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Protein

Serine/threonine-protein kinase/endoribonuclease ire-1

Gene

ire-1

Organism
Caenorhabditis elegans
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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 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
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Biological processi

Stress response, Unfolded protein response

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

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

Topology

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

GO - Cellular componenti

  • integral component of endoplasmic reticulum membrane Source: WormBase
Complete GO annotation...

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...)Sequence analysis1
Glycosylationi188N-linked (GlcNAc...)Sequence 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. 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
Contains 1 KEN domain.PROSITE-ProRule annotation
Contains 1 protein kinase domain.PROSITE-ProRule annotation

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG1027. Eukaryota.
COG0515. LUCA.
COG1520. LUCA.
GeneTreeiENSGT00390000015684.
HOGENOMiHOG000012929.
InParanoidiQ09499.
KOiK08852.
OMAiDWRDHIT.
OrthoDBiEOG091G049V.
PhylomeDBiQ09499.

Family and domain databases

Gene3Di2.140.10.10. 1 hit.
InterProiIPR010513. KEN_dom.
IPR011009. Kinase-like_dom.
IPR018391. PQQ_beta_propeller_repeat.
IPR002372. PQQ_repeat.
IPR000719. Prot_kinase_dom.
IPR018997. PUB_domain.
IPR027295. Quinoprotein_ADH-like_fam.
IPR011047. Quinoprotein_ADH-like_supfam.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF00069. Pkinase. 1 hit.
PF01011. PQQ. 2 hits.
PF06479. Ribonuc_2-5A. 1 hit.
[Graphical view]
SMARTiSM00564. PQQ. 5 hits.
SM00580. PUG. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF50998. SSF50998. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEiPS51392. KEN. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]

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.

Cross-referencesi

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.

3D structure databases

ProteinModelPortaliQ09499.
SMRiQ09499.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi6239.C41C4.4a.

PTM databases

iPTMnetiQ09499.

Proteomic databases

EPDiQ09499.
PaxDbiQ09499.
PeptideAtlasiQ09499.
PRIDEiQ09499.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi174305.
WormBaseiC41C4.4a; CE35836; WBGene00002147; ire-1.

Phylogenomic databases

eggNOGiKOG1027. Eukaryota.
COG0515. LUCA.
COG1520. LUCA.
GeneTreeiENSGT00390000015684.
HOGENOMiHOG000012929.
InParanoidiQ09499.
KOiK08852.
OMAiDWRDHIT.
OrthoDBiEOG091G049V.
PhylomeDBiQ09499.

Enzyme and pathway databases

SignaLinkiQ09499.

Miscellaneous databases

PROiQ09499.

Gene expression databases

BgeeiWBGene00002147.
ExpressionAtlasiQ09499. differential.

Family and domain databases

Gene3Di2.140.10.10. 1 hit.
InterProiIPR010513. KEN_dom.
IPR011009. Kinase-like_dom.
IPR018391. PQQ_beta_propeller_repeat.
IPR002372. PQQ_repeat.
IPR000719. Prot_kinase_dom.
IPR018997. PUB_domain.
IPR027295. Quinoprotein_ADH-like_fam.
IPR011047. Quinoprotein_ADH-like_supfam.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF00069. Pkinase. 1 hit.
PF01011. PQQ. 2 hits.
PF06479. Ribonuc_2-5A. 1 hit.
[Graphical view]
SMARTiSM00564. PQQ. 5 hits.
SM00580. PUG. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF50998. SSF50998. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEiPS51392. KEN. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiIRE1_CAEEL
AccessioniPrimary (citable) accession number: Q09499
Secondary accession number(s): Q8WRG0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 1996
Last sequence update: October 3, 2006
Last modified: November 30, 2016
This is version 138 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programCaenorhabditis annotation project

Miscellaneousi

Keywords - Technical termi

Complete proteome, Multifunctional enzyme, 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.