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Protein

HLA class II histocompatibility antigen, DRB1-11 beta chain

Gene

HLA-DRB1

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.

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

Names & Taxonomyi

Protein namesi
Recommended name:
HLA class II histocompatibility antigen, DRB1-11 beta chain
Alternative name(s):
DR-5
Short name:
DR5
DRw11
MHC class II antigen DRB1*11
Gene namesi
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 6

Organism-specific databases

HGNCiHGNC:4948 HLA-DRB1
MIMi142857 gene
neXtProtiNX_P20039

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 domaini30 – 227ExtracellularSequence analysisAdd BLAST198
Transmembranei228 – 250HelicalSequence analysisAdd BLAST23
Topological domaini251 – 266CytoplasmicSequence analysisAdd BLAST16

Keywords - Cellular componenti

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

Pathology & Biotechi

Organism-specific databases

DisGeNETi3123
MalaCardsiHLA-DRB1
MIMi609532 phenotype

Chemistry databases

ChEMBLiCHEMBL3988561

Polymorphism and mutation databases

DMDMi122254

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 29Add BLAST29
ChainiPRO_000001895530 – 266HLA class II histocompatibility antigen, DRB1-11 beta chainAdd BLAST237

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi44 ↔ 108PROSITE-ProRule annotation
Glycosylationi48N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi146 ↔ 202PROSITE-ProRule annotation
Cross-linki254Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication

Post-translational modificationi

Ubiquitinated by MARCH1 and MARCH8 at Lys-254 leading to sorting into the endosome system and down-regulation of MHC class II.1 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein, Isopeptide bond, Ubl conjugation

Proteomic databases

MaxQBiP20039
PeptideAtlasiP20039
PRIDEiP20039

PTM databases

GlyConnecti1370
iPTMnetiP20039

Expressioni

Gene expression databases

CleanExiHS_HLA-DRB1

Organism-specific databases

HPAiHPA043151

Interactioni

Subunit structurei

Heterodimer of an alpha and a beta subunit; also referred as MHC class II molecule. In the endoplasmic reticulum (ER) it 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.

Protein-protein interaction databases

IntActiP20039, 1 interactor

Structurei

Secondary structure

1266
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliP20039
SMRiP20039
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini126 – 214Ig-like C1-typeAdd BLAST89

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni30 – 124Beta-1Add BLAST95
Regioni125 – 227Beta-2Add BLAST103

Sequence similaritiesi

Belongs to the MHC class II family.Curated

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

HOVERGENiHBG012730

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

Sequence (1+)i

Sequence statusi: Complete.

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

This entry has 1 described isoform and 13 potential isoforms that are computationally mapped.Show allAlign All

P20039-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MVCLRLPGGS CMAVLTVTLM VLSSPLALAG DTRPRFLEYS TSECHFFNGT
60 70 80 90 100
ERVRFLDRYF YNQEEYVRFD SDVGEFRAVT ELGRPDEEYW NSQKDFLEDR
110 120 130 140 150
RAAVDTYCRH NYGVGESFTV QRRVHPKVTV YPSKTQPLQH HNLLVCSVSG
160 170 180 190 200
FYPGSIEVRW FRNGQEEKTG VVSTGLIHNG DWTFQTLVML ETVPRSGEVY
210 220 230 240 250
TCQVEHPSVT SPLTVEWRAR SESAQSKMLS GVGGFVLGLL FLGAGLFIYF
260
RNQKGHSGLQ PRGFLS
Length:266
Mass (Da):30,160
Last modified:February 1, 1991 - v1
Checksum:i6CFC0D44391B1059
GO

Computationally mapped potential isoform sequencesi

There are 13 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
P137602B14_HUMAN
HLA class II histocompatibility ant...
HLA-DRB1
266Annotation score:
P042292B11_HUMAN
HLA class II histocompatibility ant...
HLA-DRB1
266Annotation score:
Q9GIY32B1E_HUMAN
HLA class II histocompatibility ant...
HLA-DRB1
266Annotation score:
P137612B17_HUMAN
HLA class II histocompatibility ant...
HLA-DRB1
266Annotation score:
Q5Y7A72B1D_HUMAN
HLA class II histocompatibility ant...
HLA-DRB1
266Annotation score:
P019112B1F_HUMAN
HLA class II histocompatibility ant...
HLA-DRB1 HLA-DRB2
266Annotation score:
P019122B13_HUMAN
HLA class II histocompatibility ant...
HLA-DRB1
266Annotation score:
Q299742B1G_HUMAN
HLA class II histocompatibility ant...
HLA-DRB1
266Annotation score:
Q9TQE02B19_HUMAN
HLA class II histocompatibility ant...
HLA-DRB1
266Annotation score:
Q95IE32B1C_HUMAN
HLA class II histocompatibility ant...
HLA-DRB1
266Annotation score:
There are more potential isoformsShow all

Polymorphismi

The following alleles of DRB1-11 are known: DRB1*11:01, DRB1*11:03, DRB1*11:04, DRB1*11:05, DRB1*11:06, DRB1*11:07, DRB1*11:08, DRB1*11:09, DRB1*11:10, DRB1*11:11, DRB1*11:12, DRB1*11:13, DRB1*11:14, DRB1*11:15, DRB1*11:16, DRB1*11:17, DRB1*11:18, DRB1*11:19, DRB1*11:20, DRB1*11:21, DRB1*11:22, DRB1*11:23, DRB1*11:24, DRB1*11:25, DRB1*11:26, DRB1*11:27, DRB1*11:28, DRB1*11:29, DRB1*11:30, DRB1*11:31, DRB1*11:32, DRB1*11:33, DRB1*11:34, DRB1*11:35, DRB1*11:36, DRB1*11:37, DRB1*11:38, DRB1*11:39, DRB1*11:40, DRB1*11:41, DRB1*11:42, DRB1*11:43, DRB1*11:44, DRB1*11:45, DRB1*11:46, DRB1*11:47, DRB1*11:48, DRB1*11:49, DRB1*11:50, DRB1*11:51, DRB1*11:52, DRB1*11:53, DRB1*11:54, DRB1*11:55, DRB1*11:56, DRB1*11:57, DRB1*11:58, DRB1*11:59, DRB1*11:60, DRB1*11:61, DRB1*11:62, DRB1*11:63, DRB1*11:64, DRB1*11:65, DRB1*11:66, DRB1*11:67, DRB1*11:68, DRB1*11:69, DRB1*11:70 and DRB1*11:72. The sequence shown is that of DRB1*11:01.
Allele DRB1*11:01 is associated with self-limiting hepatitis C virus (HCV) infections [MIMi:609532].

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_05654255F → Y. Corresponds to variant dbSNP:rs1059569Ensembl.1
Natural variantiVAR_016717100R → E in allele DRB1*11:03; requires 2 nucleotide substitutions. 1
Natural variantiVAR_016718115G → V in allele DRB1*11:03 and allele DRB1*11:04. 1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M11867 mRNA Translation: AAA36274.1
M22050
, M21966, M22047, M22048, M22049 Genomic DNA Translation: AAA59713.1
AJ297587 mRNA Translation: CAC08827.1
PIRiA25324
F60748
I54448
PH0153
UniGeneiHs.534322
Hs.696211
Hs.736560

Genome annotation databases

EnsembliENST00000328980; ENSP00000331343; ENSG00000206306
ENST00000399450; ENSP00000382378; ENSG00000206240

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M11867 mRNA Translation: AAA36274.1
M22050
, M21966, M22047, M22048, M22049 Genomic DNA Translation: AAA59713.1
AJ297587 mRNA Translation: CAC08827.1
PIRiA25324
F60748
I54448
PH0153
UniGeneiHs.534322
Hs.696211
Hs.736560

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
6CPLX-ray2.45B30-219[»]
6CPNX-ray2.00B30-219[»]
6CQLX-ray2.40B30-219[»]
6CQNX-ray2.50B30-219[»]
ProteinModelPortaliP20039
SMRiP20039
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiP20039, 1 interactor

Chemistry databases

ChEMBLiCHEMBL3988561

PTM databases

GlyConnecti1370
iPTMnetiP20039

Polymorphism and mutation databases

DMDMi122254

Proteomic databases

MaxQBiP20039
PeptideAtlasiP20039
PRIDEiP20039

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000328980; ENSP00000331343; ENSG00000206306
ENST00000399450; ENSP00000382378; ENSG00000206240

Organism-specific databases

DisGeNETi3123
GeneCardsiHLA-DRB1
HGNCiHGNC:4948 HLA-DRB1
HPAiHPA043151
MalaCardsiHLA-DRB1
MIMi142857 gene
609532 phenotype
neXtProtiNX_P20039
GenAtlasiSearch...

Phylogenomic databases

HOVERGENiHBG012730

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

ChiTaRSiHLA-DRB1 human
SOURCEiSearch...

Gene expression databases

CleanExiHS_HLA-DRB1

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 namei2B1B_HUMAN
AccessioniPrimary (citable) accession number: P20039
Secondary accession number(s): Q30006, Q9GIX8
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 1, 1991
Last sequence update: February 1, 1991
Last modified: October 10, 2018
This is version 149 of the entry and version 1 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

3D-structure, 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. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. 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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