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P05538 (DQB2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 130. 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·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
HLA class II histocompatibility antigen, DQ beta 2 chain
Alternative name(s):
HLA class II histocompatibility antigen, DX beta chain
MHC class II antigen DQB2
Gene names
Name:HLA-DQB2
Synonyms:HLA-DXB
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length268 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.15

Subunit structure

Heterodimer of an alpha and a beta subunit; also referred as MHC class II molecule. Dimer formation with HLA-DQA2, but not with HLA-DQA1, 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.15

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.15

Tissue specificity

Restricted to skin Langerhans cells (at protein level). Ref.15

Sequence similarities

Belongs to the MHC class II family.

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

Sequence caution

The sequence CAA60790.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

Ontologies

Keywords
   Biological processImmunity
   Cellular componentCell membrane
Endoplasmic reticulum
Endosome
Golgi apparatus
Lysosome
Membrane
MHC II
   Coding sequence diversityAlternative splicing
Polymorphism
   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.6. 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

Non-traceable author statement Ref.6. Source: UniProtKB

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

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.6. Source: UniProtKB

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P05538-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: P05538-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-4: Missing.
     221-257: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 3232
Chain33 – 268236HLA class II histocompatibility antigen, DQ beta 2 chain
PRO_0000018992

Regions

Topological domain33 – 229197Extracellular Potential
Transmembrane230 – 25021Helical; Potential
Topological domain251 – 26818Cytoplasmic Potential
Domain128 – 21689Ig-like C1-type
Region33 – 12694Beta-1
Region127 – 229103Beta-2

Amino acid modifications

Glycosylation511N-linked (GlcNAc...) Potential
Disulfide bond47 ↔ 110 By similarity
Disulfide bond148 ↔ 204 By similarity

Natural variations

Alternative sequence1 – 44Missing in isoform 2.
VSP_045914
Alternative sequence221 – 25737Missing in isoform 2.
VSP_045915
Natural variant1611R → Q. Ref.4 Ref.15
Corresponds to variant rs1049110 [ dbSNP | Ensembl ].
VAR_069445
Natural variant2321S → G. Ref.15
VAR_069446
Natural variant2341I → V. Ref.15
VAR_069447

Experimental info

Sequence conflict1061V → L in AAA52667. Ref.6
Sequence conflict1061V → L in AAA52668. Ref.6
Sequence conflict1061V → L in AAA52669. Ref.6
Sequence conflict1061V → L in AAA52670. Ref.6
Sequence conflict266 – 2683LLH → HLL in CAA60790. Ref.2

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified February 1, 1991. Version 2.
Checksum: 2746ED6CC5D44AF2

FASTA26830,387
        10         20         30         40         50         60 
MSWKMALQIP GGFWAAAVTV MLVMLSTPVA EARDFPKDFL VQFKGMCYFT NGTERVRGVA 

        70         80         90        100        110        120 
RYIYNREEYG RFDSDVGEFQ AVTELGRSIE DWNNYKDFLE QERAAVDKVC RHNYEAELRT 

       130        140        150        160        170        180 
TLQRQVEPTV TISPSRTEAL NHHNLLVCSV TDFYPAQIKV RWFRNDQEET AGVVSTSLIR 

       190        200        210        220        230        240 
NGDWTFQILV MLEITPQRGD IYTCQVEHPS LQSPITVEWR AQSESAQSKM LSGIGGFVLG 

       250        260 
LIFLGLGLII RHRGQKGPRG PPPAGLLH 

« Hide

Isoform 2 [UniParc].

Checksum: B03817F038B6371F
Show »

FASTA22726,031

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]"Evolutionary dynamics of non-coding sequences within the class II region of the human MHC."
Beck S., Abdulla S., Alderton R.P., Glynne R.J., Gut I.G., Hosking L.K., Jackson A., Kelly A., Newell W.R., Sanseau P., Radley E., Thorpe K.L., Trowsdale J.
J. Mol. Biol. 255:1-13(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]"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].
[4]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), VARIANT GLN-161.
Tissue: Squamous cell carcinoma.
[5]"Gene organization of DC and DX subregions of the human major histocompatibility complex."
Okada K., Boss J.M., Prentice H., Spies T., Mengler R., Auffray C., Lillie J.W., Grossberger D., Strominger J.L.
Proc. Natl. Acad. Sci. U.S.A. 82:3410-3414(1985) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 38-125.
[6]"Remarkable sequence conservation of the HLA-DQB2 locus (DX beta) within the highly polymorphic DQ subregion of the human MHC."
Berdoz J., Tiercy J.-M., Rollini P., Mach B., Gorski J.
Immunogenetics 29:241-248(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 38-125.
[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: LACK OF EXPRESSION.
[8]"Absence of in vivo DNA-protein interactions in the DQA2 and DQB2 promoter regions."
Indovina P., Megiorni F., Fontemaggi G., Coni P., Mora B., Mazzilli M.C.
Hum. Immunol. 62:504-508(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: LACK OF EXPRESSION.
[9]"Invariant chain structure and MHC class II function."
Cresswell P.
Cell 84:505-507(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
[10]"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.
[11]"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.
[12]"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.
[13]"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.
[14]"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.
[15]"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-DQA1 AND HLA-DQA2, VARIANTS GLN-161; GLY-232 AND VAL-234, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M29614 Genomic DNA. No translation available.
M29615 Genomic DNA. No translation available.
X87344 Genomic DNA. Translation: CAA60790.1. Different initiation.
AL671681 Genomic DNA. No translation available.
AL672104 Genomic DNA. No translation available.
AL713890 Genomic DNA. No translation available.
BX296564 Genomic DNA. Translation: CAM26036.1.
CR936921 Genomic DNA. Translation: CAQ07315.1.
BC031995 mRNA. No translation available.
M11136 Genomic DNA. No translation available.
M24920 Genomic DNA. Translation: AAA52667.1.
M24921 Genomic DNA. Translation: AAA52668.1.
M24922 Genomic DNA. Translation: AAA52669.1.
M24923 Genomic DNA. Translation: AAA52670.1.
PIRD29312.
G35058.
RefSeqNP_001185787.1. NM_001198858.1.
UniGeneHs.731563.

3D structure databases

ProteinModelPortalP05538.
SMRP05538. Positions 36-223.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING9606.ENSP00000409159.

Polymorphism databases

DMDM122271.

Proteomic databases

PaxDbP05538.
PRIDEP05538.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000399661; ENSP00000382569; ENSG00000196610.
ENST00000411527; ENSP00000390431; ENSG00000232629. [P05538-2]
ENST00000426733; ENSP00000393969; ENSG00000226165. [P05538-2]
ENST00000430849; ENSP00000389067; ENSG00000228813.
ENST00000432486; ENSP00000410132; ENSG00000228254.
ENST00000438757; ENSP00000408884; ENSG00000224305. [P05538-2]
ENST00000456529; ENSP00000399594; ENSG00000230675. [P05538-2]
ENST00000457432; ENSP00000396502; ENSG00000229493.
GeneID3120.
KEGGhsa:3120.
UCSCuc003oby.4. human.

Organism-specific databases

CTD3120.
GeneCardsGC06M032728.
GC06Mi32708.
GC06Mj32647.
GC06Mk32703.
GC06Ml32877.
GC06Mm32757.
GC06Mn32652.
GC06Mo32814.
H-InvDBHIX0165918.
HIX0166089.
HIX0166694.
HIX0167203.
HGNCHGNC:4945. HLA-DQB2.
MIM615161. gene.
neXtProtNX_P05538.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG68200.
PhylomeDBP05538.
TreeFamTF336626.

Enzyme and pathway databases

ReactomeREACT_6900. Immune System.

Gene expression databases

ArrayExpressP05538.
GenevestigatorP05538.

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.
IPR000353. MHC_II_b_N.
[Graphical view]
PfamPF07654. C1-set. 1 hit.
PF00969. MHC_II_beta. 1 hit.
[Graphical view]
ProDomPD000328. MHC_II_b_N. 1 hit.
[Graphical view] [Entries sharing at least one domain]
SMARTSM00407. IGc1. 1 hit.
SM00921. MHC_II_beta. 1 hit.
[Graphical view]
SUPFAMSSF54452. SSF54452. 1 hit.
PROSITEPS50835. IG_LIKE. 1 hit.
PS00290. IG_MHC. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiHLA-DQB2.
GenomeRNAi3120.
NextBio12384.
PROP05538.
SOURCESearch...

Entry information

Entry nameDQB2_HUMAN
AccessionPrimary (citable) accession number: P05538
Secondary accession number(s): A6NIA5 expand/collapse secondary AC list , Q29826, Q29870, Q29871, Q29872, Q29873, Q5SR06
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1988
Last sequence update: February 1, 1991
Last modified: April 16, 2014
This is version 130 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