ERN1
Serine/threonine-protein kinase/endoribonuclease IRE1
Also known as: ERN1_HUMAN, IRE1, IRE1P
Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene
Protein identityUniProt · HPA
- UniProt accession
- O75460
- Gene
- ERN1
- Ensembl
- ENSG00000178607
- Chromosome
- 17
- Canonical length
- 977 aa
- Protein class
- Enzymes, Plasma proteins, Predicted intracellular proteins, Predicted membrane proteins, Transporters
- Quaternary structure
- Homodimer
OverviewNCBI 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]
Canonical amino-acid sequenceUniProt
977 residues, UniProt reviewed canonical sequence.
>O75460|ERN1
1 MPARRLLLLL TLLLPGLGIF GSTSTVTLPE TLLFVSTLDG SLHAVSKRTG SIKWTLKEDP
61 VLQVPTHVEE PAFLPDPNDG SLYTLGSKNN EGLTKLPFTI PELVQASPCR SSDGILYMGK
121 KQDIWYVIDL LTGEKQQTLS SAFADSLCPS TSLLYLGRTE YTITMYDTKT RELRWNATYF
181 DYAASLPEDD VDYKMSHFVS NGDGLVVTVD SESGDVLWIQ NYASPVVAFY VWQREGLRKV
241 MHINVAVETL RYLTFMSGEV GRITKWKYPF PKETEAKSKL TPTLYVGKYS TSLYASPSMV
301 HEGVAVVPRG STLPLLEGPQ TDGVTIGDKG ECVITPSTDV KFDPGLKSKN KLNYLRNYWL
361 LIGHHETPLS ASTKMLERFP NNLPKHRENV IPADSEKKSF EEVINLVDQT SENAPTTVSR
421 DVEEKPAHAP ARPEAPVDSM LKDMATIILS TFLLIGWVAF IITYPLSMHQ QQQLQHQQFQ
481 KELEKIQLLQ QQQQQLPFHP PGDTAQDGEL LDTSGPYSES SGTSSPSTSP RASNHSLCSG
541 SSASKAGSSP SLEQDDGDEE TSVVIVGKIS FCPKDVLGHG AEGTIVYRGM FDNRDVAVKR
601 ILPECFSFAD REVQLLRESD EHPNVIRYFC TEKDRQFQYI AIELCAATLQ EYVEQKDFAH
661 LGLEPITLLQ QTTSGLAHLH SLNIVHRDLK PHNILISMPN AHGKIKAMIS DFGLCKKLAV
721 GRHSFSRRSG VPGTEGWIAP EMLSEDCKEN PTYTVDIFSA GCVFYYVISE GSHPFGKSLQ
781 RQANILLGAC SLDCLHPEKH EDVIARELIE KMIAMDPQKR PSAKHVLKHP FFWSLEKQLQ
841 FFQDVSDRIE KESLDGPIVK QLERGGRAVV KMDWRENITV PLQTDLRKFR TYKGGSVRDL
901 LRAMRNKKHH YRELPAEVRE TLGSLPDDFV CYFTSRFPHL LAHTYRAMEL CSHERLFQPY
961 YFHEPPEPQP PVTPDALLocalizationUniProt · AlphaFold · HPA
Whether an antibody against ERN1 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.
- Antibody reachability
- Other membrane
- Secreted
- No
- Transmembrane segments
- 1
- Mean surface accessibility (rSASA)
- 0.37
- Highest tissue expression
- 63 nTPM
Expression across tissuesHPA
Tissue
- pancreas: 63 nTPM
- adrenal gland: 27 nTPM
- salivary gland: 14 nTPM
- liver: 13 nTPM
- bone marrow: 13 nTPM
- stomach: 10 nTPM
Single-cell type
- pdcs: 926 nCPM
- neutrophils: 711 nCPM
- adrenal cortex cells: 523 nCPM
- plasma cells: 519 nCPM
- pancreatic acinar cells: 327 nCPM
- gonadotrophs: 319 nCPM
Immune cell
- basophil: 18 nTPM
- MAIT T-cell: 9 nTPM
- plasmacytoid DC: 7.7 nTPM
- gdT-cell: 4.9 nTPM
- neutrophil: 4.8 nTPM
- memory CD8 T-cell: 4.1 nTPM
Brain region
- cerebral cortex: 12 nTPM
- hypothalamus: 11 nTPM
- cerebellum: 11 nTPM
- choroid plexus: 10 nTPM
- medulla oblongata: 9.2 nTPM
- thalamus: 9.1 nTPM
DiseaseUniProt · ClinVar · IEDB · PubMed
Four sources answering four different questions about ERN1.
Disease | ImmuneIEDB
Conditions an epitope on ERN1 was assayed in.
- type 1 diabetes mellitus T cell
Genetic constraint and essentialitygnomAD · DepMap
Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.
- gnomAD LOEUF (loss-of-function intolerance)
- 0.29
- gnomAD pLI
- 0.99
- gnomAD missense Z
- 2.27
- DepMap mean gene effect
- -0.01
- DepMap dependency class
- selective
Cancer expressionTCGA
Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).
OntologyGO
Biological processes
- cellular response to glucose stimulus
- cellular response to hydrogen peroxide
- cellular response to unfolded protein
- cellular response to vascular endothelial growth factor stimulus
- endoplasmic reticulum unfolded protein response
- endothelial cell proliferation
- insulin metabolic process
- intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress
- IRE1-mediated unfolded protein response
- mRNA catabolic process
- mRNA splicing, via endonucleolytic cleavage and ligation
- negative regulation of intrinsic apoptotic signaling pathway
- positive regulation of endoplasmic reticulum unfolded protein response
- positive regulation of JNK cascade
- positive regulation of RNA splicing
- positive regulation of vascular associated smooth muscle cell proliferation
- protein phosphorylation
- regulation of macroautophagy
- response to endoplasmic reticulum stress
Molecular functions
- ADP binding
- ATP binding
- enzyme binding
- Hsp70 protein binding
- Hsp90 protein binding
- hydrolase activity
- identical protein binding
- magnesium ion binding
- platelet-derived growth factor receptor binding
- protein homodimerization activity
- protein serine kinase activity
- protein serine/threonine kinase activity
- RNA endonuclease activity
- unfolded protein binding
Cellular components
Protein domainsUniProt · Pfam · InterPro
- Protein kinase domain
- Serine/threonine-protein kinase, active site
- KEN domain
- Protein kinase-like domain superfamily
- Quinoprotein alcohol dehydrogenase-like superfamily
- WD40/YVTN repeat-like-containing domain superfamily
- Pyrrolo-quinoline quinone beta-propeller repeat
- KEN domain superfamily
- Serine/threonine-protein kinase/endoribonuclease IRE1/2-like
- Protein kinase domain
- Ribonuclease 2-5A
KeywordsUniProt
- ADP-ribosylation
- Apoptosis
- ATP-binding
- Disulfide bond
- Endoplasmic reticulum
- Glycoprotein
- Hydrolase
- Kinase
- Magnesium
- Membrane
- Metal-binding
- Multifunctional enzyme
- Nucleotide-binding
- Phosphoprotein
- Serine/threonine-protein kinase
- Signal
- Transcription
- Transcription regulation
- Transferase
- Transmembrane
- Transmembrane helix
- Unfolded protein response
InteractionsUniProt · HPA
Protein binding partners of ERN1 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.
Antibody and autoantibody relevanceSeroatlas analysis
Seroatlas reads ERN1 as an antibody target. Whether an autoantibody or antibody against ERN1 could matter depends on whether native ERN1 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.
ERN1 is annotated as predominantly intracellular. Intracellular proteins are common autoantibody markers, becoming visible to the immune system after cell injury or altered processing, but are usually markers of disease rather than direct drivers.
Annotation status
The present source text does not explicitly label ERN1 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.
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