ERN2 endoplasmic reticulum to nucleus signaling 2 [Homo sapiens (human)] - Gene

Summary

Official Symbol: ERN2provided by HGNC
Official Full Name: endoplasmic reticulum to nucleus signaling 2provided by HGNC
Primary source: HGNC:HGNC:16942
See related: Ensembl:ENSG00000134398 MIM:604034; AllianceGenome:HGNC:16942
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: IRE1b; IRE2p; hIRE2p; IRE1-BETA
Summary: Enables several functions, including ATP binding activity; magnesium ion binding activity; and protein serine/threonine kinase activity. Involved in several processes, including apoptotic chromosome condensation; negative regulation of transcription, DNA-templated; and rRNA catabolic process. Predicted to be located in endoplasmic reticulum membrane and endoplasmic reticulum quality control compartment. Predicted to be integral component of membrane. Predicted to be part of IRE1-TRAF2-ASK1 complex. [provided by Alliance of Genome Resources, Apr 2022]
Expression: Biased expression in stomach (RPKM 26.7), colon (RPKM 17.0) and 5 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 16p12.2

Exon count:: 23

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	16	NC_000016.10 (23690310..23713222, complement)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	16	NC_060940.1 (23966114..23989027, complement)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	16	NC_000016.9 (23701631..23724543, complement)

Chromosome 16 - NC_000016.10 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

Expression

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See details

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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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

EEF1A2 and ERN2 could potentially discriminate metastatic status of mediastinal lymph node in lung adenocarcinomas harboring EGFR 19Del/L858R mutations.
Title: EEF1A2 and ERN2 could potentially discriminate metastatic status of mediastinal lymph node in lung adenocarcinomas harboring EGFR 19Del/L858R mutations.
A positive feedback bistable ERN2-XBP1S pathway regulates MUC5B-dominated mucus obstruction in idiopathic pulmonary fibrosis (IPF), providing an unfolded protein response-dependent mechanism linking the MUC5B promoter rs35705950 polymorphism with IPF pathogenesis.
Title: XBP1S Regulates MUC5B in a Promoter Variant-Dependent Pathway in Idiopathic Pulmonary Fibrosis Airway Epithelia.
IRE1beta acts as a dominant-negative suppressor of IRE1alpha and affect how barrier epithelial cells manage the response to stress at the host-environment interface.
Title: IRE1β negatively regulates IRE1α signaling in response to endoplasmic reticulum stress.
ER stress-regulated IRE1 dependent decay is involved in regulation of hepatic diseases. (review)
Title: Endoplasmic reticulum stress in the regulation of liver diseases: Involvement of Regulated IRE1α and β-dependent decay and miRNA.
The luminal event mediated by IRE1beta involves direct interaction with unfolded proteins rather than association/dissociation with BiP.
Title: Direct association of unfolded proteins with mammalian ER stress sensor, IRE1β.
Data show that IRE1beta represses translation on the ER membrane but not in the cytosol, and that this selective repression depends on the RNase activity of IRE1beta.
Title: Mammalian ER stress sensor IRE1β specifically down-regulates the synthesis of secretory pathway proteins.
Observational study of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)
Title: Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study.
Observational study of gene-disease association. (HuGE Navigator)
Title: Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip.
Clinical trial of gene-disease association and gene-environment interaction. (HuGE Navigator)
Title: Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.
RNase domain of IRE1 determines the functional specificities of each of these isoforms.
Title: RNase domains determine the functional difference between IRE1alpha and IRE1beta.

Submit: New GeneRIF Correction See all GeneRIFs (11)

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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Replication interactions

Interaction	Pubs
Knockdown of endoplasmic reticulum to nucleus signaling 2 (ERN2) by siRNA inhibits HIV-1 replication in HeLa P4/R5 cells	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

L18426 (e-PCR)
- UniSTS:34648

G06491 (e-PCR)
- UniSTS:10589

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables ATP binding	IDA Inferred from Direct Assay more info	PubMed
enables RNA endonuclease activity	IBA Inferred from Biological aspect of Ancestor more info
enables endonuclease activity	IDA Inferred from Direct Assay more info	PubMed
enables magnesium ion binding	IDA Inferred from Direct Assay more info	PubMed
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 apoptotic chromosome condensation	IMP Inferred from Mutant Phenotype 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 mRNA processing	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of DNA-templated transcription	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in protein phosphorylation	IDA Inferred from Direct Assay more info	PubMed
involved_in rRNA catabolic process	IDA Inferred from Direct Assay more info	PubMed
involved_in response to endoplasmic reticulum stress	TAS Traceable Author Statement more info	PubMed

Component	Evidence Code	Pubs
part_of IRE1-TRAF2-ASK1 complex	IBA Inferred from Biological aspect of Ancestor more info
part_of IRE1-TRAF2-ASK1 complex	ISS Inferred from Sequence or Structural Similarity more info
located_in cytosol	IDA Inferred from Direct Assay more info
located_in endoplasmic reticulum	IDA Inferred from Direct Assay more info
located_in endoplasmic reticulum quality control compartment	IEA Inferred from Electronic Annotation more info

General protein information

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Preferred Names: serine/threonine-protein kinase/endoribonuclease IRE2

Names: ER to nucleus signalling 2; IRE1 beta; IRE1, S. cerevisiae, homolog of; endoplasmic reticulum to nucleus signalling 2; inositol-requiring 1 beta; inositol-requiring protein 2

NP_001295149.2

EC 2.7.11.1

NP_150296.4

EC 2.7.11.1

XP_011544013.1

EC 2.7.11.1

XP_011544014.1

EC 2.7.11.1

XP_011544015.1

EC 2.7.11.1

XP_047289462.1

EC 2.7.11.1

XP_054235368.1

EC 2.7.11.1

XP_054235369.1

EC 2.7.11.1

XP_054235370.1

EC 2.7.11.1

XP_054235371.1

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_001308220.2 → NP_001295149.2 serine/threonine-protein kinase/endoribonuclease IRE2 isoform b precursor

Status: VALIDATED

Description

Transcript Variant: This variant (2) lacks an alternate in-frame exon in the central coding region, compared to variant 1, resulting in an isoform (b) that is shorter than isoform a.

Source sequence(s)

BU608100, EF560720, EF560739

Consensus CDS

CCDS76845.1

UniProtKB/TrEMBL

A5YM46, E7ETG2

Related

ENSP00000413812.2, ENST00000457008.6

Conserved Domains (5) summary

cd09769
Location:38 → 366

Luminal_IRE1; The Luminal domain, a dimerization domain, of the Serine/Threonine protein kinase, Inositol-requiring protein 1

cd10422
Location:733 → 858

RNase_Ire1; RNase domain (also known as the kinase extension nuclease domain) of Ire1

smart00220
Location:468 → 729

S_TKc; Serine/Threonine protein kinases, catalytic domain

COG1520
Location:41 → 237

PQQ; Outer membrane protein assembly factor BamB, contains PQQ-like beta-propeller repeat [Cell wall/membrane/envelope biogenesis]

cd13982
Location:465 → 730

STKc_IRE1; Catalytic domain of the Serine/Threonine kinase, Inositol-requiring protein 1
NM_033266.4 → NP_150296.4 serine/threonine-protein kinase/endoribonuclease IRE2 isoform a precursor

See identical proteins and their annotated locations for NP_150296.4

Status: VALIDATED

Description

Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (a).

Source sequence(s)

BU608100, EF560720, EF560739

Consensus CDS

CCDS32407.2

UniProtKB/Swiss-Prot

Q6ZNC0, Q76MJ5

UniProtKB/TrEMBL

A5YM65

Related

ENSP00000256797.5, ENST00000256797.9

Conserved Domains (5) summary

cd09769
Location:38 → 366

Luminal_IRE1; The Luminal domain, a dimerization domain, of the Serine/Threonine protein kinase, Inositol-requiring protein 1

cd10422
Location:785 → 910

RNase_Ire1; RNase domain (also known as the kinase extension nuclease domain) of Ire1

smart00220
Location:520 → 781

S_TKc; Serine/Threonine protein kinases, catalytic domain

COG1520
Location:41 → 237

PQQ; Outer membrane protein assembly factor BamB, contains PQQ-like beta-propeller repeat [Cell wall/membrane/envelope biogenesis]

cd13982
Location:517 → 782

STKc_IRE1; Catalytic domain of the Serine/Threonine kinase, Inositol-requiring protein 1

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

NC_000016.10 Reference GRCh38.p14 Primary Assembly

Range

23690310..23713222 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_047433506.1 → XP_047289462.1 serine/threonine-protein kinase/endoribonuclease IRE2 isoform X1
XM_011545711.3 → XP_011544013.1 serine/threonine-protein kinase/endoribonuclease IRE2 isoform X2

Conserved Domains (2) summary

cd09769
Location:38 → 366

Luminal_IRE1; The Luminal domain, a dimerization domain, of the Serine/Threonine protein kinase, Inositol-requiring protein 1

COG1520
Location:41 → 237

PQQ; Outer membrane protein assembly factor BamB, contains PQQ-like beta-propeller repeat [Cell wall/membrane/envelope biogenesis]
XM_011545713.2 → XP_011544015.1 serine/threonine-protein kinase/endoribonuclease IRE2 isoform X4

Conserved Domains (2) summary

cd09769
Location:38 → 366

Luminal_IRE1; The Luminal domain, a dimerization domain, of the Serine/Threonine protein kinase, Inositol-requiring protein 1

COG1520
Location:41 → 237

PQQ; Outer membrane protein assembly factor BamB, contains PQQ-like beta-propeller repeat [Cell wall/membrane/envelope biogenesis]
XM_011545712.3 → XP_011544014.1 serine/threonine-protein kinase/endoribonuclease IRE2 isoform X3

Conserved Domains (2) summary

cd09769
Location:38 → 366

Luminal_IRE1; The Luminal domain, a dimerization domain, of the Serine/Threonine protein kinase, Inositol-requiring protein 1

COG1520
Location:41 → 237

PQQ; Outer membrane protein assembly factor BamB, contains PQQ-like beta-propeller repeat [Cell wall/membrane/envelope biogenesis]

RNA

XR_950727.2 RNA Sequence

Related

ENST00000562562.1

Alternate T2T-CHM13v2.0

Genomic

NC_060940.1 Alternate T2T-CHM13v2.0

Range

23966114..23989027 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054379393.1 → XP_054235368.1 serine/threonine-protein kinase/endoribonuclease IRE2 isoform X1
XM_054379394.1 → XP_054235369.1 serine/threonine-protein kinase/endoribonuclease IRE2 isoform X2
XM_054379396.1 → XP_054235371.1 serine/threonine-protein kinase/endoribonuclease IRE2 isoform X4
XM_054379395.1 → XP_054235370.1 serine/threonine-protein kinase/endoribonuclease IRE2 isoform X3