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 15777921  12 YVGTLGtHTEIKRVAEEKVTLPCHHQLGLPEKDTLDIEWLLTDNEGNQKVVITYSSRHVYNNLTEEQKGRVAFASNFLAG 91
Cdd:cd20960   1 LLITSA-QTEIKKVAGENVTLPCHHQLGLEDQGTLDIEWLLLPSDKVEKVVITYSGDRVYNHYYPALKGRVAFTSNDLSG 79

                        90       100       110
                ....*....|....*....|....*....|....*
gi 15777921  92 DASLQIEPLKPSDEGRYTCKVKNSGRYVWSHVILK 126
Cdd:cd20960  80 DASLNISNLKLSDTGTYQCKVKKAPGYAWSKITLI 114

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 15777921  12 YVGTLGtHTEIKRVAEEKVTLPCHHQLGLPEKDTLDIEWLLTDNEGNQKVVITYSSRHVYNNLTEEQKGRVAFASNFLAG 91
Cdd:cd20960   1 LLITSA-QTEIKKVAGENVTLPCHHQLGLEDQGTLDIEWLLLPSDKVEKVVITYSGDRVYNHYYPALKGRVAFTSNDLSG 79

                        90       100       110
                ....*....|....*....|....*....|....*
gi 15777921  92 DASLQIEPLKPSDEGRYTCKVKNSGRYVWSHVILK 126
Cdd:cd20960  80 DASLNISNLKLSDTGTYQCKVKKAPGYAWSKITLI 114

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15777921    143 TEGSDLTLQCEsASGTKPIVYYWQRirekeGEDEHLPPKSR--IDYNNPGRVL-LQNLTMASSGLYQCTAGNEAGKESCV 219
Cdd:smart00410   7 KEGESVTLSCE-ASGSPPPEVTWYK-----QGGKLLAESGRfsVSRSGSTSTLtISNVTPEDSGTYTCAATNSSGSASSG 80

                   ....*
gi 15777921    220 VRVTV 224
Cdd:smart00410  81 TTLTV 85

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15777921     28 EKVTLPCHhqlgLPEKDTLDIEWLLTDNEgnqkvVITYSSRhvynnlteeqkgrvaFASNFLAGDASLQIEPLKPSDEGR 107
Cdd:smart00410  10 ESVTLSCE----ASGSPPPEVTWYKQGGK-----LLAESGR---------------FSVSRSGSTSTLTISNVTPEDSGT 65

                           90
                   ....*....|....*....
gi 15777921    108 YTCKVKNSGRYVWSHVILK 126
Cdd:smart00410  66 YTCAATNSSGSASSGTTLT 84

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 15777921  12 YVGTLGtHTEIKRVAEEKVTLPCHHQLGLPEKDTLDIEWLLTDNEGNQKVVITYSSRHVYNNLTEEQKGRVAFASNFLAG 91
Cdd:cd20960   1 LLITSA-QTEIKKVAGENVTLPCHHQLGLEDQGTLDIEWLLLPSDKVEKVVITYSGDRVYNHYYPALKGRVAFTSNDLSG 79

                        90       100       110
                ....*....|....*....|....*....|....*
gi 15777921  92 DASLQIEPLKPSDEGRYTCKVKNSGRYVWSHVILK 126
Cdd:cd20960  80 DASLNISNLKLSDTGTYQCKVKKAPGYAWSKITLI 114

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15777921    143 TEGSDLTLQCEsASGTKPIVYYWQRirekeGEDEHLPPKSR--IDYNNPGRVL-LQNLTMASSGLYQCTAGNEAGKESCV 219
Cdd:smart00410   7 KEGESVTLSCE-ASGSPPPEVTWYK-----QGGKLLAESGRfsVSRSGSTSTLtISNVTPEDSGTYTCAATNSSGSASSG 80

                   ....*
gi 15777921    220 VRVTV 224
Cdd:smart00410  81 TTLTV 85

First immunoglobulin variable (IgV) domain of poliovirus receptor (PVR, also known as CD155 and necl-5), and similar domains; The members here are composed of the first immunoglobulin (Ig) domain of poliovirus receptor (PVR, also known as CD155 and nectin-like protein 5 (necl-5)). Poliovirus (PV) binds to its cellular receptor (PVR/CD155) to initiate infection. CD155 is a membrane-anchored, single-span glycoprotein; its extracellular region has three Ig-like domains. There are four different isotypes of CD155 (referred to as alpha, beta, gamma, and delta), that result from alternate splicing of the CD155 mRNA, and have identical extracellular domains. CD155-beta and CD155-gamma are secreted; CD155-alpha and CD155-delta are membrane-bound and function as PV receptors. The virus recognition site is contained in the amino-terminal domain, D1. Having the virus attachment site on the receptor distal from the plasma membrane may be important for successful initiation of infection of cells by the virus. CD155 binds in the poliovirus "canyon" with a footprint similar to that of the intercellular adhesion molecule-1 receptor on human rhinoviruses. This group also includes the first Ig-like domain of nectin-1 (also known as poliovirus receptor related protein(PVRL)1; CD111), nectin-3 (also known as PVRL 3), nectin-4 (also known as PVRL4; LNIR receptor)and DNAX accessory molecule 1 (DNAM-1; CD226).

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15777921  19 HTEIKRVAEEKVTLPCHHQLGLPEKDTLdIEWLLTDNeGNQKVVITYSSRHVYNnLTEEQKGRVAFASNFLAG-DASLQI 97
Cdd:cd05718   6 PTEVTGFLGGSVTLPCSLTSPGTTKITQ-VTWMKIGA-GSSQNVAVFHPQYGPS-VPNPYAERVEFLAARLGLrNATLRI 82

                        90
                ....*....|....*
gi 15777921  98 EPLKPSDEGRYTCKV 112
Cdd:cd05718  83 RNLRVEDEGNYICEF 97

Immunoglobulin I-set domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15777921   143 TEGSDLTLQCEsASGTKPIVYYWQRirekegEDEHLPPKSRIDY-NNPGRVLL--QNLTMASSGLYQCTAGNEAGKESCV 219
Cdd:pfam07679  13 QEGESARFTCT-VTGTPDPEVSWFK------DGQPLRSSDRFKVtYEGGTYTLtiSNVQPDDSGKYTCVATNSAGEAEAS 85

                  ....*
gi 15777921   220 VRVTV 224
Cdd:pfam07679  86 AELTV 90

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15777921   133 KPKCELEGEPT---EGSDLTLQCESASGTKPiVYYWQRIREKEGEDEHLPpksRIDYNNPGRVLLQNLTMASSGLYQCTA 209
Cdd:pfam13927   1 KPVITVSPSSVtvrEGETVTLTCEATGSPPP-TITWYKNGEPISSGSTRS---RSLSGSNSTLTISNVTRSDAGTYTCVA 76

                  ..
gi 15777921   210 GN 211
Cdd:pfam13927  77 SN 78

Immunoglobulin V-Type;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15777921     30 VTLPCHHQLGLPEKDTLDieWLlTDNEGNQKVVITYSSRHVYNNLTEEQKGRVAFASNFLAGDASLQIEPLKPSDEGRYT 109
Cdd:smart00406   2 VTLSCKFSGSTFSSYYVS--WV-RQPPGKGLEWLGYIGSNGSSYYQESYKGRFTISKDTSKNDVSLTISNLRVEDTGTYY 78

                   ...
gi 15777921    110 CKV 112
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 15777921  30 VTLPCHHQlGLPEkdtLDIEWLLtdnEGNQKVVITYSSRHVYNnlteeqkgrvafasnflaGDASLQIEPLKPSDEGRYT 109
Cdd:cd00096   1 VTLTCSAS-GNPP---PTITWYK---NGKPLPPSSRDSRRSEL------------------GNGTLTISNVTLEDSGTYT 55

                        90
                ....*....|....*
gi 15777921 110 CKVKNSGRYVWSHVI 124
Cdd:cd00096  56 CVASNSAGGSASASV 70

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 15777921 148 LTLQCEsASGTKPIVYYWQrireKEGEDEHLPPKSRIDYNNPGRVL-LQNLTMASSGLYQCTAGNEAGKES 217
Cdd:cd00096   1 VTLTCS-ASGNPPPTITWY----KNGKPLPPSSRDSRRSELGNGTLtISNVTLEDSGTYTCVASNSAGGSA 66

Immunoglobulin I-set domain;

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 15777921    74 LTEEQKGRVAFasnfLAGDASLQIEPLKPSDEGRYTCKVKNSGRYVWSHVILK 126
Cdd:pfam07679  41 LRSSDRFKVTY----EGGTYTLTISNVQPDDSGKYTCVATNSAGEAEASAELT 89

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 15777921  28 EKVTLPCHHQLGLPEKdtldIEWLLTDNegNQKVVITYSSRHVYNNLTEEQKGRVA-FASNFLAGDASLQIEPLKPSDEG 106
Cdd:cd16091  13 EDCILPCSFTPGSEVV----IHWYKQDS--DIKVHSYYYGKDQLESQDQRYRNRTSlFKDQISNGNASLLLRRVQLQDEG 86

                        90       100
                ....*....|....*....|.
gi 15777921 107 RYTCKVKNSGRYVWSHVILKA 127
Cdd:cd16091  87 RYKCYTSTIIGNQESFVNLKV 107

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 15777921   144 EGSDLTLQCESASGTKPIVYYWQrireKEGEDEHLPPKSRIDYNNPGR--VLLQNLTMASSGLYQCTA 209
Cdd:pfam00047  10 EGDSATLTCSASTGSPGPDVTWS----KEGGTLIESLKVKHDNGRTTQssLLISNVTKEDAGTYTCVV 73

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 15777921  30 VTLPC--HHQLGLPEKDTLDIEWL-LTDNEGNQKVVITYSSRH--VYNNLteeqKGRVAF--ASNflaGDASLQIEPLKP 102
Cdd:cd05877  15 VTLPCryHYEPELSAPRKIRVKWTkLEVDYAKEEDVLVAIGTRhkSYGSY----QGRVFLrrADD---LDASLVITDLRL 87

                        90
                ....*....|
gi 15777921 103 SDEGRYTCKV 112
Cdd:cd05877  88 EDYGRYRCEV 97

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 15777921  28 EKVTLPCHHQLGLPekdTLDIEWLLTDNEGNQKVVITYSSRHvyNNLTEEQKGRVAfASNFLAGDASLQIEPLKPSDEGR 107
Cdd:cd00099  14 ESVTLSCEVSSSFS---STYIYWYRQKPGQGPEFLIYLSSSK--GKTKGGVPGRFS-GSRDGTSSFSLTISNLQPEDSGT 87

                        90
                ....*....|.
gi 15777921 108 YTCKVKNSGRY 118
Cdd:cd00099  88 YYCAVSESGGT 98

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 15777921   144 EGSDLTLQCE------------------SASGTKPIVYYWQRIREKEGEDEHLPPKSRIDYNNpGRVLLQNLTMASSGLY 205
Cdd:pfam07686  10 LGGSVTLPCTysssmseastsvywyrqpPGKGPTFLIAYYSNGSEEGVKKGRFSGRGDPSNGD-GSLTIQNLTLSDSGTY 88

                          90       100
                  ....*....|....*....|
gi 15777921   206 QC-TAGNEAGKESCVVRVTV 224
Cdd:pfam07686  89 TCaVIPSGEGVFGKGTRLTV 108

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 15777921  28 EKVTLPCHH--QLGLPE----KDTLDIEW--LLTDNEGNQKVVITYSSRHVYNnLTEEQKGRVAFASNFLA-GDASLQIE 98
Cdd:cd05878  13 TSVTLPCYFidPPHPVTpstaPLAPRIKWskVSVDGKKEKEVVLLVATEGRVR-VNSAYQGRVSLPNYPAIpSDATLEVQ 91

                        90
                ....*....|....
gi 15777921  99 PLKPSDEGRYTCKV 112
Cdd:cd05878  92 SLRASDSGLYRCEV 105

Second Ig-like domain of Junctional adhesion molecule-1 (JAM1); a member of the I-set of IgSF domains; The members here are composed of the second Ig-like domain of Junctional adhesion molecule-1 (JAM1). JAM1 is an immunoglobulin superfamily (IgSF) protein with two Ig-like domains in its extracellular region; it plays a role in the formation of endothelial and epithelial tight junction and acts as a receptor for mammalian reovirus sigma-1. The IgSF is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. The two sheets are linked together by a conserved disulfide bond between B strand and F strand. 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 second Ig-like domain of JAM1 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, the A strand of the I-set is discontinuous but lacks 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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15777921 134 PKCELEGEPTEGSDLTLQCESASGTKPIVYYWQrireKEGEDEHLPPKSRIDYNNP--------GRVLLQNLTMASSGLY 205
Cdd:cd20950   1 PTVNIPSSATIGNRAVLTCSEPDGSPPSEYTWF----KDGVVMPTNPKSTRAFSNSsysldpttGELVFDPLSASDTGEY 76

                ....*....
gi 15777921 206 QCTAGNEAG 214
Cdd:cd20950  77 SCEARNGYG 85

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 15777921    26 AEEKVTLPCHHQLGLPEkdtLDIEWLLTDNEGNQkvvitySSRHVYNNLTEeqkgrvafasnflaGDASLQIEPLKPSDE 105
Cdd:pfam00047  10 EGDSATLTCSASTGSPG---PDVTWSKEGGTLIE------SLKVKHDNGRT--------------TQSSLLISNVTKEDA 66

                          90
                  ....*....|.
gi 15777921   106 GRYTCKVKNSG 116
Cdd:pfam00047  67 GTYTCVVNNPG 77

First immunoglobulin (Ig) domain of nectin-4, and similar domains; The members here are composed of the first immunoglobulin (Ig) domain of nectin-4 (also known as poliovirus receptor related protein 4 or LNIR receptor). Nectin-4 belongs to the nectin family, which is 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 nectin-4 trans-interacts with nectin-1. Nectin-4 has also been shown to interact with the actin filament-binding protein, afadin. Unlike the other nectins, which are widely expressed in adult tissues, nectin-4 is mainly expressed during embryogenesis, and is not detected in normal adult tissue or in serum. Nectin-4 is re-expressed in breast carcinoma, and patients having metastatic breast cancer have a circulating form of nectin-4 formed from the ectodomain

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15777921  30 VTLPCHHQLGLPEKdTLDIEWLLTDN-EGNQKVVITYSSRHVynNLTEEQKGRVAFASNFLAGDASLQIEPLKPSDEGRY 108
Cdd:cd05888  11 AKLPCFYRGDSGEQ-VGQVAWARVDAgEGAQEIALLHSKYGL--HVFPAYEGRVEQPPPPRPADGSVLLRNAVQADEGEY 87

                ....
gi 15777921 109 TCKV 112
Cdd:cd05888  88 ECRV 91

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 15777921  30 VTLPCHH--QLGLPEKDtLDIEWLLTDNEgnQKVVITYSSRHVYNNLTEEQKGRVAFASNFLA-GDASLQIEPLKPSDEG 106
Cdd:cd20934  15 ATLRCSFspEPGFSLAQ-LSVFWQLTDTK--QLVHSFTESQDQGRDQGSAYANRTALFPDLLAqGNASLRLQRVRVADEG 91

                        90
                ....*....|..
gi 15777921 107 RYTC--KVKNSG 116
Cdd:cd20934  92 SYTCfvSVQDFG 103

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

                        10        20
                ....*....|....*....|....*
gi 15777921  91 GDASLQIEPLKPSDEGRYTCKVKNS 115
Cdd:cd05724  50 DDGNLLIAEARKSDEGTYKCVATNM 74