ID:DRA_HUMAN DESCRIPTION: RecName: Full=HLA class II histocompatibility antigen, DR alpha chain; AltName: Full=MHC class II antigen DRA; 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. Late endosome 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. PTM: Ubiquitinated by MARCH1 or MARCH8 at Lys-244 leading to down- regulation of MHC class II. When associated with ubiquitination of the beta subunit of HLA-DR: HLA-DRB4 'Lys-254', the down- regulation of MHC class II may be highly effective. POLYMORPHISM: The following alleles of DRA are known: DRA*01:01 and DRA*01:02. The sequence shown is that of DRA*01:01. POLYMORPHISM: Genetic variations in HLA-DRA influence susceptibility to hepatitis B virus (HBV) infection [MIM:610424]. SIMILARITY: Belongs to the MHC class II family. SIMILARITY: Contains 1 Ig-like C1-type (immunoglobulin-like) domain. SEQUENCE CAUTION: Sequence=CAA25076.1; Type=Erroneous initiation; Note=Translation N-terminally extended;
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 P01903
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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:0005515 protein binding GO:0023026 MHC class II protein complex binding GO:0032395 MHC class II receptor activity GO:0042605 peptide antigen binding
Biological Process: GO:0002376 immune system process GO:0002503 peptide antigen assembly with MHC class II protein complex GO:0002504 antigen processing and presentation of peptide or polysaccharide antigen via MHC class II GO:0002506 polysaccharide assembly with MHC class II protein complex GO:0006955 immune response GO:0016032 viral process 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:0050890 cognition GO:0060333 interferon-gamma-mediated signaling pathway
AK301134 - Homo sapiens cDNA FLJ51113 complete cds, highly similar to HLA class II histocompatibility antigen, DRalpha chain precursor. AK297032 - Homo sapiens cDNA FLJ57318 complete cds, highly similar to HLA class II histocompatibility antigen, DRalpha chain precursor. AK301354 - Homo sapiens cDNA FLJ51117 complete cds, highly similar to HLA class II histocompatibility antigen, DRalpha chain precursor. AK301190 - Homo sapiens cDNA FLJ51114 complete cds, moderately similar to HLA class II histocompatibility antigen, DRalpha chain precursor. AK313123 - Homo sapiens cDNA, FLJ93608, Homo sapiens major histocompatibility complex, class II, DR alpha(HLA-DRA), mRNA. AK304429 - Homo sapiens cDNA FLJ52115 complete cds, highly similar to HLA class II histocompatibility antigen, DRalpha chain precursor. BC071659 - Homo sapiens major histocompatibility complex, class II, DR alpha, mRNA (cDNA clone MGC:87851 IMAGE:5162925), complete cds. BC032350 - Homo sapiens major histocompatibility complex, class II, DR alpha, mRNA (cDNA clone MGC:40279 IMAGE:5214156), complete cds. AK310161 - Homo sapiens cDNA, FLJ17203. J00197 - human hla-dr alpha-chain mrna for the leader and nh2-term. M60333 - Human MHC class II HLA-DRA mRNA, complete cds. M60334 - Human MHC class II HLA-DR-alpha mRNA, complete cds. J00194 - human hla-dr antigen alpha-chain mrna & ivs fragments. J00195 - human hla-dr alpha-chain mrna; partial. JD336492 - Sequence 317516 from Patent EP1572962. K01171 - Human HLA-DR alpha-chain mRNA. M35979 - Human MHC class II HLA-DR-alpha chain mRNA, 5' end. AB528984 - Synthetic construct DNA, clone: pF1KE0913, Homo sapiens HLA-DRA gene for major histocompatibility complex, class II, DR alpha, without stop codon, in Flexi system. DQ894789 - Synthetic construct Homo sapiens clone IMAGE:100009249; FLH178456.01L; RZPDo839D06127D major histocompatibility complex, class II, DR alpha (HLA-DRA) gene, encodes complete protein. KJ896980 - Synthetic construct Homo sapiens clone ccsbBroadEn_06374 HLA-DRA gene, encodes complete protein. CU687128 - Synthetic construct Homo sapiens gateway clone IMAGE:100022780 5' read HLA-DRA mRNA. DQ891595 - Synthetic construct clone IMAGE:100004225; FLH178460.01X; RZPDo839D06128D major histocompatibility complex, class II, DR alpha (HLA-DRA) gene, encodes complete protein. KJ896981 - Synthetic construct Homo sapiens clone ccsbBroadEn_06375 HLA-DRA gene, encodes complete protein. CR457013 - Homo sapiens full open reading frame cDNA clone RZPDo834G105D for gene HLA-DRA, major histocompatibility complex, class II, DR alpha; complete cds, incl. stopcodon. J00193 - human histocompatibility system hla-dr heavy chain. V00523 - Human mRNA for histocompatibility antigen HLA-DR (fragment). The alpha chain. AF522250 - Homo sapiens MHC class II antigen (HLA-DQA1/DRA) mRNA, complete cds. V00528 - Human mRNA fragment coding for histocompatibility antigen HLA-DR. JD091040 - Sequence 72064 from Patent EP1572962. JD330603 - Sequence 311627 from Patent EP1572962. JD264621 - Sequence 245645 from Patent EP1572962. JD263544 - Sequence 244568 from Patent EP1572962. JD523878 - Sequence 504902 from Patent EP1572962. JD555929 - Sequence 536953 from Patent EP1572962. JD539517 - Sequence 520541 from Patent EP1572962. JD048985 - Sequence 30009 from Patent EP1572962.
Biochemical and Signaling Pathways
BioCarta from NCI Cancer Genome Anatomy Project h_th1th2Pathway - Th1/Th2 Differentiation h_mhcPathway - Antigen Processing and Presentation h_bbcellPathway - Bystander B Cell Activation h_ctla4Pathway - The Co-Stimulatory Signal During T-cell Activation h_il5Pathway - IL 5 Signaling Pathway h_inflamPathway - Cytokines and Inflammatory Response h_blymphocytePathway - B Lymphocyte Cell Surface Molecules h_eosinophilsPathway - The Role of Eosinophils in the Chemokine Network of Allergy h_tcraPathway - Lck and Fyn tyrosine kinases in initiation of TCR Activation h_asbcellPathway - Antigen Dependent B Cell Activation h_CSKPathway - Activation of Csk by cAMP-dependent Protein Kinase Inhibits Signaling through the T Cell Receptor
Reactome (by CSHL, EBI, and GO)
Protein P01903 (Reactome details) participates in the following event(s):
US Server
Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
