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

Gene ID: 10595, updated on 3-Apr-2024

Summary

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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
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Genomic context

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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_000016.10Genomic Context describing neighboring genes Neighboring gene ReSE screen-validated silencer GRCh37_chr16:23651698-23651932 Neighboring gene H3K27ac hESC enhancer GRCh37_chr16:23653060-23653849 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 10585 Neighboring gene partner and localizer of BRCA2 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 10586 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr16:23698309-23698810 Neighboring gene dynactin subunit 5 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr16:23716303-23716803 Neighboring gene H3K27ac hESC enhancer GRCh37_chr16:23740522-23741453 Neighboring gene polo like kinase 1 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr16:23766235-23766880 Neighboring gene OCT4-NANOG-H3K4me1 hESC enhancer GRCh37_chr16:23797941-23798576 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr16:23798577-23799212 Neighboring gene CRISPRi-validated cis-regulatory element chr16.1865 Neighboring gene CRISPRi-validated cis-regulatory element chr16.1866 Neighboring gene calcineurin like EF-hand protein 2 Neighboring gene CRISPRi-validated cis-regulatory element chr16.1867 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr16:23846913-23847460 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr16:23847461-23848006 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 10589 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 10590 Neighboring gene ReSE screen-validated silencer GRCh37_chr16:23858657-23858875 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 10591 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr16:23877081-23877727 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 10592 Neighboring gene protein kinase C beta Neighboring gene GATA motif-containing MPRA enhancer 73 Neighboring gene ReSE screen-validated silencer GRCh37_chr16:23915426-23915611 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 10593 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 10594 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 10595 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 7285 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 10596 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 10597 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 10598 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr16:24066265-24066934 Neighboring gene NANOG-H3K27ac hESC enhancer GRCh37_chr16:24086836-24087648 Neighboring gene NANOG-H3K27ac hESC enhancer GRCh37_chr16:24087649-24088461 Neighboring gene NANOG-H3K4me1 hESC enhancer GRCh37_chr16:24119013-24119512 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr16:24146937-24147472 Neighboring gene H3K27ac hESC enhancer GRCh37_chr16:24148009-24148544 Neighboring gene H3K27ac hESC enhancer GRCh37_chr16:24148545-24149080 Neighboring gene Sharpr-MPRA regulatory region 8464 Neighboring gene microRNA 1273h

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. IRE1β negatively regulates IRE1α signaling in response to endoplasmic reticulum stress. Grey MJ, et al. J Cell Biol, 2020 Feb 3. PMID 31985747, Free PMC Article
  2. Direct association of unfolded proteins with mammalian ER stress sensor, IRE1β. Oikawa D, et al. PLoS One, 2012. PMID 23236464, Free PMC Article
  3. Mammalian ER stress sensor IRE1β specifically down-regulates the synthesis of secretory pathway proteins. Nakamura D, et al. FEBS Lett, 2011 Jan 3. PMID 21146530
  4. EEF1A2 and ERN2 could potentially discriminate metastatic status of mediastinal lymph node in lung adenocarcinomas harboring EGFR 19Del/L858R mutations. Xia L, et al. Thorac Cancer, 2020 Oct. PMID 32881299, Free PMC Article
  5. Endoplasmic reticulum stress in the regulation of liver diseases: Involvement of Regulated IRE1α and β-dependent decay and miRNA. Rashid HO, et al. J Gastroenterol Hepatol, 2017 May. PMID 27774654

See all (23) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. 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.
  2. 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.
  3. 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.
  4. 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.
  5. 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.
  6. 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.
  7. 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.
  8. Observational study of gene-disease association. (HuGE Navigator)
    Title: Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip.
  9. 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.
  10. 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)

Genotypes

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

Homology

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
NP_150296.4
XP_011544013.1
XP_011544014.1
XP_011544015.1
XP_047289462.1
XP_054235368.1
XP_054235369.1
XP_054235370.1
XP_054235371.1

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)

  1. 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

  2. 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

  1. NC_000016.10 Reference GRCh38.p14 Primary Assembly

    Range
    23690310..23713222 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_047433506.1 → XP_047289462.1  serine/threonine-protein kinase/endoribonuclease IRE2 isoform X1

  2. 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]

  3. 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]

  4. 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

  1. XR_950727.2 RNA Sequence

    Related
    ENST00000562562.1

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060940.1 Alternate T2T-CHM13v2.0

    Range
    23966114..23989027 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054379393.1 → XP_054235368.1  serine/threonine-protein kinase/endoribonuclease IRE2 isoform X1

  2. XM_054379394.1 → XP_054235369.1  serine/threonine-protein kinase/endoribonuclease IRE2 isoform X2

  3. XM_054379396.1 → XP_054235371.1  serine/threonine-protein kinase/endoribonuclease IRE2 isoform X4

  4. XM_054379395.1 → XP_054235370.1  serine/threonine-protein kinase/endoribonuclease IRE2 isoform X3

RNA

  1. XR_008489048.1 RNA Sequence

Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q76MJ5.4 GenPept UniProtKB/Swiss-Prot:Q76MJ5

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