Immunoglobulin Variable (IgV) domain in HERV-H LTR-associating 2 (HHLA2); The members here are composed of the immunoglobulin variable (IgV) region in HERV-H LTR-associating 2 (HHLA2; also known as B7-H7/B7 homolog 7). HHLA2 is a member of the B7 family of immune regulatory proteins. Mature human HHLA2 consists of an extracellular domain (ECD) with three immunoglobulin-like domains, a transmembrane segment, and a cytoplasmic domain. HHLA2 is widely expressed in human cancers including non-small cell lung carcinoma (NSCLS), triple negative breast cancer (TNBC), and melanoma, but has limited expression on normal tissues. Interestingly, unlike other members of B7 family, HHLA2 is not expressed in mice or rats. HHLA2 functions as a T cell coinhibitory molecules as it inhibits the proliferation of activated CD4(+) and CD8(+) T cells and their cytokine production. Furthermore, HHLA2 is constitutively expressed on the surface of human monocytes and is induced on B cells after stimulation, however it is not inducible on T cells.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462586810  33 PMNEQIVIGRLDEDIILPSSFERGSEVVIHWKYQDS-YKVHSYYKGSDHLESQDPRYANRTSLFYNEIQNGNASLFFRRV 111
Cdd:cd16091     1 AVSEVIVVCLLSEDCILPCSFTPGSEVVIHWYKQDSdIKVHSYYYGKDQLESQDQRYRNRTSLFKDQISNGNASLLLRRV 80

                          90       100
                  ....*....|....*....|....*..
gi 2462586810 112 SLLDEGIYTCYVGTAIQVITNKVVLKV 138
Cdd:cd16091    81 QLQDEGRYKCYTSTIIGNQESFVNLKV 107

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 2462586810 140 VFLTPVMKYEKRNTNSFLICSVLSVYPRPI-ITWKMDNTPISENNMEETGSL---DSFSINSPLNIT----GSNSSYECT 211
Cdd:cd00098     2 VTLLPPSPEEKGGGKVTLVCLVSGFYPKDItVTWLKNGVPLTSGVSTSSPVEpndGTYSVTSSLTVPpsdwDEGATYTCV 81

                  ....*....
gi 2462586810 212 IENSLLKQT 220
Cdd:cd00098    82 VTHESLKSP 90

Immunoglobulin Variable (IgV) domain in HERV-H LTR-associating 2 (HHLA2); The members here are composed of the immunoglobulin variable (IgV) region in HERV-H LTR-associating 2 (HHLA2; also known as B7-H7/B7 homolog 7). HHLA2 is a member of the B7 family of immune regulatory proteins. Mature human HHLA2 consists of an extracellular domain (ECD) with three immunoglobulin-like domains, a transmembrane segment, and a cytoplasmic domain. HHLA2 is widely expressed in human cancers including non-small cell lung carcinoma (NSCLS), triple negative breast cancer (TNBC), and melanoma, but has limited expression on normal tissues. Interestingly, unlike other members of B7 family, HHLA2 is not expressed in mice or rats. HHLA2 functions as a T cell coinhibitory molecules as it inhibits the proliferation of activated CD4(+) and CD8(+) T cells and their cytokine production. Furthermore, HHLA2 is constitutively expressed on the surface of human monocytes and is induced on B cells after stimulation, however it is not inducible on T cells.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462586810  33 PMNEQIVIGRLDEDIILPSSFERGSEVVIHWKYQDS-YKVHSYYKGSDHLESQDPRYANRTSLFYNEIQNGNASLFFRRV 111
Cdd:cd16091     1 AVSEVIVVCLLSEDCILPCSFTPGSEVVIHWYKQDSdIKVHSYYYGKDQLESQDQRYRNRTSLFKDQISNGNASLLLRRV 80

                          90       100
                  ....*....|....*....|....*..
gi 2462586810 112 SLLDEGIYTCYVGTAIQVITNKVVLKV 138
Cdd:cd16091    81 QLQDEGRYKCYTSTIIGNQESFVNLKV 107

Immunoglobulin V-Type;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462586810  239 VSLSCQpvndyFSPNQ--DFKVTWSRMKSGTFSVLAYYLSSSQNTIINES---RFSWNKELiNQSDFSMNLMDLNLSDSG 313
Cdd:smart00406   2 VTLSCK-----FSGSTfsSYYVSWVRQPPGKGLEWLGYIGSNGSSYYQESykgRFTISKDT-SKNDVSLTISNLRVEDTG 75

                   ....
gi 2462586810  314 EYLC 317
Cdd:smart00406  76 TYYC 79

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 2462586810 140 VFLTPVMKYEKRNTNSFLICSVLSVYPRPI-ITWKMDNTPISENNMEETGSL---DSFSINSPLNIT----GSNSSYECT 211
Cdd:cd00098     2 VTLLPPSPEEKGGGKVTLVCLVSGFYPKDItVTWLKNGVPLTSGVSTSSPVEpndGTYSVTSSLTVPpsdwDEGATYTCV 81

                  ....*....
gi 2462586810 212 IENSLLKQT 220
Cdd:cd00098    82 VTHESLKSP 90

Immunoglobulin C1-set domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462586810 140 VFLTPVMKYEKRNTNSfLICSVLSVYPRPI-ITWKMDNTPISENNMEETGSLD---SFSINSPLNITGSN----SSYECT 211
Cdd:pfam07654   1 VYVFPPSPEELGKPNT-LTCLVTGFYPPDItVTWLKNGQEVTEGVKTTPPSPNsdwTYQLSSYLTVTPSDwesgDEYTCR 79

                  ...
gi 2462586810 212 IEN 214
Cdd:pfam07654  80 VEH 82

Immunoglobulin Variable (IgV) domain in HERV-H LTR-associating 2 (HHLA2); The members here are composed of the immunoglobulin variable (IgV) region in HERV-H LTR-associating 2 (HHLA2; also known as B7-H7/B7 homolog 7). HHLA2 is a member of the B7 family of immune regulatory proteins. Mature human HHLA2 consists of an extracellular domain (ECD) with three immunoglobulin-like domains, a transmembrane segment, and a cytoplasmic domain. HHLA2 is widely expressed in human cancers including non-small cell lung carcinoma (NSCLS), triple negative breast cancer (TNBC), and melanoma, but has limited expression on normal tissues. Interestingly, unlike other members of B7 family, HHLA2 is not expressed in mice or rats. HHLA2 functions as a T cell coinhibitory molecules as it inhibits the proliferation of activated CD4(+) and CD8(+) T cells and their cytokine production. Furthermore, HHLA2 is constitutively expressed on the surface of human monocytes and is induced on B cells after stimulation, however it is not inducible on T cells.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462586810  33 PMNEQIVIGRLDEDIILPSSFERGSEVVIHWKYQDS-YKVHSYYKGSDHLESQDPRYANRTSLFYNEIQNGNASLFFRRV 111
Cdd:cd16091     1 AVSEVIVVCLLSEDCILPCSFTPGSEVVIHWYKQDSdIKVHSYYYGKDQLESQDQRYRNRTSLFKDQISNGNASLLLRRV 80

                          90       100
                  ....*....|....*....|....*..
gi 2462586810 112 SLLDEGIYTCYVGTAIQVITNKVVLKV 138
Cdd:cd16091    81 QLQDEGRYKCYTSTIIGNQESFVNLKV 107

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 2462586810  33 PMNEQIVIGRLDEDIILPSSFE---RGSEVVIHW-KYQDSYKVHSYYKGSDHLESQDPRYANRTSLFYNEIQNGNASLFF 108
Cdd:cd20984     1 TVTAKHLAGNIGEDGILSCTFTpdiKLSDIVIQWlKEGDSGLVHEFKEGKDELSRQSPMFRGRTSLFADQVHVGNASLRL 80

                          90
                  ....*....|....*...
gi 2462586810 109 RRVSLLDEGIYTCYVGTA 126
Cdd:cd20984    81 KNVQLTDAGTYLCIISNS 98

Immunoglobulin (Ig)-like domain of myelin oligodendrocyte glycoprotein (MOG); The members here are composed of the immunoglobulin (Ig)-like domain of myelin oligodendrocyte glycoprotein (MOG). MOG, a minor component of the myelin sheath, is an important CNS-specific autoantigen, linked to the pathogenesis of multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE). It is a transmembrane protein having an extracellular Ig domain. MOG is expressed in the CNS on the outermost lamellae of the myelin sheath, and on the surface of oligodendrocytes, and may participate in the completion, compaction, and/or maintenance of myelin. This group also includes butyrophilin (BTN). BTN is the most abundant protein in bovine milk-fat globule membrane (MFGM).

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 2462586810  66 QDSYKVHSYYKGSDHLESQDPRYANRTSLFYNEIQNGNASLFFRRVSLLDEGIYTCY 122
Cdd:cd05713    41 QFSPVVHLYRDGQDQEEEQMPEYRGRTELLKDAIAEGSVALRIHNVRPSDEGQYTCF 97

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 2462586810  39 VIGRLDEDIILP---SSFERGSEVVIHWKYQDSYKVHS----YYKGSDHLESQDPRYANRTSlfyneIQNGNASLFFRRV 111
Cdd:pfam07686   6 VTVALGGSVTLPctySSSMSEASTSVYWYRQPPGKGPTfliaYYSNGSEEGVKKGRFSGRGD-----PSNGDGSLTIQNL 80

                          90       100
                  ....*....|....*....|....*...
gi 2462586810 112 SLLDEGIYTCYVGTA-IQVITNKVVLKV 138
Cdd:pfam07686  81 TLSDSGTYTCAVIPSgEGVFGKGTRLTV 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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 2462586810  59 VVIHWKYQDSyKVHSYYKGSDHLESQDPRYANRTSLFYNEIQNGNASLFFRRVSLLDEGIYTC---YVGTAIQVITNKV 134
Cdd:cd20947    33 LIVYWEMEDK-NIIQFVHGEEDLKVQHSSYRQRARLLKDQLSLGNAALQITDVKLQDAGVYRCmisYGGADYKRITVKV 110

Immunoglobulin Variable (V) domain of the Coxsackievirus and Adenovirus Receptor (CAR), and similar proteins; The members here are composed of the Variable (V) domain of the Coxsackievirus and Adenovirus Receptor (CAR), and similar proteins. CAR, which is encoded by human CXADR gene, is a cell adhesion molecule of the Immunoglobulin (Ig) superfamily. The CAR acts as a type I membrane receptor for group B1-B6 coxsackie viruses and subgroup C adenoviruses. For instance, adenovirus interacts with the coxsackievirus and adenovirus receptor to enter epithelial airway cells. The CAR is also shown to be involved in physiological processes such as neuronal and heart development, epithelial tight junction integrity, and tumor suppression. The CAR is a component of the epithelial apical junction complex that may function as a homophilic cell adhesion molecule and is essential for tight junction integrity. The CAR is also involved in transepithelial migration of leukocytes through adhesive interactions with JAML a transmembrane protein of the plasma membrane of leukocytes. The interaction between both receptors also mediates the activation of gamma-delta T-cells, a subpopulation of T-cells residing in epithelia and involved in tissue homeostasis and repair. The CAR is composed of one V-set and one C2-set Ig module, a single transmembrane helix, and an intracellular domain. This group belongs to the V-set of IgSF domains, having A, B, E and D strands in one beta-sheet and A', G, F, C, C' and C" in the other

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462586810  44 DEDIILPSSFERGSEVV----IHWKYQDSYKVHSY---YKGSDHLESQDPRYANRTSlFYNEIQNGNASLFFRRVSLLDE 116
Cdd:cd20960    15 GENVTLPCHHQLGLEDQgtldIEWLLLPSDKVEKVvitYSGDRVYNHYYPALKGRVA-FTSNDLSGDASLNISNLKLSDT 93

                          90       100
                  ....*....|....*....|.
gi 2462586810 117 GIYTCYVGTAIQVITNKVVLK 137
Cdd:cd20960    94 GTYQCKVKKAPGYAWSKITLI 114

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 2462586810  39 VIGRLDEDIILPSSFERGSEVVI--------HWKYQDSYKVHSYYKGSDHLESqdprYANRTSLFYNEIQNGNASLFFRR 110
Cdd:cd05718     9 VTGFLGGSVTLPCSLTSPGTTKItqvtwmkiGAGSSQNVAVFHPQYGPSVPNP----YAERVEFLAARLGLRNATLRIRN 84

                          90
                  ....*....|....*
gi 2462586810 111 VSLLDEGIYTCYVGT 125
Cdd:cd05718    85 LRVEDEGNYICEFAT 99

Immunoglobulin (Ig) variable (V) domain of T-cell receptor (TCR) beta chain; The members here are composed of the immunoglobulin (Ig) variable domain of the beta chain of alpha/beta T-cell antigen receptors (TCRs). TCRs mediate antigen recognition by T lymphocytes, and are composed of alpha and beta, or gamma and delta, polypeptide chains with variable (V) and constant (C) regions. This group includes the variable domain of the alpha chain of alpha/beta TCRs. Alpha/beta TCRs recognize antigen as peptide fragments presented by major histocompatibility complex (MHC) molecules. The variable domain of TCRs is responsible for antigen recognition, and is located at the N-terminus of the receptor. Gamma/delta TCRs recognize intact protein antigens directly without antigen processing and recognize MHC independently of the bound peptide. Members of this group contain standard Ig superfamily V-set AGFCC'C"/DEB domain topology.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462586810 233 KMQSEHVSLSCQPVNDYFSpnqdfkVTWSRMKSG-TFSVLAYYLSSSQNTIIN--ESRFSWNKEliNQSDFSMNLMDLNL 309
Cdd:cd05899    10 KRRGQSVTLRCSQKSGHDN------MYWYRQDPGkGLQLLFYSYGGGLNEEGDlpGDRFSASRP--SLTRSSLTIKSAEP 81

                          90
                  ....*....|...
gi 2462586810 310 SDSGEYLCNISSD 322
Cdd:cd05899    82 EDSAVYLCASSLG 94

Immunoglobulin domain of Cluster of Differentiation (CD) 1; member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin domain of Cluster of Differentiation (CD) 1. CD1 family of transmembrane glycoproteins, are structurally related to the major histocompatibility complex (MHC) proteins and form heterodimers with beta-2-microglobulin. They mediate the presentation of primarily lipid and glycolipid antigens of self or microbial origin to T cells. The human genome contains five CD1 family genes (CD1a, CD1b, CD1c, CD1d, and CD1e) organized in a cluster on chromosome 1. The CD1 family members are thought to differ in their cellular localization and specificity for particular lipid ligands. CD1a localizes to the plasma membrane and to recycling vesicles of the early endocytic system. Alternative splicing results in multiple transcript variants. Immunoglobulin (Ig) domain of major histocompatibility complex (MHC) class I alpha chain. Class I MHC proteins bind antigenic peptide fragments and present them to CD8+ T lymphocytes. Class I molecules consist of a transmembrane alpha chain and a small chain called the beta-2-microglobulin. The alpha chain contains three extracellular domains, two of which fold together to form the peptide-binding cleft (alpha1 and alpha2), and one which has an Ig fold (alpha3). Peptide binding to class I molecules occurs in the endoplasmic reticulum (ER) and involves both chaperones and dedicated factors to assist in peptide loading. Class I MHC molecules are expressed on most nucleated cells. C1-set Ig domains 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 2462586810 157 LICSVLSVYPRPI-ITWKMDNTPISeNNMEETGSL----DSFSINSPLNIT-GSNSSYECTIENSLLKQTWTGRW 225
Cdd:cd21029    20 LSCHVTGFYPRPIeVTWLRDGQEQM-DGTQSGGILpnhdGTYQLRKTLDIApGEGAGYSCRVDHSSLKQDLIVYW 93

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2462586810 157 LICSVLSvYPRPIITWKMDNTPISENNMEETGSLDSFSInspLNITGSNSS----YECTIEN 214
Cdd:pfam13927  21 LTCEATG-SPPPTITWYKNGEPISSGSTRSRSLSGSNST---LTISNVTRSdagtYTCVASN 78

Immunoglobulin I-set domain;

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462586810 165 YPRPIITWKMDNTPISEN---NMEETGSLDSFSINsplNITGSNS-SYECTIENSLLKQT 220
Cdd:pfam07679  27 TPDPEVSWFKDGQPLRSSdrfKVTYEGGTYTLTIS---NVQPDDSgKYTCVATNSAGEAE 83