Immunoglobulin (Ig)-like variable (V) domain of the Signal-Regulatory Protein (SIRP); The members here are composed of the immunoglobulin (Ig)-like domain of the Signal-Regulatory Protein (SIRP). The SIRPs belong to the "paired receptors" class of membrane proteins that comprise several genes coding for proteins with similar extracellular regions, but very different transmembrane/cytoplasmic regions with different (activating or inhibitory) signaling potentials. They are commonly on NK cells, but are also on many myeloid cells. Their extracellular region contains three immunoglobulin superfamily domains, a single V-set, and two C1-set IgSF domains. Their cytoplasmic tails that contain either ITIMs or transmembrane regions have positively charged residues that allow an association with adaptor proteins, such as DAP12/KARAP, containing ITAMs. There are 3 distinct SIRP members: alpha, beta, and gamma. SIRP alpha (also known as CD172a or SRC homology 2 domain-containing protein tyrosine phosphatase substrate 1/Shps-1) is a membrane receptor that interacts with a ligand CD47 expressed on many cells and gives an inhibitory signal through immunoreceptor tyrosine-based inhibition motifs in the cytoplasmic region that interact with phosphatases SHP-1 and SHP-2. SIRP beta has a short cytoplasmic region and associates with a transmembrane adapter protein DAP12 containing immunoreceptor tyrosine-based activation motifs to give an activating signal. SIRP gamma contains a very short cytoplasmic region lacking obvious signaling motifs, but also binds CD47 with much less affinity. Members of this group contain standard Ig superfamily V-set AGFCC'C"/DEB domain topology.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2052056   35 QVIQPDKSVSVAAGESAILHCTVTSLIPVGPIQWFRGAGPARELIYNQKEGHFPRVTTVSESTKRENMDFSISISNITPA 114
Cdd:cd16097   1 QVIQPEKSVSVAAGESATLHCTVTSLIPVGPIQWFRGAGPGRELIYNQKEGHFPRVTTVSDLTKRNNMDFSIRISNITPA 80

                        90       100       110
                ....*....|....*....|....*....|.
gi 2052056  115 DAGTYYCVKFRKGSP-DTEFKSGAGTELSVR 144
Cdd:cd16097  81 DAGTYYCVKFRKGSPdDVEFKSGAGTELSVR 111

Signal-regulatory protein (SIRP) immunoglobulin-like domain 2; member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig)-like domain in Signal-Regulatory Protein (SIRP), domain 2 (C1 repeat 1). The SIRPs belong to the "paired receptors" class of membrane proteins that comprise several genes coding for proteins with similar extracellular regions, but very different transmembrane/cytoplasmic regions with different (activating or inhibitory) signaling potentials. They are commonly on NK cells, but are also on many myeloid cells. Their extracellular region contains three Immunoglobulin superfamily domains, a single V-set and two C1-set IgSF domains. Their cytoplasmic tails contain either ITIMs or transmembrane regions that have positively charged residues that allow an association with adaptor proteins, such as DAP12/KARAP, containing ITAMs. There are 3 distinct SIRP members: alpha, beta, and gamma. SIRP alpha (also known as CD172a or SRC homology 2 domain-containing protein tyrosine phosphatase substrate 1/Shps-1) is a membrane receptor that interacts with a ligand CD47 expressed on many cells and gives an inhibitory signal through immunoreceptor tyrosine-based inhibition motifs in the cytoplasmic region that interact with phosphatases SHP-1 and SHP-2. SIRP beta has a short cytoplasmic region and associates with a transmembrane adapter protein DAP12 containing immunoreceptor tyrosine-based activation motifs to give an activating signal. SIRP gamma contains a very short cytoplasmic region lacking obvious signaling motifs, but also binds CD47, but with much less affinity.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2052056  146 KPSAPVVSGPAARATPQHTVSFTCESHGFSPRDITLKWFKNGNELSDFQTNVDPVGESVSYSIHSTAKVVLTREDVHSQV 225
Cdd:cd05772   1 KPSQPLVSGPSGRATPGQTVSFTCKSHGFSPRDITLKWFKNGNELSALQTTVFPEGDSVSYSVSSTVQVVLTKDDVHSQL 80

                        90       100
                ....*....|....*....|...
gi 2052056  226 ICEVAHVTLQgDPLRGTANLSET 248
Cdd:cd05772  81 TCEVAHVTLQ-APLRGTANLSDI 102

Immunoglobulin (Ig)-like variable (V) domain of the Signal-Regulatory Protein (SIRP); The members here are composed of the immunoglobulin (Ig)-like domain of the Signal-Regulatory Protein (SIRP). The SIRPs belong to the "paired receptors" class of membrane proteins that comprise several genes coding for proteins with similar extracellular regions, but very different transmembrane/cytoplasmic regions with different (activating or inhibitory) signaling potentials. They are commonly on NK cells, but are also on many myeloid cells. Their extracellular region contains three immunoglobulin superfamily domains, a single V-set, and two C1-set IgSF domains. Their cytoplasmic tails that contain either ITIMs or transmembrane regions have positively charged residues that allow an association with adaptor proteins, such as DAP12/KARAP, containing ITAMs. There are 3 distinct SIRP members: alpha, beta, and gamma. SIRP alpha (also known as CD172a or SRC homology 2 domain-containing protein tyrosine phosphatase substrate 1/Shps-1) is a membrane receptor that interacts with a ligand CD47 expressed on many cells and gives an inhibitory signal through immunoreceptor tyrosine-based inhibition motifs in the cytoplasmic region that interact with phosphatases SHP-1 and SHP-2. SIRP beta has a short cytoplasmic region and associates with a transmembrane adapter protein DAP12 containing immunoreceptor tyrosine-based activation motifs to give an activating signal. SIRP gamma contains a very short cytoplasmic region lacking obvious signaling motifs, but also binds CD47 with much less affinity. Members of this group contain standard Ig superfamily V-set AGFCC'C"/DEB domain topology.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2052056   35 QVIQPDKSVSVAAGESAILHCTVTSLIPVGPIQWFRGAGPARELIYNQKEGHFPRVTTVSESTKRENMDFSISISNITPA 114
Cdd:cd16097   1 QVIQPEKSVSVAAGESATLHCTVTSLIPVGPIQWFRGAGPGRELIYNQKEGHFPRVTTVSDLTKRNNMDFSIRISNITPA 80

                        90       100       110
                ....*....|....*....|....*....|.
gi 2052056  115 DAGTYYCVKFRKGSP-DTEFKSGAGTELSVR 144
Cdd:cd16097  81 DAGTYYCVKFRKGSPdDVEFKSGAGTELSVR 111

Signal-regulatory protein (SIRP) immunoglobulin-like domain 2; member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig)-like domain in Signal-Regulatory Protein (SIRP), domain 2 (C1 repeat 1). The SIRPs belong to the "paired receptors" class of membrane proteins that comprise several genes coding for proteins with similar extracellular regions, but very different transmembrane/cytoplasmic regions with different (activating or inhibitory) signaling potentials. They are commonly on NK cells, but are also on many myeloid cells. Their extracellular region contains three Immunoglobulin superfamily domains, a single V-set and two C1-set IgSF domains. Their cytoplasmic tails contain either ITIMs or transmembrane regions that have positively charged residues that allow an association with adaptor proteins, such as DAP12/KARAP, containing ITAMs. There are 3 distinct SIRP members: alpha, beta, and gamma. SIRP alpha (also known as CD172a or SRC homology 2 domain-containing protein tyrosine phosphatase substrate 1/Shps-1) is a membrane receptor that interacts with a ligand CD47 expressed on many cells and gives an inhibitory signal through immunoreceptor tyrosine-based inhibition motifs in the cytoplasmic region that interact with phosphatases SHP-1 and SHP-2. SIRP beta has a short cytoplasmic region and associates with a transmembrane adapter protein DAP12 containing immunoreceptor tyrosine-based activation motifs to give an activating signal. SIRP gamma contains a very short cytoplasmic region lacking obvious signaling motifs, but also binds CD47, but with much less affinity.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2052056  146 KPSAPVVSGPAARATPQHTVSFTCESHGFSPRDITLKWFKNGNELSDFQTNVDPVGESVSYSIHSTAKVVLTREDVHSQV 225
Cdd:cd05772   1 KPSQPLVSGPSGRATPGQTVSFTCKSHGFSPRDITLKWFKNGNELSALQTTVFPEGDSVSYSVSSTVQVVLTKDDVHSQL 80

                        90       100
                ....*....|....*....|...
gi 2052056  226 ICEVAHVTLQgDPLRGTANLSET 248
Cdd:cd05772  81 TCEVAHVTLQ-APLRGTANLSDI 102

Immunoglobulin C1-set domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2052056    155 PAARATPQHTVSFTCESHGFSPRDITLKWFKNGNELSDFQTNVDPVGES-VSYSIHSTAKVVLTREDVHSQVICEVAHVT 233
Cdd:pfam07654   5 PPSPEELGKPNTLTCLVTGFYPPDITVTWLKNGQEVTEGVKTTPPSPNSdWTYQLSSYLTVTPSDWESGDEYTCRVEHEG 84

                  .
gi 2052056    234 L 234
Cdd:pfam07654  85 L 85

Immunoglobulin C-Type;

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 2052056     164 TVSFTCESHGFSPRDITLKWFKNGNELSDFQTNVDPVGES-VSYSIHSTAKVVLTREDVHSQVICEVAHVTLQG 236
Cdd:smart00407   1 KATLVCLVSGFYPPDITVTWLRNGQEVTEGVSTTDPLKNSdGTYFLSSYLTVPASTWESGDVYTCQVTHEGLKE 74

Immunoglobulin C1-set domain;

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 2052056    266 NQVNVTCQVRKFYPQRLQLTWLENGnVSRTETASTVTE--NKDGTYNWMSWLLVNVSAHRDDVKLTCQVEHDG 336
Cdd:pfam07654  13 KPNTLTCLVTGFYPPDITVTWLKNG-QEVTEGVKTTPPspNSDWTYQLSSYLTVTPSDWESGDEYTCRVEHEG 84

Immunoglobulin (Ig)-like variable (V) domain of the Signal-Regulatory Protein (SIRP); The members here are composed of the immunoglobulin (Ig)-like domain of the Signal-Regulatory Protein (SIRP). The SIRPs belong to the "paired receptors" class of membrane proteins that comprise several genes coding for proteins with similar extracellular regions, but very different transmembrane/cytoplasmic regions with different (activating or inhibitory) signaling potentials. They are commonly on NK cells, but are also on many myeloid cells. Their extracellular region contains three immunoglobulin superfamily domains, a single V-set, and two C1-set IgSF domains. Their cytoplasmic tails that contain either ITIMs or transmembrane regions have positively charged residues that allow an association with adaptor proteins, such as DAP12/KARAP, containing ITAMs. There are 3 distinct SIRP members: alpha, beta, and gamma. SIRP alpha (also known as CD172a or SRC homology 2 domain-containing protein tyrosine phosphatase substrate 1/Shps-1) is a membrane receptor that interacts with a ligand CD47 expressed on many cells and gives an inhibitory signal through immunoreceptor tyrosine-based inhibition motifs in the cytoplasmic region that interact with phosphatases SHP-1 and SHP-2. SIRP beta has a short cytoplasmic region and associates with a transmembrane adapter protein DAP12 containing immunoreceptor tyrosine-based activation motifs to give an activating signal. SIRP gamma contains a very short cytoplasmic region lacking obvious signaling motifs, but also binds CD47 with much less affinity. Members of this group contain standard Ig superfamily V-set AGFCC'C"/DEB domain topology.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2052056   35 QVIQPDKSVSVAAGESAILHCTVTSLIPVGPIQWFRGAGPARELIYNQKEGHFPRVTTVSESTKRENMDFSISISNITPA 114
Cdd:cd16097   1 QVIQPEKSVSVAAGESATLHCTVTSLIPVGPIQWFRGAGPGRELIYNQKEGHFPRVTTVSDLTKRNNMDFSIRISNITPA 80

                        90       100       110
                ....*....|....*....|....*....|.
gi 2052056  115 DAGTYYCVKFRKGSP-DTEFKSGAGTELSVR 144
Cdd:cd16097  81 DAGTYYCVKFRKGSPdDVEFKSGAGTELSVR 111

Signal-regulatory protein (SIRP) immunoglobulin-like domain 2; member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig)-like domain in Signal-Regulatory Protein (SIRP), domain 2 (C1 repeat 1). The SIRPs belong to the "paired receptors" class of membrane proteins that comprise several genes coding for proteins with similar extracellular regions, but very different transmembrane/cytoplasmic regions with different (activating or inhibitory) signaling potentials. They are commonly on NK cells, but are also on many myeloid cells. Their extracellular region contains three Immunoglobulin superfamily domains, a single V-set and two C1-set IgSF domains. Their cytoplasmic tails contain either ITIMs or transmembrane regions that have positively charged residues that allow an association with adaptor proteins, such as DAP12/KARAP, containing ITAMs. There are 3 distinct SIRP members: alpha, beta, and gamma. SIRP alpha (also known as CD172a or SRC homology 2 domain-containing protein tyrosine phosphatase substrate 1/Shps-1) is a membrane receptor that interacts with a ligand CD47 expressed on many cells and gives an inhibitory signal through immunoreceptor tyrosine-based inhibition motifs in the cytoplasmic region that interact with phosphatases SHP-1 and SHP-2. SIRP beta has a short cytoplasmic region and associates with a transmembrane adapter protein DAP12 containing immunoreceptor tyrosine-based activation motifs to give an activating signal. SIRP gamma contains a very short cytoplasmic region lacking obvious signaling motifs, but also binds CD47, but with much less affinity.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2052056  146 KPSAPVVSGPAARATPQHTVSFTCESHGFSPRDITLKWFKNGNELSDFQTNVDPVGESVSYSIHSTAKVVLTREDVHSQV 225
Cdd:cd05772   1 KPSQPLVSGPSGRATPGQTVSFTCKSHGFSPRDITLKWFKNGNELSALQTTVFPEGDSVSYSVSSTVQVVLTKDDVHSQL 80

                        90       100
                ....*....|....*....|...
gi 2052056  226 ICEVAHVTLQgDPLRGTANLSET 248
Cdd:cd05772  81 TCEVAHVTLQ-APLRGTANLSDI 102

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 2052056  254 TLEVTQQPVR--AENQVNVTCQVRKFYPQRLQLTWLENGN-VSRTETASTVTENKDGTYNWMSWLLVNVSAHRDDVKLTC 330
Cdd:cd00098   1 TVTLLPPSPEekGGGKVTLVCLVSGFYPKDITVTWLKNGVpLTSGVSTSSPVEPNDGTYSVTSSLTVPPSDWDEGATYTC 80

                        90
                ....*....|....*
gi 2052056  331 QVEHDGQPA-VSKSH 344
Cdd:cd00098  81 VVTHESLKSpLSKTW 95

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 2052056  150 PVVSGPAARATPQHTVSFTCESHGFSPRDITLKWFKNGNELSDFQTNVDPV-GESVSYSIHSTAKVVLTREDVHSQVICE 228
Cdd:cd00098   2 VTLLPPSPEEKGGGKVTLVCLVSGFYPKDITVTWLKNGVPLTSGVSTSSPVePNDGTYSVTSSLTVPPSDWDEGATYTCV 81

                ....*..
gi 2052056  229 VAHVTLQ 235
Cdd:cd00098  82 VTHESLK 88

Class I major histocompatibility complex (MHC) alpha chain, alpha3 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 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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2052056  251 VPPTLEVTQQPvRAENQVNVTCQVRKFYPQRLQLTWLENG-NVSRTETASTVTENKDGTYNwmSWLLVNVSAhRDDVKLT 329
Cdd:cd07698   1 DPPKVHVTHHP-RSDGESTLRCWALGFYPAEITLTWQRDGeDQTQDMELVETRPNGDGTFQ--KWAAVVVPS-GEEQRYT 76

                        90
                ....*....|....*....
gi 2052056  330 CQVEHdgqPAVSKSHDLKV 348
Cdd:cd07698  77 CHVQH---EGLPEPLTLRW 92

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        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2052056  251 VPPTLEVTQQPVRAENQVNVTCQVRKFYPQRLQLTWLENGNVSRTETAST-VTENKDGTYNWMSWLLVNVSahrDDVKLT 329
Cdd:cd21029   1 VKPRVRLSSRPSPGDGHLQLSCHVTGFYPRPIEVTWLRDGQEQMDGTQSGgILPNHDGTYQLRKTLDIAPG---EGAGYS 77

                ....*..
gi 2052056  330 CQVEHDG 336
Cdd:cd21029  78 CRVDHSS 84

Immunoglobulin domain of Zn-alpha2-glycoprotein (ZAG); member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin domain of Zn-alpha2-glycoprotein (ZAG). ZAG is a soluble protein that is present in serum and other body fluids. ZAG stimulates lipid degradation in adipocytes and causes the extensive fat losses associated with some advanced cancers. The 2.8 angstrom crystal structure of ZAG resembles a class I major histocompatibility complex (MHC) heavy chain, but ZAG does not bind the class I light chain beta-2-microglobulin. The ZAG structure includes a large groove analogous to class I MHC peptide binding grooves. Instead of a peptide, the ZAG groove contains a nonpeptidic compound that may be implicated in lipid catabolism under normal or pathological conditions. IgC_MHC_I_alpha3; 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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2052056  252 PPTLEVTQQPVRAENQVnVTCQVRKFYPQRLQLTWLENGNVSRTETASTVTENKDGTYnwMSWLLVNVSAHrDDVKLTCQ 331
Cdd:cd21010   4 PPSVSVTSHVAPGKNRT-LKCLAYDFYPRGISLHWTRAGKVQESESGGDVLPSGNGTY--QSWVVVEVPPQ-DRAPYSCH 79

                ....*....
gi 2052056  332 VEHDG--QP 338
Cdd:cd21010  80 VEHSSlaQP 88

Immunoglobulin C-Type;

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 2052056     164 TVSFTCESHGFSPRDITLKWFKNGNELSDFQTNVDPVGES-VSYSIHSTAKVVLTREDVHSQVICEVAHVTLQG 236
Cdd:smart00407   1 KATLVCLVSGFYPPDITVTWLRNGQEVTEGVSTTDPLKNSdGTYFLSSYLTVPASTWESGDVYTCQVTHEGLKE 74

CH2 domain (second constant Ig domain of the heavy chain) in immunoglobulin mu chain; member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin constant domain (IgC) of mu heavy chains. 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 2052056  163 HTVSFTCESHGFSPRDITLKWFKNGNELSDF--QTNVDPVGESV-SYSIHSTAKVVLTREDVHSQVICEVAH 231
Cdd:cd16093  18 RTATFVCLATGFSPKTISFKWLRNGKEVTSStgAVVEEPKEDGKtLYSATSFLTITESEWKSQTEFTCEFKH 89

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 2052056  144 RAKPSAPVVsgPAARATPQHTVSFTCESHGFSPRDITLKWFKNGNELSDF--QTNVDPVGESvSYSIHSTAKVVLTREDV 221
Cdd:cd05766   1 RVQPSVKVS--PTKTGPLEHPNLLVCSVTGFYPAEIEVKWFRNGQEETAGvvSTELIPNGDW-TFQILVMLETTPRRGDV 77

                        90
                ....*....|....*....
gi 2052056  222 HSqviCEVAHVTLQgDPLR 240
Cdd:cd05766  78 YT---CQVEHSSLQ-SPLT 92

Immunoglobulin C1-set domain;

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 2052056    266 NQVNVTCQVRKFYPQRLQLTWLENGnVSRTETASTVTE--NKDGTYNWMSWLLVNVSAHRDDVKLTCQVEHDG 336
Cdd:pfam07654  13 KPNTLTCLVTGFYPPDITVTWLKNG-QEVTEGVKTTPPspNSDWTYQLSSYLTVTPSDWESGDEYTCRVEHEG 84

Class II major histocompatibility complex (MHC) alpha chain immunoglobulin domain; member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig) domain of the major histocompatibility complex (MHC) class II alpha 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 had 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 2052056  251 VPPTLEV-TQQPVRAeNQVNV-TCQVRKFYPQRLQLTWLENG-NVSRTETASTVTENKDGTYNWMSWLlvNVSAHRDDVk 327
Cdd:cd05767   1 VPPEVTVfPKSPVEL-GEPNTlICFVDNFFPPVINVTWLRNGqPVTDGVSETVFLPREDHSFRKFSYL--PFTPSEGDI- 76

                        90
                ....*....|....*
gi 2052056  328 LTCQVEHDG--QPAV 340
Cdd:cd05767  77 YDCRVEHWGleEPLL 91

H-2 class I histocompatibility complex TLA (thymus leukemia antigen); member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the major histocompatibility complex (MHC) H-2 class I histocompatibility complex TLA (thymus leukemia antigen). The murine MHC class I histocompatibility TLA (Thymus leukemia antigen), which is encoded in the T region by T3 and T18 genes, is expressed mainly by intestinal epithelial cells and thymocytes. The murine TLAs are class I, beta-2-microglobulin-associated glycoproteins. The TLA function is not defined by antigen presentation, but rather by its relatively high affinity binding to CD8-alpha-alpha compared with CD8-alpha-beta. The existence of a human homolog for murine TLA remains unresolved. This group is a member of the C1-set Ig domains, which 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 2052056  252 PPTLEVTQQPvRAENQVNVTCQVRKFYPQRLQLTWLENGN--VSRTETASTVTENkDGTYNwmSWLLVNVSAHRDDvKLT 329
Cdd:cd21012   5 PPKTHVTHHP-RPEGYVTLRCWALGFYPAHITLTWQLNGEelIQDTELVETRPAG-DGTFQ--KWAAVVVPSGEEQ-KYT 79

                ....*....
gi 2052056  330 CQVEHDGQP 338
Cdd:cd21012  80 CHVYHEGLP 88

Class Ia major histocompatibility complex (MHC) immunoglobulin domain of human leukocyte antigen (HLA) B and similar proteins; member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the class Ia major histocompatibility complex (MHC) immunoglobulin domain of human leukocyte antigen (HLA) B and similar proteins. The classical class I molecules (HLA-A, -B, and -C) are responsible for the presentation of endogenous antigen to CD8+ T cells. The receptor is a heterodimer, and is composed of a heavy alpha chain and smaller beta chain. The alpha chain is encoded by a variant HLA-B gene, and the beta chain (beta-2-microglobulin) is an invariant beta-2-microglobulin molecule. The beta-2-microglobulin protein is coded for by a separate region of the human genome. Human leukocyte antigen (HLA) B*3501 (B35) is a common human allele involved in mediating protective immunity against HIV. 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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2052056  252 PPTLEVTQQPVrAENQVNVTCQVRKFYPQRLQLTWLENGNvSRTETASTVTENKDGTYNWMSWLLVNVSAHRDDvKLTCQ 331
Cdd:cd21026   5 PPKTHVTHHPI-SDHEATLRCWALGFYPAEITLTWQRDGE-DQTQDTELVETRPAGDRTFQKWAAVVVPSGEEQ-RYTCH 81

                ....*..
gi 2052056  332 VEHDGQP 338
Cdd:cd21026  82 VQHEGLP 88

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2052056   38 QPDKSVSVAAGESAILHCTVTSL-IPVGPIQWFR---GAGPAReLIY------NQKEGHFPRvTTVSESTKRENMDFSIS 107
Cdd:cd04982   3 QPQLSITREESKSVTISCKVSGIdFSTTYIHWYRqkpGQALER-LLYvsstsaVRKDSGKTK-NKFEARKDVGKSTSTLT 80

                        90       100       110
                ....*....|....*....|....*....|....*..
gi 2052056  108 ISNITPADAGTYYCVKFRKGSpDTEFKS-GAGTELSV 143
Cdd:cd04982  81 ITNLEKEDSATYYCAYWESGS-GYYIKVfGSGTKLIV 116

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        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2052056  147 PSAPVVSGPAARATPQHTVSFTCESHGFSPRDITLKWFKNGNELSD---FQTNVDPVGESvSYSIHSTAKVVL---TRED 220
Cdd:cd05768   1 PSVYLLPPPEEELSLNETVTLTCLVKGFYPEDIFVSWLQNGEPLPSadyKTTAPVPESDG-SFFVYSKLNVSTadwNSGD 79

                        90       100
                ....*....|....*....|
gi 2052056  221 VHSqviCEVAHvtlQGDPLR 240
Cdd:cd05768  80 VFS---CVVGH---EALPLQ 93

Second immunoglobulin (Ig)-like domain of nectin-like molcule-1 (Necl-1); member of the I-set of Ig superfamily domains; The members here are composed of the second immunoglobulin (Ig)-like domain of nectin-like molcule-1 (Necl-1; also known as cell adhesion molecule3 (CADM3)). These nectin-like molecules have similar domain structures to those of nectins. At least five nectin-like molecules have been identified (Necl-1 through Necl-5). These have an extracellular region containing three Ig-like domains, one transmembrane region, and one cytoplasmic region. The N-terminal Ig-like domain of the extracellular region belongs to the V-type subfamily of Ig domains is essential to cell-cell adhesion and plays a part in the interaction with the envelope glycoprotein D of various viruses. Necl-1 and Necl-2 have Ca(2+)-independent homophilic and heterophilic cell-cell adhesion activity. Necl-1 is specifically expressed in neural tissue and is important to the formation of synapses, axon bundles, and myelinated axons. Necl-2 is expressed in a wide variety of tissues and is a putative tumour suppressor gene which is downregulated in aggressive neuroblastoma. Ig domains are likely to participate in ligand binding and recognition.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2052056  147 PSAPVVSGPAARATPQHTVSFTCESHGFSPRdITLKWFKNGNELSDFQTNVDPVGESVSYSIHSTAKVVLTREDVHSQVI 226
Cdd:cd07705   4 PQKPQITGYESAFKEKDKAKLRCTSSGSKPA-ANIKWRKGDQELEGAPTSVQEDGNGKTFTVSSSVEFQVTREDDGAEIT 82

                        90
                ....*....|
gi 2052056  227 CEVAHVTLQG 236
Cdd:cd07705  83 CSVGHESLHD 92

Immunoglobulin light chain Constant domain; member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig) light chain constant (C) domain. 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. There are five types of heavy chains (alpha, gamma, delta, epsilon, and mu), which determine the type of immunoglobulin: IgA, IgG, IgD, IgE, and IgM, respectively. In higher vertebrates, there are two types of light chain, designated kappa and lambda, which seem to be functionally identical, and can associate with any of the heavy chains.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2052056  252 PPTLEVTQQPVRAE--NQVNVTCQVRKFYPQRLQLTWLENGN-VSRTETASTVTENKDGTYNWMSWLLVNVSAHRDDVKL 328
Cdd:cd07699   1 APSVTIFPPSSEELssGKATLVCLINKFYPGFATVTWKVDGStVSSGVTTSKTEQQSDNTYSMSSYLTLSSSDWNKHKVY 80

                        90
                ....*....|....*.
gi 2052056  329 TCQVEHDG-QPAVSKS 343
Cdd:cd07699  81 TCEVTHEGlSSTITKS 96

Class Ib major histocompatibility complex (MHC) immunoglobulin domain of human leukocyte antigen (HLA) E; member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the Class Ib major histocompatibility complex (MHC) immunoglobulin domain of human leukocyte antigen (HLA) E. HLA-E is the first human class Ib major histocompatibility complex molecule to be crystallized. Like other MHC class I molecules, HLA-E is a heterodimer consisting of an a heavy chain and light chain beta-2-microglobulin. HLA-E is highly conserved and almost nonpolymorphic, and has recently been shown to be the first specialized ligand for natural killer cell receptors. 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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2052056  252 PPTLEVTQQPVrAENQVNVTCQVRKFYPQRLQLTWLENGNvSRTETASTVTENKDGTYNWMSWLLVNVSAHRDDVkLTCQ 331
Cdd:cd21024   5 PPKTHVTHHPI-SDHEATLRCWALGFYPAEITLTWQQDGE-GHTQDTELVETRPAGDGTFQKWAAVVVPSGEEQR-YTCH 81

                ....*..
gi 2052056  332 VEHDGQP 338
Cdd:cd21024  82 VQHEGLP 88

Class Ia major histocompatibility complex (MHC) immunoglobulin domain of H2-Dd; member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the Class Ia major histocompatibility complex (MHC) immunoglobulin domain of H2-Dd. Mouse MHC is composed of 11 subclasses. It includes the classical MHC class I (MHC-Ia) that comprises H-2D, H-2K and H-2L subclasses, the non-classical MHC class I (MHCIb) that comprises H-2Q, H-2M and H-2T subclasses, the classical MHC class II (MHC-IIa) that includes H-2A(I-A) and H-2E(I-E) subclasses, and the non-classical MHC class II (MHC-IIb) comprises H-2M and H-2O. H-2K, H-2D, and H-2L are 80 to 90% homologous at the amino acid level yet appear to be involved in different recognition reactions and are differentially expressed on lymphoid cells. 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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2052056  252 PPTLEVTQQPvRAENQVNVTCQVRKFYPQRLQLTWLENGNvSRTETASTVTENKDGTYNWMSWLLVNVSAHRDDvKLTCQ 331
Cdd:cd21020   5 PPKAHVTHHR-RPEGDVTLRCWALGFYPADITLTWQLNGE-ELTQEMELVETRPAGDGTFQKWASVVVPLGKEQ-KYTCH 81

                ....*..
gi 2052056  332 VEHDGQP 338
Cdd:cd21020  82 VEHEGLP 88

Class Ib major histocompatibility complex (MHC) immunoglobulin domain of human leukocyte antigen H; member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the Class Ib major histocompatibility complex (MHC) immunoglobulin domain of human leukocyte antigen H (HLA-H). HLA-H (also known as hereditary hemochromatosis protein; HFE) is a major histocompatibility complex (MHC) class I-like protein that is mutated in Hereditary Hemochromatosis. HFE is a protein of 343 amino acids that includes a signal peptide, an extracellular transferrin receptor-binding region (a1 and a2), an immunoglobulin-like domain (a3), a transmembrane region, and a short cytoplasmic tail. HFE binds beta-2-microglobulin to form a heterodimer expressed at the cell surface. It binds transferrin receptor (TFRC) in its extracellular alpha1-alpha2 domain. HFE plays an important part in the regulation of hepcidin expression in response to iron overload and the liver is important in the pathophysiology of HFE-associated hemochromatosis. Nine HFE splicing variants have been reported with transcripts lacking exon 2 or exon 3, or exons 2-3, 2-4, or 2-5. Diverse mutations involving HFE introns and exons discovered in persons with hemochromatosis or their family members cause or probably cause high iron phenotypes. 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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2052056  250 RVPPTLEVTQQPVraENQVNVTCQVRKFYPQRLQLTWLENGNV--SRTETASTVTENKDGTYNwmSWLLVNVSAHRDDvK 327
Cdd:cd21021   2 QVPPLVKVTHHVT--SSVTTLRCRALNYYPQNITMKWLKDKQPmdAKEFEPKDVLPNGDGTYQ--GWITLAVPPGEEQ-R 76

                        90
                ....*....|....*
gi 2052056  328 LTCQVEHDG--QPAV 340
Cdd:cd21021  77 YTCQVEHPGldQPLI 91

Class Ib major histocompatibility complex (MHC) immunoglobulin domain of human leukocyte antigen (HLA) F; member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the Class Ib major histocompatibility complex (MHC) immunoglobulin domain of human leukocyte antigen alpha chain F (HLA-F). HLA-F, encoded by the HLA-F gene in humans, belongs to the non-classical HLA class I heavy chain paralogs. This class I molecule mainly exists as a heterodimer associated with the invariant light chain beta-2-microglobulin. HLA-F molecules can interact with both activating and inhibitory receptors on immune cells, such as NK cells, and can present a diverse panel of peptides. 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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2052056  252 PPTLEVTQQPVrAENQVNVTCQVRKFYPQRLQLTWLENGNvSRTETASTVTENKDGTYNWMSWLLVNVSAHRDDvKLTCQ 331
Cdd:cd21023   5 PPKAHVAHHPI-SDHEATLRCWALGFYPAEITLTWQRDGE-EQTQDTELVETRPAGDGTFQKWAAVVVPPGEEQ-RYTCH 81

                ....*..
gi 2052056  332 VEHDGQP 338
Cdd:cd21023  82 VQHEGLP 88

Class Ib major histocompatibility complex (MHC) immunoglobulin domain of human leukocyte antigen (HLA) G; member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the Class Ib major histocompatibility complex (MHC) immunoglobulin domain of human leukocyte antigen (HLA) G. HLA-G histocompatibility antigen (also known as human leukocyte antigen G ; HLA-G) is a protein that in humans is encoded by the HLA-G gene. HLA-G belongs to the HLA nonclassical class I heavy chain paralogs. This class I molecule is a heterodimer consisting of a heavy chain and light chain, beta-2-microglobulin. The heavy chain is anchored in the membrane. HLA-G may play a role in immune tolerance in pregnancy, being expressed in the placenta by extravillous trophoblast cells (EVT), while the classical MHC class I genes (HLA-A and HLA-B) are not. Immunoglobulin (Ig) domain of major histocompatibility complex (MHC) class I and class II. 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. MHC class II molecules play a key role in the initiation of the antigen-specific immune repose. 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 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 had 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 2052056  252 PPTLEVTQQPVrAENQVNVTCQVRKFYPQRLQLTWLENGNvSRTETASTVTENKDGTYNWMSWLLVNVSAHRDDvKLTCQ 331
Cdd:cd21022   4 PPKTHVTHHPV-FDYEATLRCWALGFYPAEIILTWQRDGE-DQTQDVELVETRPAGDGTFQKWAAVVVPSGEEQ-RYTCH 80

                ....*..
gi 2052056  332 VEHDGQP 338
Cdd:cd21022  81 VQHEGLP 87

Class Ia major histocompatibility complex (MHC) immunoglobulin domain of human leukocyte antigen (HLA) H2Db and H2Ld; member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the Class Ia major histocompatibility complex (MHC) immunoglobulin domain of human leukocyte antigen (HLA) H2Db and H2Ld. H-2Ld complexed with peptide QL9 (or p2Ca) and complexed with influenza virus peptide NP366-374 (ASNEN-METM), respectively are high-affinity alloantigens for the 2C T cell receptor (TCR). The a1-a2 super domains of H-2Ld, H-2Db, and H-2Kb closely superimpose. 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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2052056  253 PTLEVTQQPvRAENQVNVTCQVRKFYPQRLQLTWLENGNvSRTETASTVTENKDGTYNWMSWLLVNVSAHRDDvKLTCQV 332
Cdd:cd21018   6 PKAHVTHHP-RSKGEVTLRCWALGFYPADITLTWQLNGE-ELTQDMELVETRPAGDGTFQKWASVVVPLGKEQ-NYTCRV 82

                ....*.
gi 2052056  333 EHDGQP 338
Cdd:cd21018  83 YHEGLP 88

CH2 domain (second constant Ig domain of the heavy chain) in immunoglobulin mu chain; member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin constant domain (IgC) of mu heavy chains. 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        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2052056  252 PPTLEVTQQPVRA-ENQVNVT--CQVRKFYPQRLQLTWLENGNV---SRTETASTVTENKDGTYNWMSWLLVNVSAHRDD 325
Cdd:cd16093   1 PPTVSLHAPSREEfLGNRTATfvCLATGFSPKTISFKWLRNGKEvtsSTGAVVEEPKEDGKTLYSATSFLTITESEWKSQ 80

                        90
                ....*....|.
gi 2052056  326 VKLTCQVEHDG 336
Cdd:cd16093  81 TEFTCEFKHKG 91

Class II major histocompatibility complex (MHC) beta chain immunoglobulin domain of histocompatibility antigen (HLA) DR; member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the Class II major histocompatibility complex (MHC) beta chain immunoglobulin domain of histocompatibility antigen (HLA) DR. HLA-DR is an MHC class II cell surface receptor encoded by the human leukocyte antigen complex on chromosome 6 region 6p21.31. HLA-DR is also involved in several autoimmune conditions, disease susceptibility, and disease resistance including seronegative-rheumatoid arthritis, penicillamine-induced myasthenia, schizophrenia, Goodpasture syndrome, systemic lupus erythematosus, Alzheimers, tuberculoid leprosy, and Hashimoto's thyroiditis. HLA-DR molecules are upregulated in response to signaling. HLA-DR is an alphabeta heterodimer cell surface receptor, each subunit of which contains two extracellular domains, a membrane-spanning domain, and a cytoplasmic tail. Both alpha and beta chains are anchored in the membrane. The DR beta chain is encoded by 4 loci, however no more than 3 functional loci are present in a single individual, and no more than two on a single chromosome. Sometimes an individual may only possess 2 copies of the same locus, DRB1*. The HLA-DRB1 locus is ubiquitous and encodes a very large number of functionally variable gene products (HLA-DR1 to HLA-DR17). The HLA-DRB3 locus encodes the HLA-DR52 specificity, is moderately variable and is variably associated with certain HLA-DRB1 types. The HLA-DRB4 locus encodes the HLA-DR53 specificity, has some variation, and is associated with certain HLA-DRB1 types. The HLA-DRB5 locus encodes the HLA-DR51 specificity, which is typically invariable, and is linked to the HLA-DR2 types. Three genetically distinct isotypes of class II MHC molecules are found in humans (HLA-DR, HLA-DQ, and HLA-DP), and two in mice (I-E and I-A). 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 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 had 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 2052056  250 RVPPTLEV---TQQPVRAENQVnvTCQVRKFYPQRLQLTWLENGNVSRTETAST-VTENKDGTYNWMswLLVNVSAHRDD 325
Cdd:cd21000   1 RVEPKVTVypaKTQPLQHHNLL--VCSVNGFYPGSIEVRWFRNGQEEKAGVVSTgLIQNGDWTFQTL--VMLETVPRSGE 76