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Aliases for ERN1 Gene

Aliases for ERN1 Gene

  • Endoplasmic Reticulum To Nucleus Signaling 1 2 3
  • IRE1a 3 4 6
  • IRE1 3 4 6
  • Endoplasmic Reticulum-To-Nucleus Signaling 1 3 4
  • Inositol-Requiring Protein 1 3 4
  • Inositol-Requiring Enzyme 1 2 3
  • ER To Nucleus Signalling 1 2 3
  • Ire1-Alpha 3 4
  • HIRE1p 3 4
  • Serine/Threonine-Protein Kinase/Endoribonuclease IRE1 3
  • Protein Kinase/Endoribonuclease 3
  • Inositol-Requiring 1 3
  • EC 2.7.11 63
  • IRE1P 3

External Ids for ERN1 Gene

Summaries for ERN1 Gene

Entrez Gene Summary for ERN1 Gene

  • The protein encoded by this gene is the ER to nucleus signalling 1 protein, a human homologue of the yeast Ire1 gene product. This protein possesses intrinsic kinase activity and an endoribonuclease activity and it is important in altering gene expression as a response to endoplasmic reticulum-based stress signals. [provided by RefSeq, Jul 2008]

GeneCards Summary for ERN1 Gene

ERN1 (Endoplasmic Reticulum To Nucleus Signaling 1) is a Protein Coding gene. Among its related pathways are Biosynthesis of the N-glycan precursor (dolichol lipid-linked oligosaccharide, LLO) and transfer to a nascent protein and Translational Control. GO annotations related to this gene include identical protein binding and magnesium ion binding. An important paralog of this gene is ERN2.

UniProtKB/Swiss-Prot for ERN1 Gene

  • Senses unfolded proteins in the lumen of the endoplasmic reticulum via its N-terminal domain which leads to enzyme auto-activation. The active endoribonuclease domain splices XBP1 mRNA to generate a new C-terminus, converting it into a potent unfolded-protein response transcriptional activator and triggering growth arrest and apoptosis.

Tocris Summary for ERN1 Gene

  • IRE1 (also known as endoplasmic reticulum to nucleus signaling (ERN) 1) is a transmembrane resident ER protein that possesses both kinase and endonuclease domains. Both yeast (IRE1) and mammalian (IRE1alpha) homologs are involved in the degradation of misfolded proteins, as part of the unfolded protein response (UPR) pathway. IRE1 (yeast) is involved in the endonucleolytic cleavage of HAC1 mRNA, whereas IRE1alpha (human) catalyzes the splicing of X-box binding protein (XBP) 1 mRNA. XBP1 mRNA splicing triggers upregulation of genes involved in the ERAD pathway, induction of XBP1 expression and the synthesis of ER chaperones.

Gene Wiki entry for ERN1 Gene

No data available for PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for ERN1 Gene

Genomics for ERN1 Gene

Genomic Location for ERN1 Gene

Start:
64,039,142 bp from pter
End:
64,130,819 bp from pter
Size:
91,678 bases
Orientation:
Minus strand

Genomic View for ERN1 Gene

UCSC Golden Path with GeneCards custom track
Cytogenetic band:
Genomic Location for ERN1 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for ERN1 Gene

Regulatory Elements for ERN1 Gene

Proteins for ERN1 Gene

  • Protein details for ERN1 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    O75460-ERN1_HUMAN
    Recommended name:
    Serine/threonine-protein kinase/endoribonuclease IRE1
    Protein Accession:
    O75460
    Secondary Accessions:
    • A1L457
    • A8K8N8
    • A8MXS7
    • Q59EE2

    Protein attributes for ERN1 Gene

    Size:
    977 amino acids
    Molecular mass:
    109735 Da
    Cofactor:
    Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
    Quaternary structure:
    • Interacts with DAB2IP (via PH domain); the interaction occurs in a ER stress-induced dependent manner and is required for subsequent recruitment of TRAF2 to ERN1 (By similarity). Homodimer; disulfide-linked. Dimer formation is driven by hydrophobic interactions within the N-terminal luminal domains and stabilized by disulfide bridges. Also binds HSPA5, a negative regulator of the unfolded protein response. This interaction may disrupt homodimerization and prevent activation of ERN1. Interacts with TAOK3 and TRAF2.

    Three dimensional structures from OCA and Proteopedia for ERN1 Gene

    Alternative splice isoforms for ERN1 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for ERN1 Gene

Proteomics data for ERN1 Gene at MOPED

Selected DME Specific Peptides for ERN1 Gene

Post-translational modifications for ERN1 Gene

Other Protein References for ERN1 Gene

ENSEMBL proteins:
Reactome Protein details:
REFSEQ proteins:

Domains for ERN1 Gene

Gene Families for ERN1 Gene

Suggested Antigen Peptide Sequences for ERN1 Gene

GenScript: Design optimal peptide antigens:

Graphical View of Domain Structure for InterPro Entry

O75460

UniProtKB/Swiss-Prot:

ERN1_HUMAN
Domain:
  • Contains 1 KEN domain.:
    • O75460
  • Contains 1 protein kinase domain.:
    • O75460
Family:
  • Belongs to the protein kinase superfamily. Ser/Thr protein kinase family.:
    • O75460
genes like me logo Genes that share domains with ERN1: view

Function for ERN1 Gene

Molecular function for ERN1 Gene

UniProtKB/Swiss-Prot CatalyticActivity: ATP + a protein = ADP + a phosphoprotein.
UniProtKB/Swiss-Prot EnzymeRegulation: The kinase domain is activated by trans-autophosphorylation. Kinase activity is required for activation of the endoribonuclease domain.
UniProtKB/Swiss-Prot Function: Senses unfolded proteins in the lumen of the endoplasmic reticulum via its N-terminal domain which leads to enzyme auto-activation. The active endoribonuclease domain splices XBP1 mRNA to generate a new C-terminus, converting it into a potent unfolded-protein response transcriptional activator and triggering growth arrest and apoptosis.

Enzyme Numbers (IUBMB) for ERN1 Gene

Gene Ontology (GO) - Molecular Function for ERN1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000287 magnesium ion binding IDA 9637683
GO:0004519 endonuclease activity --
GO:0004521 endoribonuclease activity TAS --
GO:0004540 ribonuclease activity --
GO:0004672 protein kinase activity --
genes like me logo Genes that share ontologies with ERN1: view
genes like me logo Genes that share phenotypes with ERN1: view

Animal Models for ERN1 Gene

MGI Knock Outs for ERN1:

miRNA for ERN1 Gene

miRTarBase miRNAs that target ERN1

No data available for Transcription Factor Targeting and HOMER Transcription for ERN1 Gene

Localization for ERN1 Gene

Subcellular locations from UniProtKB/Swiss-Prot for ERN1 Gene

Endoplasmic reticulum membrane; Single-pass type I membrane protein.

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for ERN1 Gene COMPARTMENTS Subcellular localization image for ERN1 gene
Compartment Confidence
endoplasmic reticulum 5
nucleus 2
plasma membrane 2
cytosol 1
extracellular 1
golgi apparatus 1
mitochondrion 1
peroxisome 1

Gene Ontology (GO) - Cellular Components for ERN1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005637 nuclear inner membrane IEA --
GO:0005737 cytoplasm IDA 19622636
GO:0005739 mitochondrion IEA --
GO:0005783 endoplasmic reticulum IDA 23529610
GO:0005789 endoplasmic reticulum membrane TAS --
genes like me logo Genes that share ontologies with ERN1: view

Pathways for ERN1 Gene

genes like me logo Genes that share pathways with ERN1: view

Pathways by source for ERN1 Gene

Gene Ontology (GO) - Biological Process for ERN1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001935 endothelial cell proliferation IDA 23529610
GO:0006351 transcription, DNA-templated IEA --
GO:0006355 regulation of transcription, DNA-templated IEA --
GO:0006379 mRNA cleavage IDA 21317875
GO:0006397 mRNA processing --
genes like me logo Genes that share ontologies with ERN1: view

Compounds for ERN1 Gene

(2) Tocris Compounds for ERN1 Gene

Compound Action Cas Number
4mu8C Inhibits IRE1alpha endoribonuclease activity [14003-96-4]
STF 083010 Inhibits IRE1alpha endonuclease activity [307543-71-1]

(3) HMDB Compounds for ERN1 Gene

Compound Synonyms Cas Number PubMed IDs
Adenosine triphosphate
  • 5'-(tetrahydrogen triphosphate) Adenosine
56-65-5
ADP
  • adenosindiphosphorsaeure
58-64-0
Magnesium
  • Magnesium
7439-95-4

(1) Drugbank Compounds for ERN1 Gene

Compound Synonyms Cas Number Type Actions PubMed IDs
N~2~-1H-benzimidazol-5-yl-N~4~-(3-cyclopropyl-1H-pyrazol-5-yl)pyrimidine-2,4-diamine
target

(11) Novoseek inferred chemical compound relationships for ERN1 Gene

Compound -log(P) Hits PubMed IDs
tunicamycin 77.5 1
thapsigargin 71.9 3
inositol 40.5 5
palmitate 28 1
oleic acid 24.6 1
genes like me logo Genes that share compounds with ERN1: view

Transcripts for ERN1 Gene

Unigene Clusters for ERN1 Gene

Endoplasmic reticulum to nucleus signaling 1:
Representative Sequences:

Alternative Splicing Database (ASD) splice patterns (SP) for ERN1 Gene

No ASD Table

Relevant External Links for ERN1 Gene

GeneLoc Exon Structure for
ERN1
ECgene alternative splicing isoforms for
ERN1

Expression for ERN1 Gene

mRNA expression in normal human tissues for ERN1 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for ERN1 Gene

This gene is overexpressed in Pancreas (4.2) and Whole Blood (4.1).

Integrated Proteomics: protein expression from ProteomicsDB, PaxDb, MOPED, and MaxQB for ERN1 Gene

SOURCE GeneReport for Unigene cluster for ERN1 Gene Hs.700027

mRNA Expression by UniProt/SwissProt for ERN1 Gene

O75460-ERN1_HUMAN
Tissue specificity: Ubiquitously expressed. High levels observed in pancreatic tissue.
genes like me logo Genes that share expressions with ERN1: view

Orthologs for ERN1 Gene

This gene was present in the common ancestor of animals and fungi.

Orthologs for ERN1 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia ERN1 35
  • 99.49 (n)
  • 99.69 (a)
ERN1 36
  • 100 (a)
OneToOne
cow
(Bos Taurus)
Mammalia ERN1 35
  • 88.81 (n)
  • 94.49 (a)
ERN1 36
  • 94 (a)
OneToOne
dog
(Canis familiaris)
Mammalia ERN1 35
  • 90.67 (n)
  • 95.49 (a)
ERN1 36
  • 94 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Ern1 35
  • 89.08 (n)
  • 93.53 (a)
Ern1 16
Ern1 36
  • 92 (a)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia ERN1 36
  • 80 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia ERN1 36
  • 87 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Ern1 35
  • 88.67 (n)
  • 93.51 (a)
chicken
(Gallus gallus)
Aves ERN1 36
  • 80 (a)
OneToOne
LOC417414 35
  • 76.63 (n)
  • 83.49 (a)
lizard
(Anolis carolinensis)
Reptilia ERN1 36
  • 78 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia ern2 35
  • 61.83 (n)
  • 59.54 (a)
Str.12018 35
zebrafish
(Danio rerio)
Actinopterygii ern1 36
  • 67 (a)
OneToOne
ern2 35
  • 61.25 (n)
  • 61.85 (a)
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP004176 35
  • 53.63 (n)
  • 49.39 (a)
fruit fly
(Drosophila melanogaster)
Insecta Ire1 35
  • 56.21 (n)
  • 52.25 (a)
Ire1 36
  • 34 (a)
OneToMany
ire-1 37
  • 53 (a)
worm
(Caenorhabditis elegans)
Secernentea ire-1 35
  • 51.29 (n)
  • 48.84 (a)
ire-1 36
  • 39 (a)
OneToMany
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes IRE1 36
  • 22 (a)
OneToMany
sea squirt
(Ciona savignyi)
Ascidiacea CSA.5230 36
  • 15 (a)
OneToOne
Species with no ortholog for ERN1:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for ERN1 Gene

ENSEMBL:
Gene Tree for ERN1 (if available)
TreeFam:
Gene Tree for ERN1 (if available)

Paralogs for ERN1 Gene

Paralogs for ERN1 Gene

Selected SIMAP similar genes for ERN1 Gene using alignment to 1 proteins:

genes like me logo Genes that share paralogs with ERN1: view

Variants for ERN1 Gene

Sequence variations from dbSNP and Humsavar for ERN1 Gene

SNP ID Clin Chr 17 pos Sequence Context AA Info Type MAF
rs28406 -- 64,067,192(+) CTTTA(A/C)CACTC intron-variant
rs77684 -- 64,049,624(+) TACCC(C/T)CAGGG intron-variant
rs107403 -- 64,066,473(+) TTTAA(G/T)AACTC intron-variant
rs107404 -- 64,066,532(+) ATGAA(A/G)CAGTC intron-variant
rs111372 -- 64,062,790(+) CTCCT(C/T)CAACT intron-variant

Structural Variations from Database of Genomic Variants (DGV) for ERN1 Gene

Variant ID Type Subtype PubMed ID
nsv833511 CNV Loss 17160897
nsv483108 CNV Loss 15286789

Relevant External Links for ERN1 Gene

HapMap Linkage Disequilibrium report
ERN1

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for ERN1 Gene

Disorders for ERN1 Gene

(3) Novoseek inferred disease relationships for ERN1 Gene

Disease -log(P) Hits PubMed IDs
necrosis 16.9 3
tumors 5.06 5
cancer 4.59 2

Relevant External Links for ERN1

Genetic Association Database (GAD)
ERN1
Human Genome Epidemiology (HuGE) Navigator
ERN1
genes like me logo Genes that share disorders with ERN1: view

No data available for UniProtKB/Swiss-Prot for ERN1 Gene

Publications for ERN1 Gene

  1. A stress response pathway from the endoplasmic reticulum to the nucleus requires a novel bifunctional protein kinase/endoribonuclease (Ire1p) in mammalian cells. (PMID: 9637683) Tirasophon W. … Kaufman R.J. (Genes Dev. 1998) 2 3 4 23
  2. Activation of caspase-12, an endoplastic reticulum (ER) resident caspase, through tumor necrosis factor receptor-associated factor 2- dependent mechanism in response to the ER stress. (PMID: 11278723) Yoneda T. … Tohyama M. (J. Biol. Chem. 2001) 3 4 23
  3. Structure and intermolecular interactions of the luminal dimerization domain of human IRE1alpha. (PMID: 12637535) Liu C.Y. … Kaufman R.J. (J. Biol. Chem. 2003) 3 4 23
  4. Activation signal of nuclear factor-kappa B in response to endoplasmic reticulum stress is transduced via IRE1 and tumor necrosis factor receptor-associated factor 2. (PMID: 12843613) Kaneko M. … Nomura Y. (Biol. Pharm. Bull. 2003) 3 23
  5. IRE1 signaling affects cell fate during the unfolded protein response. (PMID: 17991856) Lin J.H. … Walter P. (Science 2007) 3 23

Products for ERN1 Gene

  • Addgene plasmids for ERN1

Sources for ERN1 Gene

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