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 33414525  32 QVSEDPVVALVDTDATLRCSFSPEPGFSLRQLNLIWQLTDTKQLVHSFTE----GRDQGSAYANRTALFPDLLVQGNASL 107
Cdd:cd20934   1 RVPEDPVVALVGTDATLRCSFSPEPGFSLAQLSVFWQLTDTKQLVHSFTEsqdqGRDQGSAYANRTALFPDLLAQGNASL 80

                        90       100       110
                ....*....|....*....|....*....|....*
gi 33414525 108 RLQRVRVTDEGSYTCFVSIQDFDSAAVSLQVAAPY 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 33414525  32 QVSEDPVVALVDTDATLRCSFSPEPGFSLRQLNLIWQLTDTKQLVHSFTE----GRDQGSAYANRTALFPDLLVQGNASL 107
Cdd:cd20934   1 RVPEDPVVALVGTDATLRCSFSPEPGFSLAQLSVFWQLTDTKQLVHSFTEsqdqGRDQGSAYANRTALFPDLLAQGNASL 80

                        90       100       110
                ....*....|....*....|....*....|....*
gi 33414525 108 RLQRVRVTDEGSYTCFVSIQDFDSAAVSLQVAAPY 142
Cdd:cd20934  81 RLQRVRVADEGSYTCFVSVQDFGSAAVSLQVAAPF 115

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 33414525 161 VTITCSsYQGYPEAEVFW-KDGQGLPltgnvttSQMANERGLFDVHSVLR---VVLGANGTYSCLVRNPVLQQDAH 232
Cdd:cd00096   1 VTLTCS-ASGNPPPTITWyKNGKPLP-------PSSRDSRRSELGNGTLTisnVTLEDSGTYTCVASNSAGGSASA 68

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33414525     37 PVVALVDTDATLRCSFS--PEPGFSLRQLNLIWQLTDTKQLVHSftegrdqgsayanrtalfpdllVQGNASLRLQRVRV 114
Cdd:smart00410   3 SVTVKEGESVTLSCEASgsPPPEVTWYKQGGKLLAESGRFSVSR----------------------SGSTSTLTISNVTP 60

                           90       100
                   ....*....|....*....|....*
gi 33414525    115 TDEGSYTCFVSIQDFD-SAAVSLQV 138
Cdd:smart00410  61 EDSGTYTCAATNSSGSaSSGTTLTV 85

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 33414525  32 QVSEDPVVALVDTDATLRCSFSPEPGFSLRQLNLIWQLTDTKQLVHSFTE----GRDQGSAYANRTALFPDLLVQGNASL 107
Cdd:cd20934   1 RVPEDPVVALVGTDATLRCSFSPEPGFSLAQLSVFWQLTDTKQLVHSFTEsqdqGRDQGSAYANRTALFPDLLAQGNASL 80

                        90       100       110
                ....*....|....*....|....*....|....*
gi 33414525 108 RLQRVRVTDEGSYTCFVSIQDFDSAAVSLQVAAPY 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 33414525  33 VSEDPVVALVDTDATLRCSFSPEPgfSLRQLNLIWQLTDTKQLVHSFTEGRD----QGSAYANRTALFPDLLVQGNASLR 108
Cdd:cd20984   2 VTAKHLAGNIGEDGILSCTFTPDI--KLSDIVIQWLKEGDSGLVHEFKEGKDelsrQSPMFRGRTSLFADQVHVGNASLR 79

                        90
                ....*....|....*..
gi 33414525 109 LQRVRVTDEGSYTCFVS 125
Cdd:cd20984  80 LKNVQLTDAGTYLCIIS 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 33414525  31 VQVSEDPVVALVDTDATLRCSFSPEPGFSLRQLNLIWQLTDTK--QLVHSFTEGRDQGSAYANRTALFPDLLVQGNASLR 108
Cdd:cd20947   1 VTVPKDLYVVEYGSNMTIECKFPVEKQLDLAALIVYWEMEDKNiiQFVHGEEDLKVQHSSYRQRARLLKDQLSLGNAALQ 80

                        90       100       110
                ....*....|....*....|....*....|
gi 33414525 109 LQRVRVTDEGSYTCFVSIQDFDSAAVSLQV 138
Cdd:cd20947  81 ITDVKLQDAGVYRCMISYGGADYKRITVKV 110

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 33414525  38 VVALVDTDATLRCSFSPEPGFSLRQLNLIWQlTDTKQLVHSFTEGRDQ----GSAYANRTALfpDllvQGNASLRLQRVR 113
Cdd:cd16087   3 IQAYFNETAYLPCQFKNPQNISLSELVVFWQ-DQKKLVLYELYLGKEKldnvNSKYIGRTSF--D---QENWTLQLHNVQ 76

                        90
                ....*....|.
gi 33414525 114 VTDEGSYTCFV 124
Cdd:cd16087  77 IKDQGTYQCFI 87

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 33414525  29 VEVQVsEDPVVALVDTDATLRCSFSPEPGFSLRQLNliWQLTDTKQ----LVHSFTEGRDQGSAYANRTALFPDLLVQGN 104
Cdd:cd05718   1 QRVQV-PTEVTGFLGGSVTLPCSLTSPGTTKITQVT--WMKIGAGSsqnvAVFHPQYGPSVPNPYAERVEFLAARLGLRN 77

                        90
                ....*....|....*...
gi 33414525 105 ASLRLQRVRVTDEGSYTC 122
Cdd:cd05718  78 ATLRIRNLRVEDEGNYIC 95

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 33414525 161 VTITCSsYQGYPEAEVFW-KDGQGLPltgnvttSQMANERGLFDVHSVLR---VVLGANGTYSCLVRNPVLQQDAH 232
Cdd:cd00096   1 VTLTCS-ASGNPPPTITWyKNGKPLP-------PSSRDSRRSELGNGTLTisnVTLEDSGTYTCVASNSAGGSASA 68

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 33414525    33 VSEDPVVALVDTDATLRCSFSPEPgfSLRQLNLIWQLTDT----KQLVHSFTEGRDQGSaYANRTALFPDLlVQGNASLR 108
Cdd:pfam07686   1 QTPREVTVALGGSVTLPCTYSSSM--SEASTSVYWYRQPPgkgpTFLIAYYSNGSEEGV-KKGRFSGRGDP-SNGDGSLT 76

                          90
                  ....*....|....
gi 33414525   109 LQRVRVTDEGSYTC 122
Cdd:pfam07686  77 IQNLTLSDSGTYTC 90

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 33414525 157 PG-DMVTITCSSyQGYPEAEVFWkdgQGLPLTGNvtTSQMANERGLFDVHSVLRVVLGANGTYSCLVRN 224
Cdd:cd20986   8 PGtGEVQLTCQA-RGYPLAEVSW---QNVSVPAN--TSHTRTPEGLYQVTSVLRLKPQPGRNFSCMFWN 70

First immunoglobulin variable (IgV) domain of nectin-2, nectin-like protein 5, and similar domains; The members here are composed of the second immunoglobulin (Ig) domain of nectin-2 (also known as poliovirus receptor related protein 2 or Cluster of Differentiation 112 (CD112)), nectin-like protein 5 (CD155), and similar proteins. Nectins and Nectin-like molecules are a family of Ca(2+)-independent immunoglobulin-like transmembrane glycoproteins belonging to the class of adhesion receptors, consisting of nine members (nectins 1 through 4 and nectin-like proteins 1 through 5). Nectins are synaptic cell adhesion molecules (CAMs) which facilitate adhesion and signaling at various intracellular junctions. Nectins form homophilic cis-dimers, followed by homophilic and heterophilic trans-dimers involved in cell-cell adhesion. Nectin-2 and nectin-3 localize at Sertoli-spermatid junctions where they form heterophilic trans-interactions between the cells that are essential for the formation and maintenance of the junctions and for spermatid development. CD155 is the fifth member in the nectin-like molecule family, and functions as the receptor of poliovirus; therefore, CD155 is also referred to as Necl-5, or PVR. In contrast to all other family members, CD155 lacks self-adhesion capacity, yet it shares with nectins the feature to interact with other nectins. For instance, CD155 heterophilically trans-interacts with nectin-3, thereby contributing significantly to the establishment of adherens junctions between epithelial cells. This group belongs to the Constant 1 (C1)-set of IgSF domains, which has one beta-sheet that is formed by strands A-B-E-D and the other strands by G-F-C-C'.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33414525  29 VEVQVSEDPVVALVDTdATLRCSF-SPEPGFSLRQLNliWQLTDTKQLVHSFTEgrDQGSAYAN-------RTALFPDLL 100
Cdd:cd20989   1 VRVQVPPEVRGFLGGS-VTLPCHLlPPNMVTHVSQVT--WQRHDEHGSVAVFHP--KQGPSFPEserlsfvAARLGAELR 75

                        90       100
                ....*....|....*....|..
gi 33414525 101 vqgNASLRLQRVRVTDEGSYTC 122
Cdd:cd20989  76 ---NASLAMFGLRVEDEGNYTC 94

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 33414525  46 ATLRCSFSPEPgfslrQLNLIWQLtDTKQLVHSFTEGRDqgsayanrtalfpdlLVQGNASLRLQRVRVTDEGSYTCFVS 125
Cdd:cd00096   1 VTLTCSASGNP-----PPTITWYK-NGKPLPPSSRDSRR---------------SELGNGTLTISNVTLEDSGTYTCVAS 59

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33414525     37 PVVALVDTDATLRCSFS--PEPGFSLRQLNLIWQLTDTKQLVHSftegrdqgsayanrtalfpdllVQGNASLRLQRVRV 114
Cdd:smart00410   3 SVTVKEGESVTLSCEASgsPPPEVTWYKQGGKLLAESGRFSVSR----------------------SGSTSTLTISNVTP 60

                           90       100
                   ....*....|....*....|....*
gi 33414525    115 TDEGSYTCFVSIQDFD-SAAVSLQV 138
Cdd:smart00410  61 EDSGTYTCAATNSSGSaSSGTTLTV 85

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33414525    30 EVQVSEDPVVALVDTDATLRC--SFSPEPgfslrqlNLIWQLtDTKQLVHSFTEGRDqgsayanrtalfpdlLVQGNASL 107
Cdd:pfam13927   3 VITVSPSSVTVREGETVTLTCeaTGSPPP-------TITWYK-NGEPISSGSTRSRS---------------LSGSNSTL 59

                          90
                  ....*....|....*...
gi 33414525   108 RLQRVRVTDEGSYTCFVS 125
Cdd:pfam13927  60 TISNVTRSDAGTYTCVAS 77

First immunoglobulin variable (IgV) domain of nectin-1, and similar domains; The members here are composed of the first immunoglobulin (Ig) domain of nectin-1 (also known as poliovirus receptor related protein 1 (PVRL1) or cluster of differentiation (CD) 111). Nectin-1 belongs to the nectin family comprised of four transmembrane glycoproteins (nectins-1 through -4). Nectins are synaptic cell adhesion molecules (CAMs) which facilitate adhesion and signaling at various intracellular junctions. Nectins form homophilic cis-dimers, followed by homophilic and heterophilic trans-dimers involved in cell-cell adhesion. In addition nectins heterophilically trans-interact with other CAMs such as nectin-like molecules (Necls), nectin-1 for example, has been shown to trans-interact with Necl-1. Nectins also interact with various other proteins, including the actin filament (F-actin)-binding protein, afadin. Mutation in the human nectin-1 gene is associated with cleft lip/palate ectodermal dysplasia syndrome (CLPED1). Nectin-1 is a major receptor for herpes simplex virus through interaction with the viral envelope glycoprotein D.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33414525  31 VQVsEDPVVALVDTDATLRCSF-SPEPGFSLRQLNliWQ-LTD-TKQLVHSFTE--GRDQGSAYANRTALFPDLLVQGna 105
Cdd:cd05886   3 VQV-NDSMSGFIGTDVVLHCSFaNPLPSVKITQVT--WQkSTNgSKQNVAIYNPsmGVSVLPPYRERVTFLNPSFTDG-- 77

                        90
                ....*....|....*..
gi 33414525 106 SLRLQRVRVTDEGSYTC 122
Cdd:cd05886  78 TIRLSRLELEDEGVYIC 94

Class II major histocompatibility complex (MHC) beta chain immunoglobulin domain; member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig) domain of major histocompatibility complex (MHC) class II beta chain. MHC class II molecules play a key role in the initiation of the antigen-specific immune reponse. These molecules have been shown to be expressed constitutively on the cell surface of professional antigen-presenting cells (APCs), including B-lymphocytes, monocytes, and macrophages in both humans and mice. The expression of these molecules has been shown to be induced in nonprofessional APCs such as keratinocyctes and they are also expressed on the surface of activated human T cells and on T cells from other species. The MHC II molecules present antigenic peptides to CD4(+) T-lymphocytes. These peptides derive mostly from proteolytic processing via the endocytic pathway of antigens internalized by the APC. These peptides bind to the MHC class II molecules in the endosome before they are transported to the cell surface. MHC class II molecules are heterodimers, comprised of two similarly-sized membrane-spanning chains, alpha and beta. Each chain has two globular domains (N- and C-terminal) and a membrane-anchoring transmembrane segment. The two chains form a compact four-domain structure. The peptide-binding site is a cleft in the structure.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33414525 144 KPSMTLEPNKDLRPGDMVTITCSSYQGYP-EAEVFW-KDGQGLPlTGNVTTSQMANERGLFDVHSVLRVVLGANGTYSCL 221
Cdd:cd05766   3 QPSVKVSPTKTGPLEHPNLLVCSVTGFYPaEIEVKWfRNGQEET-AGVVSTELIPNGDWTFQILVMLETTPRRGDVYTCQ 81

                ....*...
gi 33414525 222 VRNPVLQQ 229
Cdd:cd05766  82 VEHSSLQS 89

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33414525   144 KPSMTLEPNkDLRPGDMVTITCSSYqGYPEAEVFW-KDGQGLPLTGNVTTSqmanerglfdvhsvlRVVLGANGTYSCLV 222
Cdd:pfam13895   1 KPVLTPSPT-VVTEGEPVTLTCSAP-GNPPPSYTWyKDGSAISSSPNFFTL---------------SVSAEDSGTYTCVA 63

                          90
                  ....*....|....*.
gi 33414525   223 RNPVLQQDAHgSVTIT 238
Cdd:pfam13895  64 RNGRGGKVSN-PVELT 78

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 33414525 161 VTITCSSYQGYPE-AEVFW-KDGQGLPlTGNVTTSQMANERGLFDVHSVLRVVLG---ANGTYSCLVRNPVLQQ 229
Cdd:cd00098  17 VTLVCLVSGFYPKdITVTWlKNGVPLT-SGVSTSSPVEPNDGTYSVTSSLTVPPSdwdEGATYTCVVTHESLKS 89

Third immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the Constant 2 (C2)-set of IgSF domains; The members here are composed of the third 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. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. This group belongs to the C2-set of IgSF domains, having A, B, and E strands in one beta-sheet and A', G, F, C, and C' in the other. Unlike other Ig domain sets, the C2-set lacks the D strand.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33414525 146 SMTLEPN-KDLRPGDMVTITCSsYQGYPEAEVFW-KDGQGLPltgnvttsqmANERGLFDVHSVLRV--VLGAN-GTYSC 220
Cdd:cd20957   3 SATIDPPvQTVDFGRTAVFNCS-VTGNPIHTVLWmKDGKPLG----------HSSRVQILSEDVLVIpsVKREDkGMYQC 71

                        90
                ....*....|....*..
gi 33414525 221 LVRNPVLQQDAHGSVTI 237
Cdd:cd20957  72 FVRNDGDSAQATAELKL 88

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 33414525  46 ATLRC--SFSPEpgfSLRQLNLIWQLTDtkQLVHSFTEGR-DQGSAYANRTalFPDLLvqGNASLRLQRVRVTDEGSYTC 122
Cdd:cd16086  12 ALLSCdyNVSVD---ELAQVRIYWQKDD--KMVLTIISGDvKVWPEYKNRT--LFDIT--NNLSIVILALRLSDRGTYTC 82

                ..
gi 33414525 123 FV 124
Cdd:cd16086  83 VV 84