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}.
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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 Genevisible; Q9EQY0; MM.
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.
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
//
