Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

HLA class II histocompatibility antigen, DQ alpha 2 chain

Gene

HLA-DQA2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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.1 Publication

GO - Molecular functioni

  • MHC class II receptor activity Source: UniProtKB

GO - Biological processi

Keywordsi

Biological processImmunity

Enzyme and pathway databases

ReactomeiR-HSA-202424 Downstream TCR signaling
R-HSA-202427 Phosphorylation of CD3 and TCR zeta chains
R-HSA-202430 Translocation of ZAP-70 to Immunological synapse
R-HSA-202433 Generation of second messenger molecules
R-HSA-2132295 MHC class II antigen presentation
R-HSA-389948 PD-1 signaling
R-HSA-877300 Interferon gamma signaling
SIGNORiP01906

Names & Taxonomyi

Protein namesi
Recommended name:
HLA class II histocompatibility antigen, DQ alpha 2 chain
Alternative name(s):
DX alpha chain
HLA class II histocompatibility antigen, DQ(6) alpha chain
HLA-DQA1
MHC class II DQA2
Gene namesi
Name:HLA-DQA2
Synonyms:HLA-DXA
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 6

Organism-specific databases

EuPathDBiHostDB:ENSG00000237541.3
HGNCiHGNC:4943 HLA-DQA2
MIMi613503 gene
neXtProtiNX_P01906

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini24 – 217ExtracellularSequence analysisAdd BLAST194
Transmembranei218 – 240HelicalSequence analysisAdd BLAST23
Topological domaini241 – 255CytoplasmicSequence analysisAdd BLAST15

Keywords - Cellular componenti

Cell membrane, Endoplasmic reticulum, Endosome, Golgi apparatus, Lysosome, Membrane, MHC II

Pathology & Biotechi

Organism-specific databases

DisGeNETi3118
OpenTargetsiENSG00000237541
PharmGKBiPA35067

Chemistry databases

DrugBankiDB00071 Insulin Pork

Polymorphism and mutation databases

BioMutaiHLA-DQA2
DMDMi122192

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 23Add BLAST23
ChainiPRO_000001897324 – 255HLA class II histocompatibility antigen, DQ alpha 2 chainAdd BLAST232

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi104N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi133 ↔ 189PROSITE-ProRule annotation
Glycosylationi144N-linked (GlcNAc...) asparagineSequence analysis1

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiP01906
PeptideAtlasiP01906
PRIDEiP01906
ProteomicsDBi51509

PTM databases

iPTMnetiP01906
PhosphoSitePlusiP01906

Expressioni

Tissue specificityi

Restricted to skin Langerhans cells, although some expression at low levels may occur at the surface of B lymphoblastoid cells.2 Publications

Gene expression databases

BgeeiENSG00000237541
CleanExiHS_HLA-DQA2
ExpressionAtlasiP01906 baseline and differential
GenevisibleiP01906 HS

Interactioni

Subunit structurei

Heterodimer of an alpha and a beta subunit; also referred as MHC class II molecule. Dimer formation with HLA-DQB2, but not with HLA-DQB1, is required for efficient exit from the endoplasmic reticulum (ER). In the ER, 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. Association with HLA-DMA also occurs in skin Langerhans cells, in post-Golgi compartments.1 Publication

Protein-protein interaction databases

IntActiP01906, 1 interactor
STRINGi9606.ENSP00000364076

Structurei

3D structure databases

ProteinModelPortaliP01906
SMRiP01906
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini113 – 205Ig-like C1-typeAdd BLAST93

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni24 – 110Alpha-1Add BLAST87
Regioni111 – 204Alpha-2Add BLAST94
Regioni205 – 217Connecting peptideAdd BLAST13

Sequence similaritiesi

Belongs to the MHC class II family.Curated

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IZMF Eukaryota
ENOG410YHX9 LUCA
GeneTreeiENSGT00900000140882
HOGENOMiHOG000112076
InParanoidiP01906
KOiK06752
OMAiCFDSSDT
OrthoDBiEOG093703IG
PhylomeDBiP01906
TreeFamiTF333797

Family and domain databases

Gene3Di2.60.40.10, 1 hit
3.10.320.10, 1 hit
InterProiView protein in InterPro
IPR007110 Ig-like_dom
IPR036179 Ig-like_dom_sf
IPR013783 Ig-like_fold
IPR003006 Ig/MHC_CS
IPR003597 Ig_C1-set
IPR011162 MHC_I/II-like_Ag-recog
IPR014745 MHC_II_a/b_N
IPR001003 MHC_II_a_N
PfamiView protein in Pfam
PF07654 C1-set, 1 hit
PF00993 MHC_II_alpha, 1 hit
SMARTiView protein in SMART
SM00407 IGc1, 1 hit
SM00920 MHC_II_alpha, 1 hit
SUPFAMiSSF48726 SSF48726, 1 hit
SSF54452 SSF54452, 1 hit
PROSITEiView protein in PROSITE
PS50835 IG_LIKE, 1 hit
PS00290 IG_MHC, 1 hit

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P01906-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MILNKALLLG ALALTAVMSP CGGEDIVADH VASYGVNFYQ SHGPSGQYTH
60 70 80 90 100
EFDGDEEFYV DLETKETVWQ LPMFSKFISF DPQSALRNMA VGKHTLEFMM
110 120 130 140 150
RQSNSTAATN EVPEVTVFSK FPVTLGQPNT LICLVDNIFP PVVNITWLSN
160 170 180 190 200
GHSVTEGVSE TSFLSKSDHS FFKISYLTFL PSADEIYDCK VEHWGLDEPL
210 220 230 240 250
LKHWEPEIPA PMSELTETLV CALGLSVGLM GIVVGTVFII QGLRSVGASR

HQGLL
Length:255
Mass (Da):28,033
Last modified:February 1, 1991 - v2
Checksum:i85B13D9FDF2905FE
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti84S → T in AAA59834 (PubMed:3036828).Curated1
Sequence conflicti101R → G in CAM26196 (PubMed:14574404).Curated1
Sequence conflicti101R → G in CAM26195 (PubMed:14574404).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_033431227V → A1 PublicationCorresponds to variant dbSNP:rs9276436Ensembl.1
Natural variantiVAR_050392247G → D1 PublicationCorresponds to variant dbSNP:rs2071800Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M29615, M29614 Genomic DNA Translation: AAA59834.1
X00453
, X00454, X00455, X00456 Genomic DNA Translation: CAA25142.1
M17237, M17235 Genomic DNA Translation: AAA59605.1
CR759848 Genomic DNA Translation: CAQ07531.1
AL773543 Genomic DNA Translation: CAI18490.1
BX248406, BX927131 Genomic DNA Translation: CAM26195.1
BX927131, BX248406 Genomic DNA Translation: CAM26196.1
AL713890 Genomic DNA Translation: CAI17623.1
AL672104 Genomic DNA Translation: CAI18437.1
CR936921 Genomic DNA Translation: CAQ07312.1
CR753846 Genomic DNA Translation: CAQ09761.1
BX927160, BX927168 Genomic DNA Translation: CAQ10975.1
BX927168, BX927160 Genomic DNA Translation: CAQ08754.1
S71248 Genomic DNA Translation: AAD14077.1
CCDSiCCDS4753.1
PIRiA02210 HLHUDX
I54439
RefSeqiNP_064440.1, NM_020056.4
UniGeneiHs.591798

Genome annotation databases

EnsembliENST00000241802; ENSP00000241802; ENSG00000206301
ENST00000374940; ENSP00000364076; ENSG00000237541
ENST00000415898; ENSP00000400695; ENSG00000231526
ENST00000443184; ENSP00000405833; ENSG00000257473
ENST00000446482; ENSP00000390725; ENSG00000225103
ENST00000447735; ENSP00000393431; ENSG00000223793
ENST00000449560; ENSP00000401098; ENSG00000233192
ENST00000453672; ENSP00000387768; ENSG00000231823
ENST00000546801; ENSP00000447668; ENSG00000233192
ENST00000551533; ENSP00000448003; ENSG00000223793
GeneIDi3118
KEGGihsa:3118
UCSCiuc003obx.4 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Entry informationi

Entry nameiDQA2_HUMAN
AccessioniPrimary (citable) accession number: P01906
Secondary accession number(s): A2BF37
, B0V0E7, O19789, Q5SQ94, Q5SR04
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: February 1, 1991
Last modified: July 18, 2018
This is version 165 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 6
    Human chromosome 6: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

We'd like to inform you that we have updated our Privacy Notice to comply with Europe’s new General Data Protection Regulation (GDPR) that applies since 25 May 2018.

Do not show this banner again
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health