ID   ERN1_MOUSE              Reviewed;         977 AA.
AC   Q9EQY0; Q9D340;
DT   16-AUG-2004, integrated into UniProtKB/Swiss-Prot.
DT   01-MAR-2001, sequence version 1.
DT   27-MAR-2024, entry version 185.
DE   RecName: Full=Serine/threonine-protein kinase/endoribonuclease IRE1 {ECO:0000305};
DE   AltName: Full=Endoplasmic reticulum-to-nucleus signaling 1 {ECO:0000303|PubMed:11146108};
DE   AltName: Full=Inositol-requiring protein 1 {ECO:0000303|PubMed:11146108};
DE   AltName: Full=Ire1-alpha {ECO:0000303|PubMed:11146108};
DE            Short=IRE1a {ECO:0000303|PubMed:11146108};
DE   Includes:
DE     RecName: Full=Serine/threonine-protein kinase;
DE              EC=2.7.11.1 {ECO:0000269|PubMed:25164867};
DE   Includes:
DE     RecName: Full=Endoribonuclease;
DE              EC=3.1.26.- {ECO:0000269|PubMed:11850408, ECO:0000269|PubMed:25164867};
DE   Flags: Precursor;
GN   Name=Ern1 {ECO:0000312|MGI:MGI:1930134};
GN   Synonyms=Ire1 {ECO:0000303|PubMed:11146108};
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND TISSUE SPECIFICITY.
RC   STRAIN=C57BL/6J {ECO:0000269|PubMed:11146108};
RC   TISSUE=Brain {ECO:0000269|PubMed:11146108};
RX   PubMed=11146108; DOI=10.1016/s0169-328x(00)00243-6;
RA   Miyoshi K., Katayama T., Imaizumi K., Taniguchi M., Mori Y., Hitomi J.,
RA   Yui D., Manabe T., Gomi F., Yoneda T., Tohyama M.;
RT   "Characterization of mouse Ire1alpha: cloning, mRNA localization in the
RT   brain and functional analysis in a neural cell line.";
RL   Brain Res. Mol. Brain Res. 85:68-76(2000).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC   STRAIN=C57BL/6J; TISSUE=Colon;
RX   PubMed=16141072; DOI=10.1126/science.1112014;
RA   Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA   Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA   Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA   Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA   Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA   Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA   Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA   Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA   Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA   Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA   Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA   Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA   Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA   Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA   Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA   Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA   Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA   Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA   Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA   Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA   Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA   Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA   Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA   Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA   Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA   van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA   Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA   Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA   Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA   Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA   Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA   Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA   Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA   Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT   "The transcriptional landscape of the mammalian genome.";
RL   Science 309:1559-1563(2005).
RN   [3] {ECO:0000305}
RP   FUNCTION, ENDORIBONUCLEASE ACTIVITY, AND SUBCELLULAR LOCATION.
RX   PubMed=11850408; DOI=10.1101/gad.964702;
RA   Lee K., Tirasophon W., Shen X., Michalak M., Prywes R., Okada T.,
RA   Yoshida H., Mori K., Kaufman R.J.;
RT   "IRE1-mediated unconventional mRNA splicing and S2P-mediated ATF6 cleavage
RT   merge to regulate XBP1 in signaling the unfolded protein response.";
RL   Genes Dev. 16:452-466(2002).
RN   [4]
RP   FUNCTION, AND ENDORIBONUCLEASE ACTIVITY.
RX   PubMed=11780124; DOI=10.1038/415092a;
RA   Calfon M., Zeng H., Urano F., Till J.H., Hubbard S.R., Harding H.P.,
RA   Clark S.G., Ron D.;
RT   "IRE1 couples endoplasmic reticulum load to secretory capacity by
RT   processing the XBP-1 mRNA.";
RL   Nature 415:92-96(2002).
RN   [5]
RP   INTERACTION WITH DAB2IP AND TRAF2.
RX   PubMed=18281285; DOI=10.1074/jbc.m710557200;
RA   Luo D., He Y., Zhang H., Yu L., Chen H., Xu Z., Tang S., Urano F., Min W.;
RT   "AIP1 is critical in transducing IRE1-mediated endoplasmic reticulum stress
RT   response.";
RL   J. Biol. Chem. 283:11905-11912(2008).
RN   [6]
RP   TISSUE SPECIFICITY, AND PHOSPHORYLATION.
RX   PubMed=30118681; DOI=10.1016/j.molcel.2018.06.038;
RA   Chang T.K., Lawrence D.A., Lu M., Tan J., Harnoss J.M., Marsters S.A.,
RA   Liu P., Sandoval W., Martin S.E., Ashkenazi A.;
RT   "Coordination between Two Branches of the Unfolded Protein Response
RT   Determines Apoptotic Cell Fate.";
RL   Mol. Cell 71:629-636.e5(2018).
RN   [7]
RP   PHOSPHORYLATION AT SER-729.
RX   PubMed=35975910; DOI=10.1002/mc.23453;
RA   Mogre S., Blazanin N., Walsh H., Ibinson J., Minnich C., Andrew Hu C.C.,
RA   Glick A.B.;
RT   "TGFbeta1 regulates HRas-mediated activation of IRE1alpha through the PERK-
RT   RPAP2 axis in keratinocytes.";
RL   Mol. Carcinog. 61:958-971(2022).
RN   [8] {ECO:0007744|PDB:4PL3, ECO:0007744|PDB:4PL4, ECO:0007744|PDB:4PL5}
RP   X-RAY CRYSTALLOGRAPHY (2.90 ANGSTROMS) OF 550-977 IN COMPLEX WITH ADP AND
RP   MAGNESIUM, FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION,
RP   AUTOPHOSPHORYLATION, COFACTOR, AND MUTAGENESIS OF PHE-889; TYR-892;
RP   ASN-906; LYS-907 AND HIS-910.
RX   PubMed=25164867; DOI=10.1038/ncomms5202;
RA   Sanches M., Duffy N.M., Talukdar M., Thevakumaran N., Chiovitti D.,
RA   Canny M.D., Lee K., Kurinov I., Uehling D., Al-awar R., Poda G.,
RA   Prakesch M., Wilson B., Tam V., Schweitzer C., Toro A., Lucas J.L.,
RA   Vuga D., Lehmann L., Durocher D., Zeng Q., Patterson J.B., Sicheri F.;
RT   "Structure and mechanism of action of the hydroxy-aryl-aldehyde class of
RT   IRE1 endoribonuclease inhibitors.";
RL   Nat. Commun. 5:4202-4202(2014).
CC   -!- FUNCTION: Serine/threonine-protein kinase and endoribonuclease that
CC       acts as a key sensor for the endoplasmic reticulum unfolded protein
CC       response (UPR) (PubMed:11850408, PubMed:25164867). In unstressed cells,
CC       the endoplasmic reticulum luminal domain is maintained in its inactive
CC       monomeric state by binding to the endoplasmic reticulum chaperone
CC       HSPA5/BiP. Accumulation of misfolded protein in the endoplasmic
CC       reticulum causes release of HSPA5/BiP, allowing the luminal domain to
CC       homodimerize, promoting autophosphorylation of the kinase domain and
CC       subsequent activation of the endoribonuclease activity
CC       (PubMed:25164867). The endoribonuclease activity is specific for XBP1
CC       mRNA and excises 26 nucleotides from XBP1 mRNA (PubMed:11850408,
CC       PubMed:25164867). The resulting spliced transcript of XBP1 encodes a
CC       transcriptional activator protein that up-regulates expression of UPR
CC       target genes (PubMed:11850408, PubMed:25164867). Acts as an upstream
CC       signal for ER stress-induced GORASP2-mediated unconventional (ER/Golgi-
CC       independent) trafficking of CFTR to cell membrane by modulating the
CC       expression and localization of SEC16A (By similarity).
CC       {ECO:0000250|UniProtKB:O75460, ECO:0000269|PubMed:11850408,
CC       ECO:0000269|PubMed:25164867}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC         [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC         COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC         ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1;
CC         Evidence={ECO:0000269|PubMed:25164867};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC         threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC         Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC         ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC         EC=2.7.11.1; Evidence={ECO:0000269|PubMed:25164867};
CC   -!- COFACTOR:
CC       Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC         Evidence={ECO:0000269|PubMed:25164867};
CC   -!- ACTIVITY REGULATION: The kinase domain is activated by trans-
CC       autophosphorylation following homodimerization. Kinase activity is
CC       required for activation of the endoribonuclease domain
CC       (PubMed:25164867). Endoribonuclease activity is specifically inhibited
CC       by hydroxy-aryl-aldehydes (HAA) MKC9989, OICR464 and OICR573
CC       (PubMed:25164867). {ECO:0000269|PubMed:25164867}.
CC   -!- SUBUNIT: Monomer (By similarity). Homodimer; disulfide-linked;
CC       homodimerization takes place in response to endoplasmic reticulum
CC       stress and promotes activation of the kinase and endoribonuclease
CC       activities (PubMed:25164867). Dimer formation is driven by hydrophobic
CC       interactions within the N-terminal luminal domains and stabilized by
CC       disulfide bridges (PubMed:25164867). Interacts (via the luminal region)
CC       with DNAJB9/ERdj4; interaction takes place in unstressed cells and
CC       promotes recruitment of HSPA5/BiP (By similarity). Interacts (via the
CC       luminal region) with HSPA5/BiP; HSPA5/BiP is a negative regulator of
CC       the unfolded protein response (UPR) that prevents homodimerization of
CC       ERN1/IRE1 and subsequent activation of the protein (By similarity).
CC       Interacts with PDIA6, a negative regulator of the UPR; the interaction
CC       is direct and disrupts homodimerization (By similarity). Interacts with
CC       DAB2IP (via PH domain); the interaction occurs in a endoplasmic
CC       reticulum stress-induced dependent manner and is required for
CC       subsequent recruitment of TRAF2 to ERN1/IRE1 (PubMed:18281285).
CC       Interacts with TAOK3 and TRAF2 (By similarity). Interacts with RNF13
CC       (By similarity). Interacts with LACC1 (By similarity). Interacts (when
CC       unphosphorylated) with DDRGK1; interaction is dependent on UFM1 and
CC       takes place in response to endoplasmic reticulum stress, regulating
CC       ERN1/IRE1-alpha stability (By similarity). Interacts (via N-terminus)
CC       with P4HB/PDIA1; the interaction is enhanced by phosphorylation of P4HB
CC       by FAM20C in response to endoplasmic reticulum stress and results in
CC       attenuation of ERN1 activity (By similarity).
CC       {ECO:0000250|UniProtKB:O75460, ECO:0000269|PubMed:18281285,
CC       ECO:0000269|PubMed:25164867}.
CC   -!- INTERACTION:
CC       Q9EQY0; P25118: Tnfrsf1a; NbExp=2; IntAct=EBI-5480799, EBI-518014;
CC       Q9EQY0; P70196: Traf6; NbExp=6; IntAct=EBI-5480799, EBI-448028;
CC   -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC       {ECO:0000269|PubMed:11850408}; Single-pass type I membrane protein
CC       {ECO:0000269|PubMed:11850408}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1 {ECO:0000269|PubMed:11146108};
CC         IsoId=Q9EQY0-1; Sequence=Displayed;
CC       Name=2 {ECO:0000305};
CC         IsoId=Q9EQY0-2; Sequence=VSP_050794, VSP_050795;
CC   -!- TISSUE SPECIFICITY: Expressed in liver (at protein level)
CC       (PubMed:30118681). Ubiquitously expressed (PubMed:11146108). High
CC       levels in thymus, liver and lung. In the brain, preferentially
CC       expressed in cortical, hippocampal and olfactory neurons
CC       (PubMed:11146108). {ECO:0000269|PubMed:11146108,
CC       ECO:0000269|PubMed:30118681}.
CC   -!- PTM: Autophosphorylated following homodimerization. Autophosphorylation
CC       promotes activation of the endoribonuclease domain (PubMed:25164867).
CC       In response to ER stress, phosphorylated at Ser-724, Ser-729 and
CC       possibly Ser-726; phosphorylation promotes oligomerization and
CC       endoribonuclease activity (PubMed:30118681). Dephosphorylated at Ser-
CC       724, Ser-729 and possibly Ser-726 by RPAP2 to abort failed ER-stress
CC       adaptation and trigger apoptosis (By similarity).
CC       {ECO:0000250|UniProtKB:O75460, ECO:0000269|PubMed:25164867,
CC       ECO:0000269|PubMed:30118681}.
CC   -!- PTM: ADP-ribosylated by PARP16 upon ER stress, which increases both
CC       kinase and endonuclease activities. {ECO:0000250|UniProtKB:O75460}.
CC   -!- SIMILARITY: Belongs to the protein kinase superfamily. Ser/Thr protein
CC       kinase family. {ECO:0000255|PROSITE-ProRule:PRU00159}.
CC   ---------------------------------------------------------------------------
CC   Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC   Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC   ---------------------------------------------------------------------------
DR   EMBL; AB031332; BAB20901.1; -; mRNA.
DR   EMBL; AK018505; BAB31243.1; -; mRNA.
DR   CCDS; CCDS25556.1; -. [Q9EQY0-1]
DR   RefSeq; NP_076402.1; NM_023913.2. [Q9EQY0-1]
DR   PDB; 4PL3; X-ray; 2.90 A; A/B=550-977.
DR   PDB; 4PL4; X-ray; 3.00 A; A/B/C/D=550-977.
DR   PDB; 4PL5; X-ray; 3.40 A; A/B/C/D=550-977.
DR   PDBsum; 4PL3; -.
DR   PDBsum; 4PL4; -.
DR   PDBsum; 4PL5; -.
DR   AlphaFoldDB; Q9EQY0; -.
DR   SMR; Q9EQY0; -.
DR   BioGRID; 219724; 4.
DR   CORUM; Q9EQY0; -.
DR   IntAct; Q9EQY0; 4.
DR   MINT; Q9EQY0; -.
DR   STRING; 10090.ENSMUSP00000001059; -.
DR   BindingDB; Q9EQY0; -.
DR   ChEMBL; CHEMBL4523450; -.
DR   GlyCosmos; Q9EQY0; 1 site, No reported glycans.
DR   GlyGen; Q9EQY0; 1 site.
DR   iPTMnet; Q9EQY0; -.
DR   PhosphoSitePlus; Q9EQY0; -.
DR   EPD; Q9EQY0; -.
DR   MaxQB; Q9EQY0; -.
DR   PaxDb; 10090-ENSMUSP00000001059; -.
DR   ProteomicsDB; 275886; -. [Q9EQY0-1]
DR   ProteomicsDB; 275887; -. [Q9EQY0-2]
DR   Pumba; Q9EQY0; -.
DR   Antibodypedia; 4011; 875 antibodies from 44 providers.
DR   DNASU; 78943; -.
DR   Ensembl; ENSMUST00000001059.9; ENSMUSP00000001059.3; ENSMUSG00000020715.10. [Q9EQY0-1]
DR   Ensembl; ENSMUST00000106801.8; ENSMUSP00000102413.2; ENSMUSG00000020715.10. [Q9EQY0-2]
DR   GeneID; 78943; -.
DR   KEGG; mmu:78943; -.
DR   UCSC; uc007lyy.1; mouse. [Q9EQY0-1]
DR   AGR; MGI:1930134; -.
DR   CTD; 2081; -.
DR   MGI; MGI:1930134; Ern1.
DR   VEuPathDB; HostDB:ENSMUSG00000020715; -.
DR   eggNOG; KOG1027; Eukaryota.
DR   GeneTree; ENSGT00940000159761; -.
DR   HOGENOM; CLU_004875_1_1_1; -.
DR   InParanoid; Q9EQY0; -.
DR   OMA; NYWVERF; -.
DR   OrthoDB; 1630at2759; -.
DR   PhylomeDB; Q9EQY0; -.
DR   TreeFam; TF313986; -.
DR   Reactome; R-MMU-381070; IRE1alpha activates chaperones.
DR   BioGRID-ORCS; 78943; 8 hits in 81 CRISPR screens.
DR   ChiTaRS; Ern1; mouse.
DR   PRO; PR:Q9EQY0; -.
DR   Proteomes; UP000000589; Chromosome 11.
DR   RNAct; Q9EQY0; Protein.
DR   Bgee; ENSMUSG00000020715; Expressed in secondary oocyte and 251 other cell types or tissues.
DR   ExpressionAtlas; Q9EQY0; baseline and differential.
DR   GO; GO:1990597; C:AIP1-IRE1 complex; IPI:ParkinsonsUK-UCL.
DR   GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR   GO; GO:0005783; C:endoplasmic reticulum; ISO:MGI.
DR   GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:MGI.
DR   GO; GO:1990630; C:IRE1-RACK1-PP2A complex; ISO:MGI.
DR   GO; GO:1990604; C:IRE1-TRAF2-ASK1 complex; ISO:MGI.
DR   GO; GO:0005739; C:mitochondrion; IDA:MGI.
DR   GO; GO:0005637; C:nuclear inner membrane; IDA:UniProtKB.
DR   GO; GO:0043531; F:ADP binding; ISO:MGI.
DR   GO; GO:0005524; F:ATP binding; ISS:UniProtKB.
DR   GO; GO:0004519; F:endonuclease activity; IDA:UniProtKB.
DR   GO; GO:0019899; F:enzyme binding; ISO:MGI.
DR   GO; GO:0030544; F:Hsp70 protein binding; ISO:MGI.
DR   GO; GO:0051879; F:Hsp90 protein binding; ISO:MGI.
DR   GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR   GO; GO:0000287; F:magnesium ion binding; ISS:UniProtKB.
DR   GO; GO:0005161; F:platelet-derived growth factor receptor binding; ISO:MGI.
DR   GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB.
DR   GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR   GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:UniProtKB.
DR   GO; GO:0004521; F:RNA endonuclease activity; IDA:UniProtKB.
DR   GO; GO:0051082; F:unfolded protein binding; IBA:GO_Central.
DR   GO; GO:0071333; P:cellular response to glucose stimulus; ISO:MGI.
DR   GO; GO:0070301; P:cellular response to hydrogen peroxide; IEA:Ensembl.
DR   GO; GO:0034620; P:cellular response to unfolded protein; ISO:MGI.
DR   GO; GO:0035924; P:cellular response to vascular endothelial growth factor stimulus; ISS:UniProtKB.
DR   GO; GO:0030968; P:endoplasmic reticulum unfolded protein response; IDA:MGI.
DR   GO; GO:0001935; P:endothelial cell proliferation; ISS:UniProtKB.
DR   GO; GO:1901142; P:insulin metabolic process; ISO:MGI.
DR   GO; GO:0070059; P:intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress; IDA:UniProtKB.
DR   GO; GO:0036498; P:IRE1-mediated unfolded protein response; IDA:UniProtKB.
DR   GO; GO:0070054; P:mRNA splicing, via endonucleolytic cleavage and ligation; ISS:UniProtKB.
DR   GO; GO:0017148; P:negative regulation of translation; TAS:MGI.
DR   GO; GO:1900103; P:positive regulation of endoplasmic reticulum unfolded protein response; ISS:UniProtKB.
DR   GO; GO:1904294; P:positive regulation of ERAD pathway; TAS:MGI.
DR   GO; GO:0043507; P:positive regulation of JUN kinase activity; IMP:ParkinsonsUK-UCL.
DR   GO; GO:0033120; P:positive regulation of RNA splicing; IDA:UniProtKB.
DR   GO; GO:1904707; P:positive regulation of vascular associated smooth muscle cell proliferation; ISO:MGI.
DR   GO; GO:0046777; P:protein autophosphorylation; IDA:UniProtKB.
DR   GO; GO:0006468; P:protein phosphorylation; ISS:UniProtKB.
DR   GO; GO:0034976; P:response to endoplasmic reticulum stress; ISO:MGI.
DR   CDD; cd09769; Luminal_IRE1; 1.
DR   CDD; cd10422; RNase_Ire1; 1.
DR   CDD; cd13982; STKc_IRE1; 1.
DR   Gene3D; 1.20.1440.180; KEN domain; 1.
DR   Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1.
DR   Gene3D; 2.130.10.10; YVTN repeat-like/Quinoprotein amine dehydrogenase; 1.
DR   InterPro; IPR045133; IRE1/2-like.
DR   InterPro; IPR010513; KEN_dom.
DR   InterPro; IPR038357; KEN_sf.
DR   InterPro; IPR011009; Kinase-like_dom_sf.
DR   InterPro; IPR018391; PQQ_beta_propeller_repeat.
DR   InterPro; IPR000719; Prot_kinase_dom.
DR   InterPro; IPR011047; Quinoprotein_ADH-like_supfam.
DR   InterPro; IPR008271; Ser/Thr_kinase_AS.
DR   InterPro; IPR015943; WD40/YVTN_repeat-like_dom_sf.
DR   PANTHER; PTHR13954; IRE1-RELATED; 1.
DR   PANTHER; PTHR13954:SF17; SERINE_THREONINE-PROTEIN KINASE_ENDORIBONUCLEASE IRE1; 1.
DR   Pfam; PF00069; Pkinase; 1.
DR   Pfam; PF06479; Ribonuc_2-5A; 1.
DR   SMART; SM00564; PQQ; 5.
DR   SMART; SM00580; PUG; 1.
DR   SMART; SM00220; S_TKc; 1.
DR   SUPFAM; SSF56112; Protein kinase-like (PK-like); 1.
DR   SUPFAM; SSF50998; Quinoprotein alcohol dehydrogenase-like; 1.
DR   PROSITE; PS51392; KEN; 1.
DR   PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR   PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
DR   Genevisible; Q9EQY0; MM.
PE   1: Evidence at protein level;
KW   3D-structure; ADP-ribosylation; Alternative splicing; Apoptosis;
KW   ATP-binding; Disulfide bond; Endoplasmic reticulum; Glycoprotein;
KW   Hydrolase; Kinase; Magnesium; Membrane; Metal-binding;
KW   Multifunctional enzyme; Nucleotide-binding; Phosphoprotein;
KW   Reference proteome; Serine/threonine-protein kinase; Signal; Transcription;
KW   Transcription regulation; Transferase; Transmembrane; Transmembrane helix;
KW   Unfolded protein response.
FT   SIGNAL          1..20
FT                   /evidence="ECO:0000255"
FT   CHAIN           21..977
FT                   /note="Serine/threonine-protein kinase/endoribonuclease
FT                   IRE1"
FT                   /id="PRO_0000024328"
FT   TOPO_DOM        21..445
FT                   /note="Lumenal"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        446..466
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        467..977
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   DOMAIN          571..832
FT                   /note="Protein kinase"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT   DOMAIN          835..963
FT                   /note="KEN"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00725"
FT   REGION          498..559
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          906..907
FT                   /note="Interacts with hydroxy-aryl-aldehyde inhibitors"
FT                   /evidence="ECO:0000269|PubMed:25164867"
FT   COMPBIAS        511..550
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   ACT_SITE        688
FT                   /note="Proton acceptor; for protein kinase activity"
FT                   /evidence="ECO:0000250|UniProtKB:P32361,
FT                   ECO:0000255|PROSITE-ProRule:PRU00159, ECO:0000255|PROSITE-
FT                   ProRule:PRU10027"
FT   BINDING         577..585
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT                   ECO:0000269|PubMed:25164867, ECO:0007744|PDB:4PL5"
FT   BINDING         599
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT                   ECO:0000269|PubMed:25164867, ECO:0007744|PDB:4PL3,
FT                   ECO:0007744|PDB:4PL4, ECO:0007744|PDB:4PL5"
FT   BINDING         643..645
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000269|PubMed:25164867,
FT                   ECO:0007744|PDB:4PL3, ECO:0007744|PDB:4PL4,
FT                   ECO:0007744|PDB:4PL5"
FT   BINDING         690..693
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000269|PubMed:25164867,
FT                   ECO:0007744|PDB:4PL3, ECO:0007744|PDB:4PL4,
FT                   ECO:0007744|PDB:4PL5"
FT   BINDING         711
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000269|PubMed:25164867,
FT                   ECO:0007744|PDB:4PL3, ECO:0007744|PDB:4PL4,
FT                   ECO:0007744|PDB:4PL5"
FT   SITE            892
FT                   /note="Interacts with hydroxy-aryl-aldehyde inhibitors"
FT                   /evidence="ECO:0000269|PubMed:25164867"
FT   MOD_RES         724
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:O75460"
FT   MOD_RES         729
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000269|PubMed:35975910"
FT   CARBOHYD        178
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   VAR_SEQ         406..408
FT                   /note="INI -> SGK (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:16141072"
FT                   /id="VSP_050794"
FT   VAR_SEQ         409..977
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:16141072"
FT                   /id="VSP_050795"
FT   MUTAGEN         889
FT                   /note="F->A: Abolishes endoribonuclease activity."
FT                   /evidence="ECO:0000269|PubMed:25164867"
FT   MUTAGEN         892
FT                   /note="Y->A: Abolishes endoribonuclease activity."
FT                   /evidence="ECO:0000269|PubMed:25164867"
FT   MUTAGEN         906
FT                   /note="N->A: Abolishes endoribonuclease activity."
FT                   /evidence="ECO:0000269|PubMed:25164867"
FT   MUTAGEN         907
FT                   /note="K->A: Abolishes endoribonuclease activity."
FT                   /evidence="ECO:0000269|PubMed:25164867"
FT   MUTAGEN         910
FT                   /note="H->A: Abolishes endoribonuclease activity."
FT                   /evidence="ECO:0000269|PubMed:25164867"
FT   STRAND          570..579
FT                   /evidence="ECO:0007829|PDB:4PL3"
FT   STRAND          581..583
FT                   /evidence="ECO:0007829|PDB:4PL3"
FT   STRAND          585..594
FT                   /evidence="ECO:0007829|PDB:4PL3"
FT   STRAND          597..601
FT                   /evidence="ECO:0007829|PDB:4PL3"
FT   TURN            603..605
FT                   /evidence="ECO:0007829|PDB:4PL3"
FT   STRAND          606..608
FT                   /evidence="ECO:0007829|PDB:4PL3"
FT   HELIX           610..617
FT                   /evidence="ECO:0007829|PDB:4PL3"
FT   STRAND          628..634
FT                   /evidence="ECO:0007829|PDB:4PL3"
FT   STRAND          637..642
FT                   /evidence="ECO:0007829|PDB:4PL3"
FT   STRAND          646..648
FT                   /evidence="ECO:0007829|PDB:4PL3"
FT   HELIX           649..654
FT                   /evidence="ECO:0007829|PDB:4PL3"
FT   HELIX           665..680
FT                   /evidence="ECO:0007829|PDB:4PL3"
FT   TURN            681..683
FT                   /evidence="ECO:0007829|PDB:4PL3"
FT   HELIX           691..693
FT                   /evidence="ECO:0007829|PDB:4PL3"
FT   STRAND          694..696
FT                   /evidence="ECO:0007829|PDB:4PL3"
FT   STRAND          707..709
FT                   /evidence="ECO:0007829|PDB:4PL3"
FT   STRAND          713..716
FT                   /evidence="ECO:0007829|PDB:4PL3"
FT   TURN            735..737
FT                   /evidence="ECO:0007829|PDB:4PL5"
FT   HELIX           740..742
FT                   /evidence="ECO:0007829|PDB:4PL3"
FT   HELIX           753..768
FT                   /evidence="ECO:0007829|PDB:4PL3"
FT   TURN            769..771
FT                   /evidence="ECO:0007829|PDB:4PL4"
FT   TURN            778..780
FT                   /evidence="ECO:0007829|PDB:4PL3"
FT   HELIX           781..787
FT                   /evidence="ECO:0007829|PDB:4PL3"
FT   STRAND          797..799
FT                   /evidence="ECO:0007829|PDB:4PL5"
FT   HELIX           800..812
FT                   /evidence="ECO:0007829|PDB:4PL3"
FT   HELIX           817..819
FT                   /evidence="ECO:0007829|PDB:4PL3"
FT   HELIX           823..828
FT                   /evidence="ECO:0007829|PDB:4PL3"
FT   HELIX           830..832
FT                   /evidence="ECO:0007829|PDB:4PL3"
FT   HELIX           835..849
FT                   /evidence="ECO:0007829|PDB:4PL3"
FT   STRAND          854..856
FT                   /evidence="ECO:0007829|PDB:4PL3"
FT   HELIX           857..862
FT                   /evidence="ECO:0007829|PDB:4PL3"
FT   HELIX           867..870
FT                   /evidence="ECO:0007829|PDB:4PL3"
FT   HELIX           874..877
FT                   /evidence="ECO:0007829|PDB:4PL3"
FT   HELIX           880..887
FT                   /evidence="ECO:0007829|PDB:4PL3"
FT   HELIX           897..909
FT                   /evidence="ECO:0007829|PDB:4PL3"
FT   HELIX           911..913
FT                   /evidence="ECO:0007829|PDB:4PL3"
FT   HELIX           916..921
FT                   /evidence="ECO:0007829|PDB:4PL3"
FT   STRAND          924..926
FT                   /evidence="ECO:0007829|PDB:4PL4"
FT   HELIX           927..936
FT                   /evidence="ECO:0007829|PDB:4PL3"
FT   HELIX           938..947
FT                   /evidence="ECO:0007829|PDB:4PL3"
FT   HELIX           948..951
FT                   /evidence="ECO:0007829|PDB:4PL4"
FT   TURN            954..956
FT                   /evidence="ECO:0007829|PDB:4PL3"
FT   HELIX           957..959
FT                   /evidence="ECO:0007829|PDB:4PL3"
SQ   SEQUENCE   977 AA;  110185 MW;  216E3E2FA2FF3F70 CRC64;
     MPARWLLLLL ALLLPPPGPG SFGRTSTVTL PETLLFVSTL DGSLHAVSKR TGSIKWTLKE
     DPVLQVPTHV EEPAFLPDPN DGSLYTLGGK NNEGLTKLPF TIPELVQASP CRSSDGILYM
     GKKQDIWYVI DLLTGEKQQT LSSAFADSLC PSTSLLYLGR TEYTITMYDT KTRELRWNAT
     YFDYAASLPE DDVDYKMSHF VSNGDGLVVT VDSESGDVLW IQNYASPVVA FYVWQGEVLR
     KVVHINVAVE TLRYLTFMSG EVGRITKWKY PFPKETEAKS KLTPTLYVGK YSTSLYASPS
     MVHEGVAVVP RGSTLPLLEG PQTDGVTIGD KGECVITPST DLKFDPGLKG KSKLNYLRNY
     WLLIGHHETP LSASTKMLER FPNNLPKHRE NVIPADSEKR SFEEVINIVG QTSDNTPTTV
     SQDVEEKLAR APAKPEAPVD SMLKDMATII LSTFLLVGWV AFIITYPLSV HQQRQLQHQQ
     FQKELEKIQL LQQQQLPFHP HGDLTQDPEF LDSSGPFSES SGTSSPSPSP RASNHSLHPS
     SSASRAGTSP SLEQDDEDEE TRMVIVGKIS FCPKDVLGHG AEGTIVYKGM FDNRDVAVKR
     ILPECFSFAD REVQLLRESD EHPNVIRYFC TEKDRQFQYI AIELCAATLQ EYVEQKDFAH
     LGLEPITLLH QTTSGLAHLH SLNIVHRDLK PHNILLSMPN AHGRIKAMIS DFGLCKKLAV
     GRHSFSRRSG VPGTEGWIAP EMLSEDCKDN PTYTVDIFSA GCVFYYVISE GNHPFGKSLQ
     RQANILLGAC NLDCFHSDKH EDVIARELIE KMIAMDPQQR PSAKHVLKHP FFWSLEKQLQ
     FFQDVSDRIE KEALDGPIVR QLERGGRAVV KMDWRENITV PLQTDLRKFR TYKGGSVRDL
     LRAMRNKKHH YRELPVEVQE TLGSIPDDFV RYFTSRFPHL LSHTYQAMEL CRHERLFQTY
     YWHEPTEPQP PVIPYAL
//