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

    Gene ID: 2081, updated on 3-Nov-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
    mouse all
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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_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_000017.11Genomic 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 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. Development of a Rapid in vivo Assay to Evaluate the Efficacy of IRE1-specific Inhibitors of the Unfolded Protein Response Using Medaka Fish. Jin B, et al. Cell Struct Funct, 2020 Feb 7. PMID 31875595, Free PMC Article
    2. Expression of IGFBP6, IGFBP7, NOV, CYR61, WISP1 and WISP2 genes in U87 glioma cells in glutamine deprivation condition. Minchenko OH, et al. Ukr Biochem J, 2016 May-Jun. PMID 29235329
    3. Hypoxic regulation of MYBL1, MEST, TCF3, TCF8, GTF2B, GTF2F2 and SNAI2 genes expression in U87 glioma cells upon IRE1 inhibition. Minchenko OH, et al. Ukr Biochem J, 2016 Nov-Dec. PMID 29235836
    4. Inhibition of IRE1 modifies hypoxic regulation of G6PD, GPI, TKT, TALDO1, PGLS and RPIA genes expression in U87 glioma cells. Minchenko OH, et al. Ukr Biochem J, 2017 Jan-Feb. PMID 29236388
    5. Deficiency of the IRE1α-Autophagy Axis Enhances the Antitumor Effects of the Oncolytic Virus M1. Li K, et al. J Virol, 2018 Mar 15. PMID 29263275, Free PMC Article

    See all (320) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. 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.
    2. 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.
    3. 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.
    4. 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.
    5. IRE1alpha determines ferroptosis sensitivity through regulation of glutathione synthesis.
      Title: IRE1α determines ferroptosis sensitivity through regulation of glutathione synthesis.
    6. 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.
    7. 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.
    8. 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.
    9. 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.
    10. 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.
    Submit: New GeneRIF Correction See all GeneRIFs (271)

    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 histone H2AS1 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 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

    NCBI Reference Sequences (RefSeq)

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    NEW Try the new Transcript table

    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_2024_08

    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

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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