Names & Taxonomy

Uniprot ID:
P04229
Entry Name:
2B11_HUMAN
Status:
reviewed
Protein Names:
HLA class II histocompatibility antigen, DRB1-1 beta chain (MHC class II antigen DRB1*1) (DR-1) (DR1)
Gene Names:
HLA-DRB1
Gene Names Primary:
HLA-DRB1
Organism:
Homo sapiens (Human)

Structure

Length:
266
Sequence:
MVCLKLPGGSCMTALTVTLMVLSSPLALAGDTRPRFLWQLKFECHFFNGTERVRLLERCIYNQEESVRFDSDVGEYRAVTELGRPDAEYWNSQKDLLEQRRAAVDTYCRHNYGVGESFTVQRRVEPKVTVYPSKTQPLQHHNLLVCSVSGFYPGSIEVRWFRNGQEEKAGVVSTGLIQNGDWTFQTLVMLETVPRSGEVYTCQVEHPSVTSPLTVEWRARSESAQSKMLSGVGGFVLGLLFLGAGLFIYFRNQKGHSGLQPTGFLS
Proteomes:
UP000005640

Subcellular location

Subcellular Location:
Cell membrane

Function

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.; (Microbial infection) Acts as a receptor for Epstein-Barr virus on lymphocytes.
Cross Reference Drug Bank:
DB05259
Gene Ontology Go:
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
MHC class II protein complex binding
peptide antigen binding
virus receptor activity
antigen processing and presentation of exogenous peptide antigen via MHC class II
cytokine-mediated signaling pathway
detection of bacterium
humoral immune response mediated by circulating immunoglobulin
immune response
immunoglobulin production involved in immunoglobulin mediated immune response
inflammatory response to antigenic stimulus
interferon-gamma-mediated signaling pathway
negative regulation of interferon-gamma production
negative regulation of T cell proliferation
positive regulation of insulin secretion involved in cellular response to glucose stimulus
protein tetramerization
regulation of interleukin-10 secretion
regulation of interleukin-4 production
T cell costimulation
T cell receptor signaling pathway
T-helper 1 type immune response
Gene Ontology Biological Process:
antigen processing and presentation of exogenous peptide antigen via MHC class II
cytokine-mediated signaling pathway
detection of bacterium
humoral immune response mediated by circulating immunoglobulin
immune response
immunoglobulin production involved in immunoglobulin mediated immune response
inflammatory response to antigenic stimulus
interferon-gamma-mediated signaling pathway
negative regulation of interferon-gamma production
negative regulation of T cell proliferation
positive regulation of insulin secretion involved in cellular response to glucose stimulus
protein tetramerization
regulation of interleukin-10 secretion
regulation of interleukin-4 production
T cell costimulation
T cell receptor signaling pathway
T-helper 1 type immune response
Gene Ontology Molecular Function:
MHC class II protein complex binding
peptide antigen binding
virus receptor activity
Gene Ontology Cellular Component:
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
Keywords:
3D-structure
Cell membrane
Complete proteome
Direct protein sequencing
Disulfide bond
Endoplasmic reticulum
Endosome
Glycoprotein
Golgi apparatus
Host cell receptor for virus entry
Host-virus interaction
Immunity
Isopeptide bond
Lysosome
MHC II
Membrane
Polymorphism
Receptor
Reference proteome
Signal
Transmembrane
Transmembrane helix
Ubl conjugation

Publication

PubMed ID:
2998758 3858829 1688595 16140993 17345114 14702039 8462990 6600932 10203026 12753659 2453563 14508706 8598037 9151859 11684289 17241953 18046453 18669648 18305173 19092054 19533806 8316295 8145819 8152483 11864610 21269460