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: Annotation score: 5 out of 5-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

Complete GO annotation...

Keywords - Biological processi

Immunity

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.

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

HGNCiHGNC:4943. HLA-DQA2.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini24 – 217194ExtracellularSequence analysisAdd
BLAST
Transmembranei218 – 24023HelicalSequence analysisAdd
BLAST
Topological domaini241 – 25515CytoplasmicSequence analysisAdd
BLAST

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

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

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA35067.

Polymorphism and mutation databases

BioMutaiHLA-DQA2.
DMDMi122192.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2323Add
BLAST
Chaini24 – 255232HLA class II histocompatibility antigen, DQ alpha 2 chainPRO_0000018973Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi104 – 1041N-linked (GlcNAc...)Sequence analysis
Disulfide bondi133 ↔ 189PROSITE-ProRule annotation
Glycosylationi144 – 1441N-linked (GlcNAc...)Sequence analysis

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

MaxQBiP01906.
PaxDbiP01906.
PeptideAtlasiP01906.
PRIDEiP01906.

PTM databases

iPTMnetiP01906.
PhosphoSiteiP01906.

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

BgeeiENSG00000206301.
CleanExiHS_HLA-DQA2.
GenevisibleiP01906. HS.

Organism-specific databases

HPAiHPA010967.

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

STRINGi9606.ENSP00000364076.

Structurei

3D structure databases

ProteinModelPortaliP01906.
SMRiP01906. Positions 25-208.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini113 – 20593Ig-like C1-typeAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni24 – 11087Alpha-1Add
BLAST
Regioni111 – 20494Alpha-2Add
BLAST
Regioni205 – 21713Connecting peptideAdd
BLAST

Sequence similaritiesi

Belongs to the MHC class II family.Curated

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IZMF. Eukaryota.
ENOG410YHX9. LUCA.
GeneTreeiENSGT00760000118970.
HOGENOMiHOG000112076.
InParanoidiP01906.
KOiK06752.
OMAiYPPSINI.
OrthoDBiEOG091G0IC9.
PhylomeDBiP01906.
TreeFamiTF333797.

Family and domain databases

Gene3Di2.60.40.10. 1 hit.
3.10.320.10. 1 hit.
InterProiIPR032431. C1-set_C.
IPR007110. Ig-like_dom.
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.
[Graphical view]
PfamiPF07654. C1-set. 1 hit.
PF16196. C1-set_C. 1 hit.
PF00993. MHC_II_alpha. 1 hit.
[Graphical view]
SMARTiSM00407. IGc1. 1 hit.
SM00920. MHC_II_alpha. 1 hit.
[Graphical view]
SUPFAMiSSF48726. SSF48726. 1 hit.
SSF54452. SSF54452. 1 hit.
PROSITEiPS50835. IG_LIKE. 1 hit.
PS00290. IG_MHC. 1 hit.
[Graphical view]

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)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti84 – 841S → T in AAA59834 (PubMed:3036828).Curated
Sequence conflicti101 – 1011R → G in CAM26196 (PubMed:14574404).Curated
Sequence conflicti101 – 1011R → G in CAM26195 (PubMed:14574404).Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti227 – 2271V → A.1 Publication
Corresponds to variant rs9276436 [ dbSNP | Ensembl ].
VAR_033431
Natural varianti247 – 2471G → D.1 Publication
Corresponds to variant rs2071800 [ dbSNP | Ensembl ].
VAR_050392

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

Cross-referencesi

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.

3D structure databases

ProteinModelPortaliP01906.
SMRiP01906. Positions 25-208.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9606.ENSP00000364076.

PTM databases

iPTMnetiP01906.
PhosphoSiteiP01906.

Polymorphism and mutation databases

BioMutaiHLA-DQA2.
DMDMi122192.

Proteomic databases

MaxQBiP01906.
PaxDbiP01906.
PeptideAtlasiP01906.
PRIDEiP01906.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

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.

Organism-specific databases

CTDi3118.
GeneCardsiHLA-DQA2.
H-InvDBHIX0058177.
HIX0166445.
HIX0166701.
HGNCiHGNC:4943. HLA-DQA2.
HPAiHPA010967.
MIMi613503. gene.
neXtProtiNX_P01906.
PharmGKBiPA35067.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IZMF. Eukaryota.
ENOG410YHX9. LUCA.
GeneTreeiENSGT00760000118970.
HOGENOMiHOG000112076.
InParanoidiP01906.
KOiK06752.
OMAiYPPSINI.
OrthoDBiEOG091G0IC9.
PhylomeDBiP01906.
TreeFamiTF333797.

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.

Miscellaneous databases

GeneWikiiHLA-DQA2.
GenomeRNAii3118.
PROiP01906.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000206301.
CleanExiHS_HLA-DQA2.
GenevisibleiP01906. HS.

Family and domain databases

Gene3Di2.60.40.10. 1 hit.
3.10.320.10. 1 hit.
InterProiIPR032431. C1-set_C.
IPR007110. Ig-like_dom.
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.
[Graphical view]
PfamiPF07654. C1-set. 1 hit.
PF16196. C1-set_C. 1 hit.
PF00993. MHC_II_alpha. 1 hit.
[Graphical view]
SMARTiSM00407. IGc1. 1 hit.
SM00920. MHC_II_alpha. 1 hit.
[Graphical view]
SUPFAMiSSF48726. SSF48726. 1 hit.
SSF54452. SSF54452. 1 hit.
PROSITEiPS50835. IG_LIKE. 1 hit.
PS00290. IG_MHC. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiDQA2_HUMAN
AccessioniPrimary (citable) accession number: P01906
Secondary accession number(s): A2BF37
, B0V0E7, O19789, Q5SQ94, Q5SR04
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: February 1, 1991
Last modified: September 7, 2016
This is version 151 of the entry and version 2 of the sequence. [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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.