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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5031561     155 GNNIQLTCQSKeGSPTPQYSWKRynilNQEQPLAQPA------SGQPVSL--KNISTDTSGYYICTSSNEEGTQFCNITV 226
Cdd:smart00410   9 GESVTLSCEAS-GSPPPEVTWYK----QGGKLLAESGrfsvsrSGSTSTLtiSNVTPEDSGTYTCAATNSSGSASSGTTL 83

                   ..
gi 5031561     227 AV 228
Cdd:smart00410  84 TV 85

Immunoglobulin V-Type;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5031561      38 SVTLPCTYHTSTSSREGlIQW-DKLLLTHTERVVIWPFSNKNYIHGElYKNRVSISNNAEQSDASITIDQLTMADNGTYE 116
Cdd:smart00406   1 SVTLSCKFSGSTFSSYY-VSWvRQPPGKGLEWLGYIGSNGSSYYQES-YKGRFTISKDTSKNDVSLTISNLRVEDTGTYY 78

                   ...
gi 5031561     117 CSV 119
Cdd:smart00406  79 CAV 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 5031561     155 GNNIQLTCQSKeGSPTPQYSWKRynilNQEQPLAQPA------SGQPVSL--KNISTDTSGYYICTSSNEEGTQFCNITV 226
Cdd:smart00410   9 GESVTLSCEAS-GSPPPEVTWYK----QGGKLLAESGrfsvsrSGSTSTLtiSNVTPEDSGTYTCAATNSSGSASSGTTL 83

                   ..
gi 5031561     227 AV 228
Cdd:smart00410  84 TV 85

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

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 5031561  153 IIGNNIQLTCQSkEGSPTPQYSWKRYNILNQE--QPLAQPASGQPVSLKNISTDTSGYYICTSSNE 216
Cdd:cd20970  15 REGENATFMCRA-EGSPEPEISWTRNGNLIIEfnTRYIVRENGTTLTIRNIRRSDMGIYLCIASNG 79

Immunoglobulin V-Type;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5031561      38 SVTLPCTYHTSTSSREGlIQW-DKLLLTHTERVVIWPFSNKNYIHGElYKNRVSISNNAEQSDASITIDQLTMADNGTYE 116
Cdd:smart00406   1 SVTLSCKFSGSTFSSYY-VSWvRQPPGKGLEWLGYIGSNGSSYYQES-YKGRFTISKDTSKNDVSLTISNLRVEDTGTYY 78

                   ...
gi 5031561     117 CSV 119
Cdd:smart00406  79 CAV 81

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 5031561   25 ETPQDVLRASQGKSVTLPCTYH---TSTSSREGLIQWDKLLLTHT--ERVVIW-PFSNKNYIHgelYKNRVSIsNNAEQS 98
Cdd:cd05877   1 ETVQAKVFSHRGGNVTLPCRYHyepELSAPRKIRVKWTKLEVDYAkeEDVLVAiGTRHKSYGS---YQGRVFL-RRADDL 76

                        90       100
                ....*....|....*....|..
gi 5031561   99 DASITIDQLTMADNGTYECSVS 120
Cdd:cd05877  77 DASLVITDLRLEDYGRYRCEVI 98

Immunoglobulin (Ig)-like domain of protein zero (P0) and similar proteins; The members here are composed of the immunoglobulin (Ig) domain of protein zero (P0), a myelin membrane adhesion molecule. P0 accounts for over 50% of the total protein in peripheral nervous system (PNS) myelin. P0 is a single-pass transmembrane glycoprotein with a highly basic intracellular domain and an extracellular Ig domain. The extracellular domain of P0 (P0-ED) is similar to the Ig variable domain, carrying one acceptor sequence for N-linked glycosylation. P0 plays a role in membrane adhesion in the spiral wraps of the myelin sheath. The intracellular domain is thought to mediate membrane apposition of the cytoplasmic faces and may, through electrostatic interactions, interact directly with lipid headgroups. It is thought that homophilic interactions of the P0 extracellular domain mediate membrane juxtaposition in the extracellular space of PNS myelin. This group also contains the Ig domain of sodium channel subunit beta-2 (SCN2B), and of epithelial V-like antigen 1 (EVA). EVA, also known as myelin protein zero-like 2, is an adhesion molecule, which may play a role in structural organization of the thymus and early lymphocyte development. SCN2B subunits play a role in determining sodium channel density and function in neurons,and in control of electrical excitability in the brain.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5031561   22 ISVETPQdVLRASQGKSVTLPCTY-HTSTSSREGLIQWDKLLLTHTERVVIWPFSNKNYIHGEL--YKNRVSISNNAEQS 98
Cdd:cd05715   1 MEVYTPR-ELNVLNGSDVRLTCTFtSCYTVGDAFSVTWTYQPEGGNTTESMFHYSKGKPYILKVgrFKDRVSWAGNPSKK 79

                        90       100       110
                ....*....|....*....|....*....|....*....
gi 5031561   99 DASITIDQLTMADNGTYECSVSLMSDLEGNTkSRVRLLV 137
Cdd:cd05715  80 DASIVISNLQFSDNGTYTCDVKNPPDIVGGH-GEIRLYV 117

Immunoglobulin (Ig)-like domain of epithelial V-like antigen (EVA) 1; The members here are composed of the immunoglobulin (Ig) domain of epithelial V-like antigen 1 (EVA 1). EVA is also known as myelin protein zero-like 2. EVA is an adhesion molecule and may play a role in the structural organization of the thymus and early lymphocyte development.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5031561   22 ISVETPQDVlRASQGKSVTLPCTYHTSTSSREGL-IQWDKLLLTHTERVVIWPFSNKNYIHGE-LYKNRVSISNNAEQSD 99
Cdd:cd05880   1 IEVYTSKEV-EAVNGTDVRLKCTFSSSAPIGDTLvITWNFRPLDGGREESVFYYHKRPYPPPDgRFKGRVVWDGNIMRRD 79

                        90       100       110
                ....*....|....*....|....*....|....*...
gi 5031561  100 ASITIDQLTMADNGTYECSVSLMSDLEGnTKSRVRLLV 137
Cdd:cd05880  80 ASILIWQLQPTDNGTYTCQVKNPPDVHG-PIGEIRLRV 116

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 5031561    155 GNNIQLTCQSkEGSPTPQYSWKRYNILNQEQPLAQPASGQPVS---LKNISTDTSGYYICTSSN 215
Cdd:pfam13927  16 GETVTLTCEA-TGSPPPTITWYKNGEPISSGSTRSRSLSGSNStltISNVTRSDAGTYTCVASN 78

Immunoglobulin (Ig)-like domain of the aggrecan-like chondroitin sulfate proteoglycan core protein (CSPG); The members here are composed of the immunoglobulin (Ig)-like domain of the aggrecan-like chondroitin sulfate proteoglycan core proteins (CSPGs). Included in this group are the Ig domains of other CSPGs: versican, and neurocan. In CSPGs, this Ig-like domain is followed by hyaluronan (HA)-binding tandem repeats, and a C-terminal region with epidermal growth factor-like, lectin-like, and complement regulatory protein-like domains. Separating these N- and C-terminal regions is a nonhomologous glycosaminoglycan attachment region. In cartilage, aggrecan forms cartilage link protein stabilized aggregates with hyaluronan (HA). These aggregates contribute to the tissue's load bearing properties. Aggrecan and versican have a wide distribution in connective tissue and extracellular matrices. Neurocan is localized almost exclusively in nervous tissue. 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 5031561   31 LRASQGKSVTLPCTY------HTSTSSREGL-IQWDKLLLTHTER--VVIWPFSNKNYIHGELYKNRVSISNNAEQ-SDA 100
Cdd:cd05878   7 VRVLLGTSVTLPCYFidpphpVTPSTAPLAPrIKWSKVSVDGKKEkeVVLLVATEGRVRVNSAYQGRVSLPNYPAIpSDA 86

                        90
                ....*....|....*....
gi 5031561  101 SITIDQLTMADNGTYECSV 119
Cdd:cd05878  87 TLEVQSLRASDSGLYRCEV 105

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5031561   24 VETPQDVLRASQGKSVTLPCTYHTSTSSReglIQWDKLLLTHTERVVIwpfsnKNYIHGELYKN-RVSISNNAEQSDASI 102
Cdd:cd04983   1 VTQSPQSLSVQEGENVTLNCNYSTSTFYY---LFWYRQYPGQGPQFLI-----YISSDSGNKKKgRFSATLDKSRKSSSL 72

                        90
                ....*....|....*...
gi 5031561  103 TIDQLTMADNGTYECSVS 120
Cdd:cd04983  73 HISAAQLSDSAVYFCALS 90

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 5031561  153 IIGNNIQLTCQSkEGSPTPQYSWKRYNILNQE--QPLAQPASGQPVSLKNISTDTSGYYICTSSNE 216
Cdd:cd20970  15 REGENATFMCRA-EGSPEPEISWTRNGNLIIEfnTRYIVRENGTTLTIRNIRRSDMGIYLCIASNG 79

Immunoglobulin (Ig)-like domain of protein zero (P0); The members here are composed of the immunoglobulin (Ig) domain of protein zero (P0), a myelin membrane adhesion molecule. P0 accounts for over 50% of the total protein in peripheral nervous system (PNS) myelin. P0 is a single-pass transmembrane glycoprotein with a highly basic intracellular domain and an Ig domain. The extracellular domain of P0 (P0-ED) is similar to the Ig variable domain, carrying one acceptor sequence for N-linked glycosylation. P0 plays a role in membrane adhesion in the spiral wraps of the myelin sheath. The intracellular domain is thought to mediate membrane apposition of the cytoplasmic faces and may, through electrostatic interactions, interact directly with lipid headgroups. It is thought that homophilic interactions of the P0 extracellular domain mediate membrane juxtaposition in the extracellular space of PNS myelin.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5031561   22 ISVETPQDVlRASQGKSVTLPCTYHTST-SSREGLIQWDKLLLTHTERVVIWPFSN-KNYI-HGELYKNRVSISNNAEQS 98
Cdd:cd05879   1 IVVYTDREV-YGTVGSDVTLSCSFWSSEwISDDISFTWHYQPDGSRDAISIFHYGKgQPYIdNVGPFKERIEWVGNPSRK 79

                        90       100       110
                ....*....|....*....|....*....|....*....
gi 5031561   99 DASITIDQLTMADNGTYECSVSLMSDLEGNTkSRVRLLV 137
Cdd:cd05879  80 DGSIVIHNLDYTDNGTFTCDVKNPPDIVGKS-SQVTLYV 117

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 5031561   24 VETPQDVLRaSQGKSVTLPCTYHTSTSSreGLIQWDKLLLTHT-ERVVIWPFSNKNYihGELYKNRVSISNNaEQSDASI 102
Cdd:cd00099   2 TQSPRSLSV-QEGESVTLSCEVSSSFSS--TYIYWYRQKPGQGpEFLIYLSSSKGKT--KGGVPGRFSGSRD-GTSSFSL 75

                        90
                ....*....|....*...
gi 5031561  103 TIDQLTMADNGTYECSVS 120
Cdd:cd00099  76 TISNLQPEDSGTYYCAVS 93

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 5031561  155 GNNIQLTCQSkEGSPTPQYSWKR--------YNILNQEQPLAQPASGQpVSLKNISTDTSGYYICTSSNEEGT 219
Cdd:cd20954  16 GQDVMLHCQA-DGFPTPTVTWKKatgstpgeYKDLLYDPNVRILPNGT-LVFGHVQKENEGHYLCEAKNGIGS 86

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 5031561    149 EGETIIGNNIQLTCQSKEGSPTPQYSWKR---YNILNQEQPLAQPASGQ-PVSLKNISTDTSGYYICTSSN 215
Cdd:pfam00047   5 TVTVLEGDSATLTCSASTGSPGPDVTWSKeggTLIESLKVKHDNGRTTQsSLLISNVTKEDAGTYTCVVNN 75

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 5031561     31 LRASQGKSVTLPCTYHTSTSSREgliqwdklllthtervVIWPFSNKNYIHGELYKNrvsisNNAEQSDASITIDQLTMA 110
Cdd:pfam00047   6 VTVLEGDSATLTCSASTGSPGPD----------------VTWSKEGGTLIESLKVKH-----DNGRTTQSSLLISNVTKE 64

                          90
                  ....*....|
gi 5031561    111 DNGTYECSVS 120
Cdd:pfam00047  65 DAGTYTCVVN 74

Immunoglobulin variable domain (IgV) in Cluster of Differentiation (CD) 80; The members here are composed of the immunoglobulin variable region (IgV) in the Cluster of Differentiation (CD) 80). Glycoproteins B7-1 (also known as cluster of differentiation (CD) 80) and B7-2 (also known as CD86) are expressed on antigen-presenting cells and deliver the co-stimulatory signal through CD28 and CTLA-4 (also known as cluster of differentiation 152/CD152) on T cells. signaling through CD28 augments the T-cell response, whereas CTLA-4 signaling attenuates it. CD80 contains two Ig-like domains, an amino-terminal immunoglobulin variable (IgV)-like domain characteristic of adhesion molecules and a membrane proximal immunoglobulin constant (IgC)-like domain similar to the constant domains of antigen receptors. Members of the Ig 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, and the IgC domain is involved in oligomerization and molecular interactions.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5031561   37 KSV----TLPCTYHTSTSS-REGLIQW---DKLLLTHTERVV-IWPfsnknyihgeLYKNR--VSISNNAeqsdaSITID 105
Cdd:cd16086   6 KSVkekaLLSCDYNVSVDElAQVRIYWqkdDKMVLTIISGDVkVWP----------EYKNRtlFDITNNL-----SIVIL 70

                        90
                ....*....|....
gi 5031561  106 QLTMADNGTYECSV 119
Cdd:cd16086  71 ALRLSDRGTYTCVV 84

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

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 5031561  157 NIQLTCQSKeGSPTPQYSWKR----YNILNQEQPLAQPASGQPV-SLKNIS-TDTSGYYICTSSNEEGTQFCN 223
Cdd:cd05733  18 NITIKCEAK-GNPQPTFRWTKdgkfFDPAKDPRVSMRRRSGTLViDNHNGGpEDYQGEYQCYASNELGTAISN 89

Immunoglobulin Variable (IgV) domain of B7-H3, a member of the B7 family of immune checkpoint molecules; The members here are composed of the immunoglobulin variable (IgV) domain of B7-H3 also known as CD276), a member of the B7 family of immune checkpoint molecules. B7-H3 is an important immune checkpoint member of the B7 family and shares homology with other B7 ligands such as programmed death ligand 1 (PD-L1). The B7 family molecules interact with CD28 on T-cells to provide co-stimulatory signals that regulate T-cell activation and T-helper cell differentiation. Although B7-H3 has been shown to have both co-stimulatory and co-inhibitory effects on T-cell responses, the most current studies describe B7-H3 as a T cell inhibitor that promotes tumor aggressiveness and proliferation. Moreover, B7-H3 is highly overexpressed on a wide range of human solid cancers and promotes tumor growth, metastasis, and drug resistance. Thus, B7-H3 expression in tumors often correlates with both negative prognosis and poor clinical outcome in cancer patients. B7-H3 protein contains a predicted signal peptide, V- and C-like Ig domains (IgV and IgC), a transmembrane region, and an intracellular tail.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5031561   27 PQDVLRASQGKSVTLPCTYHTST--SSREGLIQWDkllLTHTERVV--IWPFSNKNYIHGELYKNRVSI-SNNAEQSDAS 101
Cdd:cd20934   3 PEDPVVALVGTDATLRCSFSPEPgfSLAQLSVFWQ---LTDTKQLVhsFTESQDQGRDQGSAYANRTALfPDLLAQGNAS 79

                        90       100
                ....*....|....*....|..
gi 5031561  102 ITIDQLTMADNGTYECSVSLMS 123
Cdd:cd20934  80 LRLQRVRVADEGSYTCFVSVQD 101

First immunoglobulin variable (IgV) domain of nectin-3 (also known as poliovirus receptor related protein 3), and similar domains; The members here are composed of the first immunoglobulin (Ig) domain of nectin-3 (also known as poliovirus receptor related protein 3 (PVRL3) or cluster of differentiation (CD) 113). Nectin-3 belongs to the nectin family comprised of four transmembrane glycoproteins (nectins-1 through -4). Nectins are synaptic cell adhesion molecules (CAMs) which participate in adhesion and signaling at various intracellular junctions. Nectins form homophilic cis-dimers, followed by homophilic and heterophilic trans-dimers involved in cell-cell adhesion. For example, during spermatid development, the nectin-3,-2 trans-interaction is required for the formation of Sertoli cell-spermatid junctions in testis, and during morphogenesis of the ciliary body, the nectin-3,-1 trans-interaction is important for apex-apex adhesion between the pigment and non-pigment layers of the ciliary epithelia. Nectins also heterophilically trans-interact with other CAMs such as nectin-like molecules (Necls); nectin-3 for example, trans-interacts with Necl-5, regulating cell movement and proliferation. Other proteins with which nectin-3 interacts include the actin filament-binding protein, afadin, integrin alpha-beta3, Par-3, and PDGF receptor; its interaction with PDGF receptor regulates the latter's signaling for anti-apoptosis.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5031561   33 ASQGKSVTLPCTYHTSTSSREglIQWDKLLLTHTERVVIWPFSNKNYIHGElYKNRVSISNNAeQSDASITIDQLTMADN 112
Cdd:cd05887  11 AVWGKNVSLKCLIEVNETITQ--ISWEKIHGKSSQTVAVHHPQYGISIQGE-YQGRVSFKNYS-LNDATITLHNVGFSDS 86

                        90       100
                ....*....|....*....|....*.
gi 5031561  113 GTYECSVSLMSdlEGNTKSRVRLLVL 138
Cdd:cd05887  87 GKYICKAVTFP--LGNAQSSTTVTVL 110

Immunoglobulin (Ig)-like domain of the chondroitin sulfate proteoglycan core protein (CSPG), aggrecan; The members here are composed of the immunoglobulin (Ig)-like domain of the chondroitin sulfate proteoglycan core protein (CSPG), aggrecan. In CSPGs, the Ig-like domain is followed by hyaluronan (HA)-binding tandem repeats, and a C-terminal region with epidermal growth factor-like, lectin-like, and complement regulatory protein-like domains. Separating these N- and C-terminal regions is a nonhomologous glycosaminoglycan attachment region. In cartilage, aggrecan forms cartilage link protein stabilized aggregates with HA. These aggregates contribute to the tissue's load bearing properties. Aggrecan has a wide distribution in connective tissue and extracellular matrices. 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 5031561   22 ISVETPqdvLRASQGKSVTLPCTYHTSTSSREGL---------IQWDKLLlTHTERVVIWPFSNKNYIHGElYKNRVSIS 92
Cdd:cd05900   1 IPLESP---LRVVLGSSLLIPCYFQDPIAKDPGAptvaplsprIKWSFIS-KEKESVLLVATEGKVRVNTE-YLDRVSLP 75

                        90       100
                ....*....|....*....|....*...
gi 5031561   93 N-NAEQSDASITIDQLTMADNGTYECSV 119
Cdd:cd05900  76 NyPAIPSDATLEITELRSNDSGTYRCEV 103

Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor_like-1(FGFRL1); member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor like-1(FGFRL1). FGFRL1 is comprised of a signal peptide, three extracellular Ig-like modules, a transmembrane segment, and a short intracellular domain. FGFRL1 is expressed preferentially in skeletal tissues. Similar to FGF receptors, the expressed protein interacts specifically with heparin and with FGF2. FGFRL1 does not have a protein tyrosine kinase domain at its C-terminus; neither does its cytoplasmic domain appear to interact with a signaling partner. It has been suggested that FGFRL1 may not have any direct signaling function, but instead acts as a decoy receptor trapping FGFs and preventing them from binding other receptors.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 5031561  154 IGNNIQLTCQSkEGSPTPQYSWkryniLNQEQPLAQPASGQP------VSLKNISTDTSGYYICTSSNEEG 218
Cdd:cd05856  18 VGSSVRLKCVA-SGNPRPDITW-----LKDNKPLTPPEIGENkkkkwtLSLKNLKPEDSGKYTCHVSNRAG 82

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 5031561  158 IQLTCQSkEGSPTPQYSWKRYNILNQEQPLAQPASGQPVS---LKNISTDTSGYYICTSSNEEGTQ 220
Cdd:cd00096   1 VTLTCSA-SGNPPPTITWYKNGKPLPPSSRDSRRSELGNGtltISNVTLEDSGTYTCVASNSAGGS 65

Immunoglobulin (Ig)-like domain of vascular endothelial growth factor (VEGF) receptor (R) and similar proteins; member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig)-like domain of vascular endothelial growth factor (VEGF) receptor (R) and related proteins. The VEGFRs have an extracellular component with seven Ig-like domains, a transmembrane segment, and an intracellular tyrosine kinase domain interrupted by a kinase-insert domain. The VEGFR family consists of three members: VEGFR-1 (Flt-1), VEGFR-2 (KDR/Flk-1) and VEGFR-3 (Flt-4). VEGF-A interacts with both VEGFR-1 and VEGFR-2. VEGFR-1 binds strongest to VEGF; VEGF-2 binds more weakly. VEGFR-3 appears not to bind VEGF, but binds other members of the VEGF family (VEGF-C and -D). VEGFRs bind VEGFs with high affinity with the IG-like domains. VEGF-A is important to the growth and maintenance of vascular endothelial cells and to the development of new blood- and lymphatic-vessels in physiological and pathological states. VEGFR-2 is a major mediator of the mitogenic, angiogenic, and microvascular permeability-enhancing effects of VEGF-A. VEGFR-1 may play an inhibitory part in these processes by binding VEGF and interfering with its interaction with VEGFR-2. VEGFR-1 has a signaling role in mediating monocyte chemotaxis. VEGFR-1 and VEGFR-2 may mediate a chemotactic and a survival signal in hematopoietic stem cells or leukemia cells. VEGFR-3 has been shown to be involved in tumor angiogenesis and growth. This group also contains alpha-type platelet-derived growth factor receptor precursor (PDGFR)-alpha (CD140a), and PDGFR-beta (CD140b). PDGFRs alpha and beta have an extracellular component with five Ig-like domains, a transmembrane segment, and a cytoplasmic portion that has protein tyrosine kinase activity.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5031561   22 ISVETPQDVLRasQGKSVTLPCTYHTSTSSREGLiQWD-------KLLLTHTERVVIWPFSNKnyihgelyknRVSIsnn 94
Cdd:cd05742   5 LSPNAEPTVLP--QGETLVLNCTANVNLNEVVDF-QWTypsekegKLALLKPDIKVDWSEPGE----------FVST--- 68

                        90       100
                ....*....|....*....|....*.
gi 5031561   95 aeqsdasITIDQLTMADNGTYECSVS 120
Cdd:cd05742  69 -------LTIPEATLKDSGTYTCAAR 87

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

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 5031561  155 GNNIQLTCQSkEGSPTPQYSWKRYNI-LNQEQP--LAQPASGQPVSLKNISTDTSGYYICTSSNEEG 218
Cdd:cd05736  15 GVEASLRCHA-EGIPLPRVQWLKNGMdINPKLSkqLTLIANGSELHISNVRYEDTGAYTCIAKNEGG 80

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 5031561  155 GNNIQLTCQSKeGSPTPQYSWKR---YNILNQEQPLaQPASGQPVS------LKNISTDTSGYYICTSSNEEGT 219
Cdd:cd05726  14 GRTVTFQCETK-GNPQPAIFWQKegsQNLLFPYQPP-QPSSRFSVSptgdltITNVQRSDVGYYICQALNVAGS 85

Immunoglobulin Variable (IgV) domain in HERV-H LTR-associating 2 (HHLA2); The members here are composed of the immunoglobulin variable (IgV) region in HERV-H LTR-associating 2 (HHLA2; also known as B7-H7/B7 homolog 7). HHLA2 is a member of the B7 family of immune regulatory proteins. Mature human HHLA2 consists of an extracellular domain (ECD) with three immunoglobulin-like domains, a transmembrane segment, and a cytoplasmic domain. HHLA2 is widely expressed in human cancers including non-small cell lung carcinoma (NSCLS), triple negative breast cancer (TNBC), and melanoma, but has limited expression on normal tissues. Interestingly, unlike other members of B7 family, HHLA2 is not expressed in mice or rats. HHLA2 functions as a T cell coinhibitory molecules as it inhibits the proliferation of activated CD4(+) and CD8(+) T cells and their cytokine production. Furthermore, HHLA2 is constitutively expressed on the surface of human monocytes and is induced on B cells after stimulation, however it is not inducible on T cells.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5031561   36 GKSVTLPCTYhtsTSSREGLIQWDKLlltHTERVVIWPFSNKNYI--HGELYKNRVSISNNAEQS-DASITIDQLTMADN 112
Cdd:cd16091  12 SEDCILPCSF---TPGSEVVIHWYKQ---DSDIKVHSYYYGKDQLesQDQRYRNRTSLFKDQISNgNASLLLRRVQLQDE 85

                        90       100
                ....*....|....*....|....*
gi 5031561  113 GTYECSVslmSDLEGNTKSRVRLLV 137
Cdd:cd16091  86 GRYKCYT---STIIGNQESFVNLKV 107