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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: Annotation score: 5 out of 5-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

Complete GO annotation...

Keywords - Biological processi

Immunity

Enzyme and pathway databases

BioCyciZFISH:G66-31731-MONOMER.
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.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini30 – 227ExtracellularSequence analysisAdd BLAST198
Transmembranei228 – 250HelicalSequence analysisAdd BLAST23
Topological domaini251 – 266CytoplasmicSequence analysisAdd BLAST16

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

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

Pathology & Biotechi

Organism-specific databases

MalaCardsiHLA-DRB1.
MIMi609532. phenotype.

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...)Sequence 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.

Expressioni

Gene expression databases

BgeeiENSG00000206240.
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.

Structurei

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.
InterProiIPR007110. 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]
PfamiPF07654. C1-set. 1 hit.
PF00969. MHC_II_beta. 1 hit.
[Graphical view]
ProDomiPD000328. MHC_II_b_N. 1 hit.
[Graphical view] [Entries sharing at least one domain]
SMARTiSM00407. IGc1. 1 hit.
SM00921. MHC_II_beta. 1 hit.
[Graphical view]
SUPFAMiSSF48726. SSF48726. 1 hit.
SSF54452. SSF54452. 1 hit.
PROSITEiPS50835. IG_LIKE. 1 hit.
PS00290. IG_MHC. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

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

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

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 rs16822516dbSNPEnsembl.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
Natural variantiVAR_056543236V → M.Corresponds to variant rs2230816dbSNPEnsembl.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

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

ProteinModelPortaliP20039.
SMRiP20039.
ModBaseiSearch...
MobiDBiSearch...

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

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

Phylogenomic databases

HOVERGENiHBG012730.

Enzyme and pathway databases

BioCyciZFISH:G66-31731-MONOMER.
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

BgeeiENSG00000206240.
CleanExiHS_HLA-DRB1.

Family and domain databases

Gene3Di2.60.40.10. 1 hit.
3.10.320.10. 1 hit.
InterProiIPR007110. 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]
PfamiPF07654. C1-set. 1 hit.
PF00969. MHC_II_beta. 1 hit.
[Graphical view]
ProDomiPD000328. MHC_II_b_N. 1 hit.
[Graphical view] [Entries sharing at least one domain]
SMARTiSM00407. IGc1. 1 hit.
SM00921. MHC_II_beta. 1 hit.
[Graphical view]
SUPFAMiSSF48726. SSF48726. 1 hit.
SSF54452. SSF54452. 1 hit.
PROSITEiPS50835. IG_LIKE. 1 hit.
PS00290. IG_MHC. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry namei2B1B_HUMAN
AccessioniPrimary (citable) accession number: P20039
Secondary accession number(s): Q30006, Q9GIX8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 1991
Last sequence update: February 1, 1991
Last modified: November 2, 2016
This is version 134 of the entry and version 1 of the sequence. [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. Human chromosome 6
    Human chromosome 6: entries, gene names and cross-references to MIM
  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. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.