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 1045559607 104 QVPEDPVVALVGTDATLRCSFSPEPGFSLAQLNLIWQLTDTKQLVHSFTE----GRDQGSAYANRTALFPDLLAQGNASL 179
Cdd:cd20934     1 RVPEDPVVALVGTDATLRCSFSPEPGFSLAQLSVFWQLTDTKQLVHSFTEsqdqGRDQGSAYANRTALFPDLLAQGNASL 80

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 1045559607 180 RLQRVRVADEGSFTCFVSIRDFGSAAVSLQVAAPY 214
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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1045559607   2 TLEPNKDLRPGD--TVTITCSSYQGYPEAEVFWQdGQGVPLTGNVTTSQMANEQGLFDVHSILRVVL--GANG-TYSCLV 76
Cdd:pfam08205   2 TIEPPASLLEGEgpEVVATCSSAGGKPAPRITWY-LDGKPLEAAETSSEQDPESGLVTVTSELKLVPsrSDHGqSLTCQV 80

                  ....*....
gi 1045559607  77 RNPVLQQDA 85
Cdd:pfam08205  81 SYGALRGSI 89

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1045559607 104 QVPEDPVVALVGTDATLRCSFSPEPGFSLAQLNLIWQLTDTKQLVHSFTE----GRDQGSAYANRTALFPDLLAQGNASL 179
Cdd:cd20934     1 RVPEDPVVALVGTDATLRCSFSPEPGFSLAQLSVFWQLTDTKQLVHSFTEsqdqGRDQGSAYANRTALFPDLLAQGNASL 80

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 1045559607 180 RLQRVRVADEGSFTCFVSIRDFGSAAVSLQVAAPY 214
Cdd:cd20934    81 RLQRVRVADEGSYTCFVSVQDFGSAAVSLQVAAPF 115

CD80-like C2-set immunoglobulin domain; These domains belong to the immunoglobulin superfamily.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1045559607   2 TLEPNKDLRPGD--TVTITCSSYQGYPEAEVFWQdGQGVPLTGNVTTSQMANEQGLFDVHSILRVVL--GANG-TYSCLV 76
Cdd:pfam08205   2 TIEPPASLLEGEgpEVVATCSSAGGKPAPRITWY-LDGKPLEAAETSSEQDPESGLVTVTSELKLVPsrSDHGqSLTCQV 80

                  ....*....
gi 1045559607  77 RNPVLQQDA 85
Cdd:pfam08205  81 SYGALRGSI 89

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 1045559607 104 QVPEDPVVALvGTDATLRCSFSPEPgfSLAQLNLIWQLTDT----KQLVHSFTEGRDQGSaYANRTALFPDLlAQGNASL 179
Cdd:pfam07686   1 QTPREVTVAL-GGSVTLPCTYSSSM--SEASTSVYWYRQPPgkgpTFLIAYYSNGSEEGV-KKGRFSGRGDP-SNGDGSL 75

                          90
                  ....*....|....*
gi 1045559607 180 RLQRVRVADEGSFTC 194
Cdd:pfam07686  76 TIQNLTLSDSGTYTC 90

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 1045559607  15 VTITCSsYQGYPEAEVFWQ-DGQGVPLTGNVTTSQMANEQGLfdvhSILRVVLGANGTYSCLVRNPVLQQDAHS 87
Cdd:cd00096     1 VTLTCS-ASGNPPPTITWYkNGKPLPPSSRDSRRSELGNGTL----TISNVTLEDSGTYTCVASNSAGGSASAS 69

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1045559607  228 RPGDTVTITCsSYRGYPEAEVFW--QDGQGVPLTGNVTTSQMANEQGLFdvhsVLRVVLGANGTYSCLVRNPVlqQDAHG 305
Cdd:smart00410   7 KEGESVTLSC-EASGSPPPEVTWykQGGKLLAESGRFSVSRSGSTSTLT----ISNVTPEDSGTYTCAATNSS--GSASS 79

                   ....*
gi 1045559607  306 SVTIT 310
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 1045559607 104 QVPEDPVVALVGTDATLRCSFSPEPGFSLAQLNLIWQLTDTKQLVHSFTE----GRDQGSAYANRTALFPDLLAQGNASL 179
Cdd:cd20934     1 RVPEDPVVALVGTDATLRCSFSPEPGFSLAQLSVFWQLTDTKQLVHSFTEsqdqGRDQGSAYANRTALFPDLLAQGNASL 80

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 1045559607 180 RLQRVRVADEGSFTCFVSIRDFGSAAVSLQVAAPY 214
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 1045559607 111 VALVGTDATLRCSFSPEPgfSLAQLNLIWQLTDTKQLVHSFTEGRD----QGSAYANRTALFPDLLAQGNASLRLQRVRV 186
Cdd:cd20984     8 AGNIGEDGILSCTFTPDI--KLSDIVIQWLKEGDSGLVHEFKEGKDelsrQSPMFRGRTSLFADQVHVGNASLRLKNVQL 85

                          90
                  ....*....|.
gi 1045559607 187 ADEGSFTCFVS 197
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 1045559607 103 VQVPEDPVVALVGTDATLRCSFSPEPGFSLAQLNLIWQLTDTK--QLVHSFTEGRDQGSAYANRTALFPDLLAQGNASLR 180
Cdd:cd20947     1 VTVPKDLYVVEYGSNMTIECKFPVEKQLDLAALIVYWEMEDKNiiQFVHGEEDLKVQHSSYRQRARLLKDQLSLGNAALQ 80

                          90
                  ....*....|....*..
gi 1045559607 181 LQRVRVADEGSFTCFVS 197
Cdd:cd20947    81 ITDVKLQDAGVYRCMIS 97

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 1045559607 101 VEVQVPEDpVVALVGTDATLRCSFSPEPGFSLAQLNliWQLTDTKQ----LVHSFTEGRDQGSAYANRTALFPDLLAQGN 176
Cdd:cd05718     1 QRVQVPTE-VTGFLGGSVTLPCSLTSPGTTKITQVT--WMKIGAGSsqnvAVFHPQYGPSVPNPYAERVEFLAARLGLRN 77

                          90       100       110
                  ....*....|....*....|....*....|....
gi 1045559607 177 ASLRLQRVRVADEGSFTCFVSIRDFGSAAVSLQV 210
Cdd:cd05718    78 ATLRIRNLRVEDEGNYICEFATFPQGNRQGTTWL 111

CD80-like C2-set immunoglobulin domain; These domains belong to the immunoglobulin superfamily.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1045559607 220 TLEPNKDLRPGD--TVTITCSSYRGYPEAEVFWQdGQGVPLTGNVTTSQMANEQGLFDVHSVLRVVL--GANG-TYSCLV 294
Cdd:pfam08205   2 TIEPPASLLEGEgpEVVATCSSAGGKPAPRITWY-LDGKPLEAAETSSEQDPESGLVTVTSELKLVPsrSDHGqSLTCQV 80

                  ....*....
gi 1045559607 295 RNPVLQQDA 303
Cdd:pfam08205  81 SYGALRGSI 89

CD80-like C2-set immunoglobulin domain; These domains belong to the immunoglobulin superfamily.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1045559607   2 TLEPNKDLRPGD--TVTITCSSYQGYPEAEVFWQdGQGVPLTGNVTTSQMANEQGLFDVHSILRVVL--GANG-TYSCLV 76
Cdd:pfam08205   2 TIEPPASLLEGEgpEVVATCSSAGGKPAPRITWY-LDGKPLEAAETSSEQDPESGLVTVTSELKLVPsrSDHGqSLTCQV 80

                  ....*....
gi 1045559607  77 RNPVLQQDA 85
Cdd:pfam08205  81 SYGALRGSI 89

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 1045559607 229 PG-DTVTITCSSyRGYPEAEVFWQDgqgVPLTGNvtTSQMANEQGLFDVHSVLRVVLGANGTYSCLVRN 296
Cdd:cd20986     8 PGtGEVQLTCQA-RGYPLAEVSWQN---VSVPAN--TSHTRTPEGLYQVTSVLRLKPQPGRNFSCMFWN 70

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 1045559607 104 QVPEDPVVALvGTDATLRCSFSPEPgfSLAQLNLIWQLTDT----KQLVHSFTEGRDQGSaYANRTALFPDLlAQGNASL 179
Cdd:pfam07686   1 QTPREVTVAL-GGSVTLPCTYSSSM--SEASTSVYWYRQPPgkgpTFLIAYYSNGSEEGV-KKGRFSGRGDP-SNGDGSL 75

                          90
                  ....*....|....*
gi 1045559607 180 RLQRVRVADEGSFTC 194
Cdd:pfam07686  76 TIQNLTLSDSGTYTC 90

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 1045559607 101 VEVQVPEDpVVALVGTDATLRCSF-SPEPGFSLAQLNliWQLTDTKQLVHSFTEgrDQGSAYAN-------RTALFPDLL 172
Cdd:cd20989     1 VRVQVPPE-VRGFLGGSVTLPCHLlPPNMVTHVSQVT--WQRHDEHGSVAVFHP--KQGPSFPEserlsfvAARLGAELR 75

                          90       100
                  ....*....|....*....|..
gi 1045559607 173 aqgNASLRLQRVRVADEGSFTC 194
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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1045559607  15 VTITCSsYQGYPEAEVFWQ-DGQGVPLTGNVTTSQMANEQGLfdvhSILRVVLGANGTYSCLVRNPVLQQDAHS 87
Cdd:cd00096     1 VTLTCS-ASGNPPPTITWYkNGKPLPPSSRDSRRSELGNGTL----TISNVTLEDSGTYTCVASNSAGGSASAS 69

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 1045559607   5 PNKDLRPGDTVTITCSSYQGYPEaEVF--W-QDGQGVPLTGNVTTSQMANEQGLFDVHSILRVVLGA--NG-TYSCLV 76
Cdd:cd05768     9 PEEELSLNETVTLTCLVKGFYPE-DIFvsWlQNGEPLPSADYKTTAPVPESDGSFFVYSKLNVSTADwnSGdVFSCVV 85

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 1045559607 233 VTITCSsYRGYPEAEVFWQ-DGQGVPLTGNVTTSQMANEQGLfdvhSVLRVVLGANGTYSCLVRNPVLQQDAH 304
Cdd:cd00096     1 VTLTCS-ASGNPPPTITWYkNGKPLPPSSRDSRRSELGNGTL----TISNVTLEDSGTYTCVASNSAGGSASA 68

Immunoglobulin V-Type;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1045559607  117 DATLRCSFSpepGFSLAQLNLIWQ-LTDTKQLVHsFTEGRDQGSAYA-----NRTALFPDLlAQGNASLRLQRVRVADEG 190
Cdd:smart00406   1 SVTLSCKFS---GSTFSSYYVSWVrQPPGKGLEW-LGYIGSNGSSYYqesykGRFTISKDT-SKNDVSLTISNLRVEDTG 75

                   ....*.
gi 1045559607  191 SFTCFV 196
Cdd:smart00406  76 TYYCAV 81

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 1045559607 226 DLRPGDTVTITCSSYRGYPE-AEVFW-QDGQGVPlTGNVTTSQMANEQGLFDVHSVLRVVLG---ANGTYSCLVRNPVLQ 300
Cdd:cd00098    10 EEKGGGKVTLVCLVSGFYPKdITVTWlKNGVPLT-SGVSTSSPVEPNDGTYSVTSSLTVPPSdwdEGATYTCVVTHESLK 88

                  .
gi 1045559607 301 Q 301
Cdd:cd00098    89 S 89

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1045559607  109 PVVALVGTDATLRCSFSpepGFSLAQLNLIWQltdtkQLVHSFTEGRDQGSAYANrtalfpdllaqgNASLRLQRVRVAD 188
Cdd:smart00410   3 SVTVKEGESVTLSCEAS---GSPPPEVTWYKQ-----GGKLLAESGRFSVSRSGS------------TSTLTISNVTPED 62

                           90       100
                   ....*....|....*....|...
gi 1045559607  189 EGSFTCFVSIRDF-GSAAVSLQV 210
Cdd:smart00410  63 SGTYTCAATNSSGsASSGTTLTV 85

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 1045559607 216 KPSMTLEPNKDLRPGDTVTITCSSYRgyPEAEVFW-QDGQGVPLTGNVTTSQmANEQglfdvHSVLRVVLGANGTYSCLV 294
Cdd:cd05740     1 KPFISSNNSNPVEDKDAVTLTCEPET--QNTSYLWwFNGQSLPVTPRLTLSN-GNRT-----LTLLNVTREDAGAYQCEI 72

                  ....
gi 1045559607 295 RNPV 298
Cdd:cd05740    73 SNPV 76

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 1045559607 216 KPSMTLEPNKDLRPGDTVTITCSSYRGYP-EAEVFW-QDGQGVPlTGNVTTSQMANEQGLFDVHSVLRVVLGANGTYSCL 293
Cdd:cd05766     3 QPSVKVSPTKTGPLEHPNLLVCSVTGFYPaEIEVKWfRNGQEET-AGVVSTELIPNGDWTFQILVMLETTPRRGDVYTCQ 81

                  ....*...
gi 1045559607 294 VRNPVLQQ 301
Cdd:cd05766    82 VEHSSLQS 89

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1045559607 102 EVQVPEDPVVALVGTDATLRC--SFSPEPgfslaqlNLIWQLtDTKQLVHSFTEGRDQGSayanrtalfpdllaqGNASL 179
Cdd:pfam13927   3 VITVSPSSVTVREGETVTLTCeaTGSPPP-------TITWYK-NGEPISSGSTRSRSLSG---------------SNSTL 59

                          90
                  ....*....|....*...
gi 1045559607 180 RLQRVRVADEGSFTCFVS 197
Cdd:pfam13927  60 TISNVTRSDAGTYTCVAS 77

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1045559607 101 VEVQVPEDpVVALVGTDATLRCSF-SPEPGFSLAQLNLIWQLTDTKQLVHSFTEGRdqGSAYANRTALFPDL------LA 173
Cdd:cd05715     1 MEVYTPRE-LNVLNGSDVRLTCTFtSCYTVGDAFSVTWTYQPEGGNTTESMFHYSK--GKPYILKVGRFKDRvswagnPS 77

                          90       100
                  ....*....|....*....|...
gi 1045559607 174 QGNASLRLQRVRVADEGSFTCFV 196
Cdd:cd05715    78 KKDASIVISNLQFSDNGTYTCDV 100

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 1045559607 217 PSMTLEPNKDLRPGD--TVTITCSSYRGYPEAEVFWqDGQgvpLTGNVTTSQMANEQGLFDVHSVLRVVLG--ANG-TYS 291
Cdd:cd05719     1 PTNSLEGGPALLIGGepTLVATCISANGKPPASVTW-ETD---LKGEASTTQVRGSNGTVTVTSRYRLVPSreADGqPLT 76

                          90
                  ....*....|....*....
gi 1045559607 292 CLVRNPVLQQDAHGSVTIT 310
Cdd:cd05719    77 CVVEHPSLEKDQRISVTLN 95

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 1045559607 103 VQVpEDPVVALVGTDATLRCSF-SPEPGFSLAQLNliWQ--LTDTKQLVHSFTE--GRDQGSAYANRTALFPDLLAQGna 177
Cdd:cd05886     3 VQV-NDSMSGFIGTDVVLHCSFaNPLPSVKITQVT--WQksTNGSKQNVAIYNPsmGVSVLPPYRERVTFLNPSFTDG-- 77

                          90
                  ....*....|....*..
gi 1045559607 178 SLRLQRVRVADEGSFTC 194
Cdd:cd05886    78 TIRLSRLELEDEGVYIC 94

Second immunoglobulin (Ig) domain of nectin-3 and nectin-4 (poliovirus receptor related protein 4), 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 nectin-3 (also known as poliovirus receptor related protein 3 or cluster of differentiation (CD) 113) and nectin-4 (poliovirus receptor related protein 4). Nectin-3 and nectin-4 belong to the nectin family comprised of four transmembrane glycoproteins (nectin-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. 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. Nectin-3 has also been shown to form a heterophilic trans-interaction with nectin-1 in ciliary epithelia, establishing the apex-apex adhesion between the pigment and non-pigment cell layers. Nectin-4 has recently been identified in several types of breast carcinoma and can be used as a histological and serological marker for breast cancer.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1045559607 217 PSMTLEPNKDLRP---GDTVTITCSSYRGYPEAEVFWQDGQGvplTGNVTTSQMANEQGLFDVHSVLRVVLGANG-TYSC 292
Cdd:cd07704     1 PLVSLNPGPALLIdggNETLAASCTAETGKPAASVTWETDLG---GMESSRTFEHNRTATVTSEYHLVPTRFANGrPLTC 77

                          90
                  ....*....|
gi 1045559607 293 LVRNPVLQQD 302
Cdd:cd07704    78 VVSHPALQQD 87

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 1045559607 108 DPVVALVGTDATLRCSFSPEPGFSLAQlnLIWQLTDTKQ------LVHsFTEGRDQGSAYANRTAlFPDLLAQGNASLRL 181
Cdd:cd05888     1 DVVTVVLGQDAKLPCFYRGDSGEQVGQ--VAWARVDAGEgaqeiaLLH-SKYGLHVFPAYEGRVE-QPPPPRPADGSVLL 76

                          90       100       110
                  ....*....|....*....|....*....|.
gi 1045559607 182 QRVRVADEGSFTCFVSIRDFGS--AAVSLQV 210
Cdd:cd05888    77 RNAVQADEGEYECRVSTFPAGNfqAELRLRV 107

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1045559607 216 KPSMTLEPnKDLRPGDTVTITCSSYrGYPEAEVFWQdGQGVPLTGNvttsqmaneQGLFdvhsVLRVVLGANGTYSCLVR 295
Cdd:pfam13895   1 KPVLTPSP-TVVTEGEPVTLTCSAP-GNPPPSYTWY-KDGSAISSS---------PNFF----TLSVSAEDSGTYTCVAR 64

                          90
                  ....*....|....*
gi 1045559607 296 NPVLQQDAHgSVTIT 310
Cdd:pfam13895  65 NGRGGKVSN-PVELT 78

Second immunoglobulin (Ig) domain of nectin-3 and nectin-4 (poliovirus receptor related protein 4), 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 nectin-3 (also known as poliovirus receptor related protein 3 or cluster of differentiation (CD) 113) and nectin-4 (poliovirus receptor related protein 4). Nectin-3 and nectin-4 belong to the nectin family comprised of four transmembrane glycoproteins (nectin-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. 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. Nectin-3 has also been shown to form a heterophilic trans-interaction with nectin-1 in ciliary epithelia, establishing the apex-apex adhesion between the pigment and non-pigment cell layers. Nectin-4 has recently been identified in several types of breast carcinoma and can be used as a histological and serological marker for breast cancer.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1045559607  12 GDTVTITCSSYQGYPEAEVFWQDGQGvplTGNVTTSQMANEQGLFDVHSILRVVLGANG-TYSCLVRNPVLQQD 84
Cdd:cd07704    17 NETLAASCTAETGKPAASVTWETDLG---GMESSRTFEHNRTATVTSEYHLVPTRFANGrPLTCVVSHPALQQD 87