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Gene Expression
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HLA-DRB1 (P04229) - Overview - Molecular Target Synopsis


HLA-DRB1, HLA class II histocompatibility antigen, DRB1-1 beta chain
UniProt P04229

Also Known as 2B11_HUMAN, HLA-DRB1

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., (Microbial infection) Acts as a receptor for Epstein-Barr virus on lymphocytes. 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. (Microbial infection) Interacts with Epstein-Barr virus gp42 protein (PubMed:11864610, PubMed:9151859).

4C56 deposition date (2013-09-10)
Inspect Structure
See all 3D Structures for HLA-DRB1

Isoforms / Transcripts (Protein Coding)

Protein Length Ensembl Gene Ensembl Transcript Ensembl Protein Uniprot Isoform


HLA-DRB1 is targeted by Approved Drug N/A. (see details)

Sub-cellular localization

UniProt: HLA-DRB1 is active in the following subcellular-locations: Cell membrane, Endoplasmic reticulum membrane, Endosome membrane, Golgi apparatus, Late endosome membrane, Lysosome membrane, trans-Golgi network membrane.
GO terms: HLA-DRB1 is active in the following subcellular-locations: clathrin-coated endocytic vesicle membrane, endocytic vesicle membrane, ER to Golgi transport vesicle membrane, external side of plasma membrane, extracellular exosome, Golgi membrane, integral component of lumenal side of endoplasmic reticulum membrane, late endosome membrane, lysosomal membrane, MHC class II protein complex, plasma membrane, trans-Golgi network membrane, transport vesicle membrane.

GO terms

Mutations in Cancer

Please click the link to see mutations reported in COSMIC - Cell Lines Project
Please click the link to see mutations reported in COSMIC
Please click the link to see mutations reported in Cancer Gene Census
Please click the link to see mutations reported in ICGC
(see details)

3D Structures

There are 42 structures (69 chains) solved for HLA-DRB1
1 are solved in complex with at least one small molecule ligand

(see details)
Molecular Target 3D Synopsis

Screening and Chemistry

HLA-DRB1 has been screened with 53 compounds (115 bioactivities), 34 compounds have bioactivities that show binding affinity of <= 500nM (52 bioactivities). (see details)