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Details on Person UniProt:P01909 HLA-DQA1
| Class:Id | ReferenceGeneProduct:56261 |
|---|---|
| _chainChangeLog | signal peptide:1-23 added on Fri February 6 2015;chain:24-254 added on Fri February 6 2015 |
| _displayName | UniProt:P01909 HLA-DQA1 |
| _timestamp | 2024-11-03 20:00:30 |
| chain | signal peptide:1-23 chain:24-254 |
| checksum | 84E12B5A80E2A028 |
| comment | 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. 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.INTERACTION 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. |
| description | recommendedName: HLA class II histocompatibility antigen, DQ alpha 1 chain alternativeName: DC-1 alpha chain alternativeName: DC-alpha alternativeName: HLA-DCA alternativeName: MHC class II DQA1 |
| geneName | HLA-DQA1 |
| identifier | P01909 |
| isSequenceChanged | FALSE |
| keyword | 3D-structure Adaptive immunity Cell membrane Direct protein sequencing Disulfide bond Endoplasmic reticulum Endosome Glycoprotein Golgi apparatus Immunity Lysosome Membrane MHC II Proteomics identification Reference proteome Signal Transmembrane Transmembrane helix |
| 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:8987656] Weiser, JD [InstanceEdit:9037114] Weiser, JD [InstanceEdit:9637257] Weiser, JD [InstanceEdit:9657908] Weiser, JD [InstanceEdit:9676415] Weiser, JD [InstanceEdit:9715482] Weiser, JD [InstanceEdit:9852000] Weiser, Joel, 2023-11-03 [InstanceEdit:9926675] Weiser, Joel, 2024-11-03 |
| name | HLA-DQA1 |
| referenceDatabase | [ReferenceDatabase:2] UniProt |
| referenceGene | [ReferenceDNASequence:8992417] ENSEMBL:ENSG00000196735 HLA-DQA1 [Homo sapiens] |
| secondaryIdentifier | DQA1_HUMAN O19630 O19706 P01907 P01908 P04225 P04226 P05536 P79553 Q06751 Q29876 Q29994 Q2Q6Y6 Q2Q6Y7 Q2Q6Y8 Q2WCM3 Q30064 Q30067 Q30068 Q30070 Q30071 Q30072 Q30073 Q30086 Q30101 Q5Y7D5 Q5Y7F5 Q6ICU6 Q6PR46 Q6QDB1 Q860W2 Q860W4 Q9BD37 Q9TPM3 Q9UM31 |
| sequenceLength | 254 |
| species | [Species:48887] Homo sapiens |
| (referenceEntity) | [EntityWithAccessionedSequence:197585] HLA class II histocompatibility antigen, DQ [plasma membrane] [Homo sapiens] [EntityWithAccessionedSequence:2130529] HLA class II histocompatibility antigen, DQ [endocytic vesicle membrane] [Homo sapiens] [EntityWithAccessionedSequence:2130568] HLA class II histocompatibility antigen, DQ [trans-Golgi network membrane] [Homo sapiens] [EntityWithAccessionedSequence:2130595] HLA class II histocompatibility antigen, DQ [clathrin-coated endocytic vesicle membrane] [Homo sapiens] [EntityWithAccessionedSequence:2130686] HLA class II histocompatibility antigen, DQ [lysosomal membrane] [Homo sapiens] [EntityWithAccessionedSequence:2130699] HLA class II histocompatibility antigen, DQ [ER to Golgi transport vesicle membrane] [Homo sapiens] [EntityWithAccessionedSequence:2130716] HLA class II histocompatibility antigen, DQ [lumenal side of endoplasmic reticulum membrane] [Homo sapiens] [EntityWithAccessionedSequence:2130733] HLA class II histocompatibility antigen, DQ [transport vesicle membrane] [Homo sapiens] [EntityWithAccessionedSequence:2214382] HLA class II histocompatibility antigen, DQ [Golgi membrane] [Homo sapiens] |
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No pathways have been reviewed or authored by UniProt:P01909 HLA-DQA1 (56261)
