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Protein

Serine/threonine-protein kinase/endoribonuclease ire-1

Gene

ire-1

Organism
Caenorhabditis elegans
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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 xbp-1 precursor mRNA to produce the mature form which then induces transcription of UPR target genes. Unfolded protein response (UPR) transcriptional activation by ire-1, as well as translational attenuation by pek-1 in a complementary pathway, maintains ER homeostasis (PubMed:11779465). Regulates the transcriptional up-regulation of nucleoside-diphosphatase apy-1 upon ER stress (PubMed:18216284). By activating the UPR pathway during non-lethal hypoxia pre-conditioning, confers adaptive protection to subsequent exposure to hypoxia (PubMed:20733002). ire-1 and pek-1 are redundant genes that control a pathway essential for larval development and survival (PubMed:11779465).3 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Cofactori

Mg2+By similarity

Enzyme regulationi

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

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei546ATPPROSITE-ProRule annotation1
Active sitei636Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi524 – 532ATPPROSITE-ProRule annotation9

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • endoribonuclease activity Source: WormBase
  • protein serine/threonine kinase activity Source: WormBase

GO - Biological processi

  • endoplasmic reticulum unfolded protein response Source: WormBase
  • mRNA splicing via endonucleolytic cleavage and ligation involved in unfolded protein response Source: WormBase
  • nematode larval development Source: WormBase
  • nucleic acid phosphodiester bond hydrolysis Source: WormBase
  • positive regulation of intrinsic apoptotic signaling pathway by p53 class mediator Source: WormBase
  • positive regulation of transcription from RNA polymerase II promoter in response to endoplasmic reticulum stress Source: UniProtKB
  • positive regulation of transcription from RNA polymerase II promoter involved in unfolded protein response Source: WormBase
  • protein phosphorylation Source: WormBase
  • response to hypoxia Source: UniProtKB
  • response to topologically incorrect protein Source: WormBase
  • response to tunicamycin Source: UniProtKB

Keywordsi

Molecular functionHydrolase, Kinase, Multifunctional enzyme, Serine/threonine-protein kinase, Transferase
Biological processStress response, Unfolded protein response
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiR-CEL-381070 IRE1alpha activates chaperones
SignaLinkiQ09499

Names & Taxonomyi

Protein namesi
Recommended name:
Serine/threonine-protein kinase/endoribonuclease ire-1
Alternative name(s):
Inositol-requiring protein 2
Including the following 2 domains:
Gene namesi
Name:ire-1
ORF Names:C41C4.4
OrganismiCaenorhabditis elegans
Taxonomic identifieri6239 [NCBI]
Taxonomic lineageiEukaryotaMetazoaEcdysozoaNematodaChromadoreaRhabditidaRhabditoideaRhabditidaePeloderinaeCaenorhabditis
Proteomesi
  • UP000001940 Componenti: Chromosome II

Organism-specific databases

WormBaseiC41C4.4a ; CE35836 ; WBGene00002147 ; ire-1

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini22 – 438LumenalSequence analysisAdd BLAST417
Transmembranei439 – 455HelicalSequence analysisAdd BLAST17
Topological domaini456 – 967CytoplasmicSequence analysisAdd BLAST512

Keywords - Cellular componenti

Endoplasmic reticulum, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi723G → R in zc14; loss of adaptive protection conferred by non-lethal hypoxia treatment. Prevents transcriptional up-regulation of apy-1 upon ER stress. Reduced UDPase activity upon ER stress. 2 Publications1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 21Sequence analysisAdd BLAST21
ChainiPRO_000002439022 – 967Serine/threonine-protein kinase/endoribonuclease ire-1Add BLAST946

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi100N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi188N-linked (GlcNAc...) asparagineSequence analysis1
Modified residuei672Phosphoserine; by autocatalysisBy similarity1

Post-translational modificationi

Autophosphorylated mainly on serine residues.By similarity

Keywords - PTMi

Glycoprotein, Phosphoprotein

Proteomic databases

EPDiQ09499
PaxDbiQ09499
PeptideAtlasiQ09499
PRIDEiQ09499

PTM databases

iPTMnetiQ09499

Expressioni

Gene expression databases

BgeeiWBGene00002147
ExpressionAtlasiQ09499 baseline and differential

Interactioni

Protein-protein interaction databases

STRINGi6239.C41C4.4a

Structurei

3D structure databases

ProteinModelPortaliQ09499
SMRiQ09499
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini518 – 778Protein kinasePROSITE-ProRule annotationAdd BLAST261
Domaini781 – 909KENPROSITE-ProRule annotationAdd BLAST129

Sequence similaritiesi

Belongs to the protein kinase superfamily. Ser/Thr protein kinase family.PROSITE-ProRule annotation

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG1027 Eukaryota
COG0515 LUCA
COG1520 LUCA
GeneTreeiENSGT00390000015684
HOGENOMiHOG000012929
InParanoidiQ09499
KOiK08852
OMAiMDWRENI
OrthoDBiEOG091G049V
PhylomeDBiQ09499

Family and domain databases

Gene3Di1.20.1440.180, 1 hit
2.130.10.10, 1 hit
InterProiView protein in InterPro
IPR033523 IRE2
IPR010513 KEN_dom
IPR038357 KEN_sf
IPR011009 Kinase-like_dom_sf
IPR018391 PQQ_beta_propeller_repeat
IPR002372 PQQ_repeat
IPR000719 Prot_kinase_dom
IPR018997 PUB_domain
IPR011047 Quinoprotein_ADH-like_supfam
IPR008271 Ser/Thr_kinase_AS
IPR015943 WD40/YVTN_repeat-like_dom_sf
PANTHERiPTHR13954:SF15 PTHR13954:SF15, 1 hit
PfamiView protein in Pfam
PF00069 Pkinase, 1 hit
PF01011 PQQ, 2 hits
PF06479 Ribonuc_2-5A, 1 hit
SMARTiView protein in SMART
SM00564 PQQ, 5 hits
SM00580 PUG, 1 hit
SM00220 S_TKc, 1 hit
SUPFAMiSSF50998 SSF50998, 1 hit
SSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
PS51392 KEN, 1 hit
PS50011 PROTEIN_KINASE_DOM, 1 hit
PS00108 PROTEIN_KINASE_ST, 1 hit

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q09499-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MRATFHLFTF IFLLLFSSVI CISTPGFRND HESIGDDEEK TSSTILVSTI
60 70 80 90 100
DGRLRALDSE TGEIKWTLQE EPVLRSPSAV KQGFTFLPNP LDGSLYVLKN
110 120 130 140 150
SSLKKLPFNI PQLVHASPCK GNDGILYAGS KKDVWFGIDP KTGLKVETLS
160 170 180 190 200
SASADRICPA NQKQTIFLGR TEYRVSMFDE KNRGKTWNAT FNDYSAHLLP
210 220 230 240 250
EVNTWPFKHY ASSSHGYILT FDRETGEMRW EQDLKQPVVA LYLLRDDGLH
260 270 280 290 300
KLPFEVMGKE TMENVAKNIF TVDQWPTVLG VNAADPQTTS LTNQFFPALF
310 320 330 340 350
VGESSFGLYA IEALVDHQTI TYSPKLLGPP LLEGPAPIAL TEMEKEEYLP
360 370 380 390 400
PRRPIIRNIP PSITHKTSDG EYLLLGYHDR PMMTMATIIP TRYPVPGPHK
410 420 430 440 450
AIGSTIERPP PQLLGPVEPQ KHEDTSFILL LLNNHPIPFY ATLVTMFALL
460 470 480 490 500
LTVIWQCGRQ WDQQKSTSRM DSFEIVNNPG ESRSAQTSKQ SNRGSFGWAN
510 520 530 540 550
RKIEIPEGWM AVGSKLMYSP SDILGTGCEG TVVYRGTFDG REVAVKRVVS
560 570 580 590 600
EFVKFAHREA DLLRESDTHP HVIRYFCMES DSQFRYLALE LCIASLNDYV
610 620 630 640 650
EQKEVQQNVT IALRDIMKQA TDGLAHLHAS KIVHRDMKPQ NVLITMASQR
660 670 680 690 700
GEMRAVISDF GLCKRVQPGK NSISRGIASG LAGTDGWIAP EVLISASTSY
710 720 730 740 750
PVDIFSLGCI FYYVLTSGTH PFGKSLHRQA NIVNGEYTLN KLADLDDWSL
760 770 780 790 800
ADDLISSMLN VEPLHRLTAD AVLNHPFFWT SEKRLAYFSD VSDRVEKEED
810 820 830 840 850
NSPVVRRIET DARIVVCGGW REKICDALKE DLRKFRTYKS FSVRDLLRAM
860 870 880 890 900
RNKKHHYREL PEDVRQSLGD IPDQFLHYFT SRFPRLLLHV YKATEYCSGE
910 920 930 940 950
AVFKRYYSDD VRARMYPIVE EEERVRKKIK EEMANEVWAR APKPVEQRTP
960
LKLDKRNIKK KSNPNTD
Length:967
Mass (Da):109,822
Last modified:October 3, 2006 - v2
Checksum:i94947E3DED9C8687
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF435952 mRNA Translation: AAL30828.1
Z48045 Genomic DNA Translation: CAA88100.2
PIRiT19874
RefSeqiNP_001254135.1, NM_001267206.1
UniGeneiCel.24223

Genome annotation databases

EnsemblMetazoaiC41C4.4a; C41C4.4a; WBGene00002147
GeneIDi174305
KEGGicel:CELE_C41C4.4
UCSCiC41C4.4 c. elegans

Similar proteinsi

Entry informationi

Entry nameiIRE1_CAEEL
AccessioniPrimary (citable) accession number: Q09499
Secondary accession number(s): Q8WRG0
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 1, 1996
Last sequence update: October 3, 2006
Last modified: May 23, 2018
This is version 149 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programCaenorhabditis annotation project

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Caenorhabditis elegans
    Caenorhabditis elegans: entries, gene names and cross-references to WormBase
  2. SIMILARITY comments
    Index of protein domains and families

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