InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: HLA-DRA

Summary

InnateDB Protein

IDBP-239683.7

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

HLA-DRA

Protein Name

major histocompatibility complex, class II, DR alpha

Synonyms

HLA-DRA1; MLRW;

Species

Homo sapiens

Ensembl Protein

ENSP00000378786

InnateDB Gene

IDBG-80796 (HLA-DRA)

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; Single-pass type I membrane protein. Endoplasmic reticulum membrane; Single-pass type I membrane protein. Golgi apparatus, trans-Golgi network membrane; Single-pass type I membrane protein. Endosome membrane; Single- pass type I membrane protein. Lysosome membrane; Single-pass type I membrane protein. Late endosome membrane; Single-pass type I membrane protein. 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

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 29 experimentally validated interaction(s) in this database.

Experimentally validated
Total	29 [view]
Protein-Protein	26 [view]
Protein-DNA	3 [view]
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Gene Ontology

Molecular Function

Accession	GO Term
GO:0005515	protein binding
GO:0023026	MHC class II protein complex binding
GO:0032395	MHC class II receptor activity
GO:0042605	peptide antigen binding

Biological Process

GO:0002503	peptide antigen assembly with MHC class II protein complex
GO:0002504	antigen processing and presentation of peptide or polysaccharide antigen via MHC class II
GO:0002506	polysaccharide assembly with MHC class II protein complex
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:0050890	cognition
GO:0060333	interferon-gamma-mediated signaling pathway

Cellular Component

GO:0000139	Golgi membrane
GO:0005764	lysosome
GO:0005765	lysosomal membrane
GO:0005886	plasma membrane
GO:0005887	integral component of plasma membrane
GO:0009986	cell surface
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

PDB ID

InterPro

IPR001003 MHC class II, alpha chain, N-terminal
IPR003597 Immunoglobulin C1-set
IPR007110 Immunoglobulin-like domain
IPR011162 MHC classes I/II-like antigen recognition protein

PFAM

PF00993
PF07654

PRINTS

PIRSF

SMART

SM00920
SM00407

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt

P01903