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FLASH GENE
Symbol ERN1 contributors: mct - updated : 16-07-2010
HGNC name endoplasmic reticulum to nucleus signaling 1
HGNC id 3449
Location 17q23.3      Physical location : 62.120.389 - 62.207.502
Synonym name
  • inositol-requiring 1
  • protein kinase/endoribonuclease
  • ER to nucleus signaling 1
  • Synonym symbol(s) IRE1, IRE1P, FLJ30999, MGC163277, MGC163279, IRE1alpha, IRE1a
    EC.number 2.7.11.1
    DNA
    TYPE functioning gene
    STRUCTURE 87.11 kb     22 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    Physical map
    HAN11 17q24.2 WD-repeat protein LOC51204 17q24.2 clone HQ0477 PRO0477p LOC390806 17 similar to Hypothetical protein FLJ14668 MAP3K3 17q24.2 mitogen-activated protein kinase kinase kinase 3 MGC10986 17q24.2 hypothetical protein MGC10986 LYK5 17q24.2 protein kinase LYK5 GK001 17q24.2 GK001 protein DDX42 17q24.2 DEAD (Asp-Glu-Ala-Asp) box polypeptide 42 FTSJ3 17q23 FtsJ homolog 3 (E. coli) PSMC5 17q24-q25 proteasome (prosome, macropain) 26S subunit, ATPase, 5 SMARCD2 17q23-q24 SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily d, member 2 LOC388410 17 LOC388410 CSH2 17q23.3-q24.2 chorionic somatomammotropin hormone 2 GH2 17q23 growth hormone 2 CSH1 17q23.3-q24.2 chorionic somatomammotropin hormone 1 (placental lactogen) CSHL1 17q23.3-q24.2 chorionic somatomammotropin hormone-like 1 GH1 17q24 growth hormone 1 CD79B 17q23 CD79B antigen (immunoglobulin-associated beta) SCN4A 17q23 sodium channel, voltage-gated, type IV, alpha ICAM2 17q23-q25 intercellular adhesion molecule 2 ERN1 16p12 ER to nucleus signalling 1 FLJ30999 17q24.2 hypothetical protein FLJ30999 HT008 17q24.2 uncharacterized hypothalamus protein HT008 LOC253013 17q24.2 similar to ribosomal protein L31 PECAM1 17q23 platelet/endothelial cell adhesion molecule (CD31 antigen)
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    22 - 4005 109.6 977 - 2009 19135427
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • kinase/RNase domains extended by 43AAs at its N terminus, a kinase domain activated by trans-autophosphorylation
  • a RNase domain in the cytosolic region
  • HOMOLOGY
    interspecies homolog to murine Ern1 (93.3pc)
    homolog to rattus Ern1 (93.8pc)
    intraspecies
    Homologene
    FAMILY
  • protein kinase superfamily
  • Ser/Thr protein kinase family
  • CATEGORY enzyme , transport
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    intracellular,nucleus
    text
  • transported to the nucleus after proteolytic cleavage
  • ER-resident, type I transmembrane protein with a luminal domain sensing UPR and a cytosolic domain passing the signal on to components further downstream via its kinase and endoribonuclease (RNase) activities
  • basic FUNCTION
  • involved in electron transport, protein amino acid phosphorylation
  • has an intrinsic kinase activity and an endoribonuclease activity
  • has a unique function of relieving ER stress in cells
  • induces unconventional splicing of mRNA coding a specific transcription factor for activating the unfolded protein response
  • activating chaperone genes in response to stress in the ER and also activating JNK
  • promote cell survival by reducing misfolded protein levels
  • type I transmembrane Ser/Thr kinase that also has site-specific endoribonuclease (RNase) activity
  • induction of ER quality control proteins is mediated by ERN1 which activates the transcription factor XBP1 via an unconventional splicing event
  • oligomerizes in the ER membrane and oligomerization correlates with the onset of ERN1 phosphorylation and RNase activity
  • its activity is governed by a timer that may be important in switching the UPR (unfolded protein response) from the initially cytoprotective phase to the apoptotic mode
  • splices the precursor unspliced form of X-box–binding protein 1 messenger RNA (XBP1u mRNA) on the ER membrane to yield an active transcription factor (XBP1s), leading to the alleviation of the stress
  • endoribonuclease activity of ERN1 appears to be required for AMPK activation in response to nitric oxide
  • RNase activity of ERN11 participates in AMPK activation and subsequent signaling through multiple AMPK-dependent pathways in response to nitrosative stress
  • plays an essential role in ER stress-mediated aggregation of mutant HTT via the inhibition of autophagy flux and thus neuronal toxicity of mutant HTT aggregates in Huntington disease
  • ER stress sensor protein, activated via trans-autophosphorylation in response to ER stress triggered by thapsigargin or tunicamycin
  • directs a key unfolded protein response signaling pathway that controls the fidelity of ER protein folding
  • CELLULAR PROCESS cell life, cell death/apoptosis
    nucleotide, transcription, regulation
    protein
    PHYSIOLOGICAL PROCESS electron transport
    PATHWAY
    metabolism
    signaling
    ERN1-XBP1 pathway is involved in osteoblast differentiation through promoting SP7 transcription
    a component
  • the cytosolic domain of IRE1alpha forms a complex with BAK1 and with BAX, complex that is essential for IRE1alpha activation
  • homodimer, disulfide-linked; dimer formation is driven by hydrophobic interactions within the N-terminal luminal domains and stabilized by disulfide bridges
  • INTERACTION
    DNA
    RNA
    small molecule metal binding, nucleotide,
  • ions Mg2+
  • ATP
  • protein
  • TRAF2 was proposed to bind to ERN1 during ER stress response
  • binds HSPA5, a negative regulator of the unfolded protein response (interaction may disrupt homodimerization and prevent activation of ERN1)
  • CD59 (complement defense 59) mRNA is a novel cleavage target of ERN1
  • directly binds to USP14 and the interaction between ERN1 and USP14 is inhibited by ER stress
  • HSPA1A binding to ERN1 enhances ERN1/XBP1 signaling at the ER and inhibits ER stress-induced apoptosis
  • ERN1 target XBP1, and are essential for bone morphogenic protein 2-induced osteoblast differentiation
  • directs proteasomal and lysosomal degradation of misfolded rhodopsin
  • cell & other
    REGULATION
    activated by BAX and BAK1
    Other unfolded protein response (UPR) induction leads to proteolytic cleavage of ERN1
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
    In mice, IRE1alpha inactivation results in widespread developmental defects, leading to embryonic death after 12.5 days of gestation, and IRE1alpha was activated predominantly in the placenta