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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
3F7V_B      112 APTVSIFPPSSEQLTSGGASVVCFLNNFYPKDINVKWKIDGSERQNGVLNSWTDQDSkDSTYSMSSTLTLTKDEYERHNS 191
Cdd:cd07699   1 APSVTIFPPSSEELSSGKATLVCLINKFYPGFATVTWKVDGSTVSSGVTTSKTEQQS-DNTYSMSSYLTLSSSDWNKHKV 79

                        90       100
                ....*....|....*....|
3F7V_B      192 YTCEATHKTSTSPIVKSFNR 211
Cdd:cd07699  80 YTCEVTHEGLSSTITKSFNR 99

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
3F7V_B      112 APTVSIFPPSSEQLTSGGASVVCFLNNFYPKDINVKWKIDGSERQNGVLNSWTDQDSkDSTYSMSSTLTLTKDEYERHNS 191
Cdd:cd07699   1 APSVTIFPPSSEELSSGKATLVCLINKFYPGFATVTWKVDGSTVSSGVTTSKTEQQS-DNTYSMSSYLTLSSSDWNKHKV 79

                        90       100
                ....*....|....*....|
3F7V_B      192 YTCEATHKTSTSPIVKSFNR 211
Cdd:cd07699  80 YTCEVTHEGLSSTITKSFNR 99

Immunoglobulin C-Type;

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
3F7V_B         130 ASVVCFLNNFYPKDINVKWKIDGSERQNGVLNSWTDQDsKDSTYSMSSTLTLTKDEYERHNSYTCEATHKTSTSP 204
Cdd:smart00407   2 ATLVCLVSGFYPPDITVTWLRNGQEVTEGVSTTDPLKN-SDGTYFLSSYLTVPASTWESGDVYTCQVTHEGLKEP 75

Immunoglobulin V-set domain; This domain is found in antibodies as well as neural protein P0 and CTL4 amongst others.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
3F7V_B          6 QSPAILSVSPGERVSFSCRASQSI---GTDIHWYQQRTNGSPRLLIKYASES--ISGIPSRFSGSG--SGTDFTLSINSV 78
Cdd:pfam07686   1 QTPREVTVALGGSVTLPCTYSSSMseaSTSVYWYRQPPGKGPTFLIAYYSNGseEGVKKGRFSGRGdpSNGDGSLTIQNL 80

                          90       100
                  ....*....|....*....|....*...
3F7V_B         79 ESEDIANYYCQQSNRWPFTFGSGTKLEI 106
Cdd:pfam07686  81 TLSDSGTYTCAVIPSGEGVFGKGTRLTV 108

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
3F7V_B      112 APTVSIFPPSSEQLTSGGASVVCFLNNFYPKDINVKWKIDGSERQNGVLNSWTDQDSkDSTYSMSSTLTLTKDEYERHNS 191
Cdd:cd07699   1 APSVTIFPPSSEELSSGKATLVCLINKFYPGFATVTWKVDGSTVSSGVTTSKTEQQS-DNTYSMSSYLTLSSSDWNKHKV 79

                        90       100
                ....*....|....*....|
3F7V_B      192 YTCEATHKTSTSPIVKSFNR 211
Cdd:cd07699  80 YTCEVTHEGLSSTITKSFNR 99

Immunoglobulin variable domain (IgV); The members here are composed of the immunoglobulin variable domain (IgV). The IgV family contains the standard Ig superfamily V-set AGFCC'C"/DEB domain topology, and are components of immunoglobulin (Ig) and T cell receptors. The basic structure of Ig molecules is a tetramer of two light chains and two heavy chains linked by disulfide bonds. In Ig, each chain is composed of one variable domain (IgV) and one or more constant domains (IgC); these names reflect the fact that the variability in sequences is higher in the variable domain than in the constant domain. Within the variable domain, there are regions of even more variability called the hypervariable or complementarity-determining regions (CDRs) which are responsible for antigen binding. A predominant feature of most Ig domains is the disulfide bridge connecting 2 beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E and, D strands in one sheet and A', G, F, C, C', and C" strands in the other.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
3F7V_B        4 LTQSPAILSVSPGERVSFSCRASQSIGTD-IHWYQQRTNGSPRLLIKYASES---ISGIPSRFSGSGSG-TDFTLSINSV 78
Cdd:cd00099   1 VTQSPRSLSVQEGESVTLSCEVSSSFSSTyIYWYRQKPGQGPEFLIYLSSSKgktKGGVPGRFSGSRDGtSSFSLTISNL 80

                        90       100       110
                ....*....|....*....|....*....|.
3F7V_B       79 ESEDIANYYCQQS---NRWPFTFGSGTKLEI 106
Cdd:cd00099  81 QPEDSGTYYCAVSesgGTDKLTFGSGTRLTV 111

Immunoglobulin C-Type;

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
3F7V_B         130 ASVVCFLNNFYPKDINVKWKIDGSERQNGVLNSWTDQDsKDSTYSMSSTLTLTKDEYERHNSYTCEATHKTSTSP 204
Cdd:smart00407   2 ATLVCLVSGFYPPDITVTWLRNGQEVTEGVSTTDPLKN-SDGTYFLSSYLTVPASTWESGDVYTCQVTHEGLKEP 75

T cell receptor (TCR) beta chain constant immunoglobulin domain; member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the T cell receptor (TCR) beta chain constant immunoglobulin domain. TCRs mediate antigen recognition by T lymphocytes, and are composed of alpha and beta, or gamma and delta, polypeptide chains with variable (V) and constant (C) regions. This group includes the variable domain of the beta chain. Alpha/beta TCRs recognize antigen as peptide fragments presented by major histocompatibility complex (MHC) molecules. The antigen binding site is formed by the variable domains of the alpha and beta chains, located at the N-terminus of each chain. Alpha/beta TCRs recognize antigens differently from gamma/delta TCRs.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
3F7V_B      112 APTVSIFPPSS-EQLTSGGASVVCFLNNFYPKDINVKWKIDGSERQNGVLnswTDQDSK---DSTYSMSSTLTLTKDEYE 187
Cdd:cd05769   2 PPTVALFPPSEaEIRNKRKATLVCLATGFYPDHVSLSWKVNGKEVKDGVA---TDPQALrenTSTYSLSSRLRVSATEWF 78

                        90       100
                ....*....|....*....|....
3F7V_B      188 R-HNSYTCEATH--KTSTSPIVKS 208
Cdd:cd05769  79 NpRNTFTCIVKFygGTDTDTWTQG 102

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
3F7V_B        4 LTQSPAILSVSPGERVSFSCraSQSIGTD-IHWYQQRTNGSPRLLIKYASES---ISGIP-SRFSGSG-SGTDFTLSINS 77
Cdd:cd05899   1 VTQSPRYLIKRRGQSVTLRC--SQKSGHDnMYWYRQDPGKGLQLLFYSYGGGlneEGDLPgDRFSASRpSLTRSSLTIKS 78

                        90       100       110
                ....*....|....*....|....*....|
3F7V_B       78 VESEDIANYYC---QQSNRWPFTFGSGTKL 104
Cdd:cd05899  79 AEPEDSAVYLCassLGGGADEAYFGPGTRL 108

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
3F7V_B           8 PAILSVSPGERVSFSCRASQSIGTDIHWYQQRtngsPRLLIKyasesisgiPSRFSGSGSGTDFTLSINSVESEDIANYY 87
Cdd:smart00410   1 PPSVTVKEGESVTLSCEASGSPPPEVTWYKQG----GKLLAE---------SGRFSVSRSGSTSTLTISNVTPEDSGTYT 67

                           90
                   ....*....|....*....
3F7V_B          88 CQQSNRWPFTFGsGTKLEI 106
Cdd:smart00410  68 CAATNSSGSASS-GTTLTV 85

Immunoglobulin V-set domain; This domain is found in antibodies as well as neural protein P0 and CTL4 amongst others.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
3F7V_B          6 QSPAILSVSPGERVSFSCRASQSI---GTDIHWYQQRTNGSPRLLIKYASES--ISGIPSRFSGSG--SGTDFTLSINSV 78
Cdd:pfam07686   1 QTPREVTVALGGSVTLPCTYSSSMseaSTSVYWYRQPPGKGPTFLIAYYSNGseEGVKKGRFSGRGdpSNGDGSLTIQNL 80

                          90       100
                  ....*....|....*....|....*...
3F7V_B         79 ESEDIANYYCQQSNRWPFTFGSGTKLEI 106
Cdd:pfam07686  81 TLSDSGTYTCAVIPSGEGVFGKGTRLTV 108

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
3F7V_B      113 PTVSIFPPSS-EQLTSGGASVVCFLNNFYPKDINVKWKIDGSERQNGVLNSWTDQDSkDSTYSMSSTLTLTKDEYERHNS 191
Cdd:cd05847   1 PTVQILHSSCaSTLTSETIQLLCLISGYTPSTIEVEWLVDGQVATLSAASTAPQKEE-GGTFSTTSKLNVTQEDWKSGKT 79

                        90
                ....*....|.
3F7V_B      192 YTCEATHKTST 202
Cdd:cd05847  80 YTCKVTHQGTT 90

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
3F7V_B      113 PTVSIFPPSSEQLTSGGAsVVCFLNNFYPKDINVKWKIDGSERQNGVLNSWTDQDSkDSTYsmsSTLTLTKDEYERHNSY 192
Cdd:cd21000   4 PKVTVYPAKTQPLQHHNL-LVCSVNGFYPGSIEVRWFRNGQEEKAGVVSTGLIQNG-DWTF---QTLVMLETVPRSGEVY 78

                        90
                ....*....|...
3F7V_B      193 TCEATHKTSTSPI 205
Cdd:cd21000  79 TCQVEHPSVTSPL 91

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
3F7V_B      113 PTVSIFPpSSEQLTSGGASVVCFLNNFYPKDINVKWKID---GSERQNGVLNSW--TDQDSKDSTYSMSSTLTLTKDEYE 187
Cdd:cd05771   1 PRVRLSP-KNLVKPDLPQTLSCHIAGYYPLDVDVEWLREepgGSESQVSRDGVSlsSHRQSVDGTYSISSYLTLEPGTEN 79

                        90       100
                ....*....|....*....|.
3F7V_B      188 RHNSYTCEATHKTSTSPIVKS 208
Cdd:cd05771  80 RGATYTCRVTHVSLEEPLSVS 100

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
3F7V_B      111 AAPTVSIFPPSSEQLTSGGAsVVCFLNNFYPKDINVKWKIDGSERQNGVLNSWTDQDSkDSTYSMSSTLTLTKdeyERHN 190
Cdd:cd21001   2 VEPTVTISPSRTEALNHHNL-LVCSVTDFYPGQIKVRWFRNDQEETAGVVSTPLIRNG-DWTFQILVMLEMTP---QRGD 76

                        90
                ....*....|....*
3F7V_B      191 SYTCEATHKTSTSPI 205
Cdd:cd21001  77 VYTCHVEHPSLQSPI 91

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
3F7V_B      113 PTVSIFPPSSEQLTSGgASVVCFLNNFYPKDINVKWKIDGSERQNGVlNSWTDQDSKDSTYSMSSTLTLTKdeyERHNSY 192
Cdd:cd05766   4 PSVKVSPTKTGPLEHP-NLLVCSVTGFYPAEIEVKWFRNGQEETAGV-VSTELIPNGDWTFQILVMLETTP---RRGDVY 78

                        90
                ....*....|...
3F7V_B      193 TCEATHKTSTSPI 205
Cdd:cd05766  79 TCQVEHSSLQSPL 91

CH1 domain (first constant Ig domain of the heavy chain) in immunoglobulin heavy alpha, delta, epsilon, gamma, and mu chains; member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the first immunoglobulin constant-1 set domain of alpha, delta, epsilon, gamma, and mu heavy chains. This domain is found on the Fab antigen-binding 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. This group belongs to the C1-set of IgSF domains, which are classical Ig-like domains resembling the antibody constant domain. C1-set domains are found almost exclusively in molecules involved in the immune system, such as in immunoglobulin light and heavy chains, in the major histocompatibility complex (MHC) class I and II complex molecules, and in various T-cell receptors.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
3F7V_B      112 APTVSIFPPSSEQLTSGGASVVCFLNNFYPKDINVKWKIDGSERQNGVLNSWTDQDSKDSTYSMSSTLTLTKDEYERHNS 191
Cdd:cd04985   1 APTVFPLQSATKSQSNGPVALGCLISDYFPESITVSWQKNTNSITSGFTRTFPVVLRSGGDYSCSSQLTVPLQEWNSGEV 80

                        90
                ....*....|..
3F7V_B      192 YTCEATHKTSTS 203
Cdd:cd04985  81 YKCQVQHSASNS 92

Signal-regulatory protein (SIRP) immunoglobulin-like domain 3; 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 3 (C1 repeat 2). 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 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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
3F7V_B      118 FPPS---SEQLTSGG--ASVVCFLNNFYPKDINVKWKIDGSERQNGVLNSWTDqdSKDSTYSMSSTLTLTKDEYERHNSY 192
Cdd:cd16085   1 VPPTlevTQQPTMVWnqVNVTCQVEKFYPQRLQLTWLENGNVSRTETPSTLTV--NKDGTYNWTSWLLVNVSAHREDVVL 78

                ....*.
3F7V_B      193 TCEATH 198
Cdd:cd16085  79 TCQVEH 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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
3F7V_B      112 APTVSIFPpsSEQLTSGGASV-VCFLNNFYPKDINVKWKIDGSERQNGVlnSWTD-QDSKDSTYSMSSTLTLTKdeyERH 189
Cdd:cd05767   2 PPEVTVFP--KSPVELGEPNTlICFVDNFFPPVINVTWLRNGQPVTDGV--SETVfLPREDHSFRKFSYLPFTP---SEG 74

                        90
                ....*....|....*...
3F7V_B      190 NSYTCEATHKTSTSPIVK 207
Cdd:cd05767  75 DIYDCRVEHWGLEEPLLK 92

CH1 domain (first constant Ig domain of the heavy chain) in immunoglobulin heavy alpha chain; member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the first immunoglobulin constant-1 set domain of alpha chains. It belongs to a family composed of the first immunoglobulin constant-1 set domain of alpha, epsilon, gamma, and mu heavy chains. This domain is found on the Fab antigen-binding 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. This group belongs to the C1-set of IgSF domains, which are classical Ig-like domains resembling the antibody constant domain. C1-set domains are found almost exclusively in molecules involved in the immune system, such as in immunoglobulin light and heavy chains, in the major histocompatibility complex (MHC) class I and II complex molecules, and in various T-cell receptors.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
3F7V_B      113 PTVsiFPPSSEQ-LTSGGASVVCFLNNFYPKDINVKWKIDGSErqnGVLNSWTDQDSKDSTYSMSSTLTLTKDEYERHNS 191
Cdd:cd21818   2 PTV--FPLSLCPsLSSDPVVIGCLVQGFFPEPVNVTWNYSGKG---GTARNFPAMLASGGRYTQSSQLTLPADQCPEGEA 76

                        90
                ....*....|.
3F7V_B      192 YTCEATHKTST 202
Cdd:cd21818  77 YKCSVQHYSPS 87

Class II major histocompatibility complex (MHC) beta chain immunoglobulin domain of histocompatibility antigen (HLA) DP; 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) DP. HLA class II histocompatibility antigen, DP(W2) beta chain is a protein that in humans is encoded by the HLA-DPB1 gene. It plays a central role in the immune system by presenting peptides derived from extracellular proteins. MHC class II molecules are encoded by three different loci, HLA-DR, -DQ, and -DP, which are about 70% similar to each other. HLA-DP is an alphabeta heterodimer cell-surface receptor. Each DP subunit (alpha-subunit, beta-subunit) is composed of a alpha-helical N-terminal domain, an IgG-like beta sheet, a membrane spanning domain, and a cytoplasmic domain. The alpha-helical domain forms the sides of the peptide binding groove. The beta sheet regions form the base of the binding groove and the bulk of the molecule as well as the inter-subunit (non-covalent) binding region. Individuals carrying the MHCII allele, HLA-DP2, are at risk for chronic beryllium disease (CBD), a debilitating inflammatory lung condition caused by the reaction of CD4 T cells to inhaled beryllium. 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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
3F7V_B      133 VCFLNNFYPKDINVKWKIDGSERQNGVLNSWTDQDSkDSTYSMSSTLTLTKdeyERHNSYTCEATHKTSTSPI 205
Cdd:cd21003  23 VCHVTDFYPGNIQVRWFLNGQEETAGVVSTNLIHNG-DWTFQILVMLEMTP---QQGDVYTCQVEHPSLDSPV 91

CH1 domain (first constant Ig domain of the heavy chain) in immunoglobulin heavy mu chain; member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the first immunoglobulin constant-1 set domain of mu chains. It belongs to a family composed of the first immunoglobulin constant-1 set domain of alpha, delta, epsilon, gamma, and mu heavy chains. This domain is found on the Fab antigen-binding 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. This group belongs to the C1-set of IgSF domains, which are classical Ig-like domains resembling the antibody constant domain. C1-set domains are found almost exclusively in molecules involved in the immune system, such as in immunoglobulin light and heavy chains, in the major histocompatibility complex (MHC) class I and II complex molecules, and in various T-cell receptors.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
3F7V_B      112 APTVsiFP-PSSEQLTSGGASVVCFLNNFYPKDINVKWKIDGSERQNGVLNSWTDQdsKDSTYSMSSTLTLTKDEYERHN 190
Cdd:cd21819   1 APTL--FPlVSCGSSTSDPVTVGCLATDFLPDSITFSWTDDNNSLTTGVKTYPSVL--TGGTYTASSQLQVPESEWKSKE 76

                ....*...
3F7V_B      191 SYTCEATH 198
Cdd:cd21819  77 NFYCKVEH 84

Fourth immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; Members here are composed the fourth immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, Robo3), and three mammalian Slit homologs (Slit-1, Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, and Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
3F7V_B       13 VSPGERVSFSCRASQSIGTDIHWyqqRTNGSPRLLIKYASESISgipSRFSGSGSGtdfTLSINSVESEDIANYYCQQSN 92
Cdd:cd05726  11 VALGRTVTFQCETKGNPQPAIFW---QKEGSQNLLFPYQPPQPS---SRFSVSPTG---DLTITNVQRSDVGYYICQALN 81

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
3F7V_B      107 KRADAAPTVSIFPPSSEQltsgGASVVCFLNNFYPKDINVKWKIDGsERQNGVLNSWTDQDSKDSTYSMSSTLTLTKDEY 186
Cdd:cd21026   1 QRADPPKTHVTHHPISDH----EATLRCWALGFYPAEITLTWQRDG-EDQTQDTELVETRPAGDRTFQKWAAVVVPSGEE 75

                        90
                ....*....|....*....
3F7V_B      187 ERhnsYTCEATHKTSTSPI 205
Cdd:cd21026  76 QR---YTCHVQHEGLPKPL 91

Class II major histocompatibility complex (MHC) alpha chain immunoglobulin domain of histocompatibility antigen (HLA) I-A; 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 alpha chain of histocompatibility antigen (HLA) 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 molecules have the same basic features insofar as peptide loading and presentation, although each interacts with distinctly different sets of peptides. They also differ in that there is a relatively high incidence of deletion of the I-E a gene in both inbred strains of mice as well as wild mice and the lack of the reverse situation i.e. the deletion of I-A genes. A detailed structural understanding of the similarities and differences between I-A and the paralogous I-E could help illuminate the respective roles these molecules play 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. 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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
3F7V_B      112 APTVSIFPpSSEQLTSGGASVVCFLNNFYPKDINVKWKIDGSERQNGVLNSwTDQDSKDSTYSMSSTLTLTKDEyerHNS 191
Cdd:cd21006   2 APQATVFP-KSPVLLGQPNTLICFVDNIFPPVINITWLRNSKSVTDGVYET-SFLVNRDHSFHKLSYLTFIPSD---DDI 76

                        90
                ....*....|....*....
3F7V_B      192 YTCEATHKTSTSPIVKSFN 210
Cdd:cd21006  77 YDCKVEHWGLEEPVLKHWE 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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
3F7V_B      113 PTVSIFP------PSSEQLTsggasvvCFLNNFYPKDINVKWkidgseRQNGVLNSWTDQDSK------DSTYSMSSTLT 180
Cdd:cd21002   4 PSVRVAPttpfntREPVMLA-------CHVWGFYPADVTITW------LKNGDPVAPHSSAPKtaqpngDWTYQTQVTLA 70

                        90       100       110
                ....*....|....*....|....*....|
3F7V_B      181 LT---KDeyerhnSYTCEATHKTSTSPIVK 207
Cdd:cd21002  71 VTpspGD------TYTCSVQHASLPEPLLE 94

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
3F7V_B      119 PP---SSEQLTSGGASVVCFLNNFYPKDINVKWKIDGSERQNGVLNSWTDQDSKDSTYSMSSTLTLTKDEYERhnsYTCE 195
Cdd:cd21021   4 PPlvkVTHHVTSSVTTLRCRALNYYPQNITMKWLKDKQPMDAKEFEPKDVLPNGDGTYQGWITLAVPPGEEQR---YTCQ 80

                        90
                ....*....|.
3F7V_B      196 ATHKTSTSPIV 206
Cdd:cd21021  81 VEHPGLDQPLI 91

agrin-responsive first immunoglobulin-like domains (Ig1) of the MuSK ectodomain; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin-like domains (Ig1) of the Muscle-specific kinase (MuSK). MuSK is a receptor tyrosine kinase specifically expressed in skeletal muscle, where it plays a central role in the formation and maintenance of the neuromuscular junction (NMJ). MuSK is activated by agrin, a neuron-derived heparan sulfate proteoglycan. The activation of MUSK in myotubes regulates the formation of NMJs through the regulation of different processes including the specific expression of genes in subsynaptic nuclei, the reorganization of the actin cytoskeleton and the clustering of the acetylcholine receptors (AChR) in the postsynaptic membrane. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. 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. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the MuSK lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
3F7V_B        6 QSPAILSVSPGERVSFSCRASQSIGTDIHWYqqRTNGSPRLLIKyasesisgipsRFSGSGSGTdfTLSINSVESEDIAN 85
Cdd:cd20970   7 QPSFTVTAREGENATFMCRAEGSPEPEISWT--RNGNLIIEFNT-----------RYIVRENGT--TLTIRNIRRSDMGI 71

                        90       100
                ....*....|....*....|.
3F7V_B       86 YYCQQSNRWPFTFGSGTKLEI 106
Cdd:cd20970  72 YLCIASNGVPGSVEKRITLQV 92

Immunoglobulin (Ig)-like variable (V) domain of Cluster of Differentiation (CD) 8 alpha chain; The members here are composed of the immunoglobulin (Ig)-like variable domain of the Cluster of Differentiation (CD) 8 alpha. The CD8 glycoprotein plays an essential role in the control of T-cell selection, maturation, and the T-cell receptor (TCR)-mediated response to peptide antigen. CD8 is comprised of alpha and beta subunits and is expressed as either an alpha/alpha or alpha/beta dimer. Both dimeric isoforms can serve as a coreceptor for T cell activation and differentiation, however they have distinct physiological roles, different cellular distributions, unique binding partners, etc. Each CD8 subunit is comprised of an extracellular domain containing a V-type Ig-like domain, a single pass transmembrane portion, and a short intracellular domain. The Ig domain of CD8 alpha binds to antibodies. Members of this group contain standard Ig superfamily V-set AGFCC'C"/DEB domain topology.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
3F7V_B        7 SPAILSVSPGERVSFSCRASQSIGTDIHWYQQRTN--GSPRLLIKYASESISGIP-----SRFSGSGSGTDFTLSINSVE 79
Cdd:cd05720   4 SPRKRDAQLGQKVELVCEVLNSVPQGCSWLFQPRGsaPQPTFLLYLSSSNKTKWAegldsKRFSGSRSGSSYVLTLKDFR 83

                ....*....
3F7V_B       80 SEDIANYYC 88
Cdd:cd05720  84 KEDEGYYFC 92

CH2 domain (second constant Ig domain of the heavy chain) in immunoglobulin heavy alpha chain; member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin constant-1 set domain (IgC) of alpha 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. This group belongs to the C1-set of IgSF domains, which are classical Ig-like domains resembling the antibody constant domain. C1-set domains are found almost exclusively in molecules involved in the immune system, such as in immunoglobulin light and heavy chains, in the major histocompatibility complex (MHC) class I and II complex molecules, and in various T-cell receptors.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
3F7V_B      113 PTVSIFPPSSEQLTSG-GASVVCFLNnfypkdinvkwkidGSERQNGVLNSWTDQDSKDST-----------YSMSSTLT 180
Cdd:cd04986   2 PRLSLQRPALEDLLLGsNASLTCTLS--------------GLKDPEGATFTWEPSGGKEAIqgpperdscgcYSVSSVLP 67