Browse HLA-DRA

Summary
SymbolHLA-DRA
Namemajor histocompatibility complex, class II, DR alpha
Aliases HLA-DRA1; MLRW; MHC cell surface glycoprotein; MHC class II antigen DRA; histocompatibility antigen HLA-DR a ......
Chromosomal Location6p21.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Basic function annotation.
> Subcellular Location, Domain and Function
> Gene Ontology
> KEGG and Reactome Pathway
> Subcellular Location, Domain and Function
 
Subcellular Location 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.
Domain PF07654 Immunoglobulin C1-set domain
PF00993 Class II histocompatibility antigen
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.

> Gene Ontology
 
Biological Process GO:0002396 MHC protein complex assembly
GO:0002399 MHC class II protein complex assembly
GO:0002429 immune response-activating cell surface receptor signaling pathway
GO:0002478 antigen processing and presentation of exogenous peptide antigen
GO:0002495 antigen processing and presentation of peptide antigen via MHC class II
GO:0002501 peptide antigen assembly with MHC protein complex
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:0002505 antigen processing and presentation of polysaccharide antigen via MHC class II
GO:0002506 polysaccharide assembly with MHC class II protein complex
GO:0002694 regulation of leukocyte activation
GO:0002696 positive regulation of leukocyte activation
GO:0002757 immune response-activating signal transduction
GO:0002764 immune response-regulating signaling pathway
GO:0002768 immune response-regulating cell surface receptor signaling pathway
GO:0007159 leukocyte cell-cell adhesion
GO:0019882 antigen processing and presentation
GO:0019884 antigen processing and presentation of exogenous antigen
GO:0019886 antigen processing and presentation of exogenous peptide antigen via MHC class II
GO:0022407 regulation of cell-cell adhesion
GO:0022409 positive regulation of cell-cell adhesion
GO:0031294 lymphocyte costimulation
GO:0031295 T cell costimulation
GO:0034341 response to interferon-gamma
GO:0042110 T cell activation
GO:0045785 positive regulation of cell adhesion
GO:0048002 antigen processing and presentation of peptide antigen
GO:0050851 antigen receptor-mediated signaling pathway
GO:0050852 T cell receptor signaling pathway
GO:0050863 regulation of T cell activation
GO:0050865 regulation of cell activation
GO:0050867 positive regulation of cell activation
GO:0050870 positive regulation of T cell activation
GO:0050890 cognition
GO:0051249 regulation of lymphocyte activation
GO:0051251 positive regulation of lymphocyte activation
GO:0060333 interferon-gamma-mediated signaling pathway
GO:0065006 protein-carbohydrate complex assembly
GO:0070486 leukocyte aggregation
GO:0070489 T cell aggregation
GO:0071346 cellular response to interferon-gamma
GO:0071593 lymphocyte aggregation
GO:0071823 protein-carbohydrate complex subunit organization
GO:1903037 regulation of leukocyte cell-cell adhesion
GO:1903039 positive regulation of leukocyte cell-cell adhesion
Molecular Function GO:0003823 antigen binding
GO:0023023 MHC protein complex binding
GO:0023026 MHC class II protein complex binding
GO:0032395 MHC class II receptor activity
GO:0033218 amide binding
GO:0042277 peptide binding
GO:0042605 peptide antigen binding
Cellular Component GO:0005765 lysosomal membrane
GO:0005770 late endosome
GO:0005802 trans-Golgi network
GO:0010008 endosome membrane
GO:0012507 ER to Golgi transport vesicle membrane
GO:0030133 transport vesicle
GO:0030134 ER to Golgi transport vesicle
GO:0030135 coated vesicle
GO:0030136 clathrin-coated vesicle
GO:0030139 endocytic vesicle
GO:0030176 integral component of endoplasmic reticulum membrane
GO:0030658 transport vesicle membrane
GO:0030659 cytoplasmic vesicle membrane
GO:0030662 coated vesicle membrane
GO:0030665 clathrin-coated vesicle membrane
GO:0030666 endocytic vesicle membrane
GO:0030669 clathrin-coated endocytic vesicle membrane
GO:0031227 intrinsic component of endoplasmic reticulum membrane
GO:0031902 late endosome membrane
GO:0031984 organelle subcompartment
GO:0032588 trans-Golgi network membrane
GO:0042611 MHC protein complex
GO:0042613 MHC class II protein complex
GO:0044440 endosomal part
GO:0045334 clathrin-coated endocytic vesicle
GO:0071556 integral component of lumenal side of endoplasmic reticulum membrane
GO:0098552 side of membrane
GO:0098553 lumenal side of endoplasmic reticulum membrane
GO:0098791 Golgi subcompartment
GO:0098852 lytic vacuole membrane
> KEGG and Reactome Pathway
 
KEGG hsa04145 Phagosome
hsa04514 Cell adhesion molecules (CAMs)
hsa04612 Antigen processing and presentation
hsa04640 Hematopoietic cell lineage
hsa04672 Intestinal immune network for IgA production
Reactome R-HSA-1280218: Adaptive Immune System
R-HSA-388841: Costimulation by the CD28 family
R-HSA-1280215: Cytokine Signaling in Immune system
R-HSA-202424: Downstream TCR signaling
R-HSA-202433: Generation of second messenger molecules
R-HSA-168256: Immune System
R-HSA-913531: Interferon Signaling
R-HSA-877300: Interferon gamma signaling
R-HSA-2132295: MHC class II antigen presentation
R-HSA-389948: PD-1 signaling
R-HSA-202427: Phosphorylation of CD3 and TCR zeta chains
R-HSA-202403: TCR signaling
R-HSA-202430: Translocation of ZAP-70 to Immunological synapse
Summary
SymbolHLA-DRA
Namemajor histocompatibility complex, class II, DR alpha
Aliases HLA-DRA1; MLRW; MHC cell surface glycoprotein; MHC class II antigen DRA; histocompatibility antigen HLA-DR a ......
Chromosomal Location6p21.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Literatures that report relations between HLA-DRA and anti-tumor immunity. The specific mechanism were also collected if the literature reports that a gene specifically promotes or inhibits the infiltration or function of T/NK cells.
> Text Mining
 
  Literatures describing the relation between HLA-DRA and anti-tumor immunity in human cancer.
PMID Cancer type Relation to immunity Evidence sentences
26500140Diffuse Large B-Cell LymphomaPromote immunityFOXP1 knockdown in ABC-DLBCL cells led to increased cell-surface expression of HLA-DRA and CD74. We propose that FOXP1 represents a novel regulator of genes targeted by the class II MHC transactivator CIITA (MHC II and CD74) and therapeutically targeting the FOXP1 pathway may improve antigen presentation and immune surveillance in high-risk DLBCL patients.
26183926MelanomaInhibit immunity (T cell function)Taken together, our results illustrate a novel immune escape mechanism that can be activated by aberrant expression of MHC class II molecules, which by attracting tumor-specific CD4(+) T cells elicit a local inflammatory response dominated by TNF that, in turn, inhibits cytotoxic CD8(+) T-cell responses.
27496866Head and Neck CarcinomaPromote immunity (T cell function); essential for immunotherapyCD137 agonist mAb urelumab enhanced cetuximab-activated NK-cell survival, DC maturation, and tumor antigen cross-presentation. Urelumab boosted DC maturation markers, CD86 and HLA DR, and antigen-processing machinery (APM) components TAP1/2, leading to increased tumor antigen cross-presentation. These results suggest a beneficial effect of combination immunotherapy using cetuximab and CD137 agonist in HNC.
25229656Cervical CarcinomaPromote immunity (NK cell function)Indeed, in the presence of HPV-VLPs, DCs further activated NK cells by inducing the upregulation of cell surface activation markers (CD69 and HLADR). The function of NK cells was also improved as shown by an increase in IFN-γ secretion and cytotoxic activity against an HPV+ cell line
Summary
SymbolHLA-DRA
Namemajor histocompatibility complex, class II, DR alpha
Aliases HLA-DRA1; MLRW; MHC cell surface glycoprotein; MHC class II antigen DRA; histocompatibility antigen HLA-DR a ......
Chromosomal Location6p21.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content High-throughput screening data (e.g. CRISPR-Cas9, shRNA and RNAi) for T cell-mediated killing. Genetic screen techniques can identify mechanisms of tumor cell resistance (e.g., PTPN2) and sensitivity (e.g., APLNR) to killing by cytotoxic T cells, the central effectors of anti-tumor immunity. After comprehensively searching, eight groups of screening data sets were collected in the current database. In this tab, users can check whether their selected genes cause resistance or increase sensitivity to T cell-mediated killing in various data sets.
> High-throughput Screening
  Statistical results of HLA-DRA in screening data sets for detecting immune reponses.
PMID Screening System Cancer Type Cell Line Data Set Statistical Results Relation to immunity
29301958CRISPR-Cas9 melanomaB16F10Pmel-1 T cell NA/NSNA/NS
29301958CRISPR-Cas9 melanomaB16F10OT-1 T cell NA/NSNA/NS
28783722CRISPR-Cas9 melanomaMel6242CT-CRISPR NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX+Anti-PD1 NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX NA/NSNA/NS
25691366RNAiBreast cancerMCF7Luc-CTL assay NA/NSNA/NS
24476824shRNAmelanomaB16Primary screen NA/NSNA/NS
24476824shRNAmelanomaB16Secondary screen NA/NSNA/NS
Summary
SymbolHLA-DRA
Namemajor histocompatibility complex, class II, DR alpha
Aliases HLA-DRA1; MLRW; MHC cell surface glycoprotein; MHC class II antigen DRA; histocompatibility antigen HLA-DR a ......
Chromosomal Location6p21.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Transcriptomic and genomic profiling of pre-treated tumor biopsies from responders and non-responders to immunotherapy. These data were used to identify signatures and mechanisms of response to checkpoint blockade (e.g., anti-PDL1 and anti-PD1). One example is that mutations in the gene PBRM1 benefit clinical survival of patients with clear cell renal cell carcinoma. After comprehensively searching, we collected 5 and 6 of transcriptomic and genomic data sets, respectively. In this tab, users can check whether their selected genes have significant difference of expression or mutation between responders and non-responders in various data sets.
> Expression difference between responders and non-responders
> Mutation difference between responders and non-responders
> Expression difference between responders and non-responders
 
Points in the above scatter plot represent the expression difference of HLA-DRA in various data sets.
No PMID Cancer type Group Drug # Res # NRes Log2 (Fold Change) P value Anno
126997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)1412-0.1770.819
226997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)65-0.7810.726
326997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)870.2820.851
428552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 9160.9130.206
528552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 590.1330.953
628552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 471.9090.544
729033130MelanomaallAnti-PD-1 (nivolumab) 26230.4510.499
829033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 15110.8270.754
929033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 1112-0.040.99
1029301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 481.0490.755
1129301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 2001
1229301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 281.2370.82
1329443960Urothelial cancerallAnti-PD-L1 (atezolizumab) 68230-0.0550.772
> Mutation difference between responders and non-responders
 
Points in the above scatter plot represent the mutation difference of HLA-DRA in various data sets.
No PMID Cancer type Group Drug # Res # NRes % Mut/Res % Mut/NRes % Diff (R vs NR) Pval Anno
125765070Non-small cell lung cancer (NSCLC)allAnti-PD-1 (pembrolizumab) 14170001
225765070Non-small cell lung cancer (NSCLC)smokingAnti-PD-1 (pembrolizumab) 1030001
325765070Non-small cell lung cancer (NSCLC)non-smokingAnti-PD-1 (pembrolizumab) 4140001
426359337MelanomaallAnti-CTLA-4 (ipilimumab) 277305.5-5.50.572
526359337MelanomaBRAFiAnti-CTLA-4 (ipilimumab) 0140001
626359337Melanomanon-BRAFiAnti-CTLA-4 (ipilimumab) 275906.8-6.80.304
726997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)21170001
826997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)860001
926997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)13110001
1028552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 9160001
1128552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 590001
1228552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470001
1329033130MelanomaallAnti-PD-1 (nivolumab) 38272.602.61
1429033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 22134.504.51
1529033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 16140001
1629301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 11130001
1729301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 610001
1829301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 5120001
Summary
SymbolHLA-DRA
Namemajor histocompatibility complex, class II, DR alpha
Aliases HLA-DRA1; MLRW; MHC cell surface glycoprotein; MHC class II antigen DRA; histocompatibility antigen HLA-DR a ......
Chromosomal Location6p21.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of HLA-DRA. The immune-related signatures of 28 TIL types from Charoentong's study, which can be viewed in the download page. For each cancer type, the relative abundance of TILs were inferred by using gene set variation analysis (GSVA) based on gene expression profile. In this tab, users can examine which kinds of TILs might be regulated by the current gene.
> Lymphocyte
 
Summary
SymbolHLA-DRA
Namemajor histocompatibility complex, class II, DR alpha
Aliases HLA-DRA1; MLRW; MHC cell surface glycoprotein; MHC class II antigen DRA; histocompatibility antigen HLA-DR a ......
Chromosomal Location6p21.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of HLA-DRA. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by HLA-DRA.
> Immunoinhibitor
> Immunostimulator
> MHC molecule
> Immunoinhibitor
 
> Immunostimulator
 
> MHC molecule
 
Summary
SymbolHLA-DRA
Namemajor histocompatibility complex, class II, DR alpha
Aliases HLA-DRA1; MLRW; MHC cell surface glycoprotein; MHC class II antigen DRA; histocompatibility antigen HLA-DR a ......
Chromosomal Location6p21.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of HLA-DRA. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene.
> Chemokine
> Receptor
> Chemokine
 
> Receptor
 
Summary
SymbolHLA-DRA
Namemajor histocompatibility complex, class II, DR alpha
Aliases HLA-DRA1; MLRW; MHC cell surface glycoprotein; MHC class II antigen DRA; histocompatibility antigen HLA-DR a ......
Chromosomal Location6p21.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Distribution of HLA-DRA expression across immune and molecular subtypes.
> Immune subtype
> Molecular subtype
> Immune subtype
 
> Molecular subtype
 
Summary
SymbolHLA-DRA
Namemajor histocompatibility complex, class II, DR alpha
Aliases HLA-DRA1; MLRW; MHC cell surface glycoprotein; MHC class II antigen DRA; histocompatibility antigen HLA-DR a ......
Chromosomal Location6p21.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Associations between HLA-DRA and clinical features.
> Overall survival analysis
> Cancer stage
> Tumor grade
> Overall survival
 
> Stage
 
> Grade
 
Summary
SymbolHLA-DRA
Namemajor histocompatibility complex, class II, DR alpha
Aliases HLA-DRA1; MLRW; MHC cell surface glycoprotein; MHC class II antigen DRA; histocompatibility antigen HLA-DR a ......
Chromosomal Location6p21.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Drugs targeting HLA-DRA collected from DrugBank database.
> Drugs from DrugBank database
 

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