P01906 (DQA2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:	HLA-DQA2
Synonyms:	HLA-DXA

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	255 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at transcript 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 accomodates 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 an 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 miroenvironment has been implicated in the regulation of antigen loading into MHC II molecules, increased acidification produces increased proteolysis and efficient peptide loading.
Subunit structure	Heterodimer of an alpha and a beta subunit; also referred as MHC class II molecule. In the endoplasmic reticulum (ER) it forms an 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.
Subcellular location	Cell membrane; Single-pass type I membrane protein. Endoplasmic reticulum membrane; Single-pass type I membrane protein. Golgi apparatus › trans-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.
Tissue specificity	Expressed at low levels at the surface of B lymphoblastoid cells. Ref.7
Sequence similarities	Belongs to the MHC class II family. Contains 1 Ig-like C1-type (immunoglobulin-like) domain.
Caution	There is some controversy on whether this gene is really expressed or not.

Ontologies

Keywords
Biological process	Immunity
Cellular component	Cell membrane Endoplasmic reticulum Endosome Golgi apparatus Lysosome MHC II Membrane
Coding sequence diversity	Polymorphism
Domain	Signal Transmembrane Transmembrane helix
PTM	Disulfide bond Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	T cell costimulation Traceable author statement. Source: Reactome T cell receptor signaling pathway Traceable author statement. Source: Reactome antigen processing and presentation of peptide or polysaccharide antigen via MHC class II Inferred from electronic annotation. Source: UniProtKB-KW interferon-gamma-mediated signaling pathway Traceable author statement. Source: Reactome
Cellular component	Golgi apparatus Inferred from electronic annotation. Source: UniProtKB-SubCell MHC class II protein complex Inferred from electronic annotation. Source: UniProtKB-KW endoplasmic reticulum membrane Inferred from electronic annotation. Source: UniProtKB-SubCell endosome membrane Inferred from electronic annotation. Source: UniProtKB-SubCell integral to plasma membrane Non-traceable author statement Ref.1. Source: UniProtKB lysosomal membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	MHC class II receptor activity Non-traceable author statement Ref.1. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 23	23
	Chain	24 – 255	232	HLA class II histocompatibility antigen, DQ alpha 2 chain		PRO_0000018973
Regions
	Topological domain	24 – 217	194	Extracellular Potential
	Transmembrane	218 – 240	23	Helical; Potential
	Topological domain	241 – 255	15	Cytoplasmic Potential
	Domain	113 – 205	93	Ig-like C1-type
	Region	24 – 110	87	Alpha-1
	Region	111 – 204	94	Alpha-2
	Region	205 – 217	13	Connecting peptide
Amino acid modifications
	Glycosylation	104	1	N-linked (GlcNAc...) Potential
	Glycosylation	144	1	N-linked (GlcNAc...) Potential
	Disulfide bond	133 ↔ 189		By similarity
Natural variations
	Natural variant	227	1	V → A. Ref.4 Corresponds to variant rs9276436 [ dbSNP | Ensembl ].		VAR_033431
	Natural variant	247	1	G → D. Ref.4 Corresponds to variant rs2071800 [ dbSNP | Ensembl ].		VAR_050392
Experimental info
	Sequence conflict	84	1	S → T in AAA59834. Ref.1
	Sequence conflict	101	1	R → G in CAM26196. Ref.4
	Sequence conflict	101	1	R → G in CAM26195. Ref.4

Sequences

	Sequence		Length	Mass (Da)
	P01906 [UniParc]. Last modified February 1, 1991. Version 2. Checksum: 85B13D9FDF2905FE	FASTA	255	28,033
	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

References

	« Hide 'large scale' referencesShow '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: 3036828] [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: 6584734] [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: 3610256] [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. , 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: 14574404] [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: 8026991] [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: 2513578] [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: 9036956] [Abstract] Cited for: TISSUE SPECIFICITY.
[8]	"Invariant chain structure and MHC class II function." Cresswell P. Cell 84:505-507(1996) [PubMed: 8598037] [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: 11684289] [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: 18046453] [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: 17241953] [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: 19092054] [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: 19533806] [Abstract] Cited for: REVIEW.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	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.
IPI	IPI00005172.
PIR	HLHUDX. A02210. I54439.
RefSeq	NP_064440.1. NM_020056.4.
UniGene	Hs.591798.
3D structure databases
ProteinModelPortal	P01906.
SMR	P01906. Positions 25-206.
ModBase	Search...
Protein-protein interaction databases
STRING	P01906.
Polymorphism databases
DMDM	122192.
Proteomic databases
PRIDE	P01906.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000374940; ENSP00000364076; ENSG00000237541. ENST00000425418; ENSP00000410573; ENSG00000233192. ENST00000443184; ENSP00000405833; ENSG00000204276. ENST00000445162; ENSP00000391434; ENSG00000223793. ENST00000447735; ENSP00000393431; ENSG00000223793. ENST00000449560; ENSP00000401098; ENSG00000233192.
GeneID	3118.
KEGG	hsa:3118.
UCSC	uc003obx.1. human.
Organism-specific databases
CTD	3118.
GeneCards	GC06P032709.
HGNC	HGNC:4943. HLA-DQA2.
HPA	HPA010967.
MIM	613503. gene.
neXtProt	NX_P01906.
PharmGKB	PA35067.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	HBG282567.
InParanoid	P01906.
OMA	TVFSKFP.
OrthoDB	EOG4KWJTP.
PhylomeDB	P01906.
Enzyme and pathway databases
Reactome	REACT_6900. Immune System.
Gene expression databases
CleanEx	HS_HLA-DQA2.
Genevestigator	P01906.
GermOnline	ENSG00000204276. Homo sapiens.
Family and domain databases
InterPro	IPR007110. Ig-like. 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]
Gene3D	G3DSA:2.60.40.10. Ig-like_fold. 1 hit. G3DSA:3.10.320.10. MHC_II_alpha_N. 1 hit.
KO	K06752.
Pfam	PF07654. C1-set. 1 hit. PF00993. MHC_II_alpha. 1 hit. [Graphical view]
SMART	SM00407. IGc1. 1 hit. SM00920. MHC_II_alpha. 1 hit. [Graphical view]
SUPFAM	SSF54452. MHC_I/II-like_Ag-recog. 1 hit.
PROSITE	PS50835. IG_LIKE. 1 hit. PS00290. IG_MHC. 1 hit. [Graphical view]
ProtoNet	Search...
Other
DrugBank	DB00047. Insulin Glargine recombinant. DB00046. Insulin Lyspro recombinant. DB00030. Insulin recombinant. DB00071. Insulin, porcine.
NextBio	12376.
SOURCE	Search...

Entry information

Entry name

DQA2_HUMAN

Accession

Primary (citable) accession number: P01906
Secondary accession number(s): A2BF37 , B0V0E7, O19789, Q5SQ94, Q5SR04

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 21, 1986
Last sequence update:	February 1, 1991
Last modified:	January 25, 2012
This is version 112 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.