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ERN1 endoplasmic reticulum to nucleus signaling 1 [ Homo sapiens (human) ]

Gene ID: 2081, updated on 20-Jan-2019

Summary

Official Symbol
ERN1provided by HGNC
Official Full Name
endoplasmic reticulum to nucleus signaling 1provided by HGNC
Primary source
HGNC:HGNC:3449
See related
Ensembl:ENSG00000178607 MIM:604033
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
IRE1; IRE1P; IRE1a; hIRE1p
Summary
This gene encodes the transmembrane protein kinase inositol-requiring enzyme 1. The encoded protein contains two functional catalytic domains, a serine/threonine-protein kinase domain and an endoribonuclease domain. This protein functions as a sensor of unfolded proteins in the endoplasmic reticulum (ER) and triggers an intracellular signaling pathway termed the unfolded protein response (UPR). The UPR is an ER stress response that is conserved from yeast to mammals and activates genes involved in degrading misfolded proteins, regulating protein synthesis and activating molecular chaperones. This protein specifically mediates the splicing and activation of the stress response transcription factor X-box binding protein 1. [provided by RefSeq, Aug 2017]
Expression
Ubiquitous expression in adrenal (RPKM 14.0), pancreas (RPKM 8.7) and 24 other tissues See more
Orthologs

Genomic context

See ERN1 in Genome Data Viewer
Location:
17q23.3
Exon count:
22
Annotation release Status Assembly Chr Location
109 current GRCh38.p12 (GCF_000001405.38) 17 NC_000017.11 (64039142..64132469, complement)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 17 NC_000017.10 (62116502..62207502, complement)

Chromosome 17 - NC_000017.11Genomic Context describing neighboring genes Neighboring gene PRR29 antisense RNA 1 Neighboring gene proline rich 29 Neighboring gene intercellular adhesion molecule 2 Neighboring gene small nucleolar RNA, C/D box 104 Neighboring gene small nucleolar RNA, H/ACA box 50C Neighboring gene small nucleolar RNA host gene 25

Genomic regions, transcripts, and products

Expression

  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

HIV-1 interactions

Protein interactions

Protein Gene Interaction Pubs
Envelope surface glycoprotein gp120 env HIV-1 Env gp120 upregulates ERN1 (IRE1a) in SVGA cells, human fetal astrocytes, and the prefrontal cortex of gp120 transgenic mice PubMed
Tat tat HIV-1 Tat induces endoplasmic reticulum (ER) stress response proteins CASP12 (Caspase 12), DDIT3 (CHOP), ROS1, ERN-1 (p-IRE1), EIF2AK3 (p-PERK), and ATF6 in human brain microvascular endothelial cells (HBMECs) PubMed

Go to the HIV-1, Human Interaction Database

Pathways from BioSystems

  • Alzheimer's disease, organism-specific biosystem (from KEGG)
    Alzheimer's disease, organism-specific biosystemAlzheimer's disease (AD) is a chronic disorder that slowly destroys neurons and causes serious cognitive disability. AD is associated with senile plaques and neurofibrillary tangles (NFTs). Amyloid-b...
  • Alzheimer's disease, conserved biosystem (from KEGG)
    Alzheimer's disease, conserved biosystemAlzheimer's disease (AD) is a chronic disorder that slowly destroys neurons and causes serious cognitive disability. AD is associated with senile plaques and neurofibrillary tangles (NFTs). Amyloid-b...
  • Alzheimers Disease, organism-specific biosystem (from WikiPathways)
    Alzheimers Disease, organism-specific biosystemThis pathway displays current genes, proteolytic events and other processes associated with the progression of Alzheimer's disease. This pathway was adapted from KEGG on 10/7/2011. Note: mitochondria...
  • Apoptosis, organism-specific biosystem (from KEGG)
    Apoptosis, organism-specific biosystemApoptosis is a genetically programmed process for the elimination of damaged or redundant cells by activation of caspases (aspartate-specific cysteine proteases). The onset of apoptosis is controlled...
  • Apoptosis, conserved biosystem (from KEGG)
    Apoptosis, conserved biosystemApoptosis is a genetically programmed process for the elimination of damaged or redundant cells by activation of caspases (aspartate-specific cysteine proteases). The onset of apoptosis is controlled...
  • Apoptosis-related network due to altered Notch3 in ovarian cancer, organism-specific biosystem (from WikiPathways)
    Apoptosis-related network due to altered Notch3 in ovarian cancer, organism-specific biosystemResults of pathway analysis of apoptosis-related genes in OVCAR3 cells treated with Notch3 siRNA or control siRNA.
  • Autophagy - animal, organism-specific biosystem (from KEGG)
    Autophagy - animal, organism-specific biosystemAutophagy (or macroautophagy) is a cellular catabolic pathway involving in protein degradation, organelle turnover, and non-selective breakdown of cytoplasmic components, which is evolutionarily cons...
  • Autophagy - animal, conserved biosystem (from KEGG)
    Autophagy - animal, conserved biosystemAutophagy (or macroautophagy) is a cellular catabolic pathway involving in protein degradation, organelle turnover, and non-selective breakdown of cytoplasmic components, which is evolutionarily cons...
  • Corticotropin-releasing hormone signaling pathway, organism-specific biosystem (from WikiPathways)
    Corticotropin-releasing hormone signaling pathway, organism-specific biosystemCorticotropin-releasing hormone (CRH) is a neuropeptide secreted abundantly in the paraventricular nucleus of the hypothalamus, amygdala, cerebral cortex and cerebellum in the central nervous system ...
  • IRE1alpha activates chaperones, organism-specific biosystem (from REACTOME)
    IRE1alpha activates chaperones, organism-specific biosystemIRE1-alpha is a single-pass transmembrane protein that resides in the endoplasmic reticulum (ER) membrane. The C-terminus of IRE1-alpha is located in the cytosol; the N-terminus is located in the ER ...
  • Metabolism of proteins, organism-specific biosystem (from REACTOME)
    Metabolism of proteins, organism-specific biosystemProtein metabolism comprises the pathways of translation, post-translational modification and protein folding.
  • Non-alcoholic fatty liver disease (NAFLD), organism-specific biosystem (from KEGG)
    Non-alcoholic fatty liver disease (NAFLD), organism-specific biosystemNon-alcoholic fatty liver disease (NAFLD) represents a spectrum ranging from simple steatosis to more severe steatohepatitis with hepatic inflammation and fibrosis, known as nonalcoholic steatohepati...
  • Non-alcoholic fatty liver disease (NAFLD), conserved biosystem (from KEGG)
    Non-alcoholic fatty liver disease (NAFLD), conserved biosystemNon-alcoholic fatty liver disease (NAFLD) represents a spectrum ranging from simple steatosis to more severe steatohepatitis with hepatic inflammation and fibrosis, known as nonalcoholic steatohepati...
  • Photodynamic therapy-induced unfolded protein response, organism-specific biosystem (from WikiPathways)
    Photodynamic therapy-induced unfolded protein response, organism-specific biosystemPhotodynamic therapy may induce a proteotoxic stress response mediated by transcription factors heat shock factor 1 (HSF1), X-box binding protein 1 (XBP1), activating transcription factor (ATF) 6, an...
  • Protein processing in endoplasmic reticulum, organism-specific biosystem (from KEGG)
    Protein processing in endoplasmic reticulum, organism-specific biosystemThe endoplasmic reticulum (ER) is a subcellular organelle where proteins are folded with the help of lumenal chaperones. Newly synthesized peptides enter the ER via the sec61 pore and are glycosylate...
  • Protein processing in endoplasmic reticulum, conserved biosystem (from KEGG)
    Protein processing in endoplasmic reticulum, conserved biosystemThe endoplasmic reticulum (ER) is a subcellular organelle where proteins are folded with the help of lumenal chaperones. Newly synthesized peptides enter the ER via the sec61 pore and are glycosylate...
  • Unfolded Protein Response (UPR), organism-specific biosystem (from REACTOME)
    Unfolded Protein Response (UPR), organism-specific biosystemThe Unfolded Protein Response (UPR) is a regulatory system that protects the Endoplasmic Reticulum (ER) from overload. The UPR is provoked by the accumulation of improperly folded protein in the ER d...

Interactions

Products Interactant Other Gene Complex Source Pubs Description

General gene information

Markers

Homology

Clone Names

  • FLJ30999, MGC163277, MGC163279

Gene Ontology Provided by GOA

Function Evidence Code Pubs
ADP binding IDA
Inferred from Direct Assay
more info
PubMed 
ATP binding IDA
Inferred from Direct Assay
more info
PubMed 
Hsp70 protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
Hsp90 protein binding IDA
Inferred from Direct Assay
more info
PubMed 
endoribonuclease activity IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
endoribonuclease activity IDA
Inferred from Direct Assay
more info
PubMed 
endoribonuclease activity TAS
Traceable Author Statement
more info
 
enzyme binding IPI
Inferred from Physical Interaction
more info
PubMed 
identical protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
magnesium ion binding IDA
Inferred from Direct Assay
more info
PubMed 
platelet-derived growth factor receptor binding IPI
Inferred from Physical Interaction
more info
PubMed 
protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
protein homodimerization activity IDA
Inferred from Direct Assay
more info
PubMed 
protein homodimerization activity ISS
Inferred from Sequence or Structural Similarity
more info
 
protein kinase activity IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
protein serine/threonine kinase activity IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
protein serine/threonine kinase activity IDA
Inferred from Direct Assay
more info
PubMed 
protein serine/threonine kinase activity TAS
Traceable Author Statement
more info
 
unfolded protein binding IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
Process Evidence Code Pubs
IRE1-mediated unfolded protein response IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
IRE1-mediated unfolded protein response IDA
Inferred from Direct Assay
more info
PubMed 
IRE1-mediated unfolded protein response TAS
Traceable Author Statement
more info
 
RNA phosphodiester bond hydrolysis, endonucleolytic IEA
Inferred from Electronic Annotation
more info
 
activation of JUN kinase activity IDA
Inferred from Direct Assay
more info
PubMed 
cell cycle arrest ISS
Inferred from Sequence or Structural Similarity
more info
 
cellular response to glucose stimulus IDA
Inferred from Direct Assay
more info
PubMed 
cellular response to unfolded protein IDA
Inferred from Direct Assay
more info
PubMed 
cellular response to unfolded protein IMP
Inferred from Mutant Phenotype
more info
PubMed 
cellular response to vascular endothelial growth factor stimulus IDA
Inferred from Direct Assay
more info
PubMed 
endoplasmic reticulum unfolded protein response IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
endothelial cell proliferation IDA
Inferred from Direct Assay
more info
PubMed 
insulin metabolic process IDA
Inferred from Direct Assay
more info
PubMed 
intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
mRNA catabolic process TAS
Traceable Author Statement
more info
PubMed 
mRNA cleavage ISS
Inferred from Sequence or Structural Similarity
more info
 
mRNA cleavage involved in mRNA processing IDA
Inferred from Direct Assay
more info
PubMed 
mRNA splicing, via endonucleolytic cleavage and ligation IDA
Inferred from Direct Assay
more info
PubMed 
mRNA splicing, via endonucleolytic cleavage and ligation IMP
Inferred from Mutant Phenotype
more info
PubMed 
mRNA splicing, via endonucleolytic cleavage and ligation TAS
Traceable Author Statement
more info
PubMed 
peptidyl-serine autophosphorylation IDA
Inferred from Direct Assay
more info
PubMed 
peptidyl-serine trans-autophosphorylation IMP
Inferred from Mutant Phenotype
more info
PubMed 
positive regulation of RNA splicing IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of endoplasmic reticulum unfolded protein response IMP
Inferred from Mutant Phenotype
more info
PubMed 
positive regulation of vascular smooth muscle cell proliferation IMP
Inferred from Mutant Phenotype
more info
PubMed 
protein autophosphorylation IDA
Inferred from Direct Assay
more info
PubMed 
protein phosphorylation IDA
Inferred from Direct Assay
more info
PubMed 
regulation of macroautophagy TAS
Traceable Author Statement
more info
PubMed 
response to endoplasmic reticulum stress IDA
Inferred from Direct Assay
more info
PubMed 
Component Evidence Code Pubs
AIP1-IRE1 complex IEA
Inferred from Electronic Annotation
more info
 
IRE1-RACK1-PP2A complex IDA
Inferred from Direct Assay
more info
PubMed 
IRE1-TRAF2-ASK1 complex IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
IRE1-TRAF2-ASK1 complex IDA
Inferred from Direct Assay
more info
PubMed 
Ire1 complex NAS
Non-traceable Author Statement
more info
PubMed 
cytoplasm IDA
Inferred from Direct Assay
more info
PubMed 
endoplasmic reticulum IDA
Inferred from Direct Assay
more info
PubMed 
endoplasmic reticulum membrane IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
endoplasmic reticulum membrane TAS
Traceable Author Statement
more info
 
integral component of endoplasmic reticulum membrane IDA
Inferred from Direct Assay
more info
PubMed 
mitochondrion IEA
Inferred from Electronic Annotation
more info
 
nuclear inner membrane IEA
Inferred from Electronic Annotation
more info
 

General protein information

Preferred Names
serine/threonine-protein kinase/endoribonuclease IRE1
Names
ER to nucleus signalling 1
inositol-requiring 1
inositol-requiring enzyme 1
inositol-requiring protein 1
ire1-alpha
protein kinase/endoribonuclease
NP_001424.3
XP_016879836.1
XP_016879837.1

NCBI Reference Sequences (RefSeq)

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

  1. NM_001433.5NP_001424.3  serine/threonine-protein kinase/endoribonuclease IRE1 precursor

    See identical proteins and their annotated locations for NP_001424.3

    Status: REVIEWED

    Source sequence(s)
    AB209869, AC005803, AC025362, BC070350, BC130405, CA311378, DB128514
    Consensus CDS
    CCDS45762.1
    UniProtKB/Swiss-Prot
    O75460
    Related
    ENSP00000401445.2, ENST00000433197.3
    Conserved Domains (5) summary
    cd09769
    Location:30298
    Luminal_IRE1; The Luminal domain, a dimerization domain, of the Serine/Threonine protein kinase, Inositol-requiring protein 1
    cd10422
    Location:836961
    RNase_Ire1; RNase domain (also known as the kinase extension nuclease domain) of Ire1
    smart00220
    Location:571832
    S_TKc; Serine/Threonine protein kinases, catalytic domain
    cd13982
    Location:568833
    STKc_IRE1; Catalytic domain of the Serine/Threonine kinase, Inositol-requiring protein 1
    pfam13360
    Location:21220
    PQQ_2; PQQ-like domain

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 109

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p12 Primary Assembly

Genomic

  1. NC_000017.11 Reference GRCh38.p12 Primary Assembly

    Range
    64039142..64132469 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_017024347.2XP_016879836.1  serine/threonine-protein kinase/endoribonuclease IRE1 isoform X1

  2. XM_017024348.2XP_016879837.1  serine/threonine-protein kinase/endoribonuclease IRE1 isoform X2

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

  1. NM_152461.2: Suppressed sequence

    Description
    NM_152461.2: This RefSeq was permanently suppressed because it is primarily intronic sequence.
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