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 13376852  32 QVPEDPVVALVGTDATLCCSFSPEPGFSLAQLNLIWQLTDTKQLVHSFAEGQ----DQGSAYANRTALFPDLLAQGNASL 107
Cdd:cd20934   1 RVPEDPVVALVGTDATLRCSFSPEPGFSLAQLSVFWQLTDTKQLVHSFTESQdqgrDQGSAYANRTALFPDLLAQGNASL 80

                        90       100       110
                ....*....|....*....|....*....|....*
gi 13376852 108 RLQRVRVADEGSFTCFVSIRDFGSAAVSLQVAAPY 142
Cdd:cd20934  81 RLQRVRVADEGSYTCFVSVQDFGSAAVSLQVAAPF 115

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 13376852  32 QVPEDPVVALVGTDATLCCSFSPEPGFSLAQLNLIWQLTDTKQLVHSFAEGQ----DQGSAYANRTALFPDLLAQGNASL 107
Cdd:cd20934   1 RVPEDPVVALVGTDATLRCSFSPEPGFSLAQLSVFWQLTDTKQLVHSFTESQdqgrDQGSAYANRTALFPDLLAQGNASL 80

                        90       100       110
                ....*....|....*....|....*....|....*
gi 13376852 108 RLQRVRVADEGSFTCFVSIRDFGSAAVSLQVAAPY 142
Cdd:cd20934  81 RLQRVRVADEGSYTCFVSVQDFGSAAVSLQVAAPF 115

Immunoglobulin Constant 1 (IgC1) domain of Programmed death ligand 2 (PD-L2); The members here are composed of the immunoglobulin Constant 1 (IgC1) domain of Programmed death ligand 2 (PD-L2; also known as B7-DC or CD273). PD-L2 is a cell-surface ligand that competes with PD-L1 for binding to the immunosuppressive receptor programmed death-1 (PD-1). PD-1 is a member of the CD28/B7 family that plays an important role in negatively regulating immune responses upon interaction with its two ligands, PD-L1 or PD-L2. PD-L2 has a higher affinity for PD-1 but is expressed at lower levels. PD-L2 interaction with PD-1 suppresses T cell proliferation, cytokine production and cytotoxic activity. PD-L2 is expressed on tumor cells, antigen-presenting cells or APCs (such as macrophages, B cells and dendritic cells), and a variety of other immune and nonimmune cells. Tumor expression of PD-L2 may contribute to tumor evasion of immune destruction by inactivating T cells. Thus, PD-L2 is a negative predictor for prognosis among solid cancer patients.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 13376852 157 PG-DTVTITCSSyRGYPEAEVFWQDgqgVPLTGNvtTSQMANEQGLFDVHSVLRVVLGANGTYSCLVRN 224
Cdd:cd20986   8 PGtGEVQLTCQA-RGYPLAEVSWQN---VSVPAN--TSHTRTPEGLYQVTSVLRLKPQPGRNFSCMFWN 70

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13376852    156 RPGDTVTITCsSYRGYPEAEVFW--QDGQGVPLTGNVTTSQMANEQGLFdvhsVLRVVLGANGTYSCLVRNPVlqQDAHG 233
Cdd:smart00410   7 KEGESVTLSC-EASGSPPPEVTWykQGGKLLAESGRFSVSRSGSTSTLT----ISNVTPEDSGTYTCAATNSS--GSASS 79

                   ....*
gi 13376852    234 SVTIT 238
Cdd:smart00410  80 GTTLT 84

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 13376852  32 QVPEDPVVALVGTDATLCCSFSPEPGFSLAQLNLIWQLTDTKQLVHSFAEGQ----DQGSAYANRTALFPDLLAQGNASL 107
Cdd:cd20934   1 RVPEDPVVALVGTDATLRCSFSPEPGFSLAQLSVFWQLTDTKQLVHSFTESQdqgrDQGSAYANRTALFPDLLAQGNASL 80

                        90       100       110
                ....*....|....*....|....*....|....*
gi 13376852 108 RLQRVRVADEGSFTCFVSIRDFGSAAVSLQVAAPY 142
Cdd:cd20934  81 RLQRVRVADEGSYTCFVSVQDFGSAAVSLQVAAPF 115

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 13376852  39 VALVGTDATLCCSFSPEPgfSLAQLNLIWQLTDTKQLVHSFAEGQD----QGSAYANRTALFPDLLAQGNASLRLQRVRV 114
Cdd:cd20984   8 AGNIGEDGILSCTFTPDI--KLSDIVIQWLKEGDSGLVHEFKEGKDelsrQSPMFRGRTSLFADQVHVGNASLRLKNVQL 85

                        90
                ....*....|.
gi 13376852 115 ADEGSFTCFVS 125
Cdd:cd20984  86 TDAGTYLCIIS 96

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        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13376852  31 VQVPEDPVVALVGTDATLCCSFSPEPGFSLAQLNLIWQLTDTK--QLVHSFAEGQDQGSAYANRTALFPDLLAQGNASLR 108
Cdd:cd20947   1 VTVPKDLYVVEYGSNMTIECKFPVEKQLDLAALIVYWEMEDKNiiQFVHGEEDLKVQHSSYRQRARLLKDQLSLGNAALQ 80

                        90
                ....*....|....*..
gi 13376852 109 LQRVRVADEGSFTCFVS 125
Cdd:cd20947  81 ITDVKLQDAGVYRCMIS 97

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13376852   144 KPSMTLEPNK-DLRPGDTVTITCSSyRGYPEAEVFWQDGQGVPLTGNVTTSQMANEQGLFDVHSVLRvvlGANGTYSCLV 222
Cdd:pfam13927   1 KPVITVSPSSvTVREGETVTLTCEA-TGSPPPTITWYKNGEPISSGSTRSRSLSGSNSTLTISNVTR---SDAGTYTCVA 76

                  ..
gi 13376852   223 RN 224
Cdd:pfam13927  77 SN 78

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 13376852   151 PNKDLRPGDTVTITCSSYRGYPEAEVFWQDGQGVPLTGNvTTSQMANEQGLFDVHsVLRVVLGANGTYSCLVRNPVLQQD 230
Cdd:pfam00047   4 PTVTVLEGDSATLTCSASTGSPGPDVTWSKEGGTLIESL-KVKHDNGRTTQSSLL-ISNVTKEDAGTYTCVVNNPGGSAT 81

                  .
gi 13376852   231 A 231
Cdd:pfam00047  82 L 82

Immunoglobulin Constant 1 (IgC1) domain of Programmed death ligand 2 (PD-L2); The members here are composed of the immunoglobulin Constant 1 (IgC1) domain of Programmed death ligand 2 (PD-L2; also known as B7-DC or CD273). PD-L2 is a cell-surface ligand that competes with PD-L1 for binding to the immunosuppressive receptor programmed death-1 (PD-1). PD-1 is a member of the CD28/B7 family that plays an important role in negatively regulating immune responses upon interaction with its two ligands, PD-L1 or PD-L2. PD-L2 has a higher affinity for PD-1 but is expressed at lower levels. PD-L2 interaction with PD-1 suppresses T cell proliferation, cytokine production and cytotoxic activity. PD-L2 is expressed on tumor cells, antigen-presenting cells or APCs (such as macrophages, B cells and dendritic cells), and a variety of other immune and nonimmune cells. Tumor expression of PD-L2 may contribute to tumor evasion of immune destruction by inactivating T cells. Thus, PD-L2 is a negative predictor for prognosis among solid cancer patients.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 13376852 157 PG-DTVTITCSSyRGYPEAEVFWQDgqgVPLTGNvtTSQMANEQGLFDVHSVLRVVLGANGTYSCLVRN 224
Cdd:cd20986   8 PGtGEVQLTCQA-RGYPLAEVSWQN---VSVPAN--TSHTRTPEGLYQVTSVLRLKPQPGRNFSCMFWN 70

Immunoglobulin variable domain (IgV) in Cluster of Differentiation (CD) 86; The members here are composed of the immunoglobulin variable region (IgV) in the Cluster of Differentiation (CD) 86). 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 CD152) on T cells. signaling through CD28 augments the T-cell response, whereas CTLA-4 signaling attenuates it. The CTLA-4 and B7-2 monomers are both two-layer beta-sandwiches that display the chain topology characteristic of the immunoglobulin variable (V-type) domains present in antigen receptors. The front and back sheets of B7-2 are composed of AGFCC'C" and BED strands, respectively. Members of the IgV family 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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13376852  38 VVALVGTDATLCCSFSPEPGFSLAQLNLIWQlTDTKQLVHSFAEGQDQ----GSAYANRTALfpdllAQGNASLRLQRVR 113
Cdd:cd16087   3 IQAYFNETAYLPCQFKNPQNISLSELVVFWQ-DQKKLVLYELYLGKEKldnvNSKYIGRTSF-----DQENWTLQLHNVQ 76

                        90
                ....*....|.
gi 13376852 114 VADEGSFTCFV 124
Cdd:cd16087  77 IKDQGTYQCFI 87

Immunoglobulin Constant-1 (C1)-set domain; The members here are composed of C1-set domains, classical Ig-like domains resembling the antibody constant domain. Members of the IgC1 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, while the IgC domain is involved in oligomerization and molecular interactions. 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 strands by G, F, C, and C'.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13376852 154 DLRPGDTVTITCSSYRGYPE-AEVFW-QDGQGVPlTGNVTTSQMANEQGLFDVHSVLRVVLG---ANGTYSCLVRNPVLQ 228
Cdd:cd00098  10 EEKGGGKVTLVCLVSGFYPKdITVTWlKNGVPLT-SGVSTSSPVEPNDGTYSVTSSLTVPPSdwdEGATYTCVVTHESLK 88

                .
gi 13376852 229 Q 229
Cdd:cd00098  89 S 89

CH3 domain (third constant Ig domain of the heavy chain) in immunoglobulin heavy alpha, gamma, and delta chains, and CH4 domain (fourth constant Ig domain of the heavy chain) in immunoglobulin heavy alpha, epsilon, and mu chains; member of the C1-set of I; The members here are composed of the third and fourth immunoglobulin constant domain (IgC) of alpha, delta, gamma and alpha, epsilon, and mu heavy chains, respectively. This domain is found on the Fc fragment. The basic structure of Ig molecules is a tetramer of two light chains and two heavy chains linked by disulfide bonds. There are two types of light chains: kappa and lambda; each is composed of a constant domain and a variable domain. There are five types of heavy chains: alpha, delta, epsilon, gamma, and mu, all consisting of a variable domain (VH) with three (alpha, delta and gamma) or four (epsilon and mu) constant domains (CH1 to CH4). Ig molecules are modular proteins, in which the variable and constant domains have clear, conserved sequence patterns.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 13376852 151 PNKDLRPGDTVTITCSSYRGYPEaEVF--W-QDGQGVPLTGNVTTSQMANEQGLFDVHSVLRVVLGA--NG-TYSCLV 222
Cdd:cd05768   9 PEEELSLNETVTLTCLVKGFYPE-DIFvsWlQNGEPLPSADYKTTAPVPESDGSFFVYSKLNVSTADwnSGdVFSCVV 85

Immunoglobulin V-Type;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13376852     45 DATLCCSFSpepGFSLAQLNLIWQ-LTDTKQLVHsFAEGQDQGSAYA-----NRTALFPDLlAQGNASLRLQRVRVADEG 118
Cdd:smart00406   1 SVTLSCKFS---GSTFSSYYVSWVrQPPGKGLEW-LGYIGSNGSSYYqesykGRFTISKDT-SKNDVSLTISNLRVEDTG 75

                   ....*.
gi 13376852    119 SFTCFV 124
Cdd:smart00406  76 TYYCAV 81

Immunoglobulin (Ig)-like domain of human carcinoembryonic antigen (CEA) related cell adhesion molecule (CEACAM) domains 2, 4, and 6, and similar domains; The members here are composed of the second, fourth, and sixth immunoglobulin (Ig)-like domains in human carcinoembryonic antigen (CEA) related cell adhesion molecule (CEACAM) protein subfamily. The CEA family is a group of anchored or secreted glycoproteins expressed by epithelial cells, leukocytes, endothelial cells, and placenta. The CEA family is divided into the CEACAM and pregnancy-specific glycoprotein (PSG) subfamilies. This group represents the CEACAM subfamily. CEACAM1 has many important cellular functions; it is a cell adhesion molecule and a signaling molecule that regulates the growth of tumor cells, an angiogenic factor, and a receptor for bacterial and viral pathogens, including mouse hepatitis virus (MHV). In mice, four isoforms of CEACAM1 generated by alternative splicing have either two [D1, D4] or four [D1-D4] Ig-like domains on the cell surface.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13376852 144 KPSMTLEPNKDLRPGDTVTITCSSYRgyPEAEVFW-QDGQGVPLTGNVTTSQmANEQglfdvHSVLRVVLGANGTYSCLV 222
Cdd:cd05740   1 KPFISSNNSNPVEDKDAVTLTCEPET--QNTSYLWwFNGQSLPVTPRLTLSN-GNRT-----LTLLNVTREDAGAYQCEI 72

                ....
gi 13376852 223 RNPV 226
Cdd:cd05740  73 SNPV 76

Second immunoglobulin (Ig) domain of poliovirus receptor (PVR, also known as CD155 and Necl-5), and similar domains; member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig) domain of poliovirus receptor (PVR, also known as CD155 and nectin-like protein 5 (Necl-5)) and similar proteins. 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), these result from alternate splicing of the CD155 mRNA, and have identical extracellular domains. CD155-beta and CD155-gamma are secreted, while 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" and has a footprint similar to that of the intercellular adhesion molecule-1 receptor on human rhinoviruses. This group also includes the second Ig-like domain of nectin-1, also known as poliovirus receptor related protein(PVRL)1 or CD111.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13376852 145 PSMTLEPNKDLRPGD--TVTITCSSYRGYPEAEVFWqDGQgvpLTGNVTTSQMANEQGLFDVHSVLRVVLG--ANG-TYS 219
Cdd:cd05719   1 PTNSLEGGPALLIGGepTLVATCISANGKPPASVTW-ETD---LKGEASTTQVRGSNGTVTVTSRYRLVPSreADGqPLT 76

                        90
                ....*....|....*....
gi 13376852 220 CLVRNPVLQQDAHGSVTIT 238
Cdd:cd05719  77 CVVEHPSLEKDQRISVTLN 95

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13376852    30 EVQVPEDPVVALVGTDATLCC--SFSPEPgfslaqlNLIWQLTDTKQLVHSFAEGQDQGsayanrtalfpdllaqGNASL 107
Cdd:pfam13927   3 VITVSPSSVTVREGETVTLTCeaTGSPPP-------TITWYKNGEPISSGSTRSRSLSG----------------SNSTL 59

                          90
                  ....*....|....*...
gi 13376852   108 RLQRVRVADEGSFTCFVS 125
Cdd:pfam13927  60 TISNVTRSDAGTYTCVAS 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 13376852  36 DPVVALVGTDATLCCSFSPEPGFSLAQlnLIWQLTDTKQ------LVHsFAEGQDQGSAYANRTAlFPDLLAQGNASLRL 109
Cdd:cd05888   1 DVVTVVLGQDAKLPCFYRGDSGEQVGQ--VAWARVDAGEgaqeiaLLH-SKYGLHVFPAYEGRVE-QPPPPRPADGSVLL 76

                        90       100       110
                ....*....|....*....|....*....|.
gi 13376852 110 QRVRVADEGSFTCFVSIRDFGS--AAVSLQV 138
Cdd:cd05888  77 RNAVQADEGEYECRVSTFPAGNfqAELRLRV 107

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

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 13376852 152 NKDLRPGDTVTITCSSYrGYPEAEVFWQDGQGVPLTGNVTTSQMANEQGLfdvhSVLRVVLGANGTYSCLVRNPV 226
Cdd:cd20970  11 TVTAREGENATFMCRAE-GSPEPEISWTRNGNLIIEFNTRYIVRENGTTL----TIRNIRRSDMGIYLCIASNGV 80

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 13376852  46 ATLCCSFSPEPgfslaQLNLIWQLtDTKQLVHSfaegqdqgsayanrtALFPDLLAQGNASLRLQRVRVADEGSFTCFVS 125
Cdd:cd00096   1 VTLTCSASGNP-----PPTITWYK-NGKPLPPS---------------SRDSRRSELGNGTLTISNVTLEDSGTYTCVAS 59

                        90
                ....*....|.
gi 13376852 126 IRDFGSAAVSL 136
Cdd:cd00096  60 NSAGGSASASV 70

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 13376852  46 ATLCC--SFSPEpgfSLAQLNLIWQLTDtkQLVHSFAEGQ-DQGSAYANRTalFPDLLaqGNASLRLQRVRVADEGSFTC 122
Cdd:cd16086  12 ALLSCdyNVSVD---ELAQVRIYWQKDD--KMVLTIISGDvKVWPEYKNRT--LFDIT--NNLSIVILALRLSDRGTYTC 82

                ....*....
gi 13376852 123 FVSIRDFGS 131
Cdd:cd16086  83 VVQKKERGA 91

Immunoglobulin I-set domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13376852   145 PSMTLEP-NKDLRPGDTVTITCSSyRGYPEAEVFWQ-DGQGVPLTGNVTTSQMANEQGLFdvhsVLRVVLGANGTYSCLV 222
Cdd:pfam07679   1 PKFTQKPkDVEVQEGESARFTCTV-TGTPDPEVSWFkDGQPLRSSDRFKVTYEGGTYTLT----ISNVQPDDSGKYTCVA 75

                          90
                  ....*....|....*
gi 13376852   223 RNPVLQQDAHGSVTI 237
Cdd:pfam07679  76 TNSAGEAEASAELTV 90