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

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; 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: mouse all
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Genomic context

Location:: 17q23.3

Exon count:: 22

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	17	NC_000017.11 (64039142..64130144, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	17	NC_060941.1 (64909877..65000874, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	17	NC_000017.10 (62116502..62207504, complement)

Chromosome 17 - NC_000017.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

5'-tRNA[Gly(GCC)] halves generated by IRE1alpha are linked to the ER stress response.
Title: 5'-tRNA(Gly(GCC)) halves generated by IRE1α are linked to the ER stress response.
Disordered regions in the IRE1alpha ER lumenal domain mediate its stress-induced clustering.
Title: Disordered regions in the IRE1α ER lumenal domain mediate its stress-induced clustering.
Knockdown of ERN1 disturbs the expression of phosphoserine aminotransferase 1 and related genes in glioblastoma cells.
Title: Knockdown of ERN1 disturbs the expression of phosphoserine aminotransferase 1 and related genes in glioblastoma cells.
Inhibition of ERN1 affects the expression of TGIF1 and other homeobox gene expressions in U87MG glioblastoma cells.
Title: Inhibition of ERN1 affects the expression of TGIF1 and other homeobox gene expressions in U87MG glioblastoma cells.
GRP78/IRE1 and cGAS/STING pathway crosstalk through CHOP facilitates iodoacetic acid-mediated testosterone decline.
Title: GRP78/IRE1 and cGAS/STING pathway crosstalk through CHOP facilitates iodoacetic acid-mediated testosterone decline.
IRE1alpha determines ferroptosis sensitivity through regulation of glutathione synthesis.
Title: IRE1α determines ferroptosis sensitivity through regulation of glutathione synthesis.
TurboID-Based IRE1 Interactome Reveals Participants of the Endoplasmic Reticulum-Associated Protein Degradation Machinery in the Human Mast Cell Leukemia Cell Line HMC-1.2.
Title: TurboID-Based IRE1 Interactome Reveals Participants of the Endoplasmic Reticulum-Associated Protein Degradation Machinery in the Human Mast Cell Leukemia Cell Line HMC-1.2.
The IRE1alpha-XBP1 arm of the unfolded protein response is a host factor activated in SARS-CoV-2 infection.
Title: The IRE1α-XBP1 arm of the unfolded protein response is a host factor activated in SARS-CoV-2 infection.
Inhibition of signaling protein ERN1 increases the sensitivity of serine synthesis gene expressions to glucose and glutamine deprivations in U87MG glioblastoma cells.
Title: Inhibition of signaling protein ERN1 increases the sensitivity of serine synthesis gene expressions to glucose and glutamine deprivations in U87MG glioblastoma cells.
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.

Submit: New GeneRIF Correction See all GeneRIFs (272)

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)

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

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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

SHGC-173528 (e-PCR)
- UniSTS:185385

RH47240 (e-PCR)
- UniSTS:45903

G10027 (e-PCR)
- UniSTS:61621

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables 3-phosphoinositide-dependent protein kinase activity	IEA Inferred from Electronic Annotation more info
enables ADP binding	IDA Inferred from Direct Assay more info	PubMed
enables AMP-activated protein kinase activity	IEA Inferred from Electronic Annotation more info
enables ATP binding	IDA Inferred from Direct Assay more info	PubMed
enables DNA-dependent protein kinase activity	IEA Inferred from Electronic Annotation more info
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 Rho-dependent protein serine/threonine kinase activity	IEA Inferred from Electronic Annotation more info
enables enzyme binding	IPI Inferred from Physical Interaction more info	PubMed
enables eukaryotic translation initiation factor 2alpha kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H2AS1 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H2AS121 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H2AT120 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H2AXS139 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H2BS14 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H2BS36 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H3S10 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H3S28 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H3S57 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H3T11 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H3T3 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H3T45 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H3T6 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H4S1 kinase activity	IEA Inferred from Electronic Annotation more info
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 ribosomal protein S6 kinase activity	IEA Inferred from Electronic Annotation more info
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 chromatin remodeling	IEA Inferred from Electronic Annotation more info
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

EC 2.7.11.1

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)

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