IRE1_CAEEL
ID IRE1_CAEEL Reviewed; 967 AA.
AC Q09499; Q8WRG0;
DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
DT 03-OCT-2006, sequence version 2.
DT 03-AUG-2022, entry version 171.
DE RecName: Full=Serine/threonine-protein kinase/endoribonuclease ire-1;
DE AltName: Full=Inositol-requiring protein 2;
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 Flags: Precursor;
GN Name=ire-1 {ECO:0000312|WormBase:C41C4.4a};
GN ORFNames=C41C4.4 {ECO:0000312|WormBase:C41C4.4a};
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=11779465; DOI=10.1016/s0092-8674(01)00612-2;
RA Shen X., Ellis R.E., Lee K., Liu C.-Y., Yang K., Solomon A., Yoshida H.,
RA Morimoto R., Kurnit D.M., Mori K., Kaufman R.J.;
RT "Complementary signaling pathways regulate the unfolded protein response
RT and are required for C. elegans development.";
RL Cell 107:893-903(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Bristol N2;
RX PubMed=9851916; DOI=10.1126/science.282.5396.2012;
RG The C. elegans sequencing consortium;
RT "Genome sequence of the nematode C. elegans: a platform for investigating
RT biology.";
RL Science 282:2012-2018(1998).
RN [3] {ECO:0000305}
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=16184190; DOI=10.1371/journal.pgen.0010037;
RA Shen X., Ellis R.E., Sakaki K., Kaufman R.J.;
RT "Genetic interactions due to constitutive and inducible gene regulation
RT mediated by the unfolded protein response in C. elegans.";
RL PLoS Genet. 1:e37-e37(2005).
RN [4]
RP FUNCTION, AND MUTAGENESIS OF GLY-723.
RX PubMed=18216284; DOI=10.1091/mbc.e07-06-0547;
RA Uccelletti D., Pascoli A., Farina F., Alberti A., Mancini P.,
RA Hirschberg C.B., Palleschi C.;
RT "APY-1, a novel Caenorhabditis elegans apyrase involved in unfolded protein
RT response signalling and stress responses.";
RL Mol. Biol. Cell 19:1337-1345(2008).
RN [5]
RP FUNCTION, AND MUTAGENESIS OF GLY-723.
RX PubMed=20733002; DOI=10.1128/mcb.00922-10;
RA Mao X.R., Crowder C.M.;
RT "Protein misfolding induces hypoxic preconditioning via a subset of the
RT unfolded protein response machinery.";
RL Mol. Cell. Biol. 30:5033-5042(2010).
RN [6]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=23149939; DOI=10.1128/mcb.01298-12;
RA Shiimori M., Inoue K., Sakamoto H.;
RT "A specific set of exon junction complex subunits is required for the
RT nuclear retention of unspliced RNAs in Caenorhabditis elegans.";
RL Mol. Cell. Biol. 33:444-456(2013).
CC -!- FUNCTION: Senses unfolded proteins in the lumen of the endoplasmic
CC reticulum via its N-terminal domain which leads to enzyme auto-
CC activation (PubMed:11779465). The active endoribonuclease domain
CC splices xbp-1 precursor mRNA to produce the mature form which then
CC induces transcription of UPR target genes (PubMed:11779465). Unfolded
CC protein response (UPR) transcriptional activation by ire-1, as well as
CC translational attenuation by pek-1 in a complementary pathway,
CC maintains ER homeostasis (PubMed:11779465, PubMed:16184190). Regulates
CC the transcriptional up-regulation of nucleoside-diphosphatase apy-1 and
CC many other genes, upon ER stress (PubMed:18216284, PubMed:16184190). By
CC activating the UPR pathway during non-lethal hypoxia pre-conditioning,
CC confers adaptive protection to subsequent exposure to hypoxia
CC (PubMed:20733002). ire-1 and pek-1 are redundant genes that control a
CC pathway essential for larval development and survival (PubMed:11779465,
CC PubMed:16184190). Plays a role in the nuclear retention of unspliced
CC mRNAs (PubMed:23149939). {ECO:0000269|PubMed:11779465,
CC ECO:0000269|PubMed:16184190, ECO:0000269|PubMed:18216284,
CC ECO:0000269|PubMed:20733002, ECO:0000269|PubMed:23149939}.
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 -!- 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;
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250};
CC -!- ACTIVITY REGULATION: The kinase domain is activated by trans-
CC autophosphorylation. Kinase activity is required for activation of the
CC endoribonuclease domain (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:11779465}; Single-pass type I membrane protein
CC {ECO:0000269|PubMed:11779465}.
CC -!- PTM: Autophosphorylated mainly on serine residues. {ECO:0000250}.
CC -!- DISRUPTION PHENOTYPE: In combination with RNAi-mediated knockdown of
CC atf-6, causes sluggish movement, arrested development at the L2 larval
CC stage, and lethality soon thereafter; larvae have intestinal
CC degeneration and develop many vacuoles in the intestinal cells
CC (PubMed:16184190). In combination with RNAi-mediated knockdown of pek-
CC 1, larvae have intestinal degeneration and develop many vacuoles in the
CC intestinal cells (PubMed:16184190). RNAi-mediated knockdown restores
CC fertility, reduces the accumulation of unspliced tra-2 in the cytoplasm
CC and suppresses germ line masculinization caused by RNAi-mediated
CC knockdown of rnp-4/RBM8A (PubMed:23149939).
CC {ECO:0000269|PubMed:16184190, ECO:0000269|PubMed:23149939}.
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; AF435952; AAL30828.1; -; mRNA.
DR EMBL; BX284602; CAA88100.2; -; Genomic_DNA.
DR PIR; T19874; T19874.
DR RefSeq; NP_001254135.1; NM_001267206.1.
DR AlphaFoldDB; Q09499; -.
DR SMR; Q09499; -.
DR BioGRID; 39634; 3.
DR STRING; 6239.C41C4.4a; -.
DR iPTMnet; Q09499; -.
DR EPD; Q09499; -.
DR PaxDb; Q09499; -.
DR PeptideAtlas; Q09499; -.
DR PRIDE; Q09499; -.
DR EnsemblMetazoa; C41C4.4a.1; C41C4.4a.1; WBGene00002147.
DR GeneID; 174305; -.
DR KEGG; cel:CELE_C41C4.4; -.
DR UCSC; C41C4.4; c. elegans.
DR CTD; 174305; -.
DR WormBase; C41C4.4a; CE35836; WBGene00002147; ire-1.
DR eggNOG; KOG1027; Eukaryota.
DR GeneTree; ENSGT00940000167966; -.
DR HOGENOM; CLU_004875_1_1_1; -.
DR InParanoid; Q09499; -.
DR OMA; HYLPDPR; -.
DR OrthoDB; 1019877at2759; -.
DR PhylomeDB; Q09499; -.
DR Reactome; R-CEL-381070; IRE1alpha activates chaperones.
DR PRO; PR:Q09499; -.
DR Proteomes; UP000001940; Chromosome II.
DR Bgee; WBGene00002147; Expressed in germ line (C elegans) and 4 other tissues.
DR ExpressionAtlas; Q09499; baseline and differential.
DR GO; GO:0030176; C:integral component of endoplasmic reticulum membrane; ISS:WormBase.
DR GO; GO:1990604; C:IRE1-TRAF2-ASK1 complex; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004521; F:endoribonuclease activity; ISS:WormBase.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; ISS:WormBase.
DR GO; GO:0051082; F:unfolded protein binding; IBA:GO_Central.
DR GO; GO:0030968; P:endoplasmic reticulum unfolded protein response; IMP:WormBase.
DR GO; GO:0070059; P:intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress; IBA:GO_Central.
DR GO; GO:0036498; P:IRE1-mediated unfolded protein response; IBA:GO_Central.
DR GO; GO:0098787; P:mRNA cleavage involved in mRNA processing; IGI:UniProtKB.
DR GO; GO:0002119; P:nematode larval development; IGI:WormBase.
DR GO; GO:0090305; P:nucleic acid phosphodiester bond hydrolysis; ISS:WormBase.
DR GO; GO:1990440; P:positive regulation of transcription from RNA polymerase II promoter in response to endoplasmic reticulum stress; IMP:UniProtKB.
DR GO; GO:0006990; P:positive regulation of transcription from RNA polymerase II promoter involved in unfolded protein response; IMP:WormBase.
DR GO; GO:0006468; P:protein phosphorylation; ISS:WormBase.
DR GO; GO:0001666; P:response to hypoxia; IMP:UniProtKB.
DR GO; GO:0035966; P:response to topologically incorrect protein; IMP:WormBase.
DR GO; GO:1904576; P:response to tunicamycin; IMP:UniProtKB.
DR Gene3D; 1.20.1440.180; -; 1.
DR Gene3D; 2.130.10.10; -; 1.
DR InterPro; IPR045133; IRE1/2-like.
DR InterPro; IPR033523; IRE2.
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; IPR002372; PQQ_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 PANTHER; PTHR13954:SF15; PTHR13954:SF15; 1.
DR Pfam; PF00069; Pkinase; 1.
DR Pfam; PF01011; PQQ; 2.
DR Pfam; PF06479; Ribonuc_2-5A; 1.
DR SMART; SM00564; PQQ; 5.
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; Glycoprotein; Hydrolase; Kinase;
KW Membrane; Multifunctional enzyme; Nucleotide-binding; Phosphoprotein;
KW Reference proteome; Serine/threonine-protein kinase; Signal;
KW Stress response; Transferase; Transmembrane; Transmembrane helix;
KW Unfolded protein response.
FT SIGNAL 1..21
FT /evidence="ECO:0000255"
FT CHAIN 22..967
FT /note="Serine/threonine-protein kinase/endoribonuclease
FT ire-1"
FT /id="PRO_0000024390"
FT TOPO_DOM 22..438
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 439..455
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 456..967
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 518..778
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT DOMAIN 781..909
FT /note="KEN"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00725"
FT REGION 474..494
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 948..967
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 636
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 524..532
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 546
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 672
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000250"
FT CARBOHYD 100
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 188
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT MUTAGEN 723
FT /note="G->R: In zc14; loss of adaptive protection conferred
FT by non-lethal hypoxia treatment. Prevents transcriptional
FT up-regulation of apy-1 upon ER stress. Reduced UDPase
FT activity upon ER stress."
FT /evidence="ECO:0000269|PubMed:18216284,
FT ECO:0000269|PubMed:20733002"
SQ SEQUENCE 967 AA; 109822 MW; 94947E3DED9C8687 CRC64;
MRATFHLFTF IFLLLFSSVI CISTPGFRND HESIGDDEEK TSSTILVSTI DGRLRALDSE
TGEIKWTLQE EPVLRSPSAV KQGFTFLPNP LDGSLYVLKN SSLKKLPFNI PQLVHASPCK
GNDGILYAGS KKDVWFGIDP KTGLKVETLS SASADRICPA NQKQTIFLGR TEYRVSMFDE
KNRGKTWNAT FNDYSAHLLP EVNTWPFKHY ASSSHGYILT FDRETGEMRW EQDLKQPVVA
LYLLRDDGLH KLPFEVMGKE TMENVAKNIF TVDQWPTVLG VNAADPQTTS LTNQFFPALF
VGESSFGLYA IEALVDHQTI TYSPKLLGPP LLEGPAPIAL TEMEKEEYLP PRRPIIRNIP
PSITHKTSDG EYLLLGYHDR PMMTMATIIP TRYPVPGPHK AIGSTIERPP PQLLGPVEPQ
KHEDTSFILL LLNNHPIPFY ATLVTMFALL LTVIWQCGRQ WDQQKSTSRM DSFEIVNNPG
ESRSAQTSKQ SNRGSFGWAN RKIEIPEGWM AVGSKLMYSP SDILGTGCEG TVVYRGTFDG
REVAVKRVVS EFVKFAHREA DLLRESDTHP HVIRYFCMES DSQFRYLALE LCIASLNDYV
EQKEVQQNVT IALRDIMKQA TDGLAHLHAS KIVHRDMKPQ NVLITMASQR GEMRAVISDF
GLCKRVQPGK NSISRGIASG LAGTDGWIAP EVLISASTSY PVDIFSLGCI FYYVLTSGTH
PFGKSLHRQA NIVNGEYTLN KLADLDDWSL ADDLISSMLN VEPLHRLTAD AVLNHPFFWT
SEKRLAYFSD VSDRVEKEED NSPVVRRIET DARIVVCGGW REKICDALKE DLRKFRTYKS
FSVRDLLRAM RNKKHHYREL PEDVRQSLGD IPDQFLHYFT SRFPRLLLHV YKATEYCSGE
AVFKRYYSDD VRARMYPIVE EEERVRKKIK EEMANEVWAR APKPVEQRTP LKLDKRNIKK
KSNPNTD
