Immunoglobulin (Ig)-like domain of Programmed Cell Death 1 (PD1); The members here are composed of the immunoglobulin (Ig)-like domain of Programmed Cell Death 1 (PD1; also known as CD279/cluster of differentiation 279). PD1 is a cell surface receptor that is expressed on T cells and pro-B cells. The protein's structure includes an extracellular IgV domain followed by a transmembrane region and an intracellular tail. Activation of CD4+ T cells, CD8+ T cells, NKT cells, B cells, and monocytes induces PD-1 expression, immediately after which it binds two distinct ligands, PD-L1 (also known as B7-H1 or CD274/cluster of differentiation 274) and PD-L2, also known as B7-DC. PD-1 plays an important role in down regulating the immune system by preventing the activation of T-cells, reducing autoimmunity and promoting self-tolerance. The inhibitory effect of PD-1 is accomplished by promoting apoptosis in antigen specific T-cells in lymph nodes while simultaneously reducing apoptosis in regulatory T cells. A class of drugs that target PD-1, known as the PD-1 inhibitors, activate the immune system to attack tumors and treat cancer. Comparisons between the mouse PD-1 (mPD-1) and human PD-1 (hPD-1) reveals that unlike the mPD-1 which has a conventional IgSF V-set domain, hPD-1 lacks a C" strand, and instead the C' and D strands are connected by a long and flexible loop. In addition, the BC loop is not stabilized by disulfide bonding to the F strand of the ligand binding beta sheet. These differences result in different binding affinities of human and mouse PD-1 for their ligands.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
5GGR_Y        9 PPTFSPALLVVTEGDNATFTCSFSNTSESFVLNWYRMSPSNQTDKLAAFPEDRSQPGQDSRFRVTQLPNGRDFHMSVVRA 88
Cdd:cd16088   1 PPTFSPALLVVTEGANATFTCSFSNTSESFVLNWYRLSPSNQTDKLAAFPEDRSQPGQDWRFRVTQLPNGRDFHMSVVRA 80

                        90       100       110
                ....*....|....*....|....*....|..
5GGR_Y       89 RRNDSGTYLCGAISLAPKAQIKESLRAELRVT 120
Cdd:cd16088  81 RRNDSGTYLCGAISLAPKAQIKESPRAELRVT 112

Immunoglobulin (Ig)-like domain of Programmed Cell Death 1 (PD1); The members here are composed of the immunoglobulin (Ig)-like domain of Programmed Cell Death 1 (PD1; also known as CD279/cluster of differentiation 279). PD1 is a cell surface receptor that is expressed on T cells and pro-B cells. The protein's structure includes an extracellular IgV domain followed by a transmembrane region and an intracellular tail. Activation of CD4+ T cells, CD8+ T cells, NKT cells, B cells, and monocytes induces PD-1 expression, immediately after which it binds two distinct ligands, PD-L1 (also known as B7-H1 or CD274/cluster of differentiation 274) and PD-L2, also known as B7-DC. PD-1 plays an important role in down regulating the immune system by preventing the activation of T-cells, reducing autoimmunity and promoting self-tolerance. The inhibitory effect of PD-1 is accomplished by promoting apoptosis in antigen specific T-cells in lymph nodes while simultaneously reducing apoptosis in regulatory T cells. A class of drugs that target PD-1, known as the PD-1 inhibitors, activate the immune system to attack tumors and treat cancer. Comparisons between the mouse PD-1 (mPD-1) and human PD-1 (hPD-1) reveals that unlike the mPD-1 which has a conventional IgSF V-set domain, hPD-1 lacks a C" strand, and instead the C' and D strands are connected by a long and flexible loop. In addition, the BC loop is not stabilized by disulfide bonding to the F strand of the ligand binding beta sheet. These differences result in different binding affinities of human and mouse PD-1 for their ligands.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
5GGR_Y        9 PPTFSPALLVVTEGDNATFTCSFSNTSESFVLNWYRMSPSNQTDKLAAFPEDRSQPGQDSRFRVTQLPNGRDFHMSVVRA 88
Cdd:cd16088   1 PPTFSPALLVVTEGANATFTCSFSNTSESFVLNWYRLSPSNQTDKLAAFPEDRSQPGQDWRFRVTQLPNGRDFHMSVVRA 80

                        90       100       110
                ....*....|....*....|....*....|..
5GGR_Y       89 RRNDSGTYLCGAISLAPKAQIKESLRAELRVT 120
Cdd:cd16088  81 RRNDSGTYLCGAISLAPKAQIKESPRAELRVT 112

Immunoglobulin V-Type;

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
5GGR_Y          24 NATFTCSFS-NTSESFVLNWYRMSPSNQTDKLAAFP-EDRSQPGQDSRFRVTQL--PNGRDFHMSVVRARRNDSGTYLC 98
Cdd:smart00406   1 SVTLSCKFSgSTFSSYYVSWVRQPPGKGLEWLGYIGsNGSSYYQESYKGRFTISkdTSKNDVSLTISNLRVEDTGTYYC 79

Immunoglobulin (Ig)-like domain of Programmed Cell Death 1 (PD1); The members here are composed of the immunoglobulin (Ig)-like domain of Programmed Cell Death 1 (PD1; also known as CD279/cluster of differentiation 279). PD1 is a cell surface receptor that is expressed on T cells and pro-B cells. The protein's structure includes an extracellular IgV domain followed by a transmembrane region and an intracellular tail. Activation of CD4+ T cells, CD8+ T cells, NKT cells, B cells, and monocytes induces PD-1 expression, immediately after which it binds two distinct ligands, PD-L1 (also known as B7-H1 or CD274/cluster of differentiation 274) and PD-L2, also known as B7-DC. PD-1 plays an important role in down regulating the immune system by preventing the activation of T-cells, reducing autoimmunity and promoting self-tolerance. The inhibitory effect of PD-1 is accomplished by promoting apoptosis in antigen specific T-cells in lymph nodes while simultaneously reducing apoptosis in regulatory T cells. A class of drugs that target PD-1, known as the PD-1 inhibitors, activate the immune system to attack tumors and treat cancer. Comparisons between the mouse PD-1 (mPD-1) and human PD-1 (hPD-1) reveals that unlike the mPD-1 which has a conventional IgSF V-set domain, hPD-1 lacks a C" strand, and instead the C' and D strands are connected by a long and flexible loop. In addition, the BC loop is not stabilized by disulfide bonding to the F strand of the ligand binding beta sheet. These differences result in different binding affinities of human and mouse PD-1 for their ligands.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
5GGR_Y        9 PPTFSPALLVVTEGDNATFTCSFSNTSESFVLNWYRMSPSNQTDKLAAFPEDRSQPGQDSRFRVTQLPNGRDFHMSVVRA 88
Cdd:cd16088   1 PPTFSPALLVVTEGANATFTCSFSNTSESFVLNWYRLSPSNQTDKLAAFPEDRSQPGQDWRFRVTQLPNGRDFHMSVVRA 80

                        90       100       110
                ....*....|....*....|....*....|..
5GGR_Y       89 RRNDSGTYLCGAISLAPKAQIKESLRAELRVT 120
Cdd:cd16088  81 RRNDSGTYLCGAISLAPKAQIKESPRAELRVT 112

Immunoglobulin variable domain (IgV); The members here are composed of the immunoglobulin variable domain (IgV). The IgV family contains the standard Ig superfamily V-set AGFCC'C"/DEB domain topology, and 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. 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" strands in the other.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
5GGR_Y       11 TFSPALLVVTEGDNATFTCSFSNTSESFVLNWYRMSPSNQtdklaafPE---------DRSQPGQDSRFRVTqLPNGRDF 81
Cdd:cd00099   2 TQSPRSLSVQEGESVTLSCEVSSSFSSTYIYWYRQKPGQG-------PEfliylssskGKTKGGVPGRFSGS-RDGTSSF 73

                        90
                ....*....|....*..
5GGR_Y       82 HMSVVRARRNDSGTYLC 98
Cdd:cd00099  74 SLTISNLQPEDSGTYYC 90

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
5GGR_Y          14 PALLVVTEGDNATFTCSFSNTSESFVlNWYRmspsnqtdklaafpEDRSQPGQDSRFRVTQlpNGRDFHMSVVRARRNDS 93
Cdd:smart00410   1 PPSVTVKEGESVTLSCEASGSPPPEV-TWYK--------------QGGKLLAESGRFSVSR--SGSTSTLTISNVTPEDS 63

                   ....*..
5GGR_Y          94 GTYLCGA 100
Cdd:smart00410  64 GTYTCAA 70

Immunoglobulin (Ig) variable (V) domain of T-cell receptor (TCR) alpha chain and similar proteins; The members here are composed of the immunoglobulin (Ig) variable domain of the alpha 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 represents the variable domain of the alpha chain of TCRs and also includes the variable domain of delta chains of 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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
5GGR_Y       13 SPALLVVTEGDNATFTCSFSNTSESFVLnWYRMSPSNQtdklaafPE------DRSQPGQDSRFRVTQLPNGRDFHMSVV 86
Cdd:cd04983   4 SPQSLSVQEGENVTLNCNYSTSTFYYLF-WYRQYPGQG-------PQfliyisSDSGNKKKGRFSATLDKSRKSSSLHIS 75

                        90
                ....*....|..
5GGR_Y       87 RARRNDSGTYLC 98
Cdd:cd04983  76 AAQLSDSAVYFC 87

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
5GGR_Y       13 SPALLVVTEGDNATFTCSFSNTSESFVlnWYRMSPSNQTDKLAAF---PEDRSQPGQDSRFRVTQlPNGRDFHMSVVRAR 89
Cdd:cd05899   4 SPRYLIKRRGQSVTLRCSQKSGHDNMY--WYRQDPGKGLQLLFYSyggGLNEEGDLPGDRFSASR-PSLTRSSLTIKSAE 80

                        90
                ....*....|....*.
5GGR_Y       90 RNDSGTYLCgAISLAP 105
Cdd:cd05899  81 PEDSAVYLC-ASSLGG 95

Immunoglobulin I-set domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
5GGR_Y         17 LVVTEGDNATFTCSFSNTSEsFVLNWYRmspsnqtdklaafpeDRSQPGQDSRFRVTQlpNGRDFHMSVVRARRNDSGTY 96
Cdd:pfam07679  10 VEVQEGESARFTCTVTGTPD-PEVSWFK---------------DGQPLRSSDRFKVTY--EGGTYTLTISNVQPDDSGKY 71

                  ....
5GGR_Y         97 LCGA 100
Cdd:pfam07679  72 TCVA 75

Immunoglobulin (Ig) variable (V) domain of T-cell receptor (TCR) gamma chain; The members here are composed of the immunoglobulin (Ig) variable (V) domain of the gamma chain of gamma/delta T-cell receptors (TCRs). TCRs mediate antigen recognition by T lymphocytes, and are heterodimers consisting of alpha and beta chains or gamma and delta chains. Each chain contains a variable (V) and a constant (C) region. The majority of T cells contain alpha/beta TCRs, but a small subset contain gamma/delta TCRs. Alpha/beta TCRs recognize antigens as peptide fragments presented by major histocompatibility complex (MHC) molecules. Gamma/delta TCRs recognize intact protein antigens directly without antigen processing and recognize MHC independently of the bound peptide. Gamma/delta T cells can also be stimulated by non-peptide antigens such as small phosphate- or amine-containing compounds. The variable domain of gamma/delta TCRs is responsible for antigen recognition and is located at the N-terminus of the receptor. Members of this group contain the standard Ig superfamily V-set AGFCC'C"/DEB domain topology.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
5GGR_Y       20 TEGDNATFTCSFSNTS-ESFVLNWYRMSPSNQTDKL---AAFPEDRSQPGQDS-RFRVTQLPNGRDFHMSVVRARRNDSG 94
Cdd:cd04982  11 EESKSVTISCKVSGIDfSTTYIHWYRQKPGQALERLlyvSSTSAVRKDSGKTKnKFEARKDVGKSTSTLTITNLEKEDSA 90

                ....
5GGR_Y       95 TYLC 98
Cdd:cd04982  91 TYYC 94

Fifth Ig-like domain of Roundabout (Robo) homolog 1/2, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fifth Ig-like domain of Roundabout (Robo) homolog 1/2 and similar domains. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, -2, and -3), and three mammalian Slit homologs (Slit-1,-2, -3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, -2, and -3 are expressed by commissural neurons in the vertebrate spinal cord and Slits 1, -2, -3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of slit responsiveness, antagonizes slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be is the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. The fifth Ig-like domain of Robo 1 and 2 is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|.
5GGR_Y       57 FPEDRSQPGQDSRFrvTQLPNGRdfhMSVVRARRNDSGTYLCGAISLAPKA 107
Cdd:cd20952  34 LKDGVPLLGKDERI--TTLENGS---LQIKGAEKSDTGEYTCVALNLSGEA 79

Immunoglobulin Variable (IgV) domain at the N-terminus of CD33 and related Siglecs (sialic acid-binding Ig-like lectins); The members here are composed of the immunoglobulin (Ig) domain at the N-terminus of Cluster of Differentiation (CD) 33 and related Siglecs (sialic acid-binding Ig-like lectins). Siglec refers to a structurally related protein family that specifically recognizes sialic acid in oligosaccharide chains of glycoproteins and glycolipids. Siglecs are type I transmembrane proteins, organized as an extracellular module composed of Ig-like domains, an N-terminal variable set of Ig-like carbohydrate recognition domains, and 1 to 16 constant Ig-like domains, followed by transmembrane and short cytoplasmic domains. Human Siglecs are classified into two subgroups, one subgroup is comprised of sialoadhesin (Siglec-1), CD22 (Siglec-2), and MAG, the other subgroup is comprised of CD33-related Siglecs which include CD33 (Siglec-3) and human Siglecs 5-11.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
5GGR_Y       29 CSFSNTSESFVLN-----WYRMSPSNQTDKLAAF--PEDRSQPGQDSRFRVTQLPNGRDFHMSVVRARRNDSGTY 96
Cdd:cd05712  21 CSFSYPADYWVSNpvhgyWYRGGPYPKYRPPVATnnRTREVHESTQGRFRLLGDPGKKNCSLSISDARPEDSGKY 95