Overview
| Uniprot ID | P01903 |
|---|
| Protein Name | HLA class II histocompatibility antigen, DR alpha chain |
|---|
| Gene Name | HLA-DRA |
|---|
| Organism | Homo sapiens |
|---|
Kla Sites from experimental identification
| Position |
Flanking peptide |
| 172 |
REDHLFRKFHYLPFL |
Function
An alpha chain of antigen-presenting major histocompatibility complex class II (MHCII) molecule. In complex with the beta chain HLA-DRB, displays antigenic peptides on professional antigen presenting cells (APCs) for recognition by alpha-beta T cell receptor (TCR) on HLA-DR-restricted CD4-positive T cells. This guides antigen-specific T-helper effector functions, both antibody-mediated immune response and macrophage activation, to ultimately eliminate the infectious agents and transformed cells (PubMed:15265931, PubMed:15322540, PubMed:17334368, PubMed:22327072, PubMed:24190431, PubMed:27591323, PubMed:29884618, PubMed:31495665, PubMed:8145819, PubMed:9075930). Typically presents extracellular peptide antigens of 10 to 30 amino acids that arise from proteolysis of endocytosed antigens in lysosomes (PubMed:8145819). In the tumor microenvironment, presents antigenic peptides that are primarily generated in tumor-resident APCs likely via phagocytosis of apoptotic tumor cells or macropinocytosis of secreted tumor proteins (PubMed:31495665). Presents peptides derived from intracellular proteins that are trapped in autolysosomes after macroautophagy, a mechanism especially relevant for T cell selection in the thymus and central immune tolerance (PubMed:17182262, PubMed:23783831). The selection of the immunodominant epitopes follows two processing modes: 'bind first, cut/trim later' for pathogen-derived antigenic peptides and 'cut first, bind later' for autoantigens/self-peptides (PubMed:25413013). The anchor residue at position 1 of the peptide N-terminus, usually a large hydrophobic residue, is essential for high affinity interaction with MHCII molecules (PubMed:8145819)
Protein Sequence
10
MAISGVPVLG
20
FFIIAVLMSA
30
QESWAIKEEH
40
VIIQAEFYLN
50
PDQSGEFMFD
60
FDGDEIFHVD
70
MAKKETVWRL
80
EEFGRFASFE
90
AQGALANIAV
100
DKANLEIMTK
110
RSNYTPITNV
120
PPEVTVLTNS
130
PVELREPNVL
140
ICFIDKFTPP
150
VVNVTWLRNG
160
KPVTTGVSET
170
VFLPREDHLF
180
RKFHYLPFLP
190
STEDVYDCRV
200
EHWGLDEPLL
210
KHWEFDAPSP
220
LPETTENVVC
230
ALGLTVGLVG
240
IIIGTIFIIK
250
GLRKSNAAER
RGPL
Gene Ontology
| Classification |
GO ID |
Description |
| Cellular Component |
GO:0120281 |
autolysosome membrane |
| Cellular Component |
GO:0009986 |
cell surface |
| Cellular Component |
GO:0030669 |
clathrin-coated endocytic vesicle membrane |
| Cellular Component |
GO:0031901 |
early endosome membrane |
| Cellular Component |
GO:0030666 |
endocytic vesicle membrane |
| Cellular Component |
GO:0012507 |
ER to Golgi transport vesicle membrane |
| Cellular Component |
GO:0070062 |
extracellular exosome |
| Cellular Component |
GO:0000139 |
Golgi membrane |
| Cellular Component |
GO:0001772 |
immunological synapse |
| Cellular Component |
GO:0031902 |
late endosome membrane |
| Cellular Component |
GO:0098553 |
lumenal side of endoplasmic reticulum membrane |
| Cellular Component |
GO:0005765 |
lysosomal membrane |
| Cellular Component |
GO:0005764 |
lysosome |
| Cellular Component |
GO:0042613 |
MHC class II protein complex |
| Cellular Component |
GO:0005886 |
plasma membrane |
| Cellular Component |
GO:0032588 |
trans-Golgi network membrane |
| Cellular Component |
GO:0030658 |
transport vesicle membrane |
| Molecular Function |
GO:0023026 |
MHC class II protein complex binding |
| Molecular Function |
GO:0042605 |
peptide antigen binding |
| Molecular Function |
GO:0030247 |
polysaccharide binding |
| Molecular Function |
GO:0042608 |
T cell receptor binding |
| Biological Process |
GO:0002250 |
adaptive immune response |
| Biological Process |
GO:0002491 |
antigen processing and presentation of endogenous peptide antigen via MHC class II |
| Biological Process |
GO:0019886 |
antigen processing and presentation of exogenous peptide antigen via MHC class II |
| Biological Process |
GO:0002504 |
antigen processing and presentation of peptide or polysaccharide antigen via MHC class II |
| Biological Process |
GO:0050890 |
cognition |
| Biological Process |
GO:0006955 |
immune response |
| Biological Process |
GO:0002469 |
myeloid dendritic cell antigen processing and presentation |
| Biological Process |
GO:0002503 |
peptide antigen assembly with MHC class II protein complex |
| Biological Process |
GO:2000516 |
positive regulation of CD4-positive, alpha-beta T cell activation |
| Biological Process |
GO:0032831 |
positive regulation of CD4-positive, CD25-positive, alpha-beta regulatory T cell differentiation |
| Biological Process |
GO:0050778 |
positive regulation of immune response |
| Biological Process |
GO:0043382 |
positive regulation of memory T cell differentiation |
| Biological Process |
GO:0050870 |
positive regulation of T cell activation |
| Biological Process |
GO:0001916 |
positive regulation of T cell mediated cytotoxicity |
| Biological Process |
GO:0045622 |
regulation of T-helper cell differentiation |
Reference
[1] Yang Z, Yan C, Ma J, Peng P, Ren X et al.. Lactylome analysis suggests lactylation-dependent mechanisms of metabolic adaptation in hepatocellular carcinoma.. Nat Metab 5(1):61-79. 2023 Jan. PMID: 36593272.