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 1243938608  35 KVTQPEKSVSVAAGDSTVLNCTLTSLLPVGPIRWYRGVGPSRLLIYSFAGEYVPRIRNVSDTTKRNNMDFSIRISNVTPA 114
Cdd:cd16097     1 QVIQPEKSVSVAAGESATLHCTVTSLIPVGPIQWFRGAGPGRELIYNQKEGHFPRVTTVSDLTKRNNMDFSIRISNITPA 80

                          90       100       110
                  ....*....|....*....|....*....|..
gi 1243938608 115 DAGIYYCVKFQKGSSePDTEIQSGGGTEVYVL 146
Cdd:cd16097    81 DAGTYYCVKFRKGSP-DDVEFKSGAGTELSVR 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 1243938608 148 KPSPPEVSGPADRGIPDQKVNFTCKSHGFSPRNITLKWFKDGQELHPLETTVNPSGKNVSYNISSTVRVVLNSMDVNSKV 227
Cdd:cd05772     1 KPSQPLVSGPSGRATPGQTVSFTCKSHGFSPRDITLKWFKNGNELSALQTTVFPEGDSVSYSVSSTVQVVLTKDDVHSQL 80

                          90       100
                  ....*....|....*....|...
gi 1243938608 228 ICEVAHITLdRSPLRGIANLSNF 250
Cdd:cd05772    81 TCEVAHVTL-QAPLRGTANLSDI 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 1243938608  35 KVTQPEKSVSVAAGDSTVLNCTLTSLLPVGPIRWYRGVGPSRLLIYSFAGEYVPRIRNVSDTTKRNNMDFSIRISNVTPA 114
Cdd:cd16097     1 QVIQPEKSVSVAAGESATLHCTVTSLIPVGPIQWFRGAGPGRELIYNQKEGHFPRVTTVSDLTKRNNMDFSIRISNITPA 80

                          90       100       110
                  ....*....|....*....|....*....|..
gi 1243938608 115 DAGIYYCVKFQKGSSePDTEIQSGGGTEVYVL 146
Cdd:cd16097    81 DAGTYYCVKFRKGSP-DDVEFKSGAGTELSVR 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 1243938608 148 KPSPPEVSGPADRGIPDQKVNFTCKSHGFSPRNITLKWFKDGQELHPLETTVNPSGKNVSYNISSTVRVVLNSMDVNSKV 227
Cdd:cd05772     1 KPSQPLVSGPSGRATPGQTVSFTCKSHGFSPRDITLKWFKNGNELSALQTTVFPEGDSVSYSVSSTVQVVLTKDDVHSQL 80

                          90       100
                  ....*....|....*....|...
gi 1243938608 228 ICEVAHITLdRSPLRGIANLSNF 250
Cdd:cd05772    81 TCEVAHVTL-QAPLRGTANLSDI 102

Immunoglobulin C-Type;

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1243938608  269 QVNLTCRAERFYPEDLQLIWLENGNVSRNDT-PKNLTKNTDGTYNYTSLFLVNSSAHREDVVFTCQVKH 336
Cdd:smart00407   1 KATLVCLVSGFYPPDITVTWLRNGQEVTEGVsTTDPLKNSDGTYFLSSYLTVPASTWESGDVYTCQVTH 69

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1243938608   41 KSVSVAAGDSTVLNCTLTSLlPVGPIRWYRGvgPSRLLIYSfageyvPRIrnvsdTTKRNNMDFSIRISNVTPADAGIYY 120
Cdd:smart00410   2 PSVTVKEGESVTLSCEASGS-PPPEVTWYKQ--GGKLLAES------GRF-----SVSRSGSTSTLTISNVTPEDSGTYT 67

                           90       100
                   ....*....|....*....|....*.
gi 1243938608  121 C-VKFQKGSSEpdteiqsgGGTEVYV 145
Cdd:smart00410  68 CaATNSSGSAS--------SGTTLTV 85

Immunoglobulin C-Type;

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1243938608  166 KVNFTCKSHGFSPRNITLKWFKDGQELHPLETTVNPSG-KNVSYNISSTVRVVLNSMDVNSKVICEVAHITLD 237
Cdd:smart00407   1 KATLVCLVSGFYPPDITVTWLRNGQEVTEGVSTTDPLKnSDGTYFLSSYLTVPASTWESGDVYTCQVTHEGLK 73

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 1243938608  35 KVTQPEKSVSVAAGDSTVLNCTLTSLLPVGPIRWYRGVGPSRLLIYSFAGEYVPRIRNVSDTTKRNNMDFSIRISNVTPA 114
Cdd:cd16097     1 QVIQPEKSVSVAAGESATLHCTVTSLIPVGPIQWFRGAGPGRELIYNQKEGHFPRVTTVSDLTKRNNMDFSIRISNITPA 80

                          90       100       110
                  ....*....|....*....|....*....|..
gi 1243938608 115 DAGIYYCVKFQKGSSePDTEIQSGGGTEVYVL 146
Cdd:cd16097    81 DAGTYYCVKFRKGSP-DDVEFKSGAGTELSVR 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 1243938608 148 KPSPPEVSGPADRGIPDQKVNFTCKSHGFSPRNITLKWFKDGQELHPLETTVNPSGKNVSYNISSTVRVVLNSMDVNSKV 227
Cdd:cd05772     1 KPSQPLVSGPSGRATPGQTVSFTCKSHGFSPRDITLKWFKNGNELSALQTTVFPEGDSVSYSVSSTVQVVLTKDDVHSQL 80

                          90       100
                  ....*....|....*....|...
gi 1243938608 228 ICEVAHITLdRSPLRGIANLSNF 250
Cdd:cd05772    81 TCEVAHVTL-QAPLRGTANLSDI 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 1243938608 256 TVKVTQQSPTSM--NQVNLTCRAERFYPEDLQLIWLENGN-VSRNDTPKNLTKNTDGTYNYTSLFLVNSSAHREDVVFTC 332
Cdd:cd00098     1 TVTLLPPSPEEKggGKVTLVCLVSGFYPKDITVTWLKNGVpLTSGVSTSSPVEPNDGTYSVTSSLTVPPSDWDEGATYTC 80

                          90
                  ....*....|....*
gi 1243938608 333 QVKH-DQQPAITRNH 346
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 1243938608 152 PEVSGPADRGIPDQKVNFTCKSHGFSPRNITLKWFKDGQELH----PLETTVNPSGknvSYNISSTVRVVLNSMDVNSKV 227
Cdd:cd00098     2 VTLLPPSPEEKGGGKVTLVCLVSGFYPKDITVTWLKNGVPLTsgvsTSSPVEPNDG---TYSVTSSLTVPPSDWDEGATY 78

                          90
                  ....*....|..
gi 1243938608 228 ICEVAHITLDRS 239
Cdd:cd00098    79 TCVVTHESLKSP 90

Immunoglobulin C-Type;

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1243938608  269 QVNLTCRAERFYPEDLQLIWLENGNVSRNDT-PKNLTKNTDGTYNYTSLFLVNSSAHREDVVFTCQVKH 336
Cdd:smart00407   1 KATLVCLVSGFYPPDITVTWLRNGQEVTEGVsTTDPLKNSDGTYFLSSYLTVPASTWESGDVYTCQVTH 69

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 1243938608 252 RVSPTVKVTQQSPTSMNQVN-LTCRAERFYPEDLQLIWLENGNVSRND-TPKNLTKNTDGTYNYtsLFLVNSSAHREDvV 329
Cdd:cd05766     1 RVQPSVKVSPTKTGPLEHPNlLVCSVTGFYPAEIEVKWFRNGQEETAGvVSTELIPNGDWTFQI--LVMLETTPRRGD-V 77

                          90
                  ....*....|....*...
gi 1243938608 330 FTCQVKHD--QQPaITRN 345
Cdd:cd05766    78 YTCQVEHSslQSP-LTVD 94

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 1243938608 253 VSPTVKVTQqSPTSMNQVNLTCRAERFYPEDLQLIWLENGNVSRNDTPKNLTK-NTDGTYnYTSLFLVNSSAhrEDVVFT 331
Cdd:cd07698     1 DPPKVHVTH-HPRSDGESTLRCWALGFYPAEITLTWQRDGEDQTQDMELVETRpNGDGTF-QKWAAVVVPSG--EEQRYT 76

                  ....*
gi 1243938608 332 CQVKH 336
Cdd:cd07698    77 CHVQH 81

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1243938608 152 PEVSGPA-DRGIPDQKVNFTCKSHGFSPRnITLKWFKDGQELHPLETTVNPSGKNVSYNISSTVRVVLNSMDVNSKVICE 230
Cdd:pfam08205   1 PTIEPPAsLLEGEGPEVVATCSSAGGKPA-PRITWYLDGKPLEAAETSSEQDPESGLVTVTSELKLVPSRSDHGQSLTCQ 79

                  ...
gi 1243938608 231 VAH 233
Cdd:pfam08205  80 VSY 82

Second immunoglobulin (Ig)-like domain of the nectin-like molecules Necl-1 - Necl-4; member of the I-set of Ig superfamily domains; The members here are composed of the second immunoglobulin (Ig)-like domain of the nectin-like molecules Necl-1 (also known as cell adhesion molecule 3 or CADM3), Necl-2 (also known as CADM1), Necl-3 (also known as CADM2) and Necl-4 (also known as CADM4). 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. Necl-3 has been shown to accumulate in tissues of the central and peripheral nervous system, where it is expressed in ependymal cells and myelinated axons. It is observed at the interface between the axon shaft and the myelin sheath. Necl-4 is expressed on Schwann cells, and plays a key part in initiating peripheral nervous system (PNS) myelination. Necl-4 participates in cell-cell adhesion and is proposed to play a role in tumor suppression.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1243938608 146 LAKPSPPEVSGPADRGIPDQKVNFTCKSHGFSPRnITLKWFKDGQELHPLeTTVNPSGKNVSYNISSTVRVVLNSMDVNS 225
Cdd:cd05761     1 LGVPEKPVITGFTSPVVEGDEITLTCTTSGSKPA-ADIRWFKNDKELKGV-KEVQESGAGKTFTVTSTLRFRVDRDDDGV 78

                          90
                  ....*....|....*..
gi 1243938608 226 KVICEVAHITLDRSPLR 242
Cdd:cd05761    79 AVICRVDHESLTSTPKQ 95

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 1243938608 253 VSPTVKVTQQSPTSMNQVNLTCRAERFYPEDLQLIWLENGNVSRNDT-PKNLTKNTDGTYNYT-SLFLVNSSAHRedvvF 330
Cdd:cd21029     1 VKPRVRLSSRPSPGDGHLQLSCHVTGFYPRPIEVTWLRDGQEQMDGTqSGGILPNHDGTYQLRkTLDIAPGEGAG----Y 76

                  ....*..
gi 1243938608 331 TCQVKHD 337
Cdd:cd21029    77 SCRVDHS 83

Second immunoglobulin (Ig)-like domain of nectin-like molecule-3 (Necl-3); member of the I-set of Ig superfamily domains; The members here are composed of the second immunoglobulin (Ig)-like domain of nectin-like molecule-3 (Necl-3; also known as cell adhesion molecule 2 (CADM2)). 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. Necl-3 has been shown to accumulate in tissues of the central and peripheral nervous system where it is expressed in ependymal cells and myelinated axons. It is observed at the interface between the axon shaft and the myelin sheath. Ig domains are likely to participate in ligand binding and recognition.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1243938608 145 VLAKPSPPEVSGPADRGIPDQKVNFTCKSHGFSPRnITLKWFKDGQELHPLEtTVNPSGKN-VSYNISSTVRVVLNSMDV 223
Cdd:cd05884     1 VLGVPEKPQISGFTSPVMEGDHIQLTCKTSGSKPA-ADIRWFKNDKEVKDVK-YLKAEDANrKTFTVSSSLDFHVDRDDD 78

                          90
                  ....*....|....*..
gi 1243938608 224 NSKVICEVAHITLDRSP 240
Cdd:cd05884    79 GVAITCRVDHESLTATP 95

Class II major histocompatibility complex (MHC) beta chain immunoglobulin domain of histocompatibility antigen (HLA) DM; 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) DM. Human HLA-DM plays a critical role in antigen presentation to CD4 T cells by catalyzing the exchange of peptides bound to MHC class II molecules. Type 1 diabetes is correlated with DM activation and it is also implicated in viral infections such as herpes simplex virus, celiac disease, multiple sclerosis, other autoimmune diseases, and leukemia. 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 1243938608 251 IRVSPTvkvTQQSPTSmnQVNLTCRAERFYPEDLQLIWLENGNV--SRNDTPKNLTKNTDGTYNYTSLFLVNSSAhrEDv 328
Cdd:cd21002     6 VRVAPT---TPFNTRE--PVMLACHVWGFYPADVTITWLKNGDPvaPHSSAPKTAQPNGDWTYQTQVTLAVTPSP--GD- 77

                  ....*...
gi 1243938608 329 VFTCQVKH 336
Cdd:cd21002    78 TYTCSVQH 85

CH2 domain (second constant Ig domain of the heavy chain) in immunoglobulin E (IgE); member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the second constant domain of the heavy chain of immunoglobulin E (IgE). The basic structure of immunoglobulin (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). The different classes of antibodies vary in their heavy chains; the IgE class has the epsilon type. This domain (Cepsilon2) of IgE is in place of the flexible hinge region found in IgG.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1243938608 255 PTVKVTQQSPTSMNQ---VNLTCRAERFYPEDLQLIWLENGNVSRN-DTPKNLTKNTDGTYNYTSLFLVNSSAHREDVVF 330
Cdd:cd05847     1 PTVQILHSSCASTLTsetIQLLCLISGYTPSTIEVEWLVDGQVATLsAASTAPQKEEGGTFSTTSKLNVTQEDWKSGKTY 80

                  ....*.
gi 1243938608 331 TCQVKH 336
Cdd:cd05847    81 TCKVTH 86

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 1243938608 252 RVSPTVKVTQQSPTSMNQVNLTCRAERFYPEDLQLIWLENGNVSRNDTPKNLTKNT-DGTYNYTSLFLVNSSahrEDVVF 330
Cdd:cd21023     2 RADPPKAHVAHHPISDHEATLRCWALGFYPAEITLTWQRDGEEQTQDTELVETRPAgDGTFQKWAAVVVPPG---EEQRY 78

                          90
                  ....*....|....*.
gi 1243938608 331 TCQVKHD--QQPAITR 344
Cdd:cd21023    79 TCHVQHEglPQPLILR 94

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 1243938608 255 PTVKVTQQsPTSMNQVNLTCRAERFYPEDLQLIWLENGNVSRNDTPKNLTKNT-DGTYNYTSLFLVNSSahrEDVVFTCQ 333
Cdd:cd21024     6 PKTHVTHH-PISDHEATLRCWALGFYPAEITLTWQQDGEGHTQDTELVETRPAgDGTFQKWAAVVVPSG---EEQRYTCH 81

                  ....*..
gi 1243938608 334 VKHDQQP 340
Cdd:cd21024    82 VQHEGLP 88

Tapasin-R immunoglobulin-like domain; member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin-like domain on Tapasin-R. Tapasin is a V-C1 (variable-constant) immunoglobulin superfamily molecule present in the endoplasmic reticulum (ER), where it links MHC class I molecules to the transporter associated with antigen processing (TAP). Tapasin-R is a tapasin-related protein that contains similar structural motifs to Tapasin, with some marked differences, especially in the V domain, transmembrane and cytoplasmic regions. The majority of Tapasin-R is located within the ER; however, there may be some expression of Tapasin-R at the cell surface. Tapasin-R lacks an obvious ER retention signal.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1243938608 251 IRVSPTVKVTQQSPTSmnqvnLTCRAERFYPEDLQLIWLEngnVSRNDTPKNLTK----------NTDGTYNYTSLFLVN 320
Cdd:cd05771     3 VRLSPKNLVKPDLPQT-----LSCHIAGYYPLDVDVEWLR---EEPGGSESQVSRdgvslsshrqSVDGTYSISSYLTLE 74

                          90
                  ....*....|....*.
gi 1243938608 321 SSAHREDVVFTCQVKH 336
Cdd:cd05771    75 PGTENRGATYTCRVTH 90

Immunoglobulin (Ig) lambda light chain variable (V) domain; The members here are composed of the immunoglobulin (Ig) light chain, lambda type, variable (V) domain. 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 composed of a constant domain (CL) and a variable domain (VL). There are five types of heavy chains (alpha, gamma, delta, epsilon, and mu), which determines the type of immunoglobulin formed: 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. Members of this group contain standard Ig superfamily V-set AGFCC'C"/DEB domain topology.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1243938608  36 VTQPEkSVSVAAGDSTVLNCTLTSLLPVGP-IRWYRGVGPS--RLLIY--SFAGEYVP-RIRNVSDTTKRnnmdfSIRIS 109
Cdd:cd04984     2 LTQPS-SLSVSPGETVTITCTGSSGNISGNyVNWYQQKPGSapRYLIYedKHRPSGIPdRFSGSKSGNTA-----SLTIS 75

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 1243938608 110 NVTPADAGIYYCVKFQKGSsepdteIQSGGGTEVYV 145
Cdd:cd04984    76 GAQTEDEADYYCQVWDSNS------YVFGGGTKLTV 105

Class II major histocompatibility complex (MHC) beta chain immunoglobulin domain of histocompatibility antigen (HLA) DQ and I-A; 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 human histocompatibility antigen (HLA) DQ and mouse I-A. 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). I-A and I-E have the same basic features insofar as peptide loading and presentation, they differ in that each interacts with distinctly different sets of peptides, and in the incidence of deletion of their genes. A structural understanding of the similarities and differences between I-A and I-E may help with understanding their roles in peptide presentation and T cell activation. Mouse I-Ag7 has a genetic susceptibility to autoimmune diabetes due to its small, uncharged amino acid residue at position 57 of their beta chain which results in the absence of a salt bridge between beta 57 and Arg alpha 76, which is adjacent to the P9 pocket of the peptide-binding groove. Human HLA-DR, -DQ, and -DP are about 70% similar to each other. HLA-DQ (DQ) is a cell surface receptor protein found on antigen presenting cells. It is an alphabeta heterodimer of type MHC class II. The alpha and beta chains are encoded by two loci, HLA-DQA1 and HLA-DQB1, that are adjacent to each other on chromosome band 6p21.3. A person often produces two alpha-chain and two beta chain variants and thus 4 isoforms of DQ. HLA-DQ is involved in the autoimmune diseases celiac disease and diabetes mellitus type. DQ is one of several antigens involved in rejection of organ transplants. DQ2 is encoded by the HLA-DQB1*02 allele group. DQ6 is encoded by the HLA-DQB1*06 allele group. DQ2 beta-chains combine with alpha-chains, encoded by genetically linked HLA-DQA1 alleles, to form the cis-haplotype isoforms. These isoforms, nicknamed DQ2.2 and DQ2.5, are also encoded by the DQA1*0201 and DQA1*0501 genes, respectively. DQ6 beta-chains combine with alpha-chains, encoded by genetically linked HLA-DQA1 alleles, to form the cis-haplotype isoforms. For DQ6, however, cis-isoform pairing only occurs with DQ1 alpha-chains. There are many haplotypes of DQ6. Susceptibility to Leptospirosis infection was found associated with undifferentiated DQ6. DQ8 is determined by the antibody recognition of beta8 and this generally detects the gene product of DQB1*0302. DQ8 is commonly linked to autoimmune disease in the human population. DQ8 is the second most predominant isoform linked to celiac disease and the DQ most linked to Type 1 diabetes. DQ8 increases the risk for rheumatoid arthritis and is linked to the primary risk locus for RA, HLA-DR4. DR4 also plays an important role in Type 1 diabetes. DQ8 is a split antigen of the DQ3 broad antigen. MHC class II molecules play a key role in the initiation of the antigen-specific immune response. They are expressed constitutively on the cell surface of professional antigen-presenting cells (APCs), including B-lymphocytes, monocytes, and macrophages in both humans and mice, and induced in nonprofessional APCs, such as keratinocyctes; they are expressed on the surface of activated human T cells and on T cells from other species. 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, and 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 1243938608 252 RVSPTVKVTQQSPTSMNQVN-LTCRAERFYPEDLQLIWLEN------GNVSrndTPknLTKNTDGTYNYtsLFLVNSSAH 324
Cdd:cd21001     1 RVEPTVTISPSRTEALNHHNlLVCSVTDFYPGQIKVRWFRNdqeetaGVVS---TP--LIRNGDWTFQI--LVMLEMTPQ 73

                          90
                  ....*....|..
gi 1243938608 325 REDvVFTCQVKH 336
Cdd:cd21001    74 RGD-VYTCHVEH 84

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 1243938608 252 RVSPTVKVTQQSPTSMNQVNL-TCRAERFYPEDLQLIWLENGNVSRNDT-PKNLTKNTDGTYNYTSLFlvnSSAHREDVV 329
Cdd:cd21000     1 RVEPKVTVYPAKTQPLQHHNLlVCSVNGFYPGSIEVRWFRNGQEEKAGVvSTGLIQNGDWTFQTLVML---ETVPRSGEV 77

                          90
                  ....*....|....*....
gi 1243938608 330 FTCQVKHdqqPAITRNHTV 348
Cdd:cd21000    78 YTCQVEH---PSVTSPLTV 93

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1243938608 270 VNLTCRAERFYPEDLQLIWLENGNVSRNDTPKNLTKNTDGTYNYTSLFLVnsSAHREDVV--FTCQVKHD 337
Cdd:cd05772    20 VSFTCKSHGFSPRDITLKWFKNGNELSALQTTVFPEGDSVSYSVSSTVQV--VLTKDDVHsqLTCEVAHV 87

Immunoglobulin C-Type;

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1243938608  166 KVNFTCKSHGFSPRNITLKWFKDGQELHPLETTVNPSG-KNVSYNISSTVRVVLNSMDVNSKVICEVAHITLD 237
Cdd:smart00407   1 KATLVCLVSGFYPPDITVTWLRNGQEVTEGVSTTDPLKnSDGTYFLSSYLTVPASTWESGDVYTCQVTHEGLK 73

Class Ia major histocompatibility complex (MHC) immunoglobulin domain of MIC-A and MIC-B; 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 MIC-A and MIC-B. MIC-A and MIC-B are homologs that serve as stress-inducible antigens on epithelial and epithelially derived cells. Both serve as ligands for the widely expressed activating immunoreceptor NKG2D, a C-type lectin-like activating immunoreceptor. MIC-B is very similar in structure to MIC-A and likely interacts with NKG2D in an analogous manner. The interdomain flexibility observed in the MIC-A structures, a feature unique to MIC proteins among MHC class I proteins and homologs, is also displayed by MIC-B, with an interdomain relationship intermediate between the two examples of MIC-A structures. Mapping sequence variations onto the structures of MIC-A and MIC-B reveals patterns completely distinct from those displayed by classical MHC class I proteins, with a number of substitutions falling on positions likely to affect interactions with NKG2D, but with other positions lying distant from the NKG2D binding sites or buried within the core of the proteins. Members of the IgC 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 and the IgC domain is involved in oligomerization and molecular interactions.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1243938608 253 VSPTVKVTQqSPTSMNQVNLTCRAERFYPEDLQLIWLENGNVSRNDTPK--NLTKNTDGTYNytsLFLVNSSAHREDVVF 330
Cdd:cd21017     3 VPPMVNVTR-SEASEGNITVTCRASGFYPWNITLSWRQDGVSLSHDTQQwgDVLPDGNGTYQ---TWVATRICQGEEQRF 78

                  ....*.
gi 1243938608 331 TCQVKH 336
Cdd:cd21017    79 TCYMEH 84

Immunoglobulin domain; Members of the immunoglobulin superfamily are found in hundreds of proteins of different functions. Examples include antibodies, the giant muscle kinase titin and receptor tyrosine kinases. Immunoglobulin-like domains may be involved in protein-protein and protein-ligand interactions.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1243938608  38 QPEKSVSVAAGDSTVLNCTLTSLLPVGPIRWyrgvgpsrlliySFAGEYVPRIRNVSDTTKRNnMDFSIRISNVTPADAG 117
Cdd:pfam00047   1 SAPPTVTVLEGDSATLTCSASTGSPGPDVTW------------SKEGGTLIESLKVKHDNGRT-TQSSLLISNVTKEDAG 67

                  ....*
gi 1243938608 118 IYYCV 122
Cdd:pfam00047  68 TYTCV 72

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 1243938608 157 PADRGIPDQKVNFTCKSHGFSPRNITLKWFKDGQELHP--LETTVNPSGkNVSYNISSTVRVVLNSMDVnskVICEVAHI 234
Cdd:cd05766    10 PTKTGPLEHPNLLVCSVTGFYPAEIEVKWFRNGQEETAgvVSTELIPNG-DWTFQILVMLETTPRRGDV---YTCQVEHS 85

                  ....*...
gi 1243938608 235 TLDrSPLR 242
Cdd:cd05766    86 SLQ-SPLT 92

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 1243938608 269 QVNLTCRAERFYPEDLQLIWLENG-----NVSRNDTPknlTKNTDGTYNYTSLFLVNSSAHREDVVFTCQVKHDqqpAIT 343
Cdd:cd05768    18 TVTLTCLVKGFYPEDIFVSWLQNGeplpsADYKTTAP---VPESDGSFFVYSKLNVSTADWNSGDVFSCVVGHE---ALP 91