Reactome | UniProt:P01909 HLA-DQA1

Schema > ReferenceGeneProduct > Entries

UniProt:P01909 HLA-DQA1 Show undefined attributes

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: DQA101:01, DQA101:02, DQA101:03, DQA101:04, DQA101:05, DQA101:06, DQA101:07, DQA102:01, DQA103:01, DQA103:02, DQA103:03, DQA104:01, DQA104:02, DQA104:03, DQA104:04, DQA105:01, DQA105:02, DQA105:03, DQA105:04, DQA105:05, DQA105:06, DQA105:07, DQA105:08, DQA105:09, DQA106:01, DQA106:02. The sequence shown is that of DQA105:01.POLYMORPHISM DQ2 (heterodimer of DQA105:01/DQB102:01) is associated with more than 90% of celiac disease patients. A minority displays DQ8 (heterodimer of DQA103/DQB103:02). DQ0602 (heterodimer of DQA101:02/DQB1*06:02) confers dominant protection against type 1 diabetes (T1D) and strong susceptibility to narcolepsy.SIMILARITY Belongs to the MHC class II family.
crossReference	[DatabaseIdentifier:12184968] PDB:6U3M [DatabaseIdentifier:12458800] RefSeq:XP_054187030.1 [DatabaseIdentifier:12458799] RefSeq:XP_054187031.1 [DatabaseIdentifier:12458798] RefSeq:XP_054185777.1 [DatabaseIdentifier:12458797] RefSeq:NP_002113.2 [DatabaseIdentifier:12458796] RefSeq:XP_054185776.1 [DatabaseIdentifier:12286209] Pharos - Targets:P01909 [DatabaseIdentifier:12265908] PRO:P01909 [DatabaseIdentifier:12184977] PDB:6XP6 [DatabaseIdentifier:12181533] PDB:5KSA [DatabaseIdentifier:12184982] PDB:8VSP [DatabaseIdentifier:12184983] PDB:1S9V [DatabaseIdentifier:12184984] PDB:9EJH [DatabaseIdentifier:12176811] PDB:1JK8 [DatabaseIdentifier:12184976] PDB:6MFF [DatabaseIdentifier:12181393] PDB:4OZI [DatabaseIdentifier:12184978] PDB:2NNA [DatabaseIdentifier:12181395] PDB:4OZF [DatabaseIdentifier:12184985] PDB:9EJG [DatabaseIdentifier:12181532] PDB:5KSB [DatabaseIdentifier:12184975] PDB:8W86 [DatabaseIdentifier:12162413] PDB:1UVQ [DatabaseIdentifier:12184981] PDB:7SG0 [DatabaseIdentifier:12184980] PDB:7SG2 [DatabaseIdentifier:12181391] PDB:4OZG [DatabaseIdentifier:12181392] PDB:4OZH [DatabaseIdentifier:12184979] PDB:7SG1 [DatabaseIdentifier:12181416] PDB:4GG6 [DatabaseIdentifier:12184972] PDB:8W84 [DatabaseIdentifier:12184974] PDB:8W85 [DatabaseIdentifier:12184971] PDB:6MFG [DatabaseIdentifier:12184970] PDB:5KSU [DatabaseIdentifier:11515033] ENSEMBL:ENSG00000196735 [DatabaseIdentifier:11515032] ENSEMBL:ENSG00000206305 [DatabaseIdentifier:11515031] ENSEMBL:ENSG00000232062 [DatabaseIdentifier:11631614] ENSEMBL:ENSP00000364087 [DatabaseIdentifier:11631611] ENSEMBL:ENSP00000372738 [DatabaseIdentifier:11631609] ENSEMBL:ENSP00000413237 [DatabaseIdentifier:11631616] ENSEMBL:ENSP00000382586 [DatabaseIdentifier:11631615] ENSEMBL:ENSP00000339398 [DatabaseIdentifier:11631612] ENSEMBL:ENSP00000378767 [DatabaseIdentifier:11631613] ENSEMBL:ENSP00000382583 [DatabaseIdentifier:11631610] ENSEMBL:ENSP00000387892 [DatabaseIdentifier:11754309] ENSEMBL:ENST00000399675 [DatabaseIdentifier:11754308] ENSEMBL:ENST00000374949 [DatabaseIdentifier:11754312] ENSEMBL:ENST00000395363 [DatabaseIdentifier:11754313] ENSEMBL:ENST00000399678 [DatabaseIdentifier:11754311] ENSEMBL:ENST00000383251 [DatabaseIdentifier:11754315] ENSEMBL:ENST00000444296 [DatabaseIdentifier:11754310] ENSEMBL:ENST00000418023 [DatabaseIdentifier:11754314] ENSEMBL:ENST00000343139 [DatabaseIdentifier:11788318] GeneCards:HLA-DQA1 [DatabaseIdentifier:11841372] HPA:ENSG00000196735-HLA-DQA1 [DatabaseIdentifier:12125937] OpenTargets:ENSG00000196735 [DatabaseIdentifier:12137245] Orphanet:HLA-DQA1 [DatabaseIdentifier:12184973] PDB:6U3N [DatabaseIdentifier:12184969] PDB:8W83 [DatabaseIdentifier:12184967] PDB:5KSV
databaseName	UniProt
dbId	56261
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
displayName	UniProt:P01909 HLA-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:9926675] Weiser, Joel, 2024-11-03
moleculeType	Protein
name	HLA-DQA1
otherIdentifier	11724799_x_at 11750528_x_at 11753898_x_at 11756083_x_at 11758340_x_at 17007266 17028326 17038609 17041240 203290_PM_at 203290_at 212671_PM_s_at 212671_s_at 213831_PM_at 213831_at 236203_PM_at 236203_at 2903223 2903224 2903227 2903229 2903231 2903233 2903234 2903235 2903236 2903259 2903265 2903266 3117 32773_at 8118556 81488_at 8178199 8179489 A_23_P30900 A_24_P196827 A_24_P326084 A_24_P393230 A_33_P3293049 GE81121 GE863920 GE890404 GO:0000139 GO:0002250 GO:0002376 GO:0002503 GO:0002504 GO:0005515 GO:0005764 GO:0005765 GO:0005768 GO:0005783 GO:0005789 GO:0005794 GO:0005886 GO:0006955 GO:0010008 GO:0012507 GO:0016020 GO:0019882 GO:0019886 GO:0023026 GO:0030658 GO:0030666 GO:0030669 GO:0031902 GO:0032395 GO:0032588 GO:0042605 GO:0042613 GO:0046872 GO:0050778 GO:0050870 GO:0098553 HMNXSV003000947 HMNXSV003054155 HMNXSV003055601 HMNXSV003056103 Hs.120695.0.A1_3p_at Hs.198253.1.A1_3p_a_at Hs.198253.2.A1_3p_s_at ILMN_1808405 K01160_s_at M26041_s_at M34996_s_at PH_hs_0033085 TC06000400.hg TC6_cox_hap2000091.hg TC6_qbl_hap6000082.hg TC6_ssto_hap7000077.hg g4504406_3p_at p26545 p26546
physicalEntity	[EntityWithAccessionedSequence:R-HSA-197585] HLA class II histocompatibility antigen, DQ [plasma membrane] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-2130686] HLA class II histocompatibility antigen, DQ [lysosomal membrane] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-2130529] HLA class II histocompatibility antigen, DQ [endocytic vesicle membrane] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-2130595] HLA class II histocompatibility antigen, DQ [clathrin-coated endocytic vesicle membrane] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-2130733] HLA class II histocompatibility antigen, DQ [transport vesicle membrane] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-2130568] HLA class II histocompatibility antigen, DQ [trans-Golgi network membrane] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-2214382] HLA class II histocompatibility antigen, DQ [Golgi membrane] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-2130699] HLA class II histocompatibility antigen, DQ [ER to Golgi transport vesicle membrane] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-2130716] HLA class II histocompatibility antigen, DQ [lumenal side of endoplasmic reticulum membrane] - Homo sapiens
referenceDatabase	[ReferenceDatabase:2] UniProt
referenceGene	[ReferenceDNASequence:ensembl:ENSG00000196735] ENSEMBL:ENSG00000196735 HLA-DQA1 [ReferenceDNASequence:12764928] UCSC:P01909 HLA-DQA1 [ReferenceDNASequence:11379396] BioGPS Gene:3117 HLA-DQA1 [ReferenceDNASequence:11403438] COSMIC - genes:HLA-DQA1 HLA-DQA1 [ReferenceDNASequence:11414499] CTD Gene:3117 HLA-DQA1 [ReferenceDNASequence:11441054] dbSNP Gene:3117 HLA-DQA1 [ReferenceDNASequence:11819970] HGNC:4942 HLA-DQA1 [ReferenceDNASequence:11916537] KEGG:hsa:3117 HLA-DQA1 [ReferenceDNASequence:12009185] Monarch:3117 HLA-DQA1 [ReferenceDNASequence:12093278] NCBI Gene:3117 HLA-DQA1 [ReferenceDNASequence:12111106] OMIM:146880 HLA-DQA1
referenceTranscript	[ReferenceRNASequence:12640251] RefSeq:XM_054329802.1 HLA-DQA1 [ReferenceRNASequence:12640249] RefSeq:XM_054331055.1 HLA-DQA1 [ReferenceRNASequence:12640253] RefSeq:NM_002122.3 HLA-DQA1 [ReferenceRNASequence:12640250] RefSeq:XM_054329801.1 HLA-DQA1 [ReferenceRNASequence:12640252] RefSeq:XM_054331056.1 HLA-DQA1
schemaClass	ReferenceGeneProduct
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
stId	uniprot:P01909
url	http://purl.uniprot.org/uniprot/P01909

Referrals

(referenceEntity)

(interactor)