ID:DQA1_HUMAN DESCRIPTION: RecName: Full=HLA class II histocompatibility antigen, DQ alpha 1 chain; AltName: Full=DC-1 alpha chain; AltName: Full=DC-alpha; AltName: Full=HLA-DCA; AltName: Full=MHC class II DQA1; Flags: Precursor; 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 miroenvironment 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. In the endoplasmic reticulum (ER) it 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. SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endoplasmic reticulum membrane; Single-pass type I membrane protein. Golgi apparatus, trans-Golgi network membrane; Single-pass type I membrane protein. Endosome membrane; Single- pass type I membrane protein. Lysosome membrane; Single-pass type I membrane protein. Note=The MHC class II complex transits through a number of intracellular compartments in the endocytic pathway until it reaches the cell membrane for antigen presentation. POLYMORPHISM: The following alleles of DQA1 are known: DQA1*01:01, DQA1*01:02, DQA1*01:03, DQA1*01:04, DQA1*01:05, DQA1*01:06, DQA1*01:07, DQA1*02:01, DQA1*03:01, DQA1*03:02, DQA1*03:03, DQA1*04:01, DQA1*04:02, DQA1*04:03, DQA1*04:04, DQA1*05:01, DQA1*05:02, DQA1*05:03, DQA1*05:04, DQA1*05:05, DQA1*05:06, DQA1*05:07, DQA1*05:08, DQA1*05:09, DQA1*06:01, DQA1*06:02. The sequence shown is that of DQA1*05:01. POLYMORPHISM: DQ2 (heterodimer of DQA1*05:01/DQB1*02:01) is associated with more than 90% of celiac disease patients. A minority displays DQ8 (heterodimer of DQA1*03/DQB1*03:02). DQ0602 (heterodimer of DQA1*01:02/DQB1*06:02) confers dominant protection against type 1 diabetes (T1D) and strong susceptibility to narcolepsy. SIMILARITY: Belongs to the MHC class II family. SIMILARITY: Contains 1 Ig-like C1-type (immunoglobulin-like) domain. SEQUENCE CAUTION: Sequence=AAD56720.1; Type=Erroneous gene model prediction; WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/HLA-DQA1";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on P01909
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Gene Ontology (GO) Annotations with Structured Vocabulary
Molecular Function: GO:0032395 MHC class II receptor activity GO:0042605 peptide antigen binding
Biological Process: GO:0002376 immune system process GO:0002504 antigen processing and presentation of peptide or polysaccharide antigen via MHC class II GO:0006955 immune response GO:0019882 antigen processing and presentation GO:0019886 antigen processing and presentation of exogenous peptide antigen via MHC class II GO:0050852 T cell receptor signaling pathway GO:0060333 interferon-gamma-mediated signaling pathway
KU159423 - Homo sapiens major histocompatibility complex class_II DQ alpha 1 (HLA-DQA1) mRNA, complete cds. AK313975 - Homo sapiens cDNA, FLJ94624, highly similar to Homo sapiens major histocompatibility complex, class II, DQ alpha 1(HLA-DQA1), mRNA. AK130811 - Homo sapiens cDNA FLJ27301 fis, clone TMS04750, highly similar to HLA class II histocompatibility antigen, DQ(5) alpha chain precursor. BC073977 - Homo sapiens major histocompatibility complex, class II, DQ alpha 1, mRNA (cDNA clone MGC:87852 IMAGE:6014803), complete cds. BC051832 - Homo sapiens major histocompatibility complex, class II, DQ alpha 1, mRNA (cDNA clone IMAGE:5753417). AB209628 - Homo sapiens mRNA for major histocompatibility complex, class II, DQ alpha 1 precursor variant protein. E01702 - cDNA sequence coding for alpha-chain of HLA class II DQ antigen. X00452 - Human mRNA for DC classII histocompatibility antigen alpha-chain. L46875 - Homo sapiens HLA-DQA1 gene (DQA1*0101, DQA1*01021, DQA1*01022 and DQA1*0103), exon 1. L46876 - Homo sapiens HLA-DQA1 gene (DQA1*0104), exon 1. L46877 - Homo sapiens HLA-DQA1 gene (DQA1*0105), exon 1. L46878 - Homo sapiens HLA-DQA1 gene (DQA1*0201, DQA1*03011 and DQA1*0303), exon 1. L46879 - Homo sapiens HLA-DQA1 gene (DQA1*0302-DRB1*0901), exon 1. L46880 - Homo sapiens HLA-DQA1 gene (DQA1*0401 and DQA1*0601), exon 1. L46881 - Homo sapiens HLA-DQA1 gene (DQA1*05011, DQA1*05013 and DQA1*0503), exon 1. U77589 - Homo sapiens MHC class II HLA-DQ-alpha chain (HLA-DQA1) mRNA, HLA-DQA1*0104 allele, complete cds. M34996 - Human MHC cell surface glycoprotein (HLA-DQA) mRNA, 3'end. M20431 - Human MHC class II HLA-DQ-alpha (DR2-DQw1/DR4 DQw3) mRNA, partial cds, clone ROF1.1-alpha. M59802 - Human MHC class II DQA1*0103 mRNA (DQw1(w6)), partial cds. L34082 - Human (clone 96) MHC class II HLA-DQA1*0101 mRNA, partial cds. L34083 - Human (clone 13) MHC class II HLA-DQA1*01021 mRNA, partial cds. L34084 - Human (clones '72, '73) MHC class II HLA-DQA1*01022 mRNA, partial cds. L34085 - Human (clone 73) MHC class II HLA-DQA1*0103 mRNA, partial cds. L34090 - Human (clone 87) MHC class II HLA-DQA1*0401 mRNA, partial cds. L34094 - Human (clone 41) MHC class II HLA-DQA1*0601 mRNA, partial cds. L34086 - Human (clone 8) MHC class II HLA-DQ-DQA1*0104 mRNA, partial cds. L42625 - Homo sapiens (clones 1, 12) MHC class II HLA-DQA1*0105 mRNA, partial cds. M17846 - Human MHC class II DQ-alpha associated with DRw6, DQw1 protein, complete cds, clone a. M17847 - Human MHC class II DQ-alpha associated with DRw6, DQw1 protein, complete cds, clone b. AF533938 - Homo sapiens MHC class II antigen (HLA-DQA1) mRNA, HLA-DQA1*0101 allele, partial cds. AF533901 - Homo sapiens MHC class II antigen (HLA-DQA1) mRNA, HLA-DQA1*0103 allele, partial cds. AF533912 - Homo sapiens MHC class II antigen (HLA-DQA1) mRNA, HLA-DQA1*0101 allele, partial cds. AF533913 - Homo sapiens MHC class II antigen (HLA-DQA1) mRNA, HLA-DQA1*0102 allele, partial cds. AF533914 - Homo sapiens MHC class II antigen (HLA-DQA1) mRNA, HLA-DQA1*0103 allele, partial cds. AF533937 - Homo sapiens MHC class II antigen (HLA-DQA1) mRNA, HLA-DQA1*0101 allele, partial cds. AF533939 - Homo sapiens MHC class II antigen (HLA-DQA1) mRNA, HLA-DQA1*0102 allele, partial cds. AF533895 - Homo sapiens MHC class II antigen (HLA-DQA1) mRNA, HLA-DQA1*0101 allele, partial cds. AF533896 - Homo sapiens MHC class II antigen (HLA-DQA1) mRNA, HLA-DQA1*0102 allele, partial cds. AF533897 - Homo sapiens MHC class II antigen (HLA-DQA1) mRNA, HLA-DQA1*0103 allele, partial cds. AF533906 - Homo sapiens MHC class II antigen (HLA-DQA1) mRNA, HLA-DQA1*0101 allele, partial cds. AF533907 - Homo sapiens MHC class II antigen (HLA-DQA1) mRNA, HLA-DQA1*0102 allele, partial cds. AF533908 - Homo sapiens MHC class II antigen (HLA-DQA1) mRNA, HLA-DQA1*0103 allele, partial cds. AF533929 - Homo sapiens MHC class II antigen (HLA-DQA1) mRNA, HLA-DQA1*0101 allele, partial cds. AF533930 - Homo sapiens MHC class II antigen (HLA-DQA1) mRNA, HLA-DQA1*0102 allele, partial cds. AF533931 - Homo sapiens MHC class II antigen (HLA-DQA1) mRNA, HLA-DQA1*0103 allele, partial cds. JD267482 - Sequence 248506 from Patent EP1572962. JD404181 - Sequence 385205 from Patent EP1572962.
Biochemical and Signaling Pathways
Reactome (by CSHL, EBI, and GO)
Protein P01909 (Reactome details) participates in the following event(s):
US Server
Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
