IRE1_SCHPO
ID IRE1_SCHPO Reviewed; 1072 AA.
AC O94537;
DT 31-OCT-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1999, sequence version 1.
DT 03-AUG-2022, entry version 137.
DE RecName: Full=Sensor for unfolded proteins in the ER ire1 {ECO:0000303|PubMed:15821139};
DE Includes:
DE RecName: Full=Serine/threonine-protein kinase;
DE EC=2.7.11.1;
DE Includes:
DE RecName: Full=Endoribonuclease;
DE EC=3.1.26.-;
DE AltName: Full=Serine/threonine-protein kinase 4 {ECO:0000303|PubMed:15821139};
DE Flags: Precursor;
GN Name=ire1; Synonyms=ppk4; ORFNames=SPAC167.01;
OS Schizosaccharomyces pombe (strain 972 / ATCC 24843) (Fission yeast).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Taphrinomycotina;
OC Schizosaccharomycetes; Schizosaccharomycetales; Schizosaccharomycetaceae;
OC Schizosaccharomyces.
OX NCBI_TaxID=284812;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=972 / ATCC 24843;
RX PubMed=11859360; DOI=10.1038/nature724;
RA Wood V., Gwilliam R., Rajandream M.A., Lyne M.H., Lyne R., Stewart A.,
RA Sgouros J.G., Peat N., Hayles J., Baker S.G., Basham D., Bowman S.,
RA Brooks K., Brown D., Brown S., Chillingworth T., Churcher C.M., Collins M.,
RA Connor R., Cronin A., Davis P., Feltwell T., Fraser A., Gentles S.,
RA Goble A., Hamlin N., Harris D.E., Hidalgo J., Hodgson G., Holroyd S.,
RA Hornsby T., Howarth S., Huckle E.J., Hunt S., Jagels K., James K.D.,
RA Jones L., Jones M., Leather S., McDonald S., McLean J., Mooney P.,
RA Moule S., Mungall K.L., Murphy L.D., Niblett D., Odell C., Oliver K.,
RA O'Neil S., Pearson D., Quail M.A., Rabbinowitsch E., Rutherford K.M.,
RA Rutter S., Saunders D., Seeger K., Sharp S., Skelton J., Simmonds M.N.,
RA Squares R., Squares S., Stevens K., Taylor K., Taylor R.G., Tivey A.,
RA Walsh S.V., Warren T., Whitehead S., Woodward J.R., Volckaert G., Aert R.,
RA Robben J., Grymonprez B., Weltjens I., Vanstreels E., Rieger M.,
RA Schaefer M., Mueller-Auer S., Gabel C., Fuchs M., Duesterhoeft A.,
RA Fritzc C., Holzer E., Moestl D., Hilbert H., Borzym K., Langer I., Beck A.,
RA Lehrach H., Reinhardt R., Pohl T.M., Eger P., Zimmermann W., Wedler H.,
RA Wambutt R., Purnelle B., Goffeau A., Cadieu E., Dreano S., Gloux S.,
RA Lelaure V., Mottier S., Galibert F., Aves S.J., Xiang Z., Hunt C.,
RA Moore K., Hurst S.M., Lucas M., Rochet M., Gaillardin C., Tallada V.A.,
RA Garzon A., Thode G., Daga R.R., Cruzado L., Jimenez J., Sanchez M.,
RA del Rey F., Benito J., Dominguez A., Revuelta J.L., Moreno S.,
RA Armstrong J., Forsburg S.L., Cerutti L., Lowe T., McCombie W.R.,
RA Paulsen I., Potashkin J., Shpakovski G.V., Ussery D., Barrell B.G.,
RA Nurse P.;
RT "The genome sequence of Schizosaccharomyces pombe.";
RL Nature 415:871-880(2002).
RN [2]
RP IDENTIFICATION.
RX PubMed=15821139; DOI=10.1128/ec.4.4.799-813.2005;
RA Bimbo A., Jia Y., Poh S.L., Karuturi R.K.M., den Elzen N., Peng X.,
RA Zheng L., O'Connell M., Liu E.T., Balasubramanian M.K., Liu J.;
RT "Systematic deletion analysis of fission yeast protein kinases.";
RL Eukaryot. Cell 4:799-813(2005).
RN [3]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
RX PubMed=16823372; DOI=10.1038/nbt1222;
RA Matsuyama A., Arai R., Yashiroda Y., Shirai A., Kamata A., Sekido S.,
RA Kobayashi Y., Hashimoto A., Hamamoto M., Hiraoka Y., Horinouchi S.,
RA Yoshida M.;
RT "ORFeome cloning and global analysis of protein localization in the fission
RT yeast Schizosaccharomyces pombe.";
RL Nat. Biotechnol. 24:841-847(2006).
RN [4]
RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF HIS-1018.
RX PubMed=23066505; DOI=10.7554/elife.00048;
RA Kimmig P., Diaz M., Zheng J., Williams C.C., Lang A., Aragon T., Li H.,
RA Walter P.;
RT "The unfolded protein response in fission yeast modulates stability of
RT select mRNAs to maintain protein homeostasis.";
RL Elife 1:E00048-E00048(2012).
RN [5]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX DOI=10.1016/j.molcel.2020.07.019;
RA Zhao D., Zou C.X., Liu X.M., Jiang Z.D., Yu Z.Q., Suo F., Du T.Y.,
RA Dong M.Q., He W., Du L.L.;
RT "A UPR-induced soluble ER-phagy receptor acts with VAPs to confer ER stress
RT resistance.";
RL Mol. Cell 79:1-15(2020).
CC -!- FUNCTION: Endoplasmic reticulum (ER) membrane-resident
CC kinase/endoribonuclease involved in unfolded protein response (UPR)
CC (PubMed:23066505). Initiates the selective decay of a subset of ER-
CC localized-mRNAs that is required to survive ER stress
CC (PubMed:23066505). Rather than relying on a transcriptional program to
CC up-regulate genes that enhance ER protein folding capacity as in
CC S.cerevisiae, S.pombe cells reduce the amount of specific proteins
CC entering the organelle by decreasing the level of ER-targeted mRNAs
CC using ire1-dependent mRNA degradation (PubMed:23066505). The sole mRNA
CC cleaved upon ire1 activation that escapes decay is the ER chaperone
CC bip1 mRNA which is more stable and hence is present at an increased
CC steady-state after ire1 cleavage (PubMed:23066505). Promotes ER stress-
CC induced ER-phagy and via up-regulation of the protein level of the ER-
CC phagy receptor epr1 (Ref.5). {ECO:0000269|PubMed:23066505,
CC ECO:0000269|Ref.5}.
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:0000305|PubMed:15821139};
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:0000305|PubMed:15821139};
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:16823372}; Single-pass type I membrane protein
CC {ECO:0000269|PubMed:16823372}.
CC -!- DISRUPTION PHENOTYPE: Impairs ER stress-induced ER-phagy.
CC {ECO:0000269|Ref.5}.
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; CU329670; CAA22846.1; -; Genomic_DNA.
DR PIR; T37742; T37742.
DR RefSeq; NP_593384.1; NM_001018816.2.
DR AlphaFoldDB; O94537; -.
DR SMR; O94537; -.
DR BioGRID; 279225; 31.
DR STRING; 4896.SPAC167.01.1; -.
DR MaxQB; O94537; -.
DR PaxDb; O94537; -.
DR DNASU; 2542776; -.
DR EnsemblFungi; SPAC167.01.1; SPAC167.01.1:pep; SPAC167.01.
DR GeneID; 2542776; -.
DR KEGG; spo:SPAC167.01; -.
DR PomBase; SPAC167.01; -.
DR VEuPathDB; FungiDB:SPAC167.01; -.
DR eggNOG; KOG1027; Eukaryota.
DR HOGENOM; CLU_004875_2_1_1; -.
DR InParanoid; O94537; -.
DR OMA; VRYYCSE; -.
DR PhylomeDB; O94537; -.
DR Reactome; R-SPO-381070; IRE1alpha activates chaperones.
DR PRO; PR:O94537; -.
DR Proteomes; UP000002485; Chromosome I.
DR GO; GO:0005783; C:endoplasmic reticulum; HDA:PomBase.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:1990604; C:IRE1-TRAF2-ASK1 complex; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; ISM:PomBase.
DR GO; GO:0004521; F:endoribonuclease activity; IMP:PomBase.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; ISO:PomBase.
DR GO; GO:0051082; F:unfolded protein binding; IBA:GO_Central.
DR GO; GO:0036498; P:IRE1-mediated unfolded protein response; IMP:PomBase.
DR GO; GO:0006397; P:mRNA processing; IEA:InterPro.
DR GO; GO:0010628; P:positive regulation of gene expression; IMP:PomBase.
DR GO; GO:0140501; P:positive regulation of reticulophagy; IMP:PomBase.
DR GO; GO:0006468; P:protein phosphorylation; IEA:InterPro.
DR Gene3D; 1.20.1440.180; -; 1.
DR Gene3D; 2.130.10.10; -; 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; PTHR13954; 1.
DR Pfam; PF00069; Pkinase; 1.
DR Pfam; PF06479; Ribonuc_2-5A; 1.
DR SMART; SM00564; PQQ; 3.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF50998; SSF50998; 1.
DR SUPFAM; SSF56112; SSF56112; 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 ATP-binding; Endoplasmic reticulum; Hydrolase; Kinase; Membrane;
KW Nucleotide-binding; Reference proteome; Serine/threonine-protein kinase;
KW Signal; Transferase; Transmembrane; Transmembrane helix.
FT SIGNAL 1..30
FT /evidence="ECO:0000255"
FT CHAIN 31..1072
FT /note="Sensor for unfolded proteins in the ER ire1"
FT /id="PRO_0000256815"
FT TOPO_DOM 31..518
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 519..539
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 540..1072
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 654..938
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT DOMAIN 941..1072
FT /note="KEN"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00725"
FT REGION 243..262
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 553..593
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 774
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 660..668
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 682
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MUTAGEN 1018
FT /note="H->N: Blocks RNase activity and impairs the ability
FT to sustain cell growth on ER stress-inducing media."
FT /evidence="ECO:0000269|PubMed:23066505"
SQ SEQUENCE 1072 AA; 121223 MW; 5B1A60EEFC802526 CRC64;
MKSLKGRLLF LRKFVFFSLL ILLFAHGASS SSSSFNYFDK RTNGKANNEL ALFSPTADSP
SSVDGVLELP SAENVFAESS LYNAFIVATV DGSLHSYDRI TGQELWSLFT NANPGLSYTK
DENSLLSSKF LSQSNFKSYN STHGEFYSDS TLNISYLSDD DTVWFVEPID GGILYAFNLQ
TGLVRLPHSI KDLVHASPIR LLNNNVFVGS KNTTLFTIDV SNGDIVSQYP SGHRYETHHS
VHNLGTKRDS VPSGADSDLS FKDPSGKKLS ESLDLLDDFN YQVTVSNKSF VDIARTEYFI
TIYSDSNVIL DLVYIDWTPT KNEIMYESFH SSSFDSKLAL SSYDSSLHIV DTHSKFIKQN
IPLMSPAATV FDIVTLPHNK KIDKSQTPAK FPTSVLLRQP IDTYLETMFP QIARNKTEHV
YINHIGNAWF AMSERHYPLV SLAPEASFLY YNGFYIPLNS IFGLHSLMAT PKPFFALPGL
PGYDIPSYVE SEGSTKTLPS IGKKPIPLLD PNPISSTPIS ITFWVIMFLS VSFTIVTFFS
ILRIRSSEVR PLKSQKNTVS INNKIDTSKR RRKGKRRKRV SDEHSASSNF NEIESQASFE
QNQTLDILSE NIVEIQDKST DPLQKSLDSS LKSHLPEATV IQNTDGSVTV NSLTVYPEVI
GYGSHGTIVY RGVYEDREVA VKRVLMEFYD LASREITLLQ QSDNHPNIVR YYCKQKSDQF
LYIVIELCKC NLSDLIEKPI AYDDLFKSID LVSLLYQIAF GVSHLHSLDL VHRDLKPQNI
LLVVNNSPNL SKTRVRALIS DFGLSKKLDF NQSSLRNTTF EAAGSYGWRS PEILSGSLSQ
QSKEIQVKTR EGRIRQASHA TDIFALGCIF YYTLTGGMHP FGSHYDCEGN ILKGNYCLVH
LQSLGECGVL AADLIEDMIA FEPSKRPTIE VVLNHPLFWD YAKKLDFLID VSDRFEVEER
DPPSPLLQML ENNSKSVIGE NWTTCLHSSL VDNLGKYRKY DGSKILDILR VLRNKRHHYQ
DLPESVRRVL GDLPDGFTSY FVEKFPMLLL HCYHLVKDVL YEESQFKRYL EY
