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 556993754 296 PKLSLSPDPLyLLPGKEGRLACEITNYFPLQVSIRWTRKNSAEGSELEYLTQSWQTSDRDNPDGTYSVTGYVRIEATPEQ 375
Cdd:cd05771    1 PRVRLSPKNL-VKPDLPQTLSCHIAGYYPLDVDVEWLREEPGGSESQVSRDGVSLSSHRQSVDGTYSISSYLTLEPGTEN 79

                         90
                 ....*....|....
gi 556993754 376 HEALYTCHVSHSAL 389
Cdd:cd05771   80 RGATYTCRVTHVSL 93

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 556993754 296 PKLSLSPDPLyLLPGKEGRLACEITNYFPLQVSIRWTRKNSAEGSELEYLTQSWQTSDRDNPDGTYSVTGYVRIEATPEQ 375
Cdd:cd05771    1 PRVRLSPKNL-VKPDLPQTLSCHIAGYYPLDVDVEWLREEPGGSESQVSRDGVSLSSHRQSVDGTYSISSYLTLEPGTEN 79

                         90
                 ....*....|....
gi 556993754 376 HEALYTCHVSHSAL 389
Cdd:cd05771   80 RGATYTCRVTHVSL 93

Immunoglobulin C1-set domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 556993754  300 LSPDPLYLlpGKEGRLACEITNYFPLQVSIRWTrKNSAEgseleyLTQSWQTSD-RDNPDGTYSVTGYVRIEATPEQHEA 378
Cdd:pfam07654   4 FPPSPEEL--GKPNTLTCLVTGFYPPDITVTWL-KNGQE------VTEGVKTTPpSPNSDWTYQLSSYLTVTPSDWESGD 74

                          90
                  ....*....|.
gi 556993754  379 LYTCHVSHSAL 389
Cdd:pfam07654  75 EYTCRVEHEGL 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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 556993754  189 PEVQTKLSRNVMLDCGFTVDRES-NFSVEWRYQYEGSGH--LVYAYDGLRDrVEAAVDGVEmfFEELHGYGNASLLIHNV 265
Cdd:pfam07686   4 REVTVALGGSVTLPCTYSSSMSEaSTSVYWYRQPPGKGPtfLIAYYSNGSE-EGVKKGRFS--GRGDPSNGDGSLTIQNL 80

                          90       100
                  ....*....|....*....|....*....
gi 556993754  266 GVKHEGTYICTV-YMPYLHAQQAIDLVVR 293
Cdd:pfam07686  81 TLSDSGTYTCAViPSGEGVFGKGTRLTVL 109

Immunoglobulin V-Type;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 556993754   198 NVMLDCGFTVDRESNFSVEWRYQYEGSG--HLVYAYD--------GLRDRVEAAVDGVEmffeelhgyGNASLLIHNVGV 267
Cdd:smart00406   1 SVTLSCKFSGSTFSSYYVSWVRQPPGKGleWLGYIGSngssyyqeSYKGRFTISKDTSK---------NDVSLTISNLRV 71

                           90
                   ....*....|
gi 556993754   268 KHEGTYICTV 277
Cdd:smart00406  72 EDTGTYYCAV 81

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 556993754 296 PKLSLSPDPLyLLPGKEGRLACEITNYFPLQVSIRWTRKNSAEGSELEYLTQSWQTSDRDNPDGTYSVTGYVRIEATPEQ 375
Cdd:cd05771    1 PRVRLSPKNL-VKPDLPQTLSCHIAGYYPLDVDVEWLREEPGGSESQVSRDGVSLSSHRQSVDGTYSISSYLTLEPGTEN 79

                         90
                 ....*....|....
gi 556993754 376 HEALYTCHVSHSAL 389
Cdd:cd05771   80 RGATYTCRVTHVSL 93

Immunoglobulin C-Type;

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 556993754   315 LACEITNYFPLQVSIRWTRKNSAEgseleylTQSWQTSD-RDNPDGTYSVTGYVRIEA-TPEQHEaLYTCHVSHSALKN 391
Cdd:smart00407   4 LVCLVSGFYPPDITVTWLRNGQEV-------TEGVSTTDpLKNSDGTYFLSSYLTVPAsTWESGD-VYTCQVTHEGLKE 74

Immunoglobulin domain of Zn-alpha2-glycoprotein (ZAG); member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin domain of Zn-alpha2-glycoprotein (ZAG). ZAG is a soluble protein that is present in serum and other body fluids. ZAG stimulates lipid degradation in adipocytes and causes the extensive fat losses associated with some advanced cancers. The 2.8 angstrom crystal structure of ZAG resembles a class I major histocompatibility complex (MHC) heavy chain, but ZAG does not bind the class I light chain beta-2-microglobulin. The ZAG structure includes a large groove analogous to class I MHC peptide binding grooves. Instead of a peptide, the ZAG groove contains a nonpeptidic compound that may be implicated in lipid catabolism under normal or pathological conditions. IgC_MHC_I_alpha3; Immunoglobulin (Ig) domain of major histocompatibility complex (MHC) class I alpha chain. Class I MHC proteins bind antigenic peptide fragments and present them to CD8+ T lymphocytes. Class I molecules consist of a transmembrane alpha chain and a small chain called the beta-2-microglobulin. The alpha chain contains three extracellular domains, two of which fold together to form the peptide-binding cleft (alpha1 and alpha2), and one which has an Ig fold (alpha3). Peptide binding to class I molecules occurs in the endoplasmic reticulum (ER) and involves both chaperones and dedicated factors to assist in peptide loading. Class I MHC molecules are expressed on most nucleated cells.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 556993754 293 REPPKLSLSPdplYLLPGKEGRLACEITNYFPLQVSIRWTRKNSAEGSEleyltqSWqtsdRD---NPDGTYSVTGYVRI 369
Cdd:cd21010    2 QDPPSVSVTS---HVAPGKNRTLKCLAYDFYPRGISLHWTRAGKVQESE------SG----GDvlpSGNGTYQSWVVVEV 68

                         90       100
                 ....*....|....*....|
gi 556993754 370 eatPEQHEALYTCHVSHSAL 389
Cdd:cd21010   69 ---PPQDRAPYSCHVEHSSL 85

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 556993754 293 REPPKLSLSPdPLYLLPGKEGRLACEITNYFPLQVSIRWTRKNSAEGSELEYlTQSWQtsdrdNPDGTYSVtgYVRIEAT 372
Cdd:cd05766    1 RVQPSVKVSP-TKTGPLEHPNLLVCSVTGFYPAEIEVKWFRNGQEETAGVVS-TELIP-----NGDWTFQI--LVMLETT 71

                         90
                 ....*....|....*...
gi 556993754 373 PeQHEALYTCHVSHSALK 390
Cdd:cd05766   72 P-RRGDVYTCQVEHSSLQ 88

Class I major histocompatibility complex (MHC) alpha chain, alpha3 immunoglobulin domain; member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig) domain of major histocompatibility complex (MHC) class I alpha chain. Class I MHC proteins bind antigenic peptide fragments and present them to CD8+ T lymphocytes. Class I molecules consist of a transmembrane alpha chain and a small chain called the beta-2-microglobulin. The alpha chain contains three extracellular domains, two of which fold together to form the peptide-binding cleft (alpha1 and alpha2), and one which has an Ig fold (alpha3). Peptide binding to class I molecules occurs in the endoplasmic reticulum (ER) and involves both chaperones and dedicated factors to assist in peptide loading. Class I MHC molecules are expressed on most nucleated cells.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 556993754 294 EPPKLSL--SPDPlyllPGKEgRLACEITNYFPLQVSIRWTRknsaEGSELEYLTQSWQTsdRDNPDGTY--SVTGYVri 369
Cdd:cd07698    1 DPPKVHVthHPRS----DGES-TLRCWALGFYPAEITLTWQR----DGEDQTQDMELVET--RPNGDGTFqkWAAVVV-- 67

                         90       100       110
                 ....*....|....*....|....*....|.
gi 556993754 370 eatPEQHEALYTCHVSHSALkngaKKSITLK 400
Cdd:cd07698   68 ---PSGEEQRYTCHVQHEGL----PEPLTLR 91

Class Ib major histocompatibility complex (MHC) immunoglobulin domain of human leukocyte antigen (HLA) F; member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the Class Ib major histocompatibility complex (MHC) immunoglobulin domain of human leukocyte antigen alpha chain F (HLA-F). HLA-F, encoded by the HLA-F gene in humans, belongs to the non-classical HLA class I heavy chain paralogs. This class I molecule mainly exists as a heterodimer associated with the invariant light chain beta-2-microglobulin. HLA-F molecules can interact with both activating and inhibitory receptors on immune cells, such as NK cells, and can present a diverse panel of peptides. Class I MHC proteins bind antigenic peptide fragments and present them to CD8+ T lymphocytes. Class I molecules consist of a transmembrane alpha chain and a small chain called the beta-2-microglobulin. The alpha chain contains three extracellular domains, two of which fold together to form the peptide-binding cleft (alpha1 and alpha2), and one which has an Ig fold (alpha3). Peptide binding to class I molecules occurs in the endoplasmic reticulum (ER) and involves both chaperones and dedicated factors to assist in peptide loading. Class I MHC molecules are expressed on most nucleated cells.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 556993754 294 EPPKLSLSPDPLyllPGKEGRLACEITNYFPLQVSIRWTRKNSAEGSELEYLtqswqtSDRDNPDGTYSVTGYVRIEATP 373
Cdd:cd21023    4 DPPKAHVAHHPI---SDHEATLRCWALGFYPAEITLTWQRDGEEQTQDTELV------ETRPAGDGTFQKWAAVVVPPGE 74

                         90
                 ....*....|....*.
gi 556993754 374 EQHealYTCHVSHSAL 389
Cdd:cd21023   75 EQR---YTCHVQHEGL 87

Sixth immunoglobulin (Ig) domain of contactin-4; The members here are composed of the sixth immunoglobulin (Ig) domain of the neural cell adhesion molecule contactin-4. Contactins are neural cell adhesion molecules, and are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. The different contactins show different expression patterns in the central nervous system. Highest expression of contactin-4 is in testes, thyroid, small intestine, uterus, and brain. Contactin-4 plays a role in the response of neuroblastoma cells to differentiating agents, such as retinoids. The contactin 4 gene is associated with cerebellar degeneration in spinocerebellar ataxia type 16.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 556993754 195 LSRNVMLDCGFTVDRESNFSVEWRYqyegSGHLV-YAYDGLRdrveaavdgvemfFEELHGYGNA-SLLIHNVGVKHEGT 272
Cdd:cd05853   16 VGESIVLPCQVSHDHSLDIVFTWSF----NGHLIdFQKDGDH-------------FERVGGQDSAgDLMIRSIQLKHAGK 78

                         90       100
                 ....*....|....*....|....
gi 556993754 273 YICTVYMPYLHAQQAIDLVVREPP 296
Cdd:cd05853   79 YVCMVQTSVDKLSAAADLIVRGPP 102

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 556993754  189 PEVQTKLSRNVMLDCGFTVDRES-NFSVEWRYQYEGSGH--LVYAYDGLRDrVEAAVDGVEmfFEELHGYGNASLLIHNV 265
Cdd:pfam07686   4 REVTVALGGSVTLPCTYSSSMSEaSTSVYWYRQPPGKGPtfLIAYYSNGSE-EGVKKGRFS--GRGDPSNGDGSLTIQNL 80

                          90       100
                  ....*....|....*....|....*....
gi 556993754  266 GVKHEGTYICTV-YMPYLHAQQAIDLVVR 293
Cdd:pfam07686  81 TLSDSGTYTCAViPSGEGVFGKGTRLTVL 109

CH2 domain (second constant Ig domain of the heavy chain) in immunoglobulin mu chain; member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin constant domain (IgC) of mu heavy chains. This domain is found on the Fc fragment. The basic structure of Ig molecules is a tetramer of two light chains and two heavy chains linked by disulfide bonds. There are two types of light chains: kappa and lambda; each is composed of a constant domain and a variable domain. There are five types of heavy chains: alpha, delta, epsilon, gamma, and mu, all consisting of a variable domain (VH) with three (alpha, delta and gamma) or four (epsilon and mu) constant domains (CH1 to CH4). Ig molecules are modular proteins, in which the variable and constant domains have clear, conserved sequence patterns.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 556993754 295 PPKLSLSPDPLYLLPG-KEGRLACEITNYFPLQVSIRWTRknsaEGSELEYLTQSWQTSDRDNPDGTYSVTGYVRIEATP 373
Cdd:cd16093    1 PPTVSLHAPSREEFLGnRTATFVCLATGFSPKTISFKWLR----NGKEVTSSTGAVVEEPKEDGKTLYSATSFLTITESE 76

                         90
                 ....*....|....*...
gi 556993754 374 EQHEALYTCHVSHSALKN 391
Cdd:cd16093   77 WKSQTEFTCEFKHKGEIV 94

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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 556993754 293 REPPKLSLSPDPLYLLPgKEGRLACEITNYFPLQVSIRWTRKNSAEgseleyLTQSWQTSDRDNPDGTYSVtgYVRIEAT 372
Cdd:cd21003    1 RVQPKVNVSPSKKGPLQ-HHNLLVCHVTDFYPGNIQVRWFLNGQEE------TAGVVSTNLIHNGDWTFQI--LVMLEMT 71

                         90
                 ....*....|....*..
gi 556993754 373 PEQHEaLYTCHVSHSAL 389
Cdd:cd21003   72 PQQGD-VYTCQVEHPSL 87

CH1 domain (first constant Ig domain of the heavy chain) in immunoglobulin heavy epsilon and gamma 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 epsilon and gamma 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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 556993754 315 LACEITNYFPLQVSIRWtrKNSAEGSELEYLTQSWQTSdrdnpdGTYSVTGYVRIEATPEQHEaLYTCHVSHSALKNGAK 394
Cdd:cd21817   21 LGCLVTGYFPEPVTVTW--NSGSLTSGVKTFPAVLQSS------GLYTTSSQVTVPSSSWGSQ-TFTCNVEHKPSSTKVD 91

                 ...
gi 556993754 395 KSI 397
Cdd:cd21817   92 KKI 94

Class II major histocompatibility complex (MHC) alpha chain immunoglobulin domain; member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig) domain of the major histocompatibility complex (MHC) class II alpha chain. MHC class II molecules play a key role in the initiation of the antigen-specific immune reponse. These molecules have been shown to be expressed constitutively on the cell surface of professional antigen-presenting cells (APCs), including B-lymphocytes, monocytes, and macrophages in both humans and mice. The expression of these molecules has been shown to be induced in nonprofessional APCs such as keratinocyctes, and they are also expressed on the surface of activated human T cells and on T cells from other species. The MHC II molecules present antigenic peptides to CD4(+) T-lymphocytes. These peptides derive mostly from proteolytic processing via the endocytic pathway, of antigens internalized by the APC. These peptides bind to the MHC class II molecules in the endosome before they are transported to the cell surface. MHC class II molecules are heterodimers, comprised of two similarly-sized membrane-spanning chains, alpha and beta. Each chain had two globular domains (N- and C-terminal), and a membrane-anchoring transmembrane segment. The two chains form a compact four-domain structure. The peptide-binding site is a cleft in the structure.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 556993754 294 EPPKLSLSP-DPLYLlpGKEGRLACEITNYFPLQVSIRWTR--KNSAEG-SELEYLTqswqtsdrdNPDGTYSVTGYVRI 369
Cdd:cd05767    1 VPPEVTVFPkSPVEL--GEPNTLICFVDNFFPPVINVTWLRngQPVTDGvSETVFLP---------REDHSFRKFSYLPF 69

                         90       100
                 ....*....|....*....|
gi 556993754 370 eaTPEQHEaLYTCHVSHSAL 389
Cdd:cd05767   70 --TPSEGD-IYDCRVEHWGL 86

Immunoglobulin (Ig)-like domain of protein zero (P0) and similar proteins; The members here are composed of the immunoglobulin (Ig) domain of protein zero (P0), a myelin membrane adhesion molecule. P0 accounts for over 50% of the total protein in peripheral nervous system (PNS) myelin. P0 is a single-pass transmembrane glycoprotein with a highly basic intracellular domain and an extracellular Ig domain. The extracellular domain of P0 (P0-ED) is similar to the Ig variable domain, carrying one acceptor sequence for N-linked glycosylation. P0 plays a role in membrane adhesion in the spiral wraps of the myelin sheath. The intracellular domain is thought to mediate membrane apposition of the cytoplasmic faces and may, through electrostatic interactions, interact directly with lipid headgroups. It is thought that homophilic interactions of the P0 extracellular domain mediate membrane juxtaposition in the extracellular space of PNS myelin. This group also contains the Ig domain of sodium channel subunit beta-2 (SCN2B), and of epithelial V-like antigen 1 (EVA). EVA, also known as myelin protein zero-like 2, is an adhesion molecule, which may play a role in structural organization of the thymus and early lymphocyte development. SCN2B subunits play a role in determining sodium channel density and function in neurons,and in control of electrical excitability in the brain.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 556993754 199 VMLDCGFTVDR--ESNFSVEWRYQYEGSG-----HLVYAYDGLRDRVEAAVDGVeMFFEELHGYgNASLLIHNVGVKHEG 271
Cdd:cd05715   17 VRLTCTFTSCYtvGDAFSVTWTYQPEGGNttesmFHYSKGKPYILKVGRFKDRV-SWAGNPSKK-DASIVISNLQFSDNG 94

                 ....*....
gi 556993754 272 TYICTVYMP 280
Cdd:cd05715   95 TYTCDVKNP 103

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 556993754 315 LACEITNYFPLQVSIRWTR-KNSAEGSELEyltqswQTSDRDNPDGTYSvtGYVRIeATPEQHEALYTCHVSHSAL 389
Cdd:cd21021   20 LRCRALNYYPQNITMKWLKdKQPMDAKEFE------PKDVLPNGDGTYQ--GWITL-AVPPGEEQRYTCQVEHPGL 86

Sixth immunoglobulin (Ig) domain of contactin; The members here are composed of the sixth immunoglobulin (Ig) domain of contactins. Contactins are neural cell adhesion molecules and are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module via contacts between Ig domains 1 and 4, and between Ig domains 2 and 3. Contactin-2 (TAG-1, axonin-1) may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. This group also includes contactin-1 and contactin-5. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-5 is expressed specifically in the rat postnatal nervous system, peaking at about 3 weeks postnatal, and a lack of contactin-5 (NB-2) results in an impairment of neuronal activity in the rat auditory system. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 556993754 243 DGVEMFFEELHGY--------GNASLLIHNVGVKHEGTYICTVYMPYLHAQQAIDLVVREPP 296
Cdd:cd04970   41 NGVPIDLEKIEGHyrrrygkdSNGDLEIVNAQLKHAGRYTCTAQTVVDSDSASATLVVRGPP 102

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 556993754 185 FTRTPEVQTKLSRNVMLDCGFTVDRESnfSVEWryQYEGSGHLVYAY----DGLRDRVEAAVDGVEMFFEELHGyGNASL 260
Cdd:cd16091    1 AVSEVIVVCLLSEDCILPCSFTPGSEV--VIHW--YKQDSDIKVHSYyygkDQLESQDQRYRNRTSLFKDQISN-GNASL 75

                         90
                 ....*....|....*..
gi 556993754 261 LIHNVGVKHEGTYICTV 277
Cdd:cd16091   76 LLRRVQLQDEGRYKCYT 92

Immunoglobulin V-Type;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 556993754   198 NVMLDCGFTVDRESNFSVEWRYQYEGSG--HLVYAYD--------GLRDRVEAAVDGVEmffeelhgyGNASLLIHNVGV 267
Cdd:smart00406   1 SVTLSCKFSGSTFSSYYVSWVRQPPGKGleWLGYIGSngssyyqeSYKGRFTISKDTSK---------NDVSLTISNLRV 71

                           90
                   ....*....|
gi 556993754   268 KHEGTYICTV 277
Cdd:smart00406  72 EDTGTYYCAV 81

Class II major histocompatibility complex (MHC) beta chain immunoglobulin domain of histocompatibility antigen (HLA) I-E; 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) I-E. 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 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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 556993754 315 LACEITNYFPLQVSIRWTRKNSAEGSELeyltqswqTSDRDNPDGTYSVTGYVRIEATPEQHEaLYTCHVSHSALKN 391
Cdd:cd20998   25 LVCSVSDFYPGNIEVRWFRNGKEEKTGI--------VSTGLVRNGDWTFQTLVMLETVPQSGE-VYTCQVEHPSLTD 92

First immunoglobulin variable (IgV) domain of poliovirus receptor (PVR, also known as CD155 and necl-5), and similar domains; The members here are composed of the first immunoglobulin (Ig) domain of poliovirus receptor (PVR, also known as CD155 and nectin-like protein 5 (necl-5)). Poliovirus (PV) binds to its cellular receptor (PVR/CD155) to initiate infection. CD155 is a membrane-anchored, single-span glycoprotein; its extracellular region has three Ig-like domains. There are four different isotypes of CD155 (referred to as alpha, beta, gamma, and delta), that result from alternate splicing of the CD155 mRNA, and have identical extracellular domains. CD155-beta and CD155-gamma are secreted; CD155-alpha and CD155-delta are membrane-bound and function as PV receptors. The virus recognition site is contained in the amino-terminal domain, D1. Having the virus attachment site on the receptor distal from the plasma membrane may be important for successful initiation of infection of cells by the virus. CD155 binds in the poliovirus "canyon" with a footprint similar to that of the intercellular adhesion molecule-1 receptor on human rhinoviruses. This group also includes the first Ig-like domain of nectin-1 (also known as poliovirus receptor related protein(PVRL)1; CD111), nectin-3 (also known as PVRL 3), nectin-4 (also known as PVRL4; LNIR receptor)and DNAX accessory molecule 1 (DNAM-1; CD226).

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 556993754 189 PEVQTKLSRNVMLDCGFTVDRESNFS-VEWRYQYEGSGHLVYAY---------DGLRDRVEaavdgvemFFEELHGYGNA 258
Cdd:cd05718    7 TEVTGFLGGSVTLPCSLTSPGTTKITqVTWMKIGAGSSQNVAVFhpqygpsvpNPYAERVE--------FLAARLGLRNA 78

                         90       100
                 ....*....|....*....|
gi 556993754 259 SLLIHNVGVKHEGTYICTVY 278
Cdd:cd05718   79 TLRIRNLRVEDEGNYICEFA 98

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
                 ....*....|....*....|....*....|..
gi 556993754 246 EMFFEELHGYGNASLLIHNVGVKHEGTYICTV 277
Cdd:cd00096   27 SSRDSRRSELGNGTLTISNVTLEDSGTYTCVA 58