Free for academic non-profit institutions. Other users need a Commercial license

Aliases for ERN1 Gene

Aliases for ERN1 Gene

  • Endoplasmic Reticulum To Nucleus Signaling 1 2 3 5
  • Serine/Threonine-Protein Kinase/Endoribonuclease IRE1 2 3
  • 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
  • IRE1a 3 4
  • IRE1 3 4
  • Endoplasmic Reticulum-To-Nucleus Signaling 1 4
  • Protein Kinase/Endoribonuclease 3
  • Inositol-Requiring 1 3
  • EC 2.7.11 58
  • IRE1P 3

External Ids for ERN1 Gene

Previous GeneCards Identifiers for ERN1 Gene

  • GC17M061758
  • GC17M064547
  • GC17M062461
  • GC17M062594
  • GC17M062582
  • GC17M059474
  • GC17M062120
  • GC17M057488
  • GC17M062122

Summaries for ERN1 Gene

Entrez Gene Summary for ERN1 Gene

  • 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]

GeneCards Summary for ERN1 Gene

ERN1 (Endoplasmic Reticulum To Nucleus Signaling 1) is a Protein Coding gene. Diseases associated with ERN1 include Chromosome 6Pter-P24 Deletion Syndrome and Usher Syndrome, Type 2C. Among its related pathways are Protein processing in endoplasmic reticulum and Translational Control. GO annotations related to this gene include protein homodimerization activity and transferase activity, transferring phosphorus-containing groups. 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 is a transmembrane resident ER protein that possesses both kinase and endonuclease domains. Both yeast (IRE) and mammalian (IRE1alpha) homologs are involved in the degradation of misfolded proteins, as part of the unfolded protein response (UPR) pathway.

Gene Wiki entry for ERN1 Gene

Additional gene information for ERN1 Gene

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

Genomics for ERN1 Gene

Regulatory Elements for ERN1 Gene

Enhancers for ERN1 Gene
GeneHancer Identifier Enhancer Score Enhancer Sources Gene-Enhancer Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor Binding Sites within enhancer Gene Targets for Enhancer
GH17H064073 1.9 FANTOM5 Ensembl ENCODE dbSUPER 47.3 +54.9 54924 4 PKNOX1 FOXA2 MLX ARID4B SIN3A DMAP1 ZBTB7B YY1 TCF12 GATA2 ERN1 DDX5 GH1 CSHL1 MAP3K3 LIMD2 ICAM2 PECAM1 MILR1 GC17M064041
GH17H064079 2 FANTOM5 Ensembl ENCODE dbSUPER 39.4 +48.0 47964 6 HDGF PKNOX1 FOXA2 MLX ARNT ARID4B SIN3A FEZF1 DMAP1 ZBTB7B ERN1 CSHL1 GH1 SNORD104 MAP3K3 PECAM1 DDX5 PRR29 LIMD2 ICAM2
GH17H064059 1.8 FANTOM5 Ensembl ENCODE dbSUPER 42.5 +66.6 66559 9 RB1 ARID4B BATF RAD21 SCRT2 ZNF143 ATF7 ETV6 IKZF2 MIXL1 ERN1 ENSG00000265982 CSHL1 GH1 DDX5 SCN4A PLEKHM1P1 SNORD104 CD79B MAP3K3
GH17H064055 1.3 FANTOM5 ENCODE dbSUPER 24.8 +74.4 74436 1 CTCF PKNOX1 MAX EBF1 EED ZNF143 ETV6 ATF7 RUNX3 IKZF2 ERN1 CSHL1 GH1 SNORD104 PECAM1 MAP3K3 LIMD2 DDX5 GC17M064041
GH17H064173 1.9 FANTOM5 Ensembl ENCODE dbSUPER 14.4 -46.6 -46582 7 PKNOX1 FOXA2 MLX ARID4B DMAP1 YY1 SLC30A9 MXD4 NFYC REST TEX2 ERN1 SNORD104 DDX5 ICAM2 LIMD2 SNORA50C
- Elite enhancer and/or Elite enhancer-gene association Download GeneHancer data dump

Enhancers around ERN1 on UCSC Golden Path with GeneCards custom track

Promoters for ERN1 Gene
Ensembl Regulatory Elements (ENSRs) TSS Distance (bp) Size (bp) Binding Sites for Transcription Factors within promoters
ENSR00000096895 1319 2201 PKNOX1 MLX ARID4B SIN3A DMAP1 YY1 SLC30A9 ZNF143 ZNF207 SP3

Genomic Location for ERN1 Gene

Chromosome:
17
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

Genes around ERN1 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
ERN1 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for ERN1 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence 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

Selected DME Specific Peptides for ERN1 Gene

O75460:
  • VHRDLKP
  • IVHRDLK

Post-translational modifications for ERN1 Gene

Other Protein References for ERN1 Gene

Antibody Products

  • Cell Signaling Technology (CST) Antibodies for ERN1 (IRE1)
  • Abcam antibodies for ERN1

Domains & Families for ERN1 Gene

Gene Families for ERN1 Gene

IUPHAR :
Human Protein Atlas (HPA):
  • Enzymes
  • Plasma proteins
  • Predicted membrane proteins
  • Predicted secreted proteins

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 :
  • Belongs to the protein kinase superfamily. Ser/Thr protein kinase family.
Family:
  • Belongs to the protein kinase superfamily. Ser/Thr protein kinase family.
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

Phenotypes From GWAS Catalog 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:0003824 catalytic activity IEA --
GO:0004519 endonuclease activity IEA --
GO:0004521 endoribonuclease activity TAS --
GO:0004540 ribonuclease activity IEA --
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:

Animal Model Products

CRISPR Products

Inhibitory RNA Products

Clone Products

  • Addgene plasmids for ERN1
  • Applied Biological Materials Clones for ERN1
  • Vectors and viruses for ORF, Lenti, Retro, Adenovirus, AAV, and more

No data available for Human Phenotype Ontology , Transcription Factor Targets 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
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for ERN1 gene
Compartment Confidence
endoplasmic reticulum 5
mitochondrion 3
nucleus 3
plasma membrane 2
extracellular 1
peroxisome 1
cytosol 1
golgi apparatus 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,IEA 23529610
GO:0005789 endoplasmic reticulum membrane TAS --
genes like me logo Genes that share ontologies with ERN1: view

No data available for Subcellular locations from the Human Protein Atlas (HPA) for ERN1 Gene

Pathways & Interactions for ERN1 Gene

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

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 IEA --
genes like me logo Genes that share ontologies with ERN1: view

No data available for SIGNOR curated interactions for ERN1 Gene

Drugs & Compounds for ERN1 Gene

(17) Drugs for ERN1 Gene - From: DrugBank, ApexBio, HMDB, Tocris, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
N~2~-1H-benzimidazol-5-yl-N~4~-(3-cyclopropyl-1H-pyrazol-5-yl)pyrimidine-2,4-diamine Experimental Pharma Target 0
APY29 Pharma IRE1α inhibitor, Inhibits IRE1alpha autophosphorylation; activates IRE1alpha endoribonuclease activity 0
STF 083010 Pharma IRE1α endonuclease inhibitor, Inhibits IRE1alpha endonuclease activity 0
4μ8C Pharma IRE1 Rnase inhibitor, potent and non-toxic 0
ATP Nutra Agonist 0

(3) Additional Compounds for ERN1 Gene - From: Novoseek, HMDB, and Tocris

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
ADP
  • Adenosindiphosphorsaeure
  • Adenosine 5'-pyrophosphate
  • Adenosine diphosphate
  • Adenosine pyrophosphate
  • Adenosine-5'-diphosphate
Full agonist, Agonist 58-64-0
4mu8C
14003-96-4

(4) Tocris Compounds for ERN1 Gene

Compound Action Cas Number
4mu8C Inhibits IRE1alpha endoribonuclease activity 14003-96-4
APY 29 Inhibits IRE1alpha autophosphorylation; activates IRE1alpha endoribonuclease activity 1216665-49-4
Kaempferol Proapoptotic; downregulates PLK1 expression and activates mitochondrial Ca2+ uniporter 520-18-3
STF 083010 Inhibits IRE1alpha endonuclease activity 307543-71-1

(3) ApexBio Compounds for ERN1 Gene

Compound Action Cas Number
4μ8C IRE1 Rnase inhibitor, potent and non-toxic 14003-96-4
APY29 IRE1α inhibitor 1216665-49-4
STF 083010 IRE1α endonuclease inhibitor 307543-71-1
genes like me logo Genes that share compounds with ERN1: view

Drug Products

Transcripts for ERN1 Gene

Unigene Clusters for ERN1 Gene

Endoplasmic reticulum to nucleus signaling 1:
Representative Sequences:

CRISPR Products

Inhibitory RNA Products

Clone Products

  • Addgene plasmids for ERN1
  • Applied Biological Materials Clones for ERN1
  • Vectors and viruses for ORF, Lenti, Retro, Adenovirus, AAV, and more

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 from GTEx, Illumina, BioGPS, and CGAP SAGE for ERN1 Gene

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

This gene is overexpressed in Pancreas (x4.2) and Whole Blood (x4.1).

Protein differential expression in normal tissues from HIPED for ERN1 Gene

This gene is overexpressed in Plasma (24.9), Heart (15.3), Kidney (13.9), and Adrenal (7.7).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, MaxQB, and MOPED for ERN1 Gene



NURSA nuclear receptor signaling pathways regulating expression of ERN1 Gene:

ERN1

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.

Evidence on tissue expression from TISSUES for ERN1 Gene

  • Nervous system(4.5)
  • Heart(4.4)
  • Blood(4.2)
  • Liver(2.6)
  • Pancreas(2.3)
  • Intestine(2.1)
genes like me logo Genes that share expression patterns with ERN1: view

Primer Products

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery , Protein tissue co-expression partners and Phenotype-based relationships between genes and organs from Gene ORGANizer for ERN1 Gene

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 33 34
  • 99.49 (n)
dog
(Canis familiaris)
Mammalia ERN1 33 34
  • 90.67 (n)
mouse
(Mus musculus)
Mammalia Ern1 33 16 34
  • 89.08 (n)
cow
(Bos Taurus)
Mammalia ERN1 33 34
  • 88.81 (n)
rat
(Rattus norvegicus)
Mammalia Ern1 33
  • 88.67 (n)
platypus
(Ornithorhynchus anatinus)
Mammalia ERN1 34
  • 87 (a)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia ERN1 34
  • 80 (a)
OneToOne
chicken
(Gallus gallus)
Aves ERN1 34
  • 80 (a)
OneToOne
LOC417414 33
  • 76.63 (n)
lizard
(Anolis carolinensis)
Reptilia ERN1 34
  • 78 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia ern2 33
  • 61.83 (n)
Str.12018 33
zebrafish
(Danio rerio)
Actinopterygii ern1 34
  • 67 (a)
OneToOne
ern2 33
  • 61.25 (n)
fruit fly
(Drosophila melanogaster)
Insecta Ire1 33 34
  • 56.21 (n)
ire-1 35
  • 53 (a)
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP004176 33
  • 53.63 (n)
worm
(Caenorhabditis elegans)
Secernentea ire-1 33 34
  • 51.29 (n)
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes IRE1 34
  • 22 (a)
OneToMany
sea squirt
(Ciona savignyi)
Ascidiacea CSA.5230 34
  • 15 (a)
OneToOne
Species where no ortholog for ERN1 was found in the sources mined by GeneCards:
  • 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

(2) 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
rs146710304 A gastric adenocarcinoma sample 64,054,300(+) TTGCC(A/G/T)GTCCT reference, synonymous-codon, missense
rs186305118 A lung adenocarcinoma sample 64,055,926(+) GCTGG(A/C)GCTGC reference, missense
VAR_040488 A renal clear cell carcinoma sample
VAR_040493 A glioblastoma multiforme sample
VAR_040494 An ovarian serous carcinoma sample

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

Variant ID Type Subtype PubMed ID
nsv1126467 CNV deletion 24896259
nsv483108 CNV loss 15286789
nsv833511 CNV loss 17160897

Variation tolerance for ERN1 Gene

Residual Variation Intolerance Score: 47.5% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 4.04; 60.54% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for ERN1 Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
ERN1

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

Disorders for ERN1 Gene

MalaCards: The human disease database

(2) MalaCards diseases for ERN1 Gene - From: DISEASES

Disorder Aliases PubMed IDs
chromosome 6pter-p24 deletion syndrome
  • 6p subtelomeric deletion syndrome
usher syndrome, type 2c
  • usher syndrome, type 2c, gpr98/pdzd7 digenic
- elite association - COSMIC cancer census association via MalaCards
Search ERN1 in MalaCards View complete list of genes associated with diseases

Relevant External Links for ERN1

Genetic Association Database (GAD)
ERN1
Human Genome Epidemiology (HuGE) Navigator
ERN1
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
ERN1
genes like me logo Genes that share disorders with ERN1: view

No data available for UniProtKB/Swiss-Prot and Genatlas 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 RJ (Genes & development 1998) 2 3 4 22 60
  2. Structure and intermolecular interactions of the luminal dimerization domain of human IRE1alpha. (PMID: 12637535) Liu CY … Kaufman RJ (The Journal of biological chemistry 2003) 3 4 22 60
  3. 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 (The Journal of biological chemistry 2001) 3 4 22 60
  4. PARP16 is a tail-anchored endoplasmic reticulum protein required for the PERK- and IRE1α-mediated unfolded protein response. (PMID: 23103912) Jwa M … Chang P (Nature cell biology 2012) 3 4 60
  5. Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score. (PMID: 20379614) Rose JE … Uhl GR (Molecular medicine (Cambridge, Mass.) 2010) 3 45 60

Products for ERN1 Gene

  • Addgene plasmids for ERN1

Sources for ERN1 Gene

Content
Loading form....