTVKEGESVTLSC----EASGSPPPEVTWYKQGGKLLAESGR-----------------------FSVSRSGSTSTLTIS 56

                           90       100       110
                   ....*....|....*....|....*....|..
gi 24650621    180 DVKPEDGGVYRCRVdffNSPTRNFRHNLTLVV 211
Cdd:smart00410  57 NVTPEDSGTYTCAA---TNSSGSASSGTTLTV 85

Fibronectin type III domain;

                          10        20        30
                  ....*....|....*....|....*....|..
gi 24650621   699 ENSPQFRLNNLEPGREYQFLVYAVNAKGRSEP 730
Cdd:pfam00041  53 GTTTSVTLTGLKPGTEYEVRVQAVNGGGEGPP 84

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24650621    329 PNELLTAGQPMPIRCESWGSyPAAKITWLLDG--EPIRNAEVTVHSDKedgniTTSILTLKVTSENDNAELTCRATNPWF 406
Cdd:smart00410   2 PSVTVKEGESVTLSCEASGS-PPPEVTWYKQGgkLLAESGRFSVSRSG-----STSTLTISNVTPEDSGTYTCAATNSSG 75

                   .
gi 24650621    407 S 407
Cdd:smart00410  76 S 76

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24650621   442 EGQNVTFKCRADARPPVtSYSWFKNGMRMSgeSTEIMHLTQLERESAGAYACGATNTEGETRSSSLTLKV 511
Cdd:pfam13895  13 EGEPVTLTCSAPGNPPP-SYTWYKDGSAIS--SSPNFFTLSVSAEDSGTYTCVARNGRGGKVSNPVELTV 79

Third immunoglobulin domain in Cluster of Differentiation (CD) 22; member of the Constant 2 (C2)-set of IgSF domains; The members here are composed of the third immunoglobulin domain in Cluster of Differentiation (CD) 22 (also known as Siglec-2). CD22, a sialic-acid binding immunoglobulin type-lectin (Siglec) family member, is an inhibitory co-receptor of the B-cell receptor (BCR). The inhibitory function of CD22 and its restricted expression on B cells makes CD22 an attractive target against dysregulated B cells that cause autoimmune diseases and B-cell-derived cancers. CD22 plays a vital role in establishing a baseline level of B-cell inhibition, and thus is an important determinant of homeostasis in humoral immunity. Siglecs are primarily expressed on immune cells and recognize sialic acid-containing glycan ligands. Siglecs are organized as an extracellular module composed of Ig-like domains (an N-terminal variable set of Ig-like carbohydrate recognition domains, and 1 to 16 constant Ig-like domains), followed by transmembrane and short cytoplasmic domains. Human Siglecs are classified into two subgroups, one subgroup is comprised of sialoadhesin (Siglec-1), CD22 (Siglec-2), and MAG (Siglec-4, myelin-associated glycoprotein), the other subgroup is comprised of CD33-related Siglecs which include CD33 (Siglec-3) and human Siglecs 5-11. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. This group belongs to the C2-set of IgSF domains, having A, B, and E strands in one beta-sheet and A', G, F, C' in the other. Unlike other Ig domain sets, the C2-set lacks the D strand.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24650621 434 PSRLVTRaEGQNVTFKCR-ADARPPVTSYSWFKNGMRMSGESTEIMHLTQLERESAGAYACGATNTEGETRSSSLTLKVQ 512
Cdd:cd20937   9 PSDAIVR-EGDSVTMTCEvSSSNPEYTTVSWLKDGTSLKKQNTFTLNLREVTKDQSGKYCCQVSNDVGPGRSEEVFLQVQ 87

                .
gi 24650621 513 F 513
Cdd:cd20937  88 Y 88

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24650621   422 PPTVSVhlanedPSRLVTRAEGQNVTFKCRADARPPVTsYSWFKNGMRMSGESTEIM---------HLTQLERESAGAYA 492
Cdd:pfam13927   1 KPVITV------SPSSVTVREGETVTLTCEATGSPPPT-ITWYKNGEPISSGSTRSRslsgsnstlTISNVTRSDAGTYT 73

                  ....*
gi 24650621   493 CGATN 497
Cdd:pfam13927  74 CVASN 78

Second immunoglobulin (Ig)-like domain of the nectin-like molecules Necl-1 - Necl-4; member of the I-set of Ig superfamily domains; The members here are composed of the second immunoglobulin (Ig)-like domain of the nectin-like molecules Necl-1 (also known as cell adhesion molecule 3 or CADM3), Necl-2 (also known as CADM1), Necl-3 (also known as CADM2) and Necl-4 (also known as CADM4). These nectin-like molecules have similar domain structures to those of nectins. At least five nectin-like molecules have been identified (Necl-1 through Necl-5). These have an extracellular region containing three Ig-like domains, one transmembrane region, and one cytoplasmic region. The N-terminal Ig-like domain of the extracellular region belongs to the V-type subfamily of Ig domains, is essential to cell-cell adhesion, and plays a part in the interaction with the envelope glycoprotein D of various viruses. Necl-1 and Necl-2 have Ca(2+)-independent homophilic and heterophilic cell-cell adhesion activity. Necl-1 is specifically expressed in neural tissue and is important to the formation of synapses, axon bundles, and myelinated axons. Necl-2 is expressed in a wide variety of tissues, and is a putative tumour suppressor gene, which is downregulated in aggressive neuroblastoma. Necl-3 has been shown to accumulate in tissues of the central and peripheral nervous system, where it is expressed in ependymal cells and myelinated axons. It is observed at the interface between the axon shaft and the myelin sheath. Necl-4 is expressed on Schwann cells, and plays a key part in initiating peripheral nervous system (PNS) myelination. Necl-4 participates in cell-cell adhesion and is proposed to play a role in tumor suppression.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24650621 211 VPPEEPrifdaqgkEISQMAGPFREGYELFLCCQVRGGRPPPKVTWWRDDTELIGTShtSVEE---GATVMVNQLLIGTT 287
Cdd:cd05761   2 GVPEKP--------VITGFTSPVVEGDEITLTCTTSGSKPAADIRWFKNDKELKGVK--EVQEsgaGKTFTVTSTLRFRV 71

                        90
                ....*....|....
gi 24650621 288 TRDFYGIRIECRAQ 301
Cdd:cd05761  72 DRDDDGVAVICRVD 85

Second immunoglobulin (Ig)-like domain of the nectin-like molecules Necl-1 - Necl-4; member of the I-set of Ig superfamily domains; The members here are composed of the second immunoglobulin (Ig)-like domain of the nectin-like molecules Necl-1 (also known as cell adhesion molecule 3 or CADM3), Necl-2 (also known as CADM1), Necl-3 (also known as CADM2) and Necl-4 (also known as CADM4). These nectin-like molecules have similar domain structures to those of nectins. At least five nectin-like molecules have been identified (Necl-1 through Necl-5). These have an extracellular region containing three Ig-like domains, one transmembrane region, and one cytoplasmic region. The N-terminal Ig-like domain of the extracellular region belongs to the V-type subfamily of Ig domains, is essential to cell-cell adhesion, and plays a part in the interaction with the envelope glycoprotein D of various viruses. Necl-1 and Necl-2 have Ca(2+)-independent homophilic and heterophilic cell-cell adhesion activity. Necl-1 is specifically expressed in neural tissue and is important to the formation of synapses, axon bundles, and myelinated axons. Necl-2 is expressed in a wide variety of tissues, and is a putative tumour suppressor gene, which is downregulated in aggressive neuroblastoma. Necl-3 has been shown to accumulate in tissues of the central and peripheral nervous system, where it is expressed in ependymal cells and myelinated axons. It is observed at the interface between the axon shaft and the myelin sheath. Necl-4 is expressed on Schwann cells, and plays a key part in initiating peripheral nervous system (PNS) myelination. Necl-4 participates in cell-cell adhesion and is proposed to play a role in tumor suppression.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24650621 336 GQPMPIRCESWGSYPAAKITWLLDGEPIRNAEVTVHSDKEDGNITTSILTLKVTSENDNAELTCRATNPWFSGGAIEDKR 415
Cdd:cd05761  19 GDEITLTCTTSGSKPAADIRWFKNDKELKGVKEVQESGAGKTFTVTSTLRFRVDRDDDGVAVICRVDHESLTSTPKQTQQ 98

                ....
gi 24650621 416 IIRV 419
Cdd:cd05761  99 VLEV 102

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 24650621 434 PSRLVTRAEGQNVTFKCRAdARPPVTSYSWFKNGMRMSGEStEIMHLTQ-------LERESAGAYACGATNTEGETRSSS 506
Cdd:cd20978   7 PEKNVVVKGGQDVTLPCQV-TGVPQPKITWLHNGKPLQGPM-ERATVEDgtltiinVQPEDTGYYGCVATNEIGDIYTET 84

                ..
gi 24650621 507 LT 508
Cdd:cd20978  85 LL 86

Immunoglobulin I-set domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24650621   434 PSRLVTRAEGQNVTFKCRADARPPvTSYSWFKNG----------MRMSGESTEiMHLTQLERESAGAYACGATNTEGEtR 503
Cdd:pfam07679   6 KPKDVEVQEGESARFTCTVTGTPD-PEVSWFKDGqplrssdrfkVTYEGGTYT-LTISNVQPDDSGKYTCVATNSAGE-A 82

                  ....*...
gi 24650621   504 SSSLTLKV 511
Cdd:pfam07679  83 EASAELTV 90

Second immunoglobulin (Ig)-like domain of nectin-like molcule-1 (Necl-1); member of the I-set of Ig superfamily domains; The members here are composed of the second immunoglobulin (Ig)-like domain of nectin-like molcule-1 (Necl-1; also known as cell adhesion molecule3 (CADM3)). These nectin-like molecules have similar domain structures to those of nectins. At least five nectin-like molecules have been identified (Necl-1 through Necl-5). These have an extracellular region containing three Ig-like domains, one transmembrane region, and one cytoplasmic region. The N-terminal Ig-like domain of the extracellular region belongs to the V-type subfamily of Ig domains is essential to cell-cell adhesion and plays a part in the interaction with the envelope glycoprotein D of various viruses. Necl-1 and Necl-2 have Ca(2+)-independent homophilic and heterophilic cell-cell adhesion activity. Necl-1 is specifically expressed in neural tissue and is important to the formation of synapses, axon bundles, and myelinated axons. Necl-2 is expressed in a wide variety of tissues and is a putative tumour suppressor gene which is downregulated in aggressive neuroblastoma. Ig domains are likely to participate in ligand binding and recognition.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 24650621 341 IRCESWGSYPAAKITWLLDGEPIRNAEVTVhsdKEDGNITT----SILTLKVTSENDNAELTC 399
Cdd:cd07705  24 LRCTSSGSKPAANIKWRKGDQELEGAPTSV---QEDGNGKTftvsSSVEFQVTREDDGAEITC 83

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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24650621  98 RLVWAALGKTVELPCDLTPPTSQDSvklLLWFKDTTGIP---LYSLDSRGGNVKlaphaaiasDLGQRLFFSIGDNPKDS 174
Cdd:cd00099   6 RSLSVQEGESVTLSCEVSSSFSSTY---IYWYRQKPGQGpefLIYLSSSKGKTK---------GGVPGRFSGSRDGTSSF 73

                        90
                ....*....|....*..
gi 24650621 175 RLQINDVKPEDGGVYRC 191
Cdd:cd00099  74 SLTISNLQPEDSGTYYC 90

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.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 24650621 437 LVTRAEGQNVTFKCRADARPPvTSYSWFKNGMRMSgeSTEIMHLTQLERESAGAYACGATNTeGETRSSSLTLKVQ 512
Cdd:cd20948   4 DTYYLSGENLNLSCHAASNPP-AQYSWTINGTFQT--SSQELFLPAITENNEGTYTCSAHNS-LTGKNISLVLSVT 75

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.

                        10        20        30
                ....*....|....*....|....*....|....*.
gi 24650621 700 NSPQFRLNNLEPGREYQFLVYAVNAKGRSEPPVVIE 735
Cdd:cd00063  55 SETSYTLTGLKPGTEYEFRVRAVNGGGESPPSESVT 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.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 24650621 446 VTFKCRADARPPVTsYSWFKNGMRMSGESTEIM---------HLTQLERESAGAYACGATNTEGETRSSSL 507
Cdd:cd00096   1 VTLTCSASGNPPPT-ITWYKNGKPLPPSSRDSRrselgngtlTISNVTLEDSGTYTCVASNSAGGSASASV 70

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        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 24650621 327 ATPNELLTAGQPMPI-RCESWGSYPAAKITWL--LDGepirNAEVTVHSDKEDGNIT-TSILTLKVTSENDNAELTC 399
Cdd:cd07703   5 AEAQEVQAGGIPVPVaRCVSANGRPPARISWSstLNG----NANTTQVPGPDSGTVTvTSEYSLVPTPEANGKEVTC 77

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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24650621 441 AEGQnVTFKCRADARPPvTSYSWFKNGMRMSGESTEIMHLTQ--------LERESAGAYACGATNTEGETRSSSLTLKVQ 512
Cdd:cd04967  18 DEKK-VALNCRARANPV-PSYRWLMNGTEIDLESDYRYSLVDgtlvisnpSKAKDAGHYQCLATNTVGSVLSREATLQFG 95

                .
gi 24650621 513 F 513
Cdd:cd04967  96 Y 96

Second immunoglobulin (Ig)-like domain of nectin-like molecule 2 (Necl-2); member of the I-set of Ig superfamily domains; The members here are composed of the second immunoglobulin (Ig)-like domain of nectin-like molecule 2 (Necl-2; also known as cell adhesion molecule 1 (CADM1)). Nectin-like molecules (Necls) have similar domain structures to those of nectins. At least five nectin-like molecules have been identified (Necl-1 through Necl-5). These have an extracellular region containing three Ig-like domains, one transmembrane region, and one cytoplasmic region. Necl-2 has Ca(2+)-independent homophilic and heterophilic cell-cell adhesion activity. Necl-1 is expressed in a wide variety of tissues and is a putative tumour suppressor gene which is downregulated in aggressive neuroblastoma. Ig domains are likely to participate in ligand binding and recognition.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24650621 210 VVPPEEPrIFDAQgKEIsqmagpFREGYELFLCCQVRGGRPPPKVTWWRDDTELIGTShtSVEEGATVM--VNQLLIGTT 287
Cdd:cd05883   1 LVPPRNL-VIDIQ-KDT------AVEGEEIELNCTAMASKPAATIRWFKGNKELTGKS--EVEEWYSRMftVTSQLMLKV 70

                        90       100       110
                ....*....|....*....|....*....|....
gi 24650621 288 TRDFYGIRIECraqgtrLVD-PVRKDVTVQVYLK 320
Cdd:cd05883  71 TKEDDGVPVIC------LVDhPAVKDLQTQRYLE 98

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24650621   434 PSRLVTRAEGQNVTFKCRADARPPVTSYSWFKNGMRMSgESTEIMH-----------LTQLERESAGAYACGATNTEGET 502
Cdd:pfam00047   2 APPTVTVLEGDSATLTCSASTGSPGPDVTWSKEGGTLI-ESLKVKHdngrttqssllISNVTKEDAGTYTCVVNNPGGSA 80

                  ....
gi 24650621   503 RSSS 506
Cdd:pfam00047  81 TLST 84

First immunoglobulin variable (IgV) domain of nectin-2, nectin-like protein 5, and similar 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        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24650621 104 LGKTVELPCDLTPPTSQDSVKLLLWFKdttgiplysLDSRGGNVKLAPHAAIASDLGQRLFF---SIGDNPKDSRLQIND 180
Cdd:cd20989  13 LGGSVTLPCHLLPPNMVTHVSQVTWQR---------HDEHGSVAVFHPKQGPSFPESERLSFvaaRLGAELRNASLAMFG 83

                        90       100
                ....*....|....*....|.
gi 24650621 181 VKPEDGGVYRCRVDFFNSPTR 201
Cdd:cd20989  84 LRVEDEGNYTCEFATFPQGSR 104

Immunoglobulin V-Type;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24650621    107 TVELPCDLTPPTSQDSVklLLWFKDTTGIPL------YSLDSRGGNVKLAPHAAIASDLGQRLFFsigdnpkdsrLQIND 180
Cdd:smart00406   1 SVTLSCKFSGSTFSSYY--VSWVRQPPGKGLewlgyiGSNGSSYYQESYKGRFTISKDTSKNDVS----------LTISN 68

                           90
                   ....*....|.
gi 24650621    181 VKPEDGGVYRC 191
Cdd:smart00406  69 LRVEDTGTYYC 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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24650621 434 PSRLVTRAeGQNVTFKCRADARPPVTsYSWFKNGMRMSGESTEIMH-----LTQLERESAGAYACGATNTEGETrSSSLT 508
Cdd:cd05725   4 PQNQVVLV-DDSAEFQCEVGGDPVPT-VRWRKEDGELPKGRYEILDdhslkIRKVTAGDMGSYTCVAENMVGKI-EASAT 80

                ...
gi 24650621 509 LKV 511
Cdd:cd05725  81 LTV 83

Fibronectin type III domain;

                          10        20        30
                  ....*....|....*....|....*....|..
gi 24650621   699 ENSPQFRLNNLEPGREYQFLVYAVNAKGRSEP 730
Cdd:pfam00041  53 GTTTSVTLTGLKPGTEYEVRVQAVNGGGEGPP 84

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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24650621 439 TRAEGQNVTFKCRADARPPVTSYSWFKNG------------MRMSGESTEImHLTQLERESAGAYACGATNTEGETRSSS 506
Cdd:cd05750  10 TVQEGSKLVLKCEATSENPSPRYRWFKDGkelnrkrpknikIRNKKKNSEL-QINKAKLEDSGEYTCVVENILGKDTVTG 88

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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24650621 329 PNELLTAGQPMPIRCESWGSyPAAKITWLLDGEPI-RNAEVTVhSDK--EDG------NITtsiltlKVTSEnDNAELTC 399
Cdd:cd20956   9 SEQTLQPGPSVSLKCVASGN-PLPQITWTLDGFPIpESPRFRV-GDYvtSDGdvvsyvNIS------SVRVE-DGGEYTC 79

                        90       100
                ....*....|....*....|
gi 24650621 400 RATNpwfSGGAIEDKRIIRV 419
Cdd:cd20956  80 TATN---DVGSVSHSARINV 96

Second immunoglobulin (Ig)-like domain of nectin-like molecule-3 (Necl-3); member of the I-set of Ig superfamily domains; The members here are composed of the second immunoglobulin (Ig)-like domain of nectin-like molecule-3 (Necl-3; also known as cell adhesion molecule 2 (CADM2)). Nectin-like molecules have similar domain structures to those of nectins. At least five nectin-like molecules have been identified (Necl-1 through Necl-5). These have an extracellular region containing three Ig-like domains, one transmembrane region, and one cytoplasmic region. Necl-3 has been shown to accumulate in tissues of the central and peripheral nervous system where it is expressed in ependymal cells and myelinated axons. It is observed at the interface between the axon shaft and the myelin sheath. Ig domains are likely to participate in ligand binding and recognition.