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 1720390840 155 IKGPEDGGVCVVCMTSGwYPEPQVHWkdsrgENLTAFSSETHTKDAEGLFSTETLLVVRDSSVRNVTCSIFN 226
Cdd:cd20986     5 LEVPGTGEVQLTCQARG-YPLAEVSW-----QNVSVPANTSHTRTPEGLYQVTSVLRLKPQPGRNFSCMFWN 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 1720390840  36 PSDPIVAAPGGEAILPCSVFPAMNVENMEeLRWFRSR---FSEAVLFYRDQEEQKEGQMPGYSQRTLLVKdqfhqGTAAV 112
Cdd:pfam07686   2 TPREVTVALGGSVTLPCTYSSSMSEASTS-VYWYRQPpgkGPTFLIAYYSNGSEEGVKKGRFSGRGDPSN-----GDGSL 75

                          90       100       110
                  ....*....|....*....|....*....|...
gi 1720390840 113 RILNVQASDSGIYICH-FQQGVFYDEAILELKV 144
Cdd:pfam07686  76 TIQNLTLSDSGTYTCAvIPSGEGVFGKGTRLTV 108

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        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1720390840 155 IKGPEDGGVCVVCMTSGwYPEPQVHWkdsrgENLTAFSSETHTKDAEGLFSTETLLVVRDSSVRNVTCSIFN 226
Cdd:cd20986     5 LEVPGTGEVQLTCQARG-YPLAEVSW-----QNVSVPANTSHTRTPEGLYQVTSVLRLKPQPGRNFSCMFWN 70

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 1720390840  45 GGEAILPCSVFPAMNVENMEeLRWFRSRFSEAVLFYRDQEEQKEGQMPGYSQRTLLVKDQFHQGTAAVRILNVQASDSGI 124
Cdd:cd20984    12 GEDGILSCTFTPDIKLSDIV-IQWLKEGDSGLVHEFKEGKDELSRQSPMFRGRTSLFADQVHVGNASLRLKNVQLTDAGT 90

                          90       100
                  ....*....|....*....|
gi 1720390840 125 YICHFQQGVFYDEAILELKV 144
Cdd:cd20984    91 YLCIISNSKGTGNANMEYKT 110

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 1720390840  36 PSDPIVAAPGGEAILPCSVFPAMNVENMEeLRWFRSR---FSEAVLFYRDQEEQKEGQMPGYSQRTLLVKdqfhqGTAAV 112
Cdd:pfam07686   2 TPREVTVALGGSVTLPCTYSSSMSEASTS-VYWYRQPpgkGPTFLIAYYSNGSEEGVKKGRFSGRGDPSN-----GDGSL 75

                          90       100       110
                  ....*....|....*....|....*....|...
gi 1720390840 113 RILNVQASDSGIYICH-FQQGVFYDEAILELKV 144
Cdd:pfam07686  76 TIQNLTLSDSGTYTCAvIPSGEGVFGKGTRLTV 108

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 1720390840  36 PSDPIVAAPGGEAILPCSvFPAMNVENMEELRWFRSRFSEAVLFYRDQEEQKEGQMPGYSQRTLLVKDQFHQGTAAVRIL 115
Cdd:cd20947     4 PKDLYVVEYGSNMTIECK-FPVEKQLDLAALIVYWEMEDKNIIQFVHGEEDLKVQHSSYRQRARLLKDQLSLGNAALQIT 82

                          90
                  ....*....|....*..
gi 1720390840 116 NVQASDSGIYICHFQQG 132
Cdd:cd20947    83 DVKLQDAGVYRCMISYG 99

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        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1720390840 155 IKGPEDGGVCVVCMTSGwYPEPQVHWkdsrgENLTAFSSETHTKDAEGLFSTETLLVVRDSSVRNVTCSIFN 226
Cdd:cd20986     5 LEVPGTGEVQLTCQARG-YPLAEVSW-----QNVSVPANTSHTRTPEGLYQVTSVLRLKPQPGRNFSCMFWN 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 1720390840  45 GGEAILPCSvFPamNVENMEelrwfrsrFSEAVLFYRDQEEQ--------KEGQM---PGYSQRTllvkdQFHQGTAAVR 113
Cdd:cd16087     8 NETAYLPCQ-FK--NPQNIS--------LSELVVFWQDQKKLvlyelylgKEKLDnvnSKYIGRT-----SFDQENWTLQ 71

                          90
                  ....*....|....*...
gi 1720390840 114 ILNVQASDSGIYICHFQQ 131
Cdd:cd16087    72 LHNVQIKDQGTYQCFIHH 89

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

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720390840 167 CMTSGWYPEPQVHWkDSRGENLTAFSSETHTKDAEGLF---STETLLVVRDSSVRNVTCSIFNPILGQEK 233
Cdd:pfam08205  21 CSSAGGKPAPRITW-YLDGKPLEAAETSSEQDPESGLVtvtSELKLVPSRSDHGQSLTCQVSYGALRGSI 89

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 1720390840  45 GGEAILPCSVFPAMNVENMEELRWFRSRFSEAVLFYrdqeEQKEGQMPGYSQRTLLVKDQFHQG--TAAVRILNVQASDS 122
Cdd:cd20989    14 GGSVTLPCHLLPPNMVTHVSQVTWQRHDEHGSVAVF----HPKQGPSFPESERLSFVAARLGAElrNASLAMFGLRVEDE 89

                  ....*..
gi 1720390840 123 GIYICHF 129
Cdd:cd20989    90 GNYTCEF 96

Immunoglobulin (Ig)-like domain of human cartilage link protein (LP), and similar domains; The members here are composed of the immunoglobulin (Ig)-like domain similar to that found in human cartilage link protein (LP; also called hyaluronan and proteoglycan link protein). In cartilage, chondroitin-keratan sulfate proteoglycan (CSPG), aggrecan, forms cartilage link protein stabilized aggregates with hyaluronan (HA). These aggregates contribute to the tissue's load bearing properties. Aggregates having other CSPGs substituting for aggrecan may contribute to the structural integrity of many different tissues. Members of the vertebrate HPLN (hyaluronan/HA and proteoglycan binding link) protein family are physically linked adjacent to CSPG genes.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720390840  36 PSDPIVAAPGGEAILPCSVF--PAMNVENMEELRWFRSRFSEA----VLFYRDQEEQKEGqmpGYSQRTLLvkDQFHQGT 109
Cdd:cd05877     3 VQAKVFSHRGGNVTLPCRYHyePELSAPRKIRVKWTKLEVDYAkeedVLVAIGTRHKSYG---SYQGRVFL--RRADDLD 77

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 1720390840 110 AAVRILNVQASDSGIYICHFQQGVFYDEAILELKV 144
Cdd:cd05877    78 ASLVITDLRLEDYGRYRCEVIDGLEDESVVVALRL 112