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Browse ERN1

Summary
SymbolERN1
Nameendoplasmic reticulum to nucleus signaling 1
Aliases IRE1; IRE1P; inositol-requiring enzyme 1; ER to nucleus signalling 1; IRE1a; hIRE1p; endoplasmic reticulum-t ......
Chromosomal Location17q23
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 Endoplasmic reticulum membrane Single-pass type I membrane protein
Domain PF00069 Protein kinase domain
PF06479 Ribonuclease 2-5A
Function

Serine/threonine-protein kinase and endoribonuclease that acts as a key sensor for the endoplasmic reticulum unfolded protein response (UPR) (PubMed:11779464, PubMed:11175748, PubMed:12637535, PubMed:9637683, PubMed:21317875). In unstressed cells, the endoplasmic reticulum luminal domain is maintained in its inactive monomeric state by binding to the endoplasmic reticulum chaperone HSPA5/BiP (PubMed:21317875). Accumulation of misfolded protein in the endoplasmic reticulum causes release of HSPA5/BiP, allowing the luminal domain to homodimerize, promoting autophosphorylation of the kinase domain and subsequent activation of the endoribonuclease activity (PubMed:21317875). The endoribonuclease activity is specific for XBP1 mRNA and excises 26 nucleotides from XBP1 mRNA (PubMed:11779464, PubMed:24508390, PubMed:21317875). The resulting spliced transcript of XBP1 encodes a transcriptional activator protein that up-regulates expression of UPR target genes (PubMed:11779464, PubMed:24508390, PubMed:21317875).

> Gene Ontology
 
Biological Process GO:0000187 activation of MAPK activity
GO:0000394 RNA splicing, via endonucleolytic cleavage and ligation
GO:0001678 cellular glucose homeostasis
GO:0001935 endothelial cell proliferation
GO:0006379 mRNA cleavage
GO:0006397 mRNA processing
GO:0006401 RNA catabolic process
GO:0006402 mRNA catabolic process
GO:0006914 autophagy
GO:0006986 response to unfolded protein
GO:0006987 activation of signaling protein activity involved in unfolded protein response
GO:0007050 cell cycle arrest
GO:0007254 JNK cascade
GO:0007257 activation of JUN kinase activity
GO:0008380 RNA splicing
GO:0009743 response to carbohydrate
GO:0009746 response to hexose
GO:0009749 response to glucose
GO:0010506 regulation of autophagy
GO:0016236 macroautophagy
GO:0016241 regulation of macroautophagy
GO:0018105 peptidyl-serine phosphorylation
GO:0018209 peptidyl-serine modification
GO:0019439 aromatic compound catabolic process
GO:0030968 endoplasmic reticulum unfolded protein response
GO:0030969 mRNA splicing via endonucleolytic cleavage and ligation involved in unfolded protein response
GO:0031098 stress-activated protein kinase signaling cascade
GO:0032069 regulation of nuclease activity
GO:0032075 positive regulation of nuclease activity
GO:0032147 activation of protein kinase activity
GO:0032872 regulation of stress-activated MAPK cascade
GO:0032874 positive regulation of stress-activated MAPK cascade
GO:0033002 muscle cell proliferation
GO:0033120 positive regulation of RNA splicing
GO:0033500 carbohydrate homeostasis
GO:0033674 positive regulation of kinase activity
GO:0034284 response to monosaccharide
GO:0034620 cellular response to unfolded protein
GO:0034655 nucleobase-containing compound catabolic process
GO:0034976 response to endoplasmic reticulum stress
GO:0035924 cellular response to vascular endothelial growth factor stimulus
GO:0035966 response to topologically incorrect protein
GO:0035967 cellular response to topologically incorrect protein
GO:0036289 peptidyl-serine autophosphorylation
GO:0036290 protein trans-autophosphorylation
GO:0036498 IRE1-mediated unfolded protein response
GO:0042593 glucose homeostasis
GO:0043405 regulation of MAP kinase activity
GO:0043406 positive regulation of MAP kinase activity
GO:0043410 positive regulation of MAPK cascade
GO:0043484 regulation of RNA splicing
GO:0043506 regulation of JUN kinase activity
GO:0043507 positive regulation of JUN kinase activity
GO:0044270 cellular nitrogen compound catabolic process
GO:0045786 negative regulation of cell cycle
GO:0045860 positive regulation of protein kinase activity
GO:0046328 regulation of JNK cascade
GO:0046330 positive regulation of JNK cascade
GO:0046700 heterocycle catabolic process
GO:0046777 protein autophosphorylation
GO:0048659 smooth muscle cell proliferation
GO:0048660 regulation of smooth muscle cell proliferation
GO:0048661 positive regulation of smooth muscle cell proliferation
GO:0050673 epithelial cell proliferation
GO:0051403 stress-activated MAPK cascade
GO:0070054 mRNA splicing, via endonucleolytic cleavage and ligation
GO:0070055 mRNA endonucleolytic cleavage involved in unfolded protein response
GO:0070059 intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress
GO:0070302 regulation of stress-activated protein kinase signaling cascade
GO:0070304 positive regulation of stress-activated protein kinase signaling cascade
GO:0071322 cellular response to carbohydrate stimulus
GO:0071326 cellular response to monosaccharide stimulus
GO:0071331 cellular response to hexose stimulus
GO:0071333 cellular response to glucose stimulus
GO:0071900 regulation of protein serine/threonine kinase activity
GO:0071902 positive regulation of protein serine/threonine kinase activity
GO:0090305 nucleic acid phosphodiester bond hydrolysis
GO:0090501 RNA phosphodiester bond hydrolysis
GO:0090502 RNA phosphodiester bond hydrolysis, endonucleolytic
GO:0097193 intrinsic apoptotic signaling pathway
GO:0098787 mRNA cleavage involved in mRNA processing
GO:1900101 regulation of endoplasmic reticulum unfolded protein response
GO:1900103 positive regulation of endoplasmic reticulum unfolded protein response
GO:1901142 insulin metabolic process
GO:1901361 organic cyclic compound catabolic process
GO:1904705 regulation of vascular smooth muscle cell proliferation
GO:1904707 positive regulation of vascular smooth muscle cell proliferation
GO:1990579 peptidyl-serine trans-autophosphorylation
GO:1990874 vascular smooth muscle cell proliferation
Molecular Function GO:0000287 magnesium ion binding
GO:0004518 nuclease activity
GO:0004519 endonuclease activity
GO:0004521 endoribonuclease activity
GO:0004540 ribonuclease activity
GO:0004674 protein serine/threonine kinase activity
GO:0005161 platelet-derived growth factor receptor binding
GO:0030544 Hsp70 protein binding
GO:0031072 heat shock protein binding
GO:0043531 ADP binding
GO:0051879 Hsp90 protein binding
GO:0070851 growth factor receptor binding
Cellular Component GO:0005635 nuclear envelope
GO:0005637 nuclear inner membrane
GO:0030176 integral component of endoplasmic reticulum membrane
GO:0031227 intrinsic component of endoplasmic reticulum membrane
GO:0031965 nuclear membrane
GO:0061695 transferase complex, transferring phosphorus-containing groups
GO:1902554 serine/threonine protein kinase complex
GO:1902555 endoribonuclease complex
GO:1902911 protein kinase complex
GO:1905348 endonuclease complex
GO:1990332 Ire1 complex
GO:1990597 AIP1-IRE1 complex
GO:1990604 IRE1-TRAF2-ASK1 complex
GO:1990630 IRE1-RACK1-PP2A complex
> KEGG and Reactome Pathway
 
KEGG hsa04140 Regulation of autophagy
hsa04141 Protein processing in endoplasmic reticulum
hsa04210 Apoptosis
Reactome R-HSA-381070: IRE1alpha activates chaperones
R-HSA-392499: Metabolism of proteins
R-HSA-381119: Unfolded Protein Response (UPR)
Summary
SymbolERN1
Nameendoplasmic reticulum to nucleus signaling 1
Aliases IRE1; IRE1P; inositol-requiring enzyme 1; ER to nucleus signalling 1; IRE1a; hIRE1p; endoplasmic reticulum-t ......
Chromosomal Location17q23
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Literatures that report relations between ERN1 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 ERN1 and anti-tumor immunity in human cancer.
PMID Cancer type Relation to immunity Evidence sentences
25209846Hepatocellular CarcinomaInhibit immunityThe decreased expression level of CD155 was due to the involvement of the activating transcription factor 6 (ATF6) and inositol-requiring enzyme 1α (IRE1α) pathways.In addition, the IRE1α pathway contributed to the increased expression level of the ER-associated degradation (ERAD)-related molecule HRD1 and facilitated the degradation of CD155
Summary
SymbolERN1
Nameendoplasmic reticulum to nucleus signaling 1
Aliases IRE1; IRE1P; inositol-requiring enzyme 1; ER to nucleus signalling 1; IRE1a; hIRE1p; endoplasmic reticulum-t ......
Chromosomal Location17q23
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 ERN1 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
SymbolERN1
Nameendoplasmic reticulum to nucleus signaling 1
Aliases IRE1; IRE1P; inositol-requiring enzyme 1; ER to nucleus signalling 1; IRE1a; hIRE1p; endoplasmic reticulum-t ......
Chromosomal Location17q23
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 ERN1 in various data sets.
No PMID Cancer type Group Drug # Res # NRes Log2 (Fold Change) P value Anno
126997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)14120.0250.925
226997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)650.0870.906
326997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)87-0.0190.973
428552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 916-0.2260.41
528552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 59-0.3780.849
628552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 47-0.030.991
729033130MelanomaallAnti-PD-1 (nivolumab) 26230.4860.105
829033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 15110.3430.726
929033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 11120.6860.51
1029301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 480.0440.956
1129301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 2001
1229301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 280.4020.723
1329443960Urothelial cancerallAnti-PD-L1 (atezolizumab) 68230-0.2460.00155
> Mutation difference between responders and non-responders
 
Points in the above scatter plot represent the mutation difference of ERN1 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) 141705.9-5.91
225765070Non-small cell lung cancer (NSCLC)smokingAnti-PD-1 (pembrolizumab) 1030001
325765070Non-small cell lung cancer (NSCLC)non-smokingAnti-PD-1 (pembrolizumab) 41407.1-7.11
426359337MelanomaallAnti-CTLA-4 (ipilimumab) 27733.72.711
526359337MelanomaBRAFiAnti-CTLA-4 (ipilimumab) 0140001
626359337Melanomanon-BRAFiAnti-CTLA-4 (ipilimumab) 27593.73.40.31
726997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)21179.55.93.61
826997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)86250250.473
926997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)131109.1-9.10.458
1028552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 91606.2-6.21
1128552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 59011.1-11.11
1228552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470001
1329033130MelanomaallAnti-PD-1 (nivolumab) 382710.5010.50.135
1429033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 22139.109.10.519
1529033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 161412.5012.50.485
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
SymbolERN1
Nameendoplasmic reticulum to nucleus signaling 1
Aliases IRE1; IRE1P; inositol-requiring enzyme 1; ER to nucleus signalling 1; IRE1a; hIRE1p; endoplasmic reticulum-t ......
Chromosomal Location17q23
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of ERN1. 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
SymbolERN1
Nameendoplasmic reticulum to nucleus signaling 1
Aliases IRE1; IRE1P; inositol-requiring enzyme 1; ER to nucleus signalling 1; IRE1a; hIRE1p; endoplasmic reticulum-t ......
Chromosomal Location17q23
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of ERN1. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by ERN1.
> Immunoinhibitor
> Immunostimulator
> MHC molecule
> Immunoinhibitor
 
> Immunostimulator
 
> MHC molecule
 
Summary
SymbolERN1
Nameendoplasmic reticulum to nucleus signaling 1
Aliases IRE1; IRE1P; inositol-requiring enzyme 1; ER to nucleus signalling 1; IRE1a; hIRE1p; endoplasmic reticulum-t ......
Chromosomal Location17q23
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of ERN1. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene.
> Chemokine
> Receptor
> Chemokine
 
> Receptor
 
Summary
SymbolERN1
Nameendoplasmic reticulum to nucleus signaling 1
Aliases IRE1; IRE1P; inositol-requiring enzyme 1; ER to nucleus signalling 1; IRE1a; hIRE1p; endoplasmic reticulum-t ......
Chromosomal Location17q23
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Distribution of ERN1 expression across immune and molecular subtypes.
> Immune subtype
> Molecular subtype
> Immune subtype
 
> Molecular subtype
 
Summary
SymbolERN1
Nameendoplasmic reticulum to nucleus signaling 1
Aliases IRE1; IRE1P; inositol-requiring enzyme 1; ER to nucleus signalling 1; IRE1a; hIRE1p; endoplasmic reticulum-t ......
Chromosomal Location17q23
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Associations between ERN1 and clinical features.
> Overall survival analysis
> Cancer stage
> Tumor grade
> Overall survival
 
> Stage
 
> Grade
 
Summary
SymbolERN1
Nameendoplasmic reticulum to nucleus signaling 1
Aliases IRE1; IRE1P; inositol-requiring enzyme 1; ER to nucleus signalling 1; IRE1a; hIRE1p; endoplasmic reticulum-t ......
Chromosomal Location17q23
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Drugs targeting ERN1 collected from DrugBank database.
> Drugs from DrugBank database
 

  Details on drugs targeting ERN1.
ID Name Drug Type Targets #Targets
DB07382N~2~-1H-benzimidazol-5-yl-N~4~-(3-cyclopropyl-1H-pyrazol-5-yl)pyrimidine-2,4-diamineSmall MoleculeERN11