DQA2_HUMAN » HLA class II histocompatibility antigen, DQ alpha 2 chain

DQA2_HUMAN » HLA class II histocompatibility antigen, DQ alpha 2 chain
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Topology in Plasma membrane
Topologyextracellular side
cytoplasmic side
DQA2_HUMAN » HLA class II histocompatibility antigen, DQ alpha 2 chain » DX alpha chain;HLA class II histocompatibility antigen, DQ(6) alpha chain;HLA-DQA1;MHC class II DQA2;
Hydrophobic Thickness 36.0 ± 2.4 Å
Tilt Angle 0 ± 0°
ΔGtransfer -35.5 kcal/mol
ΔGfold -13.1 kcal/mol
Links UniProtKB, Pfam, Interpro, iHOP, STRING, HGNC, Reactome
Topology Out
TM Segments 219-243 (217-245)
Pathways

Allograft rejection (KEGG)

Antigen processing and presentation (KEGG)

Asthma (KEGG)

Autoimmune thyroid disease (KEGG)

Cell adhesion molecules (KEGG)

Epstein-Barr virus infection (KEGG)

Graft-versus-host disease (KEGG)

Herpes simplex infection (KEGG)

HTLV-I infection (KEGG)

Immune System (Reactome)

Influenza A (KEGG)

Intestinal immune network for IgA production (KEGG)

Leishmaniasis (KEGG)

Phagosome (KEGG)

Rheumatoid arthritis (KEGG)

Staphylococcus aureus infection (KEGG)

Systemic lupus erythematosus (KEGG)

Toxoplasmosis (KEGG)

Tuberculosis (KEGG)

Type I diabetes mellitus (KEGG)

Viral myocarditis (KEGG)

PDB none
OPM none
Complexes none
Interactions

CD4, Complex: DQA2:CD4, PubMed

DQB1, Complex: DQA2:DQB1, PubMed

Domains

AA: 29-109, PDBID: 4Z7U, Subunit A, Seq Identity:75%, Class II histocompatibility antigen, alpha domain

AA: 113-196, PDBID: 4Z7U, Subunit A, Seq Identity:98%, Immunoglobulin C1-set domain

AA: 202-254, PDBID: 4Z7U, Subunit A, Seq Identity:98%, C1-set C-terminal domain

UniProt annotation for DQA2_HUMAN » HLA class II histocompatibility antigen, DQ alpha 2 chain
FUNCTION: Binds peptides derived from antigens that access the endocytic route of antigen presenting cells (APC) and presents them on the cell surface for recognition by the CD4 T-cells. The peptide binding cleft accommodates peptides of 10-30 residues. The peptides presented by MHC class II molecules are generated mostly by degradation of proteins that access the endocytic route, where they are processed by lysosomal proteases and other hydrolases. Exogenous antigens that have been endocytosed by the APC are thus readily available for presentation via MHC II molecules, and for this reason this antigen presentation pathway is usually referred to as exogenous. As membrane proteins on their way to degradation in lysosomes as part of their normal turn-over are also contained in the endosomal/lysosomal compartments, exogenous antigens must compete with those derived from endogenous components. Autophagy is also a source of endogenous peptides, autophagosomes constitutively fuse with MHC class II loading compartments. In addition to APCs, other cells of the gastrointestinal tract, such as epithelial cells, express MHC class II molecules and CD74 and act as APCs, which is an unusual trait of the GI tract. To produce a MHC class II molecule that presents an antigen, three MHC class II molecules (heterodimers of an alpha and a beta chain) associate with a CD74 trimer in the ER to form a heterononamer. Soon after the entry of this complex into the endosomal/lysosomal system where antigen processing occurs, CD74 undergoes a sequential degradation by various proteases, including CTSS and CTSL, leaving a small fragment termed CLIP (class-II-associated invariant chain peptide). The removal of CLIP is facilitated by HLA-DM via direct binding to the alpha-beta-CLIP complex so that CLIP is released. HLA-DM stabilizes MHC class II molecules until primary high affinity antigenic peptides are bound. The MHC II molecule bound to a peptide is then transported to the cell membrane surface. In B-cells, the interaction between HLA-DM and MHC class II molecules is regulated by HLA-DO. Primary dendritic cells (DCs) also to express HLA-DO. Lysosomal microenvironment has been implicated in the regulation of antigen loading into MHC II molecules, increased acidification produces increased proteolysis and efficient peptide loading.

SUBUNIT: Heterodimer of an alpha and a beta subunit; also referred as MHC class II molecule. Dimer formation with HLA-DQB2, but not with HLA-DQB1, is required for efficient exit from the endoplasmic reticulum (ER). In the ER, forms a heterononamer; 3 MHC class II molecules bind to a CD74 homotrimer (also known as invariant chain or HLA class II histocompatibility antigen gamma chain). In the endosomal/lysosomal system; CD74 undergoes sequential degradation by various proteases; leaving a small fragment termed CLIP on each MHC class II molecule. MHC class II molecule interacts with HLA_DM, and HLA_DO in B-cells, in order to release CLIP and facilitate the binding of antigenic peptides. Association with HLA-DMA also occurs in skin Langerhans cells, in post-Golgi compartments.

TISSUE SPECIFICITY: Restricted to skin Langerhans cells, although some expression at low levels may occur at the surface of B lymphoblastoid cells.

UniProt features for DQA2_HUMAN » HLA class II histocompatibility antigen, DQ alpha 2 chain
SIGNAL 1 23
CHAIN 24 255 HLA class II histocompatibility antigen, DQ alpha 2 chain.
DOMAIN 113 205 Ig-like C1-type.
REGION 24 110 Alpha-1.
REGION 111 204 Alpha-2.
REGION 205 217 Connecting peptide.
DISULFID 133 189 By similarity.
Amino Acid Sequence for DQA2_HUMAN » HLA class II histocompatibility antigen, DQ alpha 2 chain
MILNKALLLG ALALTAVMSP CGGEDIVADH VASYGVNFYQ SHGPSGQYTH EFDGDEEFYV DLETKETVWQ LPMFSKFISF DPQSALRNMA VGKHTLEFMM RQSNSTAATN EVPEVTVFSK FPVTLGQPNT LICLVDNIFP PVVNITWLSN GHSVTEGVSE TSFLSKSDHS FFKISYLTFL PSADEIYDCK VEHWGLDEPL LKHWEPEIPA PMSELTETLV CALGLSVGLM GIVVGTVFII QGLRSVGASR HQGLL