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Q9EQY0 (ERN1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 116. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Serine/threonine-protein kinase/endoribonuclease IRE1
Alternative name(s):
Endoplasmic reticulum-to-nucleus signaling 1
Inositol-requiring protein 1
Ire1-alpha
Short name=IRE1a

Including the following 2 domains:

  1. Serine/threonine-protein kinase
    EC=2.7.11.1
  2. Endoribonuclease
    EC=3.1.26.-
Gene names
Name:Ern1
Synonyms:Ire1
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length977 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

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. Ref.3

Catalytic activity

ATP + a protein = ADP + a phosphoprotein. UniProtKB O75460

Cofactor

Magnesium By similarity. UniProtKB O75460

Enzyme regulation

The kinase domain is activated by trans-autophosphorylation. Kinase activity is required for activation of the endoribonuclease domain By similarity. UniProtKB O75460

Subunit structure

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 By similarity. Interacts with TAOK3 By similarity. 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. Interacts with TRAF2. Ref.4 UniProtKB O75460

Subcellular location

Endoplasmic reticulum membrane; Single-pass type I membrane protein Ref.3.

Tissue specificity

Ubiquitously expressed. High levels in thymus, liver and lung. In the brain, preferentially expressed in cortical, hippocampal and olfactory neurons. Ref.1

Post-translational modification

Autophosphorylated By similarity. UniProtKB O75460

ADP-ribosylated by PARP16 upon ER stress, which increases both kinase and endonuclease activities By similarity.

Sequence similarities

Belongs to the protein kinase superfamily. Ser/Thr protein kinase family.

Contains 1 KEN domain.

Contains 1 protein kinase domain.

Ontologies

Keywords
   Biological processApoptosis
Transcription
Transcription regulation
Unfolded protein response
   Cellular componentEndoplasmic reticulum
Membrane
   Coding sequence diversityAlternative splicing
   DomainSignal
Transmembrane
Transmembrane helix
   LigandATP-binding
Magnesium
Metal-binding
Nucleotide-binding
   Molecular functionHydrolase
Kinase
Serine/threonine-protein kinase
Transferase
   PTMADP-ribosylation
Disulfide bond
Glycoprotein
Phosphoprotein
   Technical termComplete proteome
Multifunctional enzyme
Reference proteome
Gene Ontology (GO)
   Biological_processRNA phosphodiester bond hydrolysis, endonucleolytic

Inferred from direct assay PubMed 15601821. Source: GOC

activation of signaling protein activity involved in unfolded protein response

Inferred from sequence or structural similarity. Source: UniProtKB

cell cycle arrest

Inferred from direct assay Ref.1. Source: UniProtKB

endoplasmic reticulum unfolded protein response

Inferred from direct assay PubMed 10882126PubMed 11430819PubMed 15601821. Source: MGI

intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress

Inferred from direct assay Ref.1. Source: MGI

mRNA processing

Inferred from electronic annotation. Source: InterPro

nucleic acid phosphodiester bond hydrolysis

Inferred from direct assay Ref.3. Source: GOC

positive regulation of endoplasmic reticulum unfolded protein response

Inferred from electronic annotation. Source: Ensembl

protein autophosphorylation

Inferred from direct assay PubMed 11430819. Source: MGI

protein phosphorylation

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentendoplasmic reticulum membrane

Inferred from direct assay PubMed 9755171. Source: MGI

integral component of endoplasmic reticulum membrane

Inferred from electronic annotation. Source: Ensembl

mitochondrion

Inferred from direct assay PubMed 23028046. Source: MGI

nuclear inner membrane

Inferred from direct assay Ref.3. Source: UniProtKB

   Molecular_functionATP binding

Inferred from sequence or structural similarity. Source: UniProtKB

endonuclease activity

Inferred from direct assay Ref.3. Source: UniProtKB

endoribonuclease activity

Inferred from direct assay PubMed 15601821. Source: MGI

magnesium ion binding

Inferred from sequence or structural similarity. Source: UniProtKB

protein serine/threonine kinase activity

Inferred from sequence or structural similarity. Source: UniProtKB

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Tnfrsf1aP251182EBI-5480799,EBI-518014

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 Ref.1 (identifier: Q9EQY0-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: Q9EQY0-2)

The sequence of this isoform differs from the canonical sequence as follows:
     406-408: INI → SGK
     409-977: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2020 Potential
Chain21 – 977957Serine/threonine-protein kinase/endoribonuclease IRE1
PRO_0000024328

Regions

Topological domain21 – 445425Lumenal Potential
Transmembrane446 – 46621Helical; Potential
Topological domain467 – 977511Cytoplasmic Potential
Domain571 – 832262Protein kinase
Domain835 – 963129KEN
Nucleotide binding577 – 5859ATP By similarity UniProtKB P32361

Sites

Active site6881Proton acceptor By similarity UniProtKB P32361
Binding site5991ATP By similarity UniProtKB O75460

Amino acid modifications

Glycosylation1781N-linked (GlcNAc...) Potential

Natural variations

Alternative sequence406 – 4083INI → SGK in isoform 2.
VSP_050794
Alternative sequence409 – 977569Missing in isoform 2.
VSP_050795

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified March 1, 2001. Version 1.
Checksum: 216E3E2FA2FF3F70

FASTA977110,185
        10         20         30         40         50         60 
MPARWLLLLL ALLLPPPGPG SFGRTSTVTL PETLLFVSTL DGSLHAVSKR TGSIKWTLKE 

        70         80         90        100        110        120 
DPVLQVPTHV EEPAFLPDPN DGSLYTLGGK NNEGLTKLPF TIPELVQASP CRSSDGILYM 

       130        140        150        160        170        180 
GKKQDIWYVI DLLTGEKQQT LSSAFADSLC PSTSLLYLGR TEYTITMYDT KTRELRWNAT 

       190        200        210        220        230        240 
YFDYAASLPE DDVDYKMSHF VSNGDGLVVT VDSESGDVLW IQNYASPVVA FYVWQGEVLR 

       250        260        270        280        290        300 
KVVHINVAVE TLRYLTFMSG EVGRITKWKY PFPKETEAKS KLTPTLYVGK YSTSLYASPS 

       310        320        330        340        350        360 
MVHEGVAVVP RGSTLPLLEG PQTDGVTIGD KGECVITPST DLKFDPGLKG KSKLNYLRNY 

       370        380        390        400        410        420 
WLLIGHHETP LSASTKMLER FPNNLPKHRE NVIPADSEKR SFEEVINIVG QTSDNTPTTV 

       430        440        450        460        470        480 
SQDVEEKLAR APAKPEAPVD SMLKDMATII LSTFLLVGWV AFIITYPLSV HQQRQLQHQQ 

       490        500        510        520        530        540 
FQKELEKIQL LQQQQLPFHP HGDLTQDPEF LDSSGPFSES SGTSSPSPSP RASNHSLHPS 

       550        560        570        580        590        600 
SSASRAGTSP SLEQDDEDEE TRMVIVGKIS FCPKDVLGHG AEGTIVYKGM FDNRDVAVKR 

       610        620        630        640        650        660 
ILPECFSFAD REVQLLRESD EHPNVIRYFC TEKDRQFQYI AIELCAATLQ EYVEQKDFAH 

       670        680        690        700        710        720 
LGLEPITLLH QTTSGLAHLH SLNIVHRDLK PHNILLSMPN AHGRIKAMIS DFGLCKKLAV 

       730        740        750        760        770        780 
GRHSFSRRSG VPGTEGWIAP EMLSEDCKDN PTYTVDIFSA GCVFYYVISE GNHPFGKSLQ 

       790        800        810        820        830        840 
RQANILLGAC NLDCFHSDKH EDVIARELIE KMIAMDPQQR PSAKHVLKHP FFWSLEKQLQ 

       850        860        870        880        890        900 
FFQDVSDRIE KEALDGPIVR QLERGGRAVV KMDWRENITV PLQTDLRKFR TYKGGSVRDL 

       910        920        930        940        950        960 
LRAMRNKKHH YRELPVEVQE TLGSIPDDFV RYFTSRFPHL LSHTYQAMEL CRHERLFQTY 

       970 
YWHEPTEPQP PVIPYAL 

« Hide

Isoform 2 [UniParc].

Checksum: 4FF98C4A4EC4D1F3
Show »

FASTA40845,303

References

« Hide 'large scale' references
[1]"Characterization of mouse Ire1alpha: cloning, mRNA localization in the brain and functional analysis in a neural cell line."
Miyoshi K., Katayama T., Imaizumi K., Taniguchi M., Mori Y., Hitomi J., Yui D., Manabe T., Gomi F., Yoneda T., Tohyama M.
Brain Res. Mol. Brain Res. 85:68-76(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY.
Strain: C57BL/6.
Tissue: Brain.
[2]"The transcriptional landscape of the mammalian genome."
Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. expand/collapse author list , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
Strain: C57BL/6J.
Tissue: Colon.
[3]"IRE1-mediated unconventional mRNA splicing and S2P-mediated ATF6 cleavage merge to regulate XBP1 in signaling the unfolded protein response."
Lee K., Tirasophon W., Shen X., Michalak M., Prywes R., Okada T., Yoshida H., Mori K., Kaufman R.J.
Genes Dev. 16:452-466(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION.
[4]"AIP1 is critical in transducing IRE1-mediated endoplasmic reticulum stress response."
Luo D., He Y., Zhang H., Yu L., Chen H., Xu Z., Tang S., Urano F., Min W.
J. Biol. Chem. 283:11905-11912(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH DAB2IP AND TRAF2.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AB031332 mRNA. Translation: BAB20901.1.
AK018505 mRNA. Translation: BAB31243.1.
RefSeqNP_076402.1. NM_023913.2.
UniGeneMm.340943.

3D structure databases

ProteinModelPortalQ9EQY0.
SMRQ9EQY0. Positions 31-370, 561-964.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

IntActQ9EQY0. 4 interactions.
MINTMINT-2631281.

Proteomic databases

PaxDbQ9EQY0.
PRIDEQ9EQY0.

Protocols and materials databases

DNASU78943.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000001059; ENSMUSP00000001059; ENSMUSG00000020715. [Q9EQY0-1]
ENSMUST00000106801; ENSMUSP00000102413; ENSMUSG00000020715. [Q9EQY0-2]
GeneID78943.
KEGGmmu:78943.
UCSCuc007lyy.1. mouse. [Q9EQY0-1]

Organism-specific databases

CTD2081.
MGIMGI:1930134. Ern1.

Phylogenomic databases

eggNOGCOG0515.
GeneTreeENSGT00390000015684.
HOGENOMHOG000012929.
HOVERGENHBG051506.
InParanoidQ9EQY0.
KOK08852.
OMAGLRKVMH.
OrthoDBEOG7C2R0H.
PhylomeDBQ9EQY0.
TreeFamTF313986.

Gene expression databases

ArrayExpressQ9EQY0.
BgeeQ9EQY0.
GenevestigatorQ9EQY0.

Family and domain databases

Gene3D2.140.10.10. 2 hits.
InterProIPR010513. KEN_dom.
IPR011009. Kinase-like_dom.
IPR018391. PQQ_beta_propeller_repeat.
IPR000719. Prot_kinase_dom.
IPR006567. PUG-dom.
IPR027295. Quinonprotein_ADH-like_fam.
IPR011047. Quinonprotein_ADH-like_supfam.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamPF00069. Pkinase. 1 hit.
PF06479. Ribonuc_2-5A. 1 hit.
[Graphical view]
SMARTSM00564. PQQ. 5 hits.
SM00580. PUG. 1 hit.
[Graphical view]
SUPFAMSSF50998. SSF50998. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEPS51392. KEN. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio349824.
PROQ9EQY0.
SOURCESearch...

Entry information

Entry nameERN1_MOUSE
AccessionPrimary (citable) accession number: Q9EQY0
Secondary accession number(s): Q9D340
Entry history
Integrated into UniProtKB/Swiss-Prot: August 16, 2004
Last sequence update: March 1, 2001
Last modified: April 16, 2014
This is version 116 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot