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Protein

HLA class II histocompatibility antigen, DQ beta 2 chain

Gene

HLA-DQB2

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
SIGNORiP05538

Names & Taxonomyi

Protein namesi
Recommended 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 namesi
Name:HLA-DQB2
Synonyms:HLA-DXB
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 6

Organism-specific databases

EuPathDBiHostDB:ENSG00000232629.8
HGNCiHGNC:4945 HLA-DQB2
MIMi615161 gene
neXtProtiNX_P05538

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 domaini33 – 229ExtracellularSequence analysisAdd BLAST197
Transmembranei230 – 250HelicalSequence analysisAdd BLAST21
Topological domaini251 – 268CytoplasmicSequence analysisAdd BLAST18

Keywords - Cellular componenti

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

Pathology & Biotechi

Organism-specific databases

DisGeNETi3120
OpenTargetsiENSG00000232629

Polymorphism and mutation databases

BioMutaiHLA-DQB2
DMDMi122271

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 32Add BLAST32
ChainiPRO_000001899233 – 268HLA class II histocompatibility antigen, DQ beta 2 chainAdd BLAST236

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi47 ↔ 110PROSITE-ProRule annotation
Glycosylationi51N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi148 ↔ 204PROSITE-ProRule annotation

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PeptideAtlasiP05538
PRIDEiP05538
ProteomicsDBi51844

PTM databases

iPTMnetiP05538
PhosphoSitePlusiP05538

Expressioni

Tissue specificityi

Restricted to skin Langerhans cells (at protein level).1 Publication

Gene expression databases

BgeeiENSG00000232629 Expressed in 120 organ(s), highest expression level in skin of abdomen
ExpressionAtlasiP05538 baseline and differential
GenevisibleiP05538 HS

Interactioni

Subunit structurei

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.1 Publication

Protein-protein interaction databases

BioGridi109365, 9 interactors

Structurei

3D structure databases

ProteinModelPortaliP05538
SMRiP05538
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini128 – 216Ig-like C1-typeAdd BLAST89

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni33 – 126Beta-1Add BLAST94
Regioni127 – 229Beta-2Add BLAST103

Sequence similaritiesi

Belongs to the MHC class II family.Curated

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

GeneTreeiENSGT00900000140849
HOGENOMiHOG000100909
HOVERGENiHBG012730
InParanoidiP05538
PhylomeDBiP05538
TreeFamiTF336626

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
IPR000353 MHC_II_b_N
PfamiView protein in Pfam
PF07654 C1-set, 1 hit
PF00969 MHC_II_beta, 1 hit
ProDomiView protein in ProDom or Entries sharing at least one domain
PD000328 MHC_II_b_N, 1 hit
SMARTiView protein in SMART
SM00407 IGc1, 1 hit
SM00921 MHC_II_beta, 1 hit
SUPFAMiSSF48726 SSF48726, 1 hit
SSF54452 SSF54452, 1 hit
PROSITEiView protein in PROSITE
PS50835 IG_LIKE, 1 hit
PS00290 IG_MHC, 1 hit

Sequences (2+)i

Sequence statusi: Complete.

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

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 2 described isoforms and 12 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: P05538-1) [UniParc]FASTAAdd to basket

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.

« Hide
        10         20         30         40         50
MSWKMALQIP GGFWAAAVTV MLVMLSTPVA EARDFPKDFL VQFKGMCYFT
60 70 80 90 100
NGTERVRGVA RYIYNREEYG RFDSDVGEFQ AVTELGRSIE DWNNYKDFLE
110 120 130 140 150
QERAAVDKVC RHNYEAELRT TLQRQVEPTV TISPSRTEAL NHHNLLVCSV
160 170 180 190 200
TDFYPAQIKV RWFRNDQEET AGVVSTSLIR NGDWTFQILV MLEITPQRGD
210 220 230 240 250
IYTCQVEHPS LQSPITVEWR AQSESAQSKM LSGIGGFVLG LIFLGLGLII
260
RHRGQKGPRG PPPAGLLH
Length:268
Mass (Da):30,387
Last modified:February 1, 1991 - v2
Checksum:i2746ED6CC5D44AF2
GO
Isoform 2 (identifier: P05538-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-4: Missing.
     221-257: Missing.

Note: No experimental confirmation available.
Show »
Length:227
Mass (Da):26,031
Checksum:iB03817F038B6371F
GO

Computationally mapped potential isoform sequencesi

There are 12 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A2ADX3A2ADX3_HUMAN
HLA class II histocompatibility ant...
HLA-DQB2
275Annotation score:
Q5SR05Q5SR05_HUMAN
HLA class II histocompatibility ant...
HLA-DQB2
264Annotation score:
A0A0G2JH31A0A0G2JH31_HUMAN
HLA class II histocompatibility ant...
HLA-DQB2
279Annotation score:
H0Y7Y7H0Y7Y7_HUMAN
HLA class II histocompatibility ant...
HLA-DQB2
218Annotation score:
Q5SQ91Q5SQ91_HUMAN
HLA class II histocompatibility ant...
HLA-DQB2
231Annotation score:
A0A140T9H0A0A140T9H0_HUMAN
HLA class II histocompatibility ant...
HLA-DQB2
218Annotation score:
A0A140T999A0A140T999_HUMAN
HLA class II histocompatibility ant...
HLA-DQB2
218Annotation score:
A0A140T9S2A0A140T9S2_HUMAN
HLA class II histocompatibility ant...
HLA-DQB2
218Annotation score:
A0A140T9J1A0A140T9J1_HUMAN
HLA class II histocompatibility ant...
HLA-DQB2
218Annotation score:
A0A140T9U9A0A140T9U9_HUMAN
HLA class II histocompatibility ant...
HLA-DQB2
218Annotation score:
There are more potential isoformsShow all

Sequence cautioni

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

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti106V → L in AAA52667 (PubMed:2564844).Curated1
Sequence conflicti106V → L in AAA52668 (PubMed:2564844).Curated1
Sequence conflicti106V → L in AAA52669 (PubMed:2564844).Curated1
Sequence conflicti106V → L in AAA52670 (PubMed:2564844).Curated1
Sequence conflicti266 – 268LLH → HLL in CAA60790 (PubMed:8568858).Curated3

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_069445161R → Q2 PublicationsCorresponds to variant dbSNP:rs1049110Ensembl.1
Natural variantiVAR_069446232S → G1 Publication1
Natural variantiVAR_069447234I → V1 Publication1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0459141 – 4Missing in isoform 2. 1 Publication4
Alternative sequenceiVSP_045915221 – 257Missing in isoform 2. 1 PublicationAdd BLAST37

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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 No translation available.
CR936921 Genomic DNA No translation available.
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
CCDSiCCDS56419.1 [P05538-2]
PIRiD29312
G35058
RefSeqiNP_001185787.1, NM_001198858.1 [P05538-2]
UniGeneiHs.731563

Genome annotation databases

EnsembliENST00000399661; 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
GeneIDi3120
KEGGihsa:3120
UCSCiuc003oby.5 human [P05538-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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 No translation available.
CR936921 Genomic DNA No translation available.
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
CCDSiCCDS56419.1 [P05538-2]
PIRiD29312
G35058
RefSeqiNP_001185787.1, NM_001198858.1 [P05538-2]
UniGeneiHs.731563

3D structure databases

ProteinModelPortaliP05538
SMRiP05538
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi109365, 9 interactors

PTM databases

iPTMnetiP05538
PhosphoSitePlusiP05538

Polymorphism and mutation databases

BioMutaiHLA-DQB2
DMDMi122271

Proteomic databases

PeptideAtlasiP05538
PRIDEiP05538
ProteomicsDBi51844

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000399661; 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
GeneIDi3120
KEGGihsa:3120
UCSCiuc003oby.5 human [P05538-1]

Organism-specific databases

CTDi3120
DisGeNETi3120
EuPathDBiHostDB:ENSG00000232629.8
GeneCardsiHLA-DQB2
H-InvDBiHIX0165918
HIX0166089
HIX0166694
HIX0167203
HGNCiHGNC:4945 HLA-DQB2
MIMi615161 gene
neXtProtiNX_P05538
OpenTargetsiENSG00000232629
GenAtlasiSearch...

Phylogenomic databases

GeneTreeiENSGT00900000140849
HOGENOMiHOG000100909
HOVERGENiHBG012730
InParanoidiP05538
PhylomeDBiP05538
TreeFamiTF336626

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
SIGNORiP05538

Miscellaneous databases

ChiTaRSiHLA-DQB2 human
GeneWikiiHLA-DQB2
GenomeRNAii3120
PROiPR:P05538
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000232629 Expressed in 120 organ(s), highest expression level in skin of abdomen
ExpressionAtlasiP05538 baseline and differential
GenevisibleiP05538 HS

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
IPR000353 MHC_II_b_N
PfamiView protein in Pfam
PF07654 C1-set, 1 hit
PF00969 MHC_II_beta, 1 hit
ProDomiView protein in ProDom or Entries sharing at least one domain
PD000328 MHC_II_b_N, 1 hit
SMARTiView protein in SMART
SM00407 IGc1, 1 hit
SM00921 MHC_II_beta, 1 hit
SUPFAMiSSF48726 SSF48726, 1 hit
SSF54452 SSF54452, 1 hit
PROSITEiView protein in PROSITE
PS50835 IG_LIKE, 1 hit
PS00290 IG_MHC, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiDQB2_HUMAN
AccessioniPrimary (citable) accession number: P05538
Secondary accession number(s): A6NIA5
, Q29826, Q29870, Q29871, Q29872, Q29873, Q5SR06
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1988
Last sequence update: February 1, 1991
Last modified: October 10, 2018
This is version 164 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. SIMILARITY comments
    Index of protein domains and families
  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. Human chromosome 6
    Human chromosome 6: entries, gene names and cross-references to MIM
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Main funding by: National Institutes of Health

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