Homo sapiens Protein: HLA-DRB5
InnateDB Protein IDBP-80829.6
Last Modified 2014-10-13 [Report errors or provide feedback]
Gene Symbol HLA-DRB5
Protein Name major histocompatibility complex, class II, DR beta 5
Synonyms HLA-DRB;
Species Homo sapiens
Ensembl Protein ENSP00000364114
InnateDB Gene IDBG-80827 (HLA-DRB5)
Protein Structure
UniProt Annotation
Function 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.
Subcellular Localization Cell membrane {ECO:0000269PubMed:18305173}; Single-pass type I membrane protein {ECO:0000269PubMed:18305173, ECO:0000305}. Endoplasmic reticulum membrane {ECO:0000269PubMed:18305173}; Single-pass type I membrane protein {ECO:0000269PubMed:18305173, ECO:0000305}. Golgi apparatus, trans-Golgi network membrane {ECO:0000269PubMed:18305173}; Single-pass type I membrane protein {ECO:0000269PubMed:18305173, ECO:0000305}. Endosome membrane {ECO:0000269PubMed:18305173}; Single-pass type I membrane protein {ECO:0000269PubMed:18305173, ECO:0000305}. Lysosome membrane {ECO:0000269PubMed:18305173}; Single-pass type I membrane protein {ECO:0000269PubMed:18305173, ECO:0000305}. Late endosome membrane {ECO:0000269PubMed:18305173}; Single-pass type I membrane protein {ECO:0000269PubMed:18305173, ECO:0000305}. Note=The MHC class II complex transits through a number of intracellular compartments in the endocytic pathway until it reaches the cell membrane for antigen presentation.
Disease Associations
Tissue Specificity
Number of Interactions This gene and/or its encoded proteins are associated with 10 experimentally validated interaction(s) in this database.
Experimentally validated
Total 10 [view]
Protein-Protein 10 [view]
Protein-DNA 0
Protein-RNA 0
Gene Ontology

Molecular Function
Accession GO Term
GO:0005515 protein binding
GO:0042605 peptide antigen binding
Biological Process
GO:0006955 immune response
GO:0019221 cytokine-mediated signaling pathway
GO:0019882 antigen processing and presentation
GO:0019886 antigen processing and presentation of exogenous peptide antigen via MHC class II
GO:0031295 T cell costimulation
GO:0050852 T cell receptor signaling pathway
GO:0060333 interferon-gamma-mediated signaling pathway
Cellular Component
GO:0000139 Golgi membrane
GO:0005765 lysosomal membrane
GO:0005886 plasma membrane
GO:0012507 ER to Golgi transport vesicle membrane
GO:0016020 membrane
GO:0030658 transport vesicle membrane
GO:0030666 endocytic vesicle membrane
GO:0030669 clathrin-coated endocytic vesicle membrane
GO:0031902 late endosome membrane
GO:0032588 trans-Golgi network membrane
GO:0042613 MHC class II protein complex
GO:0070062 extracellular vesicular exosome
GO:0071556 integral component of lumenal side of endoplasmic reticulum membrane
Protein Structure and Domains
InterPro IPR000353 MHC class II, beta chain, N-terminal
IPR003597 Immunoglobulin C1-set
IPR007110 Immunoglobulin-like domain
IPR011162 MHC classes I/II-like antigen recognition protein
PFAM PF00969
Post-translational Modifications
SwissProt Q30154
PhosphoSite PhosphoSite-
TrEMBL Q95385
UniProt Splice Variant
Entrez Gene 3127
RefSeq NP_002116
OMIM 604776
HPRD 09209
EMBL AB829537 AF122887 AJ271159 AJ427352 AJ854250 AK314834 AL713966 AM159646 AY141137 AY457037 AY604591 BC009234 FN430425 M16954 M16955 M17377 M20429 M30182 M35159 M81171 M81180 M91001 U31770 U59685 U66721 X64544 X64548 X87210 Y09342 Y13727 Z83201
GenPept AAA36276 AAA36277 AAA59715 AAA59791 AAA59818 AAA59822 AAA91838 AAA91847 AAB52229 AAB52232 AAB63983 AAD31766 AAH09234 AAN28924 AAR20446 AAV33684 BAG37353 BAO73172 CAA45842 CAA45846 CAA70524 CAA74055 CAB05668 CAB71144 CAD20460 CAI05916 CAI18079 CAJ43899 CAZ86696