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 24639446 428 GSPAIGSQRTQYGLVGDTARIECFASSVPRARHVSWTFNGQEISSESGHDYSILVDAVPGGVKSTLIIRDSQAYHYG-KY 506
Cdd:cd05758   1 GPPIITAEATQPAILGEKARLECLVFSSPPPDRIVWSWDEGFLESGSSGRFSVETFPTEPGVISVLHISGTQRSDFQtSF 80

                        90
                ....*....|....*...
gi 24639446 507 NCTVVNDYGNDVAEIQLQ 524
Cdd:cd05758  81 NCSAWNRFGEGTAIVSLG 98

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 24639446    29 RFAMEPQDQTAVVGARVTLPCRVI-NKQGTLQWTKDDfglgtsRDLSGFERYAMvgSDEEGDYSLDIYPVMLDDDARYQC 107
Cdd:pfam07679   2 KFTQKPKDVEVQEGESARFTCTVTgTPDPEVSWFKDG------QPLRSSDRFKV--TYEGGTYTLTISNVQPDDSGKYTC 73

                  ...
gi 24639446   108 QVS 110
Cdd:pfam07679  74 VAT 76

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24639446 428 GSPAIGSQRTQYGLVGDTARIECFASSVPRARHVSWTFNGQEISSESGHDYSILVDAVPGGVKSTLIIRDSQAYHYG-KY 506
Cdd:cd05758   1 GPPIITAEATQPAILGEKARLECLVFSSPPPDRIVWSWDEGFLESGSSGRFSVETFPTEPGVISVLHISGTQRSDFQtSF 80

                        90
                ....*....|....*...
gi 24639446 507 NCTVVNDYGNDVAEIQLQ 524
Cdd:cd05758  81 NCSAWNRFGEGTAIVSLG 98

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 24639446   346 PSFRQRPQSMEADVGSVVSLTCEVDSNPQPEIVWI---------QHPSDRVVGTSTNLTF-SVSNETAGRYYCKAN 411
Cdd:pfam13927   2 PVITVSPSSVTVREGETVTLTCEATGSPPPTITWYkngepissgSTRSRSLSGSNSTLTIsNVTRSDAGTYTCVAS 77

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 24639446   434 SQRTQYGLVGDTARIECFASSVPRARhVSWTFNGQEISSESGHDYSIlvdavpGGVKSTLIIRDSQAYHYGKYNCTVVN 512
Cdd:pfam13927   7 SPSSVTVREGETVTLTCEATGSPPPT-ITWYKNGEPISSGSTRSRSL------SGSNSTLTISNVTRSDAGTYTCVASN 78

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24639446    352 PQSMEADVGSVVSLTCEVDSNPQPEIVWIQ------HPSDRVVGTSTNLTFS-----VSNETAGRYYCKANvPGYAEISA 420
Cdd:smart00410   1 PPSVTVKEGESVTLSCEASGSPPPEVTWYKqggkllAESGRFSVSRSGSTSTltisnVTPEDSGTYTCAAT-NSSGSASS 79

                   ....*
gi 24639446    421 DAYVY 425
Cdd:smart00410  80 GTTLT 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 24639446     34 PQDQTAVVGARVTLPCRVI-NKQGTLQWTKDDFGLgtsrdLSGFERYAMVGSDeeGDYSLDIYPVMLDDDARYQCQVSPG 112
Cdd:smart00410   1 PPSVTVKEGESVTLSCEASgSPPPEVTWYKQGGKL-----LAESGRFSVSRSG--STSTLTISNVTPEDSGTYTCAATNS 73

                           90
                   ....*....|....*...
gi 24639446    113 pegqpaIRSTFAGLTVLV 130
Cdd:smart00410  74 ------SGSASSGTTLTV 85

Immunoglobulin I-set domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24639446   271 IVEHSQVRLECRADANPsDVRYRWFINDEPIIGGQK---------TEMVIRNVTRkfHDA-IVKCEVQNSVGKSEDSETL 340
Cdd:pfam07679  12 VQEGESARFTCTVTGTP-DPEVSWFKDGQPLRSSDRfkvtyeggtYTLTISNVQP--DDSgKYTCVATNSAGEAEASAEL 88

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 24639446 428 GSPAIGSQRTQYGLVGDTARIECFASSVPRARHVSWTFNGQEISSESGHDYSILVDAVPGGVKSTLIIRDSQAYHYG-KY 506
Cdd:cd05758   1 GPPIITAEATQPAILGEKARLECLVFSSPPPDRIVWSWDEGFLESGSSGRFSVETFPTEPGVISVLHISGTQRSDFQtSF 80

                        90
                ....*....|....*...
gi 24639446 507 NCTVVNDYGNDVAEIQLQ 524
Cdd:cd05758  81 NCSAWNRFGEGTAIVSLG 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 24639446    435 QRTQYGLVGDTARIECFASSVPRArHVSWTFNGQEISSESGHdYSILVDavpgGVKSTLIIRDSQAYHYGKYNCTVVNDY 514
Cdd:smart00410   1 PPSVTVKEGESVTLSCEASGSPPP-EVTWYKQGGKLLAESGR-FSVSRS----GSTSTLTISNVTPEDSGTYTCAATNSS 74

                           90
                   ....*....|
gi 24639446    515 GNDVAEIQLQ 524
Cdd:smart00410  75 GSASSGTTLT 84

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 24639446 134 APKITQGDVIYATEDRKVEIECVSVGGKPAAEITWI-DGlgnVLTDNIEYTVIPLPDQRRFTAKSVLRLTPKKEHHNTNF 212
Cdd:cd05759   1 DPVIEGGPVISLQAGVPYNLTCRARGAKPAAEIIWFrDG---EQLEGAVYSKELLKDGKRETTVSTLLITPSDLDTGRTF 77

                        90       100
                ....*....|....*....|.
gi 24639446 213 SCQAQNTADRTYRSAKIRVEV 233
Cdd:cd05759  78 TCRARNEAIPNGKETSITLDV 98

Immunoglobulin I-set domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24639446   346 PSFRQRPQSMEADVGSVVSLTCEVDSNPQPEIVWIQ-----HPSDRVV-----GTSTnLTFS-VSNETAGRYYCKA-NVP 413
Cdd:pfam07679   1 PKFTQKPKDVEVQEGESARFTCTVTGTPDPEVSWFKdgqplRSSDRFKvtyegGTYT-LTISnVQPDDSGKYTCVAtNSA 79

                  ....*..
gi 24639446   414 GYAEISA 420
Cdd:pfam07679  80 GEAEASA 86

Immunoglobulin I-set domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24639446    29 RFAMEPQDQTAVVGARVTLPCRVI-NKQGTLQWTKDDfglgtsRDLSGFERYAMvgSDEEGDYSLDIYPVMLDDDARYQC 107
Cdd:pfam07679   2 KFTQKPKDVEVQEGESARFTCTVTgTPDPEVSWFKDG------QPLRSSDRFKV--TYEGGTYTLTISNVQPDDSGKYTC 73

                  ...
gi 24639446   108 QVS 110
Cdd:pfam07679  74 VAT 76

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 24639446 155 CVSVGGKPAAEITWIDGLGNvltdNIEYTVIPLPDQRRFTAKSVLRLTPKKEHHNTNFSC 214
Cdd:cd07703  22 CVSANGRPPARISWSSTLNG----NANTTQVPGPDSGTVTVTSEYSLVPTPEANGKEVTC 77

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24639446     34 PQDQTAVVGARVTLPCRVI-NKQGTLQWTKDDFGLgtsrdLSGFERYAMVGSDeeGDYSLDIYPVMLDDDARYQCQVSPG 112
Cdd:smart00410   1 PPSVTVKEGESVTLSCEASgSPPPEVTWYKQGGKL-----LAESGRFSVSRSG--STSTLTISNVTPEDSGTYTCAATNS 73

                           90
                   ....*....|....*...
gi 24639446    113 pegqpaIRSTFAGLTVLV 130
Cdd:smart00410  74 ------SGSASSGTTLTV 85

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 24639446 129 LVPPEAPKI-TQGDViyATEDRKVEIECVSVGGKPAAEITWIDGlGNVLTdnIEYTVIPLPDqRRFTAKSVLRLTPKKEH 207
Cdd:cd05883   1 LVPPRNLVIdIQKDT--AVEGEEIELNCTAMASKPAATIRWFKG-NKELT--GKSEVEEWYS-RMFTVTSQLMLKVTKED 74

                        90
                ....*....|...
gi 24639446 208 HNTNFSCQAQNTA 220
Cdd:cd05883  75 DGVPVICLVDHPA 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.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 24639446 350 QRPQSMEADVGSVVSLTCEVDSNPQPEIVW------IQHPSDR--VVGTSTNLTF-SVSNETAGRYYCKAN--VPGYAE 417
Cdd:cd20970   7 QPSFTVTAREGENATFMCRAEGSPEPEISWtrngnlIIEFNTRyiVRENGTTLTIrNIRRSDMGIYLCIASngVPGSVE 85

Second immunoglobulin domain of Cluster of Differentiation (CD) 33 and related Siglecs; member of the C2-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig) domain of Cluster of Differentiation (CD) 33 (also known as sialic-acid binding immunoglobulin type-lectin 3 (Siglec-3)) and related Siglecs. CD33, a Siglec family member, is a well-known immunotherapeutic target in acute myeloid leukemia (AML). It is an inhibitory sialoadhesin expressed in human leukocytes of the myeloid lineage and some lymphoid subsets, including natural killer (NK) cells. 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. CD33 (Siglec-3) is the smallest Siglec member. It preferentially binds to alpha2-6- and alpha2-3-sialylated glycans and strongly binds to sialylated ligands on leukemic cell lines. 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. This group includes CD33-related Siglecs which belong to the C2-set of IgSF domains. Unlike the C1-set, the C2-set structures do not have a D strand.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24639446 148 DRKVEIECVSVGGKPA--AEITWidgLGNVLTDNIEYTViPLPDQRRFTAKSVLRLTPKKEHHNTNFSCQA--QNTADRT 223
Cdd:cd20987  12 GQEVTLTCSVPDNCPAlsPEFSW---LGAALTPLPPVLG-RLEEEGTTTHSSVLTFTPRPEDHGTNLTCQVkfPGATVTT 87

                ....*..
gi 24639446 224 YRSAKIR 230
Cdd:cd20987  88 ERTIQLN 94

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 24639446 129 LVPPEAPKITqGDVIYATEDRKVEIECVSVGGKPAAEITW------IDGLGNVLTDNIEYTviplpdqrrFTAKSVLRLT 202
Cdd:cd05761   1 LGVPEKPVIT-GFTSPVVEGDEITLTCTTSGSKPAADIRWfkndkeLKGVKEVQESGAGKT---------FTVTSTLRFR 70

                        90       100       110
                ....*....|....*....|....*....|..
gi 24639446 203 PKKEHHNTNFSCQAQNTA-DRTYRSAKIRVEV 233
Cdd:cd05761  71 VDRDDDGVAVICRVDHESlTSTPKQTQQVLEV 102

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24639446  40 VVGARVTLPCRV---INKQGTL--QW--TKDDFGLGTSRDLSG---FE--------RYAMVGSDEEGDYSLDIYPVMLDD 101
Cdd:cd20960  13 VAGENVTLPCHHqlgLEDQGTLdiEWllLPSDKVEKVVITYSGdrvYNhyypalkgRVAFTSNDLSGDASLNISNLKLSD 92

                        90
                ....*....|..
gi 24639446 102 DARYQCQVSPGP 113
Cdd:cd20960  93 TGTYQCKVKKAP 104

Immunoglobulin (Ig)-like domain of human cartilage link protein (LP), and similar domains; The members here are composed of the immunoglobulin (Ig)-like domain similar to that found in human cartilage link protein (LP; also called hyaluronan and proteoglycan link protein). In cartilage, chondroitin-keratan sulfate proteoglycan (CSPG), aggrecan, forms cartilage link protein stabilized aggregates with hyaluronan (HA). These aggregates contribute to the tissue's load bearing properties. Aggregates having other CSPGs substituting for aggrecan may contribute to the structural integrity of many different tissues. Members of the vertebrate HPLN (hyaluronan/HA and proteoglycan binding link) protein family are physically linked adjacent to CSPG genes.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24639446  34 PQDQTAVVGAR---VTLPCRVINKQGT-------LQWTK--DDFG--------LGT-SRDLSGFERYAMVGSDEEGDYSL 92
Cdd:cd05877   1 ETVQAKVFSHRggnVTLPCRYHYEPELsaprkirVKWTKleVDYAkeedvlvaIGTrHKSYGSYQGRVFLRRADDLDASL 80

                        90       100
                ....*....|....*....|..
gi 24639446  93 DIYPVMLDDDARYQCQVSPGPE 114
Cdd:cd05877  81 VITDLRLEDYGRYRCEVIDGLE 102

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 24639446 363 VSLTCEVDSNPQPEIVWI---------QHPSDRVVGTSTNLTFS-VSNETAGRYYCKANVPGYAEISADA 422
Cdd:cd00096   1 VTLTCSASGNPPPTITWYkngkplppsSRDSRRSELGNGTLTISnVTLEDSGTYTCVASNSAGGSASASV 70

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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24639446 443 GDTARIECFASSVPRARhVSWTFNGQEISSESGHdySILVDAvpGGVKStLIIRDSQAYHYGKYNCTVVNDYGNDVAEIQ 522
Cdd:cd05744  15 GRLCRFDCKVSGLPTPD-LFWQLNGKPVRPDSAH--KMLVRE--NGRHS-LIIEPVTKRDAGIYTCIARNRAGENSFNAE 88

                .
gi 24639446 523 L 523
Cdd:cd05744  89 L 89

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24639446    33 EPQDQTAVVGARVTLPC----RVINKQGTLQWTKDDFGLGTSRDLSGF----------ERYAMVGSDEEGDYSLDIYPVM 98
Cdd:pfam07686   2 TPREVTVALGGSVTLPCtyssSMSEASTSVYWYRQPPGKGPTFLIAYYsngseegvkkGRFSGRGDPSNGDGSLTIQNLT 81

                          90
                  ....*....|....*..
gi 24639446    99 LDDDARYQCQVSPGPEG 115
Cdd:pfam07686  82 LSDSGTYTCAVIPSGEG 98

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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24639446 348 FRQRPQSMEADVGSVVSLTCEVDSNPQPEIVW-------------IQHPSDRV-VGTSTNLTFS-VSNETAGRYYCKA-N 411
Cdd:cd05726   2 FVVKPRDQVVALGRTVTFQCETKGNPQPAIFWqkegsqnllfpyqPPQPSSRFsVSPTGDLTITnVQRSDVGYYICQAlN 81

                        90
                ....*....|....*..
gi 24639446 412 VPGyaEISADAYVYLKG 428
Cdd:cd05726  82 VAG--SILAKAQLEVTD 96

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24639446   135 PKIT-QGDVIYATEDRKVEIECvSVGGKPAAEITWidglgnvLTDNIEYTVIPLPDQRRFTAKSVLRLTPKKEHHNTNFS 213
Cdd:pfam13927   2 PVITvSPSSVTVREGETVTLTC-EATGSPPPTITW-------YKNGEPISSGSTRSRSLSGSNSTLTISNVTRSDAGTYT 73

                  ....*
gi 24639446   214 CQAQN 218
Cdd:pfam13927  74 CVASN 78

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        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24639446 132 PEAPKITqGDVIYATEDRKVEIECVSVGGKPAAEITWIDGLGNVltDNIEYTVIPLPDQRRFTAKSVLRLTPKKEHHNTN 211
Cdd:cd07705   4 PQKPQIT-GYESAFKEKDKAKLRCTSSGSKPAANIKWRKGDQEL--EGAPTSVQEDGNGKTFTVSSSVEFQVTREDDGAE 80

                        90       100
                ....*....|....*....|...
gi 24639446 212 FSCQAQNTA-DRTYRSAKIRVEV 233
Cdd:cd07705  81 ITCSVGHESlHDSDRSTSQRIEV 103

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 24639446 135 PKITQG--DVIYATEDRKVEIECvSVGGKPAAEITWIDGlGNVLTDNIEytviplpdQRRFTAKSVLRLTPKKEhHNTNF 212
Cdd:cd20978   1 PKFIQKpeKNVVVKGGQDVTLPC-QVTGVPQPKITWLHN-GKPLQGPME--------RATVEDGTLTIINVQPE-DTGYY 69

                        90
                ....*....|....*....
gi 24639446 213 SCQAQNTADRTYRSAKIRV 231
Cdd:cd20978  70 GCVATNEIGDIYTETLLHV 88

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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24639446 352 PQSMEADVGSVVSLTCEVDSNPQPEIVWIQH-------------PSDRVVGTS--------------TNLTFsvsnETAG 404
Cdd:cd05858   8 PANTSVVVGTDAEFVCKVYSDAQPHIQWLKHvekngskygpdglPYVEVLKTAgvnttdkeievlylRNVTF----EDAG 83

                        90
                ....*....|....*..
gi 24639446 405 RYYCKA-NVPGYAEISA 420
Cdd:cd05858  84 EYTCLAgNSIGISHHSA 100

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.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 24639446 461 VSWTFNGQEISsESGHdysILVDAVPggVKSTLIIRDSQAYHYGKYNCTVVNDYGNDVAEIQLQ 524
Cdd:cd05748  24 VTWSKDGQPLK-ETGR---VQIETTA--SSTSLVIKNAKRSDSGKYTLTLKNSAGEKSATINVK 81