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

Gene ID: 2081, updated on 8-Apr-2024

Summary

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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; AllianceGenome:HGNC:3449
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
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Genomic context

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See ERN1 in Genome Data Viewer
Location:
17q23.3
Exon count:
22
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 17 NC_000017.11 (64039142..64130144, complement)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 17 NC_060941.1 (64909877..65000874, complement)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 17 NC_000017.10 (62116502..62207504, complement)

Chromosome 17 - NC_000017.11Genomic Context describing neighboring genes Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 8836 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr17:62075897-62076874 Neighboring gene PRR29 antisense RNA 1 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr17:62083286-62083980 Neighboring gene proline rich 29 Neighboring gene intercellular adhesion molecule 2 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 12571 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr17:62097827-62098327 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 12573 Neighboring gene CRISPRi-validated cis-regulatory element chr17.4314 Neighboring gene CRISPRi-validated cis-regulatory element chr17.4315 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr17:62132617-62133360 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr17:62133361-62134104 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 8837 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 12576 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 12577 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 8838 Neighboring gene Sharpr-MPRA regulatory region 10488 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 12578 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 12579 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 12580 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 12581 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 12582 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 8839 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 8840 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 12583 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 12584 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 12585 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 12586 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr17:62223017-62223571 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 12587 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

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • 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

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Related articles in PubMed

  1. [Role of IRE1 in autophagy induced by vitamin E succinate in human gastric cancer cell]. Feng X, et al. Wei Sheng Yan Jiu, 2023 Jan. PMID 36750337
  2. Tumor-intrinsic IRE1α signaling controls protective immunity in lung cancer. Crowley MJP, et al. Nat Commun, 2023 Jan 9. PMID 36624093, Free PMC Article
  3. Regulation of Blos1 by IRE1 prevents the accumulation of Huntingtin protein aggregates. Bae D, et al. Mol Biol Cell, 2022 Nov 1. PMID 36044348, Free PMC Article
  4. Aqueous Extract of Descuraniae Semen Attenuates Lipopolysaccharide-Induced Inflammation and Apoptosis by Regulating the Proteasomal Degradation and IRE1α-Dependent Unfolded Protein Response in A549 Cells. Hsieh PC, et al. Front Immunol, 2022. PMID 35812413, Free PMC Article
  5. Functional role of the ER stress transducer IRE1α in CF airway epithelial inflammation. Ribeiro CMP, et al. Curr Opin Pharmacol, 2022 Aug. PMID 35749907

See all (296) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. IRE1alpha recognizes a structural motif in cholera toxin to activate an unfolded protein response.
    Title: IRE1α recognizes a structural motif in cholera toxin to activate an unfolded protein response.
  2. ERN1 knockdown modifies the hypoxic regulation of homeobox gene expression in U87MG glioblastoma cells.
    Title: ERN1 knockdown modifies the hypoxic regulation of homeobox gene expression in U87MG glioblastoma cells.
  3. Loss of function of XBP1 splicing activity of IRE1alpha favors B cell tolerance breakdown.
    Title: Loss of function of XBP1 splicing activity of IRE1α favors B cell tolerance breakdown.
  4. Innate IRE1alpha-XBP1 activation by viral single-stranded RNA and its influence on lung cytokine production during SARS-CoV-2 pneumonia.
    Title: Innate IRE1α-XBP1 activation by viral single-stranded RNA and its influence on lung cytokine production during SARS-CoV-2 pneumonia.
  5. The ER stress sensor IRE1 interacts with STIM1 to promote store-operated calcium entry, T cell activation, and muscular differentiation.
    Title: The ER stress sensor IRE1 interacts with STIM1 to promote store-operated calcium entry, T cell activation, and muscular differentiation.
  6. Valosin-containing protein (VCP/p97) is prognostically unfavorable in pediatric AML, and negatively correlates with unfolded protein response proteins IRE1 and GRP78: A report from the Children's Oncology Group.
    Title: Valosin-containing protein (VCP/p97) is prognostically unfavorable in pediatric AML, and negatively correlates with unfolded protein response proteins IRE1 and GRP78: A report from the Children's Oncology Group.
  7. Hypoxia controls the expression of genes responsible for serine synthesis in U87MG cells on ERN1-dependent manner.
    Title: Hypoxia controls the expression of genes responsible for serine synthesis in U87MG cells on ERN1-dependent manner.
  8. IRE1-mediated degradation of pre-miR-301a promotes apoptosis through upregulation of GADD45A.
    Title: IRE1-mediated degradation of pre-miR-301a promotes apoptosis through upregulation of GADD45A.
  9. Novel XBP1s-independent function of IRE1 RNase in HIF-1alpha-mediated glycolysis upregulation in human macrophages upon stimulation with LPS or saturated fatty acid.
    Title: Novel XBP1s-independent function of IRE1 RNase in HIF-1α-mediated glycolysis upregulation in human macrophages upon stimulation with LPS or saturated fatty acid.
  10. The unfolded protein response components IRE1alpha and XBP1 promote human coronavirus infection.
    Title: The unfolded protein response components IRE1α and XBP1 promote human coronavirus infection.
Submit: New GeneRIF Correction See all GeneRIFs (263)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

HIV-1 interactions

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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 PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Clone Names

  • FLJ30999, MGC163277, MGC163279

Gene Ontology Provided by GOA

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

General protein information

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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

NCBI Reference Sequences (RefSeq)

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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_001433.5 → NP_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
    A1L457, A8K8N8, A8MXS7, O75460, Q59EE2
    UniProtKB/TrEMBL
    A0A7P0TAB0
    Related
    ENSP00000401445.2, ENST00000433197.4
    Conserved Domains (5) summary
    cd09769
    Location:30 → 298
    Luminal_IRE1; The Luminal domain, a dimerization domain, of the Serine/Threonine protein kinase, Inositol-requiring protein 1
    cd10422
    Location:836 → 961
    RNase_Ire1; RNase domain (also known as the kinase extension nuclease domain) of Ire1
    smart00220
    Location:571 → 832
    S_TKc; Serine/Threonine protein kinases, catalytic domain
    cd13982
    Location:568 → 833
    STKc_IRE1; Catalytic domain of the Serine/Threonine kinase, Inositol-requiring protein 1
    pfam13360
    Location:21 → 220
    PQQ_2; PQQ-like domain

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

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

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000017.11 Reference GRCh38.p14 Primary Assembly

    Range
    64039142..64130144 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060941.1 Alternate T2T-CHM13v2.0

    Range
    64909877..65000874 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

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.
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
O75460.2 GenPept UniProtKB/Swiss-Prot:O75460

Gene LinkOut

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