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P01906 (DQA2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 135. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:HLA-DQA2
Synonyms:HLA-DXA
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length255 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

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. Ref.14

Subunit structure

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. Ref.14

Subcellular location

Cell membrane; Single-pass type I membrane protein. Endoplasmic reticulum membrane; Single-pass type I membrane protein. Golgi apparatustrans-Golgi network membrane; Single-pass type I membrane protein. Endosome membrane; Single-pass type I membrane protein. Lysosome membrane; Single-pass type I membrane protein. Note: 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. Ref.14

Tissue specificity

Restricted to skin Langerhans cells, although some expression at low levels may occur at the surface of B lymphoblastoid cells. Ref.7 Ref.14

Sequence similarities

Belongs to the MHC class II family.

Contains 1 Ig-like C1-type (immunoglobulin-like) domain.

Ontologies

Keywords
   Biological processImmunity
   Cellular componentCell membrane
Endoplasmic reticulum
Endosome
Golgi apparatus
Lysosome
Membrane
MHC II
   Coding sequence diversityPolymorphism
   DomainSignal
Transmembrane
Transmembrane helix
   PTMDisulfide bond
Glycoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processT cell costimulation

Traceable author statement. Source: Reactome

T cell receptor signaling pathway

Traceable author statement. Source: Reactome

antigen processing and presentation of exogenous peptide antigen via MHC class II

Traceable author statement. Source: Reactome

cytokine-mediated signaling pathway

Traceable author statement. Source: Reactome

immune response

Non-traceable author statement Ref.1. Source: UniProtKB

interferon-gamma-mediated signaling pathway

Traceable author statement. Source: Reactome

   Cellular_componentER to Golgi transport vesicle membrane

Traceable author statement. Source: Reactome

Golgi membrane

Traceable author statement. Source: Reactome

MHC class II protein complex

Inferred from electronic annotation. Source: UniProtKB-KW

clathrin-coated endocytic vesicle membrane

Traceable author statement. Source: Reactome

endocytic vesicle membrane

Traceable author statement. Source: Reactome

endosome membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

integral component of lumenal side of endoplasmic reticulum membrane

Traceable author statement. Source: Reactome

integral component of plasma membrane

Non-traceable author statement Ref.1. Source: UniProtKB

lysosomal membrane

Traceable author statement. Source: Reactome

plasma membrane

Traceable author statement. Source: Reactome

trans-Golgi network membrane

Traceable author statement. Source: Reactome

transport vesicle membrane

Traceable author statement. Source: Reactome

   Molecular_functionMHC class II receptor activity

Non-traceable author statement Ref.1. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2323
Chain24 – 255232HLA class II histocompatibility antigen, DQ alpha 2 chain
PRO_0000018973

Regions

Topological domain24 – 217194Extracellular Potential
Transmembrane218 – 24023Helical; Potential
Topological domain241 – 25515Cytoplasmic Potential
Domain113 – 20593Ig-like C1-type
Region24 – 11087Alpha-1
Region111 – 20494Alpha-2
Region205 – 21713Connecting peptide

Amino acid modifications

Glycosylation1041N-linked (GlcNAc...) Potential
Glycosylation1441N-linked (GlcNAc...) Potential
Disulfide bond133 ↔ 189 By similarity

Natural variations

Natural variant2271V → A. Ref.4
Corresponds to variant rs9276436 [ dbSNP | Ensembl ].
VAR_033431
Natural variant2471G → D. Ref.4
Corresponds to variant rs2071800 [ dbSNP | Ensembl ].
VAR_050392

Experimental info

Sequence conflict841S → T in AAA59834. Ref.1
Sequence conflict1011R → G in CAM26196. Ref.4
Sequence conflict1011R → G in CAM26195. Ref.4

Sequences

Sequence LengthMass (Da)Tools
P01906 [UniParc].

Last modified February 1, 1991. Version 2.
Checksum: 85B13D9FDF2905FE

FASTA25528,033
        10         20         30         40         50         60 
MILNKALLLG ALALTAVMSP CGGEDIVADH VASYGVNFYQ SHGPSGQYTH EFDGDEEFYV 

        70         80         90        100        110        120 
DLETKETVWQ LPMFSKFISF DPQSALRNMA VGKHTLEFMM RQSNSTAATN EVPEVTVFSK 

       130        140        150        160        170        180 
FPVTLGQPNT LICLVDNIFP PVVNITWLSN GHSVTEGVSE TSFLSKSDHS FFKISYLTFL 

       190        200        210        220        230        240 
PSADEIYDCK VEHWGLDEPL LKHWEPEIPA PMSELTETLV CALGLSVGLM GIVVGTVFII 

       250 
QGLRSVGASR HQGLL 

« Hide

References

« Hide 'large scale' references
[1]"Class II genes of the human major histocompatibility complex. Comparisons of the DQ and DX alpha and beta genes."
Jonsson A.-K., Hyldig-Nielsen J.-J., Servenius B., Larhammar D., Andersson G., Joergensen F., Peterson P.A., Rask L.
J. Biol. Chem. 262:8767-8777(1987) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]"Isotypic and allotypic variation of human class II histocompatibility antigen alpha-chain genes."
Auffray C., Lillie J.W., Arnot D., Grossberger D., Kappes D., Strominger J.L.
Nature 308:327-333(1984) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (CLONE LAMBDA DCH-10).
[3]"Structure and expression of HLA-DQ alpha and -DX alpha genes: interallelic alternate splicing of the HLA-DQ alpha gene and functional splicing of the HLA-DQ alpha gene using a retroviral vector."
Auffray C., Lillie J.W., Korman A.J., Boss J.M., Frechin N., Guillemot F., Cooper J., Mulligan R.C., Strominger J.L.
Immunogenetics 26:63-73(1987) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]"The DNA sequence and analysis of human chromosome 6."
Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., Andrews T.D. expand/collapse author list , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S.
Nature 425:805-811(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANTS ALA-227 AND ASP-247.
[5]"Limited polymorphism of the HLA-DQA2 promoter and identification of a variant octamer."
Rudy G., Lew A.M.
Hum. Immunol. 39:225-229(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-13.
[6]"Ancient roots for polymorphism at the HLA-DQ alpha locus in primates."
Gyllensten U.B., Erlich H.A.
Proc. Natl. Acad. Sci. U.S.A. 86:9986-9990(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 41-103.
[7]"The nonpolymorphic MHC class II isotype, HLA-DQA2, is expressed on the surface of B lymphoblastoid cells."
Rudy G.B., Lew A.M.
J. Immunol. 158:2116-2125(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY.
[8]"Invariant chain structure and MHC class II function."
Cresswell P.
Cell 84:505-507(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
[9]"Presentation of antigens by MHC class II molecules: getting the most out of them."
Villadangos J.A.
Mol. Immunol. 38:329-346(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
[10]"MHC class II molecules on the move for successful antigen presentation."
Rocha N., Neefjes J.
EMBO J. 27:1-5(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
[11]"Autophagy in MHC class II presentation: sampling from within."
Menendez-Benito V., Neefjes J.
Immunity 26:1-3(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
[12]"MHC class II transport at a glance."
Berger A.C., Roche P.A.
J. Cell Sci. 122:1-4(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
[13]"CD74 in antigen presentation, inflammation, and cancers of the gastrointestinal tract."
Beswick E.J., Reyes V.E.
World J. Gastroenterol. 15:2855-2861(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
[14]"HLA-DQA2 and HLA-DQB2 genes are specifically expressed in human Langerhans cells and encode a new HLA class II molecule."
Lenormand C., Bausinger H., Gross F., Signorino-Gelo F., Koch S., Peressin M., Fricker D., Cazenave J.P., Bieber T., Hanau D., de la Salle H., Tourne S.
J. Immunol. 188:3903-3911(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH CD74; HLA-DMA; HLA-DQB1 AND HLA-DQB2, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M29615, M29614 Genomic DNA. Translation: AAA59834.1.
X00453 expand/collapse EMBL AC list , 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.
CCDSCCDS4753.1.
PIRHLHUDX. A02210.
I54439.
RefSeqNP_064440.1. NM_020056.4.
UniGeneHs.591798.

3D structure databases

ProteinModelPortalP01906.
SMRP01906. Positions 25-208.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid109363. 1 interaction.
STRING9606.ENSP00000391434.

Chemistry

DrugBankDB00047. Insulin Glargine recombinant.
DB00046. Insulin Lyspro recombinant.
DB00030. Insulin recombinant.
DB00071. Insulin, porcine.

PTM databases

PhosphoSiteP01906.

Polymorphism databases

DMDM122192.

Proteomic databases

MaxQBP01906.
PaxDbP01906.
PRIDEP01906.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000241802; ENSP00000241802; ENSG00000206301.
ENST00000374940; ENSP00000364076; ENSG00000237541.
ENST00000415898; ENSP00000400695; ENSG00000231526.
ENST00000443184; ENSP00000405833; ENSG00000204276.
ENST00000446482; ENSP00000390725; ENSG00000225103.
ENST00000447735; ENSP00000393431; ENSG00000223793.
ENST00000449560; ENSP00000401098; ENSG00000233192.
ENST00000453672; ENSP00000387768; ENSG00000231823.
ENST00000546801; ENSP00000447668; ENSG00000233192.
ENST00000551533; ENSP00000448003; ENSG00000223793.
GeneID3118.
KEGGhsa:3118.
UCSCuc003obx.3. human.

Organism-specific databases

CTD3118.
GeneCardsGC06P032709.
GC06Pi32694.
GC06Pj32632.
GC06Pk32688.
GC06Pl32862.
GC06Pm32742.
GC06Pn32637.
GC06Po32799.
H-InvDBHIX0058177.
HIX0166445.
HIX0166701.
HGNCHGNC:4943. HLA-DQA2.
HPAHPA010967.
MIM613503. gene.
neXtProtNX_P01906.
PharmGKBPA35067.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG26577.
HOGENOMHOG000112076.
InParanoidP01906.
KOK06752.
OMAVPEMALF.
OrthoDBEOG7C2R26.
PhylomeDBP01906.
TreeFamTF333797.

Enzyme and pathway databases

ReactomeREACT_6900. Immune System.

Gene expression databases

ArrayExpressP01906.
BgeeP01906.
CleanExHS_HLA-DQA2.
GenevestigatorP01906.

Family and domain databases

Gene3D2.60.40.10. 1 hit.
3.10.320.10. 1 hit.
InterProIPR007110. 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]
PfamPF07654. C1-set. 1 hit.
PF00993. MHC_II_alpha. 1 hit.
[Graphical view]
SMARTSM00407. IGc1. 1 hit.
SM00920. MHC_II_alpha. 1 hit.
[Graphical view]
SUPFAMSSF54452. SSF54452. 1 hit.
PROSITEPS50835. IG_LIKE. 1 hit.
PS00290. IG_MHC. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiHLA-DQA2.
GenomeRNAi3118.
NextBio12376.
PROP01906.
SOURCESearch...

Entry information

Entry nameDQA2_HUMAN
AccessionPrimary (citable) accession number: P01906
Secondary accession number(s): A2BF37 expand/collapse secondary AC list , B0V0E7, O19789, Q5SQ94, Q5SR04
Entry history
Integrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: February 1, 1991
Last modified: July 9, 2014
This is version 135 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 6

Human chromosome 6: entries, gene names and cross-references to MIM