HLA-DRB1 - HLA class II histocompatibility antigen, DRB1-15 beta chain - human protein (Function)
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HLA-DRB1 »  HLA class II histocompatibility antigen, DRB1-15 beta chain
Protein also known as:  MHC class II antigen DRB1*15.
Gene name:  HLA-DRB1
Family name: MHC class II
Entry whose protein(s) existence is based on evidence at protein level
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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.  
  • UniProtKB
GO molecular function 
MHC class II protein complex bindingdefinition[GO:0023026]  
  • UniProtKB
Peptide antigen bindingdefinition[GO:0042605]  
  • UniProtKB
GO biological process 
Polysaccharide assembly with MHC class II protein complexdefinition[GO:0002506]  
  • UniProtKB
According to KEGG, this protein belongs to the following pathways:
Allograft rejection  hsa05330+3123  
Antigen processing and presentation  hsa04612+3123  
Asthma  hsa05310+3123  
Autoimmune thyroid disease  hsa05320+3123  
Cell adhesion molecules (CAMs)  hsa04514+3123  
Graft-versus-host disease  hsa05332+3123  
Hematopoietic cell lineage  hsa04640+3123  
Herpes simplex infection  hsa05168+3123  
HTLV-I infection  hsa05166+3123  
Influenza A  hsa05164+3123  
Intestinal immune network for IgA production  hsa04672+3123  
Leishmaniasis  hsa05140+3123  
Phagosome  hsa04145+3123  
Rheumatoid arthritis  hsa05323+3123  
Staphylococcus aureus infection  hsa05150+3123  
Systemic lupus erythematosus  hsa05322+3123  
Toxoplasmosis  hsa05145+3123  
Tuberculosis  hsa05152+3123  
Type I diabetes mellitus  hsa04940+3123  
Viral myocarditis  hsa05416+3123  
According to Reactome, this protein belongs to the following pathways:
Downstream TCR signaling  R-HSA-202424  
Generation of second messenger molecules  R-HSA-202433  
Interferon gamma signaling  R-HSA-877300  
MHC class II antigen presentation  R-HSA-2132295  
PD-1 signaling  R-HSA-389948  
Phosphorylation of CD3 and TCR zeta chains  R-HSA-202427  
Translocation of ZAP-70 to Immunological synapse  R-HSA-202430  
The chain shown constituted about 70% of a pool of at least seven similar beta chains.  
  • UniProtKB


Biological process 
Immunity  definition   [KW-0391]
Technical term 
Reference proteome  definition   [KW-1185]

Further external links

GeneWiki: HLA-DRB1
GenomeRNAi: 3123