Browse HLA-E

Summary
SymbolHLA-E
Namemajor histocompatibility complex, class I, E
Aliases EA1.2; EA2.1; HLA-6.2; MHC; QA1; HLA class I histocompatibility antigen, E alpha chain; MHC HLA-E alpha-1; M ......
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 Membrane; Single-pass type I membrane protein.
Domain PF07654 Immunoglobulin C1-set domain
PF00129 Class I Histocompatibility antigen
PF06623 MHC_I C-terminus
Function

Preferably binds to a peptide derived from the signal sequence of most HLA-A, -B, -C and -G molecules.

> Gene Ontology
 
Biological Process GO:0001819 positive regulation of cytokine production
GO:0001906 cell killing
GO:0001909 leukocyte mediated cytotoxicity
GO:0001910 regulation of leukocyte mediated cytotoxicity
GO:0001911 negative regulation of leukocyte mediated cytotoxicity
GO:0001912 positive regulation of leukocyte mediated cytotoxicity
GO:0001913 T cell mediated cytotoxicity
GO:0001914 regulation of T cell mediated cytotoxicity
GO:0001916 positive regulation of T cell mediated cytotoxicity
GO:0002228 natural killer cell mediated immunity
GO:0002250 adaptive immune response
GO:0002377 immunoglobulin production
GO:0002428 antigen processing and presentation of peptide antigen via MHC class Ib
GO:0002440 production of molecular mediator of immune response
GO:0002443 leukocyte mediated immunity
GO:0002449 lymphocyte mediated immunity
GO:0002456 T cell mediated immunity
GO:0002460 adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains
GO:0002474 antigen processing and presentation of peptide antigen via MHC class I
GO:0002475 antigen processing and presentation via MHC class Ib
GO:0002476 antigen processing and presentation of endogenous peptide antigen via MHC class Ib
GO:0002478 antigen processing and presentation of exogenous peptide antigen
GO:0002479 antigen processing and presentation of exogenous peptide antigen via MHC class I, TAP-dependent
GO:0002480 antigen processing and presentation of exogenous peptide antigen via MHC class I, TAP-independent
GO:0002483 antigen processing and presentation of endogenous peptide antigen
GO:0002637 regulation of immunoglobulin production
GO:0002639 positive regulation of immunoglobulin production
GO:0002683 negative regulation of immune system process
GO:0002694 regulation of leukocyte activation
GO:0002696 positive regulation of leukocyte activation
GO:0002697 regulation of immune effector process
GO:0002698 negative regulation of immune effector process
GO:0002699 positive regulation of immune effector process
GO:0002700 regulation of production of molecular mediator of immune response
GO:0002702 positive regulation of production of molecular mediator of immune response
GO:0002703 regulation of leukocyte mediated immunity
GO:0002704 negative regulation of leukocyte mediated immunity
GO:0002705 positive regulation of leukocyte mediated immunity
GO:0002706 regulation of lymphocyte mediated immunity
GO:0002707 negative regulation of lymphocyte mediated immunity
GO:0002708 positive regulation of lymphocyte mediated immunity
GO:0002709 regulation of T cell mediated immunity
GO:0002711 positive regulation of T cell mediated immunity
GO:0002715 regulation of natural killer cell mediated immunity
GO:0002716 negative regulation of natural killer cell mediated immunity
GO:0002717 positive regulation of natural killer cell mediated immunity
GO:0002819 regulation of adaptive immune response
GO:0002821 positive regulation of adaptive immune response
GO:0002822 regulation of adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains
GO:0002824 positive regulation of adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains
GO:0006959 humoral immune response
GO:0007159 leukocyte cell-cell adhesion
GO:0009306 protein secretion
GO:0019730 antimicrobial humoral response
GO:0019731 antibacterial humoral response
GO:0019882 antigen processing and presentation
GO:0019883 antigen processing and presentation of endogenous antigen
GO:0019884 antigen processing and presentation of exogenous antigen
GO:0022407 regulation of cell-cell adhesion
GO:0022409 positive regulation of cell-cell adhesion
GO:0031341 regulation of cell killing
GO:0031342 negative regulation of cell killing
GO:0031343 positive regulation of cell killing
GO:0031348 negative regulation of defense response
GO:0031349 positive regulation of defense response
GO:0032616 interleukin-13 production
GO:0032633 interleukin-4 production
GO:0032639 TRAIL production
GO:0032640 tumor necrosis factor production
GO:0032656 regulation of interleukin-13 production
GO:0032673 regulation of interleukin-4 production
GO:0032679 regulation of TRAIL production
GO:0032680 regulation of tumor necrosis factor production
GO:0032736 positive regulation of interleukin-13 production
GO:0032753 positive regulation of interleukin-4 production
GO:0032759 positive regulation of TRAIL production
GO:0032760 positive regulation of tumor necrosis factor production
GO:0032943 mononuclear cell proliferation
GO:0032944 regulation of mononuclear cell proliferation
GO:0032946 positive regulation of mononuclear cell proliferation
GO:0034340 response to type I interferon
GO:0034341 response to interferon-gamma
GO:0035740 CD8-positive, alpha-beta T cell proliferation
GO:0036037 CD8-positive, alpha-beta T cell activation
GO:0042098 T cell proliferation
GO:0042102 positive regulation of T cell proliferation
GO:0042110 T cell activation
GO:0042129 regulation of T cell proliferation
GO:0042267 natural killer cell mediated cytotoxicity
GO:0042269 regulation of natural killer cell mediated cytotoxicity
GO:0042270 protection from natural killer cell mediated cytotoxicity
GO:0042590 antigen processing and presentation of exogenous peptide antigen via MHC class I
GO:0042742 defense response to bacterium
GO:0045088 regulation of innate immune response
GO:0045089 positive regulation of innate immune response
GO:0045785 positive regulation of cell adhesion
GO:0045824 negative regulation of innate immune response
GO:0045953 negative regulation of natural killer cell mediated cytotoxicity
GO:0046631 alpha-beta T cell activation
GO:0046633 alpha-beta T cell proliferation
GO:0046634 regulation of alpha-beta T cell activation
GO:0046635 positive regulation of alpha-beta T cell activation
GO:0046640 regulation of alpha-beta T cell proliferation
GO:0046641 positive regulation of alpha-beta T cell proliferation
GO:0046651 lymphocyte proliferation
GO:0048002 antigen processing and presentation of peptide antigen
GO:0048305 immunoglobulin secretion
GO:0050670 regulation of lymphocyte proliferation
GO:0050671 positive regulation of lymphocyte proliferation
GO:0050708 regulation of protein secretion
GO:0050714 positive regulation of protein secretion
GO:0050777 negative regulation of immune response
GO:0050830 defense response to Gram-positive bacterium
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:0051023 regulation of immunoglobulin secretion
GO:0051024 positive regulation of immunoglobulin secretion
GO:0051047 positive regulation of secretion
GO:0051222 positive regulation of protein transport
GO:0051249 regulation of lymphocyte activation
GO:0051251 positive regulation of lymphocyte activation
GO:0060333 interferon-gamma-mediated signaling pathway
GO:0060337 type I interferon signaling pathway
GO:0070486 leukocyte aggregation
GO:0070489 T cell aggregation
GO:0070661 leukocyte proliferation
GO:0070663 regulation of leukocyte proliferation
GO:0070665 positive regulation of leukocyte proliferation
GO:0071346 cellular response to interferon-gamma
GO:0071357 cellular response to type I interferon
GO:0071593 lymphocyte aggregation
GO:0071706 tumor necrosis factor superfamily cytokine production
GO:0098542 defense response to other organism
GO:1903037 regulation of leukocyte cell-cell adhesion
GO:1903039 positive regulation of leukocyte cell-cell adhesion
GO:1903532 positive regulation of secretion by cell
GO:1903555 regulation of tumor necrosis factor superfamily cytokine production
GO:1903557 positive regulation of tumor necrosis factor superfamily cytokine production
GO:1904951 positive regulation of establishment of protein localization
GO:2000564 regulation of CD8-positive, alpha-beta T cell proliferation
GO:2000566 positive regulation of CD8-positive, alpha-beta T cell proliferation
GO:2001185 regulation of CD8-positive, alpha-beta T cell activation
GO:2001187 positive regulation of CD8-positive, alpha-beta T cell activation
Molecular Function GO:0003823 antigen binding
GO:0030881 beta-2-microglobulin binding
GO:0033218 amide binding
GO:0042277 peptide binding
GO:0042287 MHC protein binding
GO:0042288 MHC class I protein binding
GO:0042605 peptide antigen binding
GO:0046703 natural killer cell lectin-like receptor binding
Cellular Component GO:0005769 early endosome
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: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:0030666 endocytic vesicle membrane
GO:0030670 phagocytic vesicle membrane
GO:0031227 intrinsic component of endoplasmic reticulum membrane
GO:0031901 early endosome membrane
GO:0032398 MHC class Ib protein complex
GO:0042611 MHC protein complex
GO:0042612 MHC class I protein complex
GO:0044440 endosomal part
GO:0045335 phagocytic 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
> KEGG and Reactome Pathway
 
KEGG hsa04144 Endocytosis
hsa04145 Phagosome
hsa04514 Cell adhesion molecules (CAMs)
hsa04612 Antigen processing and presentation
hsa04650 Natural killer cell mediated cytotoxicity
Reactome R-HSA-1280218: Adaptive Immune System
R-HSA-983170: Antigen Presentation
R-HSA-1236975: Antigen processing-Cross presentation
R-HSA-983169: Class I MHC mediated antigen processing & presentation
R-HSA-1280215: Cytokine Signaling in Immune system
R-HSA-2172127: DAP12 interactions
R-HSA-2424491: DAP12 signaling
R-HSA-1236974: ER-Phagosome pathway
R-HSA-1236977: Endosomal/Vacuolar pathway
R-HSA-168256: Immune System
R-HSA-198933: Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell
R-HSA-168249: Innate Immune System
R-HSA-913531: Interferon Signaling
R-HSA-909733: Interferon alpha/beta signaling
R-HSA-877300: Interferon gamma signaling
Summary
SymbolHLA-E
Namemajor histocompatibility complex, class I, E
Aliases EA1.2; EA2.1; HLA-6.2; MHC; QA1; HLA class I histocompatibility antigen, E alpha chain; MHC HLA-E alpha-1; M ......
Chromosomal Location6p21.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Literatures that report relations between HLA-E 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-E and anti-tumor immunity in human cancer.
PMID Cancer type Relation to immunity Evidence sentences
25043048GliomaPromote immunityPeptides encompassing the mutated region are presented on major histocompatibility complexes (MHC) class II and induce mutation-specific CD4(+) T-helper-1 (TH1) responses.
29635163Acute Lymphoblastic LeukemiaPromote immunity (T cell function); increase the efficacy of immunotherapyCAR T-cells and bsAb represent the most powerful tools for major-histocompatibility complex (MHC) independent T-cell immune response against cancer.
29632715breast carcinomaPromote immunitySince recombinant DCN also elevated MHC class I surface expression in BGNlow/neg HER-2/neu+ cells, both proteoglycans might act synergistically.
27859048Chronic Lymphocytic LeukemiaInhibit immunityHLA-E allelic genotype correlates with HLA-E plasma levels and predicts early progression in chronic lymphocytic leukemia. In vitro, sHLA-E inhibited degranulation and interferon-γ production by natural killer (NK) cells when cocultivated with tumor cells.
20581241Colorectal CarcinomaPromote immunityIn contrast, downregulation of MHC class I by allele loss results in loss of T cell recognition. A strong correlation was seen between ITTC and MHC class I expression (p=0.0002). A mean survival advantage of 26.1 months was seen in patients whose tumours had strong MHC I expression and high levels of ITTC over those who had weak MHC I and low levels of ITTC (log-rank test=12.023, p=0.034).
29699516Lung CarcinomaPromote immunityReduction of MHC-I expression limits T-lymphocyte-mediated killing of Cancer-initiating cells. Following treatment with IFN-γ, both CIC enriched and non-enriched TC-1 cells expressed similar levels of MHC-I, and the increased MHC-I expression on CICs resulted in greater CTL-mediated tumor lysis and improved tumor-free survival in mice. These results suggest that the attenuated expression of MHC-I molecules by CICs represents a potential strategy of CICs to escape immune recognition, and that the development of successful immunotherapy strategies targeting CICs may decrease their resistance to T cell-mediated immune detection by enhancing CIC MHC-I expression.
Summary
SymbolHLA-E
Namemajor histocompatibility complex, class I, E
Aliases EA1.2; EA2.1; HLA-6.2; MHC; QA1; HLA class I histocompatibility antigen, E alpha chain; MHC HLA-E alpha-1; M ......
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-E 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/NS NA/NS
29301958CRISPR-Cas9 melanomaB16F10OT-1 T cell NA/NS NA/NS
28783722CRISPR-Cas9 melanomaMel6242CT-CRISPR NA/NS NA/NS
28723893CRISPR-Cas9 melanomaB16GVAX+Anti-PD1 STARS Score: 7.75; FDR: 0.001 Resistant to T cell-mediated killing
28723893CRISPR-Cas9 melanomaB16GVAX NA/NS NA/NS
25691366RNAiBreast cancerMCF7Luc-CTL assay NA/NS NA/NS
24476824shRNAmelanomaB16Primary screen NA/NS NA/NS
24476824shRNAmelanomaB16Secondary screen NA/NS NA/NS
Summary
SymbolHLA-E
Namemajor histocompatibility complex, class I, E
Aliases EA1.2; EA2.1; HLA-6.2; MHC; QA1; HLA class I histocompatibility antigen, E alpha chain; MHC HLA-E alpha-1; M ......
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-E in various data sets.
No PMID Cancer type Group Drug # Res # NRes Log2 (Fold Change) P value Anno
126997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)14120.5230.183
226997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)650.4390.822
326997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)870.5890.672
428552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 9160.4460.333
528552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 590.2530.93
628552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470.6940.855
729033130MelanomaallAnti-PD-1 (nivolumab) 26230.4020.505
829033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 15110.8020.756
929033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 1112-0.1460.961
1029301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 481.1920.686
1129301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 2001
1229301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 281.2950.778
1329443960Urothelial cancerallAnti-PD-L1 (atezolizumab) 68230-0.0170.86
> Mutation difference between responders and non-responders
 
Points in the above scatter plot represent the mutation difference of HLA-E 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) 27730001
526359337MelanomaBRAFiAnti-CTLA-4 (ipilimumab) 0140001
626359337Melanomanon-BRAFiAnti-CTLA-4 (ipilimumab) 27590001
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-E
Namemajor histocompatibility complex, class I, E
Aliases EA1.2; EA2.1; HLA-6.2; MHC; QA1; HLA class I histocompatibility antigen, E alpha chain; MHC HLA-E alpha-1; M ......
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-E. 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-E
Namemajor histocompatibility complex, class I, E
Aliases EA1.2; EA2.1; HLA-6.2; MHC; QA1; HLA class I histocompatibility antigen, E alpha chain; MHC HLA-E alpha-1; M ......
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-E. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by HLA-E.
> Immunoinhibitor
> Immunostimulator
> MHC molecule
> Immunoinhibitor
 
> Immunostimulator
 
> MHC molecule
 
Summary
SymbolHLA-E
Namemajor histocompatibility complex, class I, E
Aliases EA1.2; EA2.1; HLA-6.2; MHC; QA1; HLA class I histocompatibility antigen, E alpha chain; MHC HLA-E alpha-1; M ......
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-E. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene.
> Chemokine
> Receptor
> Chemokine
 
> Receptor
 
Summary
SymbolHLA-E
Namemajor histocompatibility complex, class I, E
Aliases EA1.2; EA2.1; HLA-6.2; MHC; QA1; HLA class I histocompatibility antigen, E alpha chain; MHC HLA-E alpha-1; M ......
Chromosomal Location6p21.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Distribution of HLA-E expression across immune and molecular subtypes.
> Immune subtype
> Molecular subtype
> Immune subtype
 
> Molecular subtype
 
Summary
SymbolHLA-E
Namemajor histocompatibility complex, class I, E
Aliases EA1.2; EA2.1; HLA-6.2; MHC; QA1; HLA class I histocompatibility antigen, E alpha chain; MHC HLA-E alpha-1; M ......
Chromosomal Location6p21.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Associations between HLA-E and clinical features.
> Overall survival analysis
> Cancer stage
> Tumor grade
> Overall survival
 
> Stage
 
> Grade
 
Summary
SymbolHLA-E
Namemajor histocompatibility complex, class I, E
Aliases EA1.2; EA2.1; HLA-6.2; MHC; QA1; HLA class I histocompatibility antigen, E alpha chain; MHC HLA-E alpha-1; M ......
Chromosomal Location6p21.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Drugs targeting HLA-E collected from DrugBank database.
> Drugs from DrugBank database
 

There is no record.