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 1025470041 138 GSVVLPCR----TSAdlpEGTSVEWTRSEPrSMFIHVFPNTSKHFAQQDRLYRDRTEMSKDFLRTGDVSLTLMYPTHRDD 213
Cdd:cd05713    16 EDAELPCHlspkMSA---EHMEVRWFRSQF-SPVVHLYRDGQDQEEEQMPEYRGRTELLKDAIAEGSVALRIHNVRPSDE 91

                          90
                  ....*....|....*....
gi 1025470041 214 GRYVCtVYRDQDVLRDTVV 232
Cdd:cd05713    92 GQYTC-FFRSGSFYEEATL 109

Immunoglobulin (Ig)-like domain of myelin oligodendrocyte glycoprotein (MOG); The members here are composed of the immunoglobulin (Ig)-like domain of myelin oligodendrocyte glycoprotein (MOG). MOG, a minor component of the myelin sheath, is an important CNS-specific autoantigen, linked to the pathogenesis of multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE). It is a transmembrane protein having an extracellular Ig domain. MOG is expressed in the CNS on the outermost lamellae of the myelin sheath, and on the surface of oligodendrocytes, and may participate in the completion, compaction, and/or maintenance of myelin. This group also includes butyrophilin (BTN). BTN is the most abundant protein in bovine milk-fat globule membrane (MFGM).

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1025470041 138 GSVVLPCR----TSAdlpEGTSVEWTRSEPrSMFIHVFPNTSKHFAQQDRLYRDRTEMSKDFLRTGDVSLTLMYPTHRDD 213
Cdd:cd05713    16 EDAELPCHlspkMSA---EHMEVRWFRSQF-SPVVHLYRDGQDQEEEQMPEYRGRTELLKDAIAEGSVALRIHNVRPSDE 91

                          90
                  ....*....|....*....
gi 1025470041 214 GRYVCtVYRDQDVLRDTVV 232
Cdd:cd05713    92 GQYTC-FFRSGSFYEEATL 109

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 1025470041 284 VLLPCRtrvYLPGGARV-EW-RDGENRTVHVYQKGSDDPEEQNLTSRTRTRMNNDPLKTGDLSLTLKHPKPGDSGIYTCR 361
Cdd:cd16091    15 CILPCS---FTPGSEVViHWyKQDSDIKVHSYYYGKDQLESQDQRYRNRTSLFKDQISNGNASLLLRRVQLQDEGRYKCY 91

                  .
gi 1025470041 362 V 362
Cdd:cd16091    92 T 92

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1025470041   16 GVVEVNEGaESVLMPCIYSGvipEDNPFLLWTRsdlspnsvhlrreNGDDLKNQNQRFRGRTSmnpdaldTGNFSLTLRK 95
Cdd:smart00410   2 PSVTVKEG-ESVTLSCEASG---SPPPEVTWYK-------------QGGKLLAESGRFSVSRS-------GSTSTLTISN 57

                           90       100
                   ....*....|....*....|....*....
gi 1025470041   96 PEQDDGGNYSCSISDGVKERTvKQIHLKV 124
Cdd:smart00410  58 VTPEDSGTYTCAATNSSGSAS-SGTTLTV 85

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

                           10        20        30
                   ....*....|....*....|....*....|....*...
gi 1025470041  340 TGDLSLTLKHPKPGDSGIYTCRVRKRVVLVMKRVHLQV 377
Cdd:smart00410  48 GSTSTLTISNVTPEDSGTYTCAATNSSGSASSGTTLTV 85

Immunoglobulin (Ig)-like domain of myelin oligodendrocyte glycoprotein (MOG); The members here are composed of the immunoglobulin (Ig)-like domain of myelin oligodendrocyte glycoprotein (MOG). MOG, a minor component of the myelin sheath, is an important CNS-specific autoantigen, linked to the pathogenesis of multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE). It is a transmembrane protein having an extracellular Ig domain. MOG is expressed in the CNS on the outermost lamellae of the myelin sheath, and on the surface of oligodendrocytes, and may participate in the completion, compaction, and/or maintenance of myelin. This group also includes butyrophilin (BTN). BTN is the most abundant protein in bovine milk-fat globule membrane (MFGM).

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1025470041 138 GSVVLPCR----TSAdlpEGTSVEWTRSEPrSMFIHVFPNTSKHFAQQDRLYRDRTEMSKDFLRTGDVSLTLMYPTHRDD 213
Cdd:cd05713    16 EDAELPCHlspkMSA---EHMEVRWFRSQF-SPVVHLYRDGQDQEEEQMPEYRGRTELLKDAIAEGSVALRIHNVRPSDE 91

                          90
                  ....*....|....*....
gi 1025470041 214 GRYVCtVYRDQDVLRDTVV 232
Cdd:cd05713    92 GQYTC-FFRSGSFYEEATL 109

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 1025470041 140 VVLPC---RTSADLpegtsVEWTRSEPrSMFIHVFPNTSKHFAQQDRLYRDRTEMSKDFLRTGDVSLTLMYPTHRDDGRY 216
Cdd:cd16091    15 CILPCsftPGSEVV-----IHWYKQDS-DIKVHSYYYGKDQLESQDQRYRNRTSLFKDQISNGNASLLLRRVQLQDEGRY 88

                          90
                  ....*....|....*...
gi 1025470041 217 VCTVYRDQDVLRDTVVLK 234
Cdd:cd16091    89 KCYTSTIIGNQESFVNLK 106

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 1025470041 284 VLLPCRtrvYLPGGARV-EW-RDGENRTVHVYQKGSDDPEEQNLTSRTRTRMNNDPLKTGDLSLTLKHPKPGDSGIYTCR 361
Cdd:cd16091    15 CILPCS---FTPGSEVViHWyKQDSDIKVHSYYYGKDQLESQDQRYRNRTSLFKDQISNGNASLLLRRVQLQDEGRYKCY 91

                  .
gi 1025470041 362 V 362
Cdd:cd16091    92 T 92

Immunoglobulin (Ig)-like domain of myelin oligodendrocyte glycoprotein (MOG); The members here are composed of the immunoglobulin (Ig)-like domain of myelin oligodendrocyte glycoprotein (MOG). MOG, a minor component of the myelin sheath, is an important CNS-specific autoantigen, linked to the pathogenesis of multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE). It is a transmembrane protein having an extracellular Ig domain. MOG is expressed in the CNS on the outermost lamellae of the myelin sheath, and on the surface of oligodendrocytes, and may participate in the completion, compaction, and/or maintenance of myelin. This group also includes butyrophilin (BTN). BTN is the most abundant protein in bovine milk-fat globule membrane (MFGM).

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1025470041 300 VEW-RDGENRTVHVYQKGSDDPEEQNLTSRTRTRMNNDPLKTGDLSLTLKHPKPGDSGIYTCRVRKRVVLVMKRVHLQV 377
Cdd:cd05713    35 VRWfRSQFSPVVHLYRDGQDQEEEQMPEYRGRTELLKDAIAEGSVALRIHNVRPSDEGQYTCFFRSGSFYEEATLELKV 113

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

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1025470041 300 VEW-RDGENRTVHVYQKGSDDPEEQNLTSRTRTRMNNDPLKTGDLSLTLKHPKPGDSGIYTCRVR 363
Cdd:cd20984    32 IQWlKEGDSGLVHEFKEGKDELSRQSPMFRGRTSLFADQVHVGNASLRLKNVQLTDAGTYLCIIS 96

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1025470041   16 GVVEVNEGaESVLMPCIYSGvipEDNPFLLWTRsdlspnsvhlrreNGDDLKNQNQRFRGRTSmnpdaldTGNFSLTLRK 95
Cdd:smart00410   2 PSVTVKEG-ESVTLSCEASG---SPPPEVTWYK-------------QGGKLLAESGRFSVSRS-------GSTSTLTISN 57

                           90       100
                   ....*....|....*....|....*....
gi 1025470041   96 PEQDDGGNYSCSISDGVKERTvKQIHLKV 124
Cdd:smart00410  58 VTPEDSGTYTCAATNSSGSAS-SGTTLTV 85

Immunoglobulin Variable (IgV) domain of B7-H2 (B7 homolog 2); The members here are composed of the immunoglobulin variable (IgV) domain of B7-H2 (B7 homolog 2 also known as ICOSL (inducible T cell costimulator ligand) or CD275). B7-H2 is a ligand for the T-cell-specific cell surface receptor ICOS and acts as a costimulatory signal for T-cell proliferation and cytokine secretion. The interaction of ICOS with ICOSL (B7-H2) regulates T cell activation and expansion, is involved in T cell dependent B cell activation, and T-helper cell differentiation. It is a member of the B7 family of immune regulatory proteins and shares homology with other B7 ligands, such as B7-1, B7-2, B7-H1 (PD-L1), PD-L2, and B7-H3. The extracellular domains of B7 proteins contain two Ig-like domains and all members have short cytoplasmic domains. These ligands are typically expressed on antigen presenting cells (such as macrophages, B cells and dendritic cells) and have the ability to regulate T-cell proliferation and function. Tumor cells are also capable of expressing the B7 family members in order to evade immune surveillance.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1025470041 129 QEVEVTEGSgSVVLPC----RTSADLpEGTSVEWTRSEPRSMFIHVFPNTSKhFAQQDRLYRDRTEMSKDFLRTGDVSLT 204
Cdd:cd20935     1 KEVRAMVGS-DVELSCicpeGSRFDL-NDLYVYWQISESETVVTYHLPQNSS-LENVDSHYRNRALLSLDSMKQGDFSLR 77

                          90       100       110
                  ....*....|....*....|....*....|...
gi 1025470041 205 LMYPTHRDDGRYVCTVYRD----QDVLRDTVVL 233
Cdd:cd20935    78 LFNVTPQDEQKFHCLVFSQslelQKVLEVVVTL 110

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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1025470041   8 LVSQHALGGVVEVNEGAESVLMpCIYSGViPEdnPFLLWTRSDLSPnsvhlrrengdDLKNQNQRFRGRTSMnpdaldtg 87
Cdd:cd20970     2 VISTPQPSFTVTAREGENATFM-CRAEGS-PE--PEISWTRNGNLI-----------IEFNTRYIVRENGTT-------- 58

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 1025470041  88 nfsLTLRKPEQDDGGNYSCSISDGVKERTVKQIHLKV 124
Cdd:cd20970    59 ---LTIRNIRRSDMGIYLCIASNGVPGSVEKRITLQV 92

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1025470041 139 SVVLPCRTSADLP-EGTSVEWTRsEPRSMFIHVFPNTSKHFAQQDRLYRDRTEMSKDFLRTGDVSLTLMYPTHRDDGRYV 217
Cdd:cd20984    14 DGILSCTFTPDIKlSDIVIQWLK-EGDSGLVHEFKEGKDELSRQSPMFRGRTSLFADQVHVGNASLRLKNVQLTDAGTYL 92

                  ...
gi 1025470041 218 CTV 220
Cdd:cd20984    93 CII 95

Immunoglobulin Variable (IgV) domain of Programmed death ligand 1 (PD-L1); The members here are composed of the immunoglobulin variable (IgV) domain of Programmed death ligand 1 (PD-L1; also known as Cluster of Differentiation 274 (CD274)). PD-L1 is a cell-surface ligand that competes with PD-L2 for binding to the immunosuppressive receptor programmed death-1 (PD-1). PD-1 is a member of the B7 family that plays an important role in negatively regulating immune responses upon interaction with its two ligands, PD-L1 or PD-L2. Like PD-L2, PD-L1 interacts with PD-1 and suppresses T cell proliferation and cytokine production. The PD-1 receptor is expressed on the surface of activated T cells, while PD-L1 is expressed on cancer cells. When PD-1 and PD-L1 bind together, they form a molecular shield protecting tumor cells from being destroyed by the immune system. Thus, inhibiting the binding of PD-L1 to PD-1 with an antibody leads to killing of tumor cells by T cells. PD-1 inhibitors (such as Pembrolizumab, Nivolumab, and Cemiplimab) and PD-L1 inhibitors (such as Atezolizumab, Avelumab, and Durvalumab ) are an emerging class of immunotherapy that stimulate lymphocytes against tumor cells.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1025470041  64 DDLKNQNQRFRGRTSMNPDALDTGNFSLTLRKPEQDDGGNYSCSISDGVKErtVKQIHLKV 124
Cdd:cd20947    52 EDLKVQHSSYRQRARLLKDQLSLGNAALQITDVKLQDAGVYRCMISYGGAD--YKRITVKV 110

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
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1025470041 308 RTVHVYQKGSDDPEEQNLTSRTRTRMNNDPLKTGDLSLTLKHPKPGDSGIYTCRVR 363
Cdd:cd20934    43 QLVHSFTESQDQGRDQGSAYANRTALFPDLLAQGNASLRLQRVRVADEGSYTCFVS 98

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
                  ....*....|....*....|...
gi 1025470041 344 SLTLKHPKPGDSGIYTCRVRKRV 366
Cdd:cd05856    59 TLSLKNLKPEDSGKYTCHVSNRA 81

Immunoglobulin V-Type;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1025470041   26 SVLMPCIYSGvIPEDNPFLLWTRSDLSPNSVHLRRENGDDLKNQNQRFRGRTSMNPDaLDTGNFSLTLRKPEQDDGGNYS 105
Cdd:smart00406   1 SVTLSCKFSG-STFSSYYVSWVRQPPGKGLEWLGYIGSNGSSYYQESYKGRFTISKD-TSKNDVSLTISNLRVEDTGTYY 78

                   ...
gi 1025470041  106 CSI 108
Cdd:smart00406  79 CAV 81

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 1025470041 284 VLLPCRTRVYLPggARVEWrdgenrtvhvYQKGSDDPEEQNLTSRTrtrmnndplKTGDLSLTLKHPKPGDSGIYTCRVR 363
Cdd:cd00096     1 VTLTCSASGNPP--PTITW----------YKNGKPLPPSSRDSRRS---------ELGNGTLTISNVTLEDSGTYTCVAS 59

Immunoglobulin (Ig)-like domain of the chondroitin sulfate proteoglycan core protein (CSPG), versican; The members here are composed of the immunoglobulin (Ig)-like domain of the chondroitin sulfate proteoglycan core protein (CSPG), versican. 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, the CSPG aggrecan (not included in this group) forms cartilage link protein stabilized aggregates with HA. These aggregates contribute to the tissue's load bearing properties. Like aggrecan, versican has a wide distribution in connective tissue and extracellular matrices. 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 1025470041  24 AESVLMPCIY--------SGVIPEDNPFLLWTRSDLSPNSVHLRRENGDDLKNQN----QRFRGRTSMNPDALDTGNFSL 91
Cdd:cd05901    12 SGSVVLPCRFstlptlppSYNITSEFLRIKWTKIQVDKNGKDHKETTVLVAQNGIikigQEYMGRVSVPSHPEDQGDASL 91

                          90       100       110
                  ....*....|....*....|....*....|...
gi 1025470041  92 TLRKPEQDDGGNYSCSISDGVkERTVKQIHLKV 124
Cdd:cd05901    92 TIVKLRASDAGVYRCEVMHGI-EDTQDTVSLDV 123