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Details on Person UniProt:P01903 HLA-DRA
| Class:Id | ReferenceGeneProduct:56273 |
|---|---|
| _chainChangeLog | signal peptide:1-25 added on Fri February 6 2015;chain:26-254 added on Fri February 6 2015 |
| _displayName | UniProt:P01903 HLA-DRA |
| _timestamp | 2026-02-20 21:39:06 |
| chain | signal peptide:1-25 chain:26-254 |
| checksum | 3CD1CDBA89D92350 |
| comment | FUNCTION An alpha chain of antigen-presenting major histocompatibility complex class II (MHCII) molecule. In complex with the beta chain HLA-DRB, displays antigenic peptides on professional antigen presenting cells (APCs) for recognition by alpha-beta T cell receptor (TCR) on HLA-DR-restricted CD4-positive T cells. This guides antigen-specific T-helper effector functions, both antibody-mediated immune response and macrophage activation, to ultimately eliminate the infectious agents and transformed cells (PubMed:15265931, PubMed:15322540, PubMed:17334368, PubMed:22327072, PubMed:24190431, PubMed:27591323, PubMed:29884618, PubMed:31495665, PubMed:8145819, PubMed:9075930). Typically presents extracellular peptide antigens of 10 to 30 amino acids that arise from proteolysis of endocytosed antigens in lysosomes (PubMed:8145819). In the tumor microenvironment, presents antigenic peptides that are primarily generated in tumor-resident APCs likely via phagocytosis of apoptotic tumor cells or macropinocytosis of secreted tumor proteins (PubMed:31495665). Presents peptides derived from intracellular proteins that are trapped in autolysosomes after macroautophagy, a mechanism especially relevant for T cell selection in the thymus and central immune tolerance (PubMed:17182262, PubMed:23783831). The selection of the immunodominant epitopes follows two processing modes: 'bind first, cut/trim later' for pathogen-derived antigenic peptides and 'cut first, bind later' for autoantigens/self-peptides (PubMed:25413013). The anchor residue at position 1 of the peptide N-terminus, usually a large hydrophobic residue, is essential for high affinity interaction with MHCII molecules (PubMed:8145819).SUBUNIT Heterotrimer that consists of an alpha chain HLA-DRA, a beta chain HLA-DRB and a peptide (peptide-MHCII) (PubMed:11080454, PubMed:11163233, PubMed:12244309, PubMed:16079912, PubMed:17583734, PubMed:18697946, PubMed:31619516, PubMed:32668259, PubMed:7477400, PubMed:9354468, PubMed:9782128). Newly synthesized alpha and beta chains forms a heterodimer (MHCII) that associates with the CD74/invariant chain (Ii) in the endoplasmic reticulum (ER). Ii is a trimer composed of three subunits and each subunit interacts with one MHCII dimer, blocking the peptide-binding cleft (PubMed:7479981). As a result, MHCII molecules cannot bind peptides present in the ER (PubMed:7479981). The complex of MHCII and CD74/Ii is transported in vesicles from ER to Golgi to lysosomes, where it encounters antigenic peptides generated via proteolysis of endocytosed antigens. MHCII dimers are dissociated from CD74/Ii by the combined action of proteolysis and HLA-DM (PubMed:21115828, PubMed:23260142, PubMed:25413013). Lysosomal enzymes such as cathepsin, degrade CD74/Ii leaving a 24 amino acid remnant called class II-associated Ii or CLIP. Interacts (via the peptide binding cleft) with CLIP; this interaction inhibits antigen peptide binding before entry in the endosomal compartment (PubMed:7477400, PubMed:9075930). The displacement of CLIP and replacement by a high affinity peptide in lysosomes is performed by HLA-DM heterodimer. HLA-DM catalyzes CLIP dissociation from MHCII, stabilizes empty MHCII and mediates the selection of high affinity peptides (PubMed:11070170, PubMed:23260142, PubMed:9075930). Interacts with HLA-DM heterodimer; this interaction is direct (PubMed:25413013). Interacts (via alpha-1 domain) with TCR (via CDRs) (PubMed:17334368, PubMed:29884618). Interacts (via alpha-2 domain) with CD4 (via Ig-like V-type domain); this interaction increases the affinity of TCR for peptide-MHCII (PubMed:27114505).SUBUNIT (Microbial infection) Interacts with Epstein-Barr virus BZLF2/gp42.SUBUNIT (Microbial infection) Interacts with Staphylococcus aureus enterotoxin A/entA, enterotoxin B/entB, enterotoxin C1/entC1, enterotoxin D/entD, and enterotoxin H/entH.INTERACTION The MHCII complex transits through a number of intracellular compartments in the endocytic pathway until it reaches the cell membrane for antigen presentation (PubMed:18305173, PubMed:9075930). Component of immunological synapses at the interface between T cell and APC (PubMed:15322540, PubMed:29884618).TISSUE SPECIFICITY Expressed in professional APCs: macrophages, dendritic cells and B cells (at protein level) (PubMed:15322540, PubMed:23783831, PubMed:31495665). Expressed in thymic epithelial cells (at protein level) (PubMed:23783831).INDUCTION Up-regulated in dendritic cells upon maturation.DOMAIN The alpha-1 domain is a structural part of the peptide-binding cleft. It contains one alpha helix and 4 beta sheets, respectively forming part of the wall and the floor of the peptide-binding cleft. The other 4 beta sheets of the floor and the second alpha helix wall is formed by the beta-1 domain of HLA-DRB. Forms hydrogen bonds with the peptide main chain via conserved amino acids (PubMed:17583734, PubMed:29884618, PubMed:8145819, PubMed:9354468, PubMed:9782128). The peptide-bound alpha-1 domain forms hydrogen bonds with CDR2 and CDR3 alpha-domain of TCR (PubMed:29884618).DOMAIN The alpha-2 Ig-like domain mediates the interaction with CD4 coreceptor.PTM Ubiquitinated by MARCHF1 or MARCHF8 at Lys-244 leading to down-regulation of MHCII. When associated with ubiquitination of the beta chain at 'Lys-254', the down-regulation of MHCII 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*01:02.SIMILARITY Belongs to the MHC class II family.SEQUENCE CAUTION Truncated N-terminus. |
| description | recommendedName: HLA class II histocompatibility antigen, DR alpha chain alternativeName: MHC class II antigen DRA |
| geneName | HLA-DRA HLA-DRA1 |
| identifier | P01903 |
| isSequenceChanged | FALSE |
| keyword | 3D-structure Adaptive immunity Cell membrane Cytoplasmic vesicle Direct protein sequencing Disulfide bond Endoplasmic reticulum Endosome Glycoprotein Host-virus interaction Immunity Isopeptide bond Lysosome Membrane MHC II Proteomics identification Reference proteome Signal Transmembrane Transmembrane helix Ubl conjugation |
| modified | [InstanceEdit:84067] Schmidt, EE, 2003-12-18 04:29:09 [InstanceEdit:143527] Schmidt, EE, 2004-11-12 07:45:10 [InstanceEdit:217385] Schmidt, EE, 2008-03-27 06:23:53 [InstanceEdit:354386] Schmidt, EE, 2008-06-18 04:45:12 [InstanceEdit:384350] Kanapin, AA, 2008-11-26 14:00:39 [InstanceEdit:392885] Kanapin, AA, 2009-03-09 12:07:18 [InstanceEdit:400710] Schmidt, EE, 2009-03-25 05:33:35 [InstanceEdit:423310] Kanapin, AA [InstanceEdit:435478] Kanapin, AA [InstanceEdit:435871] Kanapin, AA [InstanceEdit:447347] Kanapin, AA [InstanceEdit:525883] Kanapin, AA [InstanceEdit:613449] Kanapin, AA [InstanceEdit:797602] Kanapin, AA [InstanceEdit:937368] Yung, CK [InstanceEdit:1042053] Yung, CK [InstanceEdit:1220657] Yung, CK [InstanceEdit:1300696] Yung, CK [InstanceEdit:1301627] Yung, CK [InstanceEdit:1551960] Weiser, JD [InstanceEdit:1995863] Weiser, JD [InstanceEdit:2132304] Weiser, JD [InstanceEdit:2265580] Weiser, JD [InstanceEdit:2587579] Weiser, JD [InstanceEdit:5083144] Weiser, JD [InstanceEdit:5433710] Weiser, JD [InstanceEdit:5618415] Weiser, JD [InstanceEdit:5634237] Weiser, JD [InstanceEdit:5673015] Weiser, JD [InstanceEdit:6791590] Weiser, JD [InstanceEdit:8987656] Weiser, JD [InstanceEdit:9037114] Weiser, JD [InstanceEdit:9616384] Weiser, JD [InstanceEdit:9637257] Weiser, JD [InstanceEdit:9657908] Weiser, JD [InstanceEdit:9676415] Weiser, JD [InstanceEdit:9688885] Weiser, JD [InstanceEdit:9715482] Weiser, JD [InstanceEdit:9730071] Weiser, JD [InstanceEdit:9773244] Weiser, Joel [InstanceEdit:9852000] Weiser, Joel, 2023-11-03 [InstanceEdit:9917590] Weiser, Joel, 2024-08-09 [InstanceEdit:9926675] Weiser, Joel, 2024-11-03 [InstanceEdit:9983091] Weiser, Joel, 2026-02-20 |
| name | HLA-DRA |
| referenceDatabase | [ReferenceDatabase:2] UniProt |
| referenceGene | [ReferenceDNASequence:8988362] ENSEMBL:ENSG00000204287 HLA-DRA [Homo sapiens] |
| secondaryIdentifier | DRA_HUMAN A2BET4 Q30160 Q6IAZ1 Q861I2 Q9TP70 |
| sequenceLength | 254 |
| species | [Species:48887] Homo sapiens |
| (referenceEntity) | [EntityWithAccessionedSequence:197588] HLA class II histocompatibility antigen, DR alpha chain precursor [plasma membrane] [Homo sapiens] [EntityWithAccessionedSequence:2130442] HLA class II histocompatibility antigen, DR alpha chain precursor [clathrin-coated endocytic vesicle membrane] [Homo sapiens] [EntityWithAccessionedSequence:2130463] HLA class II histocompatibility antigen, DR alpha chain precursor [endocytic vesicle membrane] [Homo sapiens] [EntityWithAccessionedSequence:2130480] HLA class II histocompatibility antigen, DR alpha chain precursor [ER to Golgi transport vesicle membrane] [Homo sapiens] [EntityWithAccessionedSequence:2130530] HLA class II histocompatibility antigen, DR alpha chain precursor [transport vesicle membrane] [Homo sapiens] [EntityWithAccessionedSequence:2130586] HLA class II histocompatibility antigen, DR alpha chain precursor [trans-Golgi network membrane] [Homo sapiens] [EntityWithAccessionedSequence:2130665] HLA class II histocompatibility antigen, DR alpha chain precursor [lumenal side of endoplasmic reticulum membrane] [Homo sapiens] [EntityWithAccessionedSequence:2130677] HLA class II histocompatibility antigen, DR alpha chain precursor [lysosomal membrane] [Homo sapiens] [EntityWithAccessionedSequence:2214390] HLA class II histocompatibility antigen, DR alpha chain precursor [Golgi membrane] [Homo sapiens] |
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No pathways have been reviewed or authored by UniProt:P01903 HLA-DRA (56273)
