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Protein

Mitogen-activated protein kinase pmk-1

Gene

pmk-1

Organism
Caenorhabditis elegans
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Serine/threonine kinase which responds to activation by environmental stress and pro-inflammatory cytokines by phosphorylating downstream targets. Phosphorylates snk-1 which probably regulates skn-1 nuclear translocation in response to oxidative stress (PubMed:16166371). Probably by activating skn-1, involved in the up-regulation of gcs-1 and glutathione-S-transferase gst-4 expression upon bacteria infection (PubMed:22216003). Up-regulates expression of gcs-1 in intestinal cells upon arsenite treatment (PubMed:16166371). Functions downstream of the MAPKK sek-1 and the MAPKKK nsy-1 as the MAP kinase which regulates pathogen resistance and responses to oxidative stress (PubMed:11703092, PubMed:12142542, PubMed:18394898, PubMed:16166371). Required for expression of antimicrobial peptide nlp-29 in response to fungal infection or physical injury (PubMed:18394898). May play a redundant role with other MAP kinases in susceptibility to anoxia, downstream of tir-1/nsy-1 (PubMed:21212236). Phosphorylates transcription factor rnt-1 during oxidative stress which results in rnt-1 stabilization in the intestine (PubMed:22308034). Probably downstream of nsy-1 and sek-1, involved in germline apoptosis induced by heavy metals, such as Cu2+ (PubMed:19497412).8 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.3 Publications

Cofactori

Mg2+2 Publications, Mn2+1 PublicationNote: Divalent cations such as magnesium or manganese.1 Publication

Enzyme regulationi

Activated by phosphorylation on threonine and tyrosine. Inhibited by pyridinyl-imidazole related compounds.1 Publication

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei64 – 641ATPPROSITE-ProRule annotation
Active sitei179 – 1791Proton acceptorPROSITE-ProRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi41 – 499ATPPROSITE-ProRule annotation

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • MAP kinase activity Source: UniProtKB
  • metal ion binding Source: UniProtKB-KW
  • protein kinase activity Source: WormBase
  • protein serine/threonine kinase activity Source: WormBase
  • transcription factor binding Source: WormBase

GO - Biological processi

  • defense response to fungus Source: UniProtKB
  • defense response to Gram-negative bacterium Source: WormBase
  • defense response to Gram-positive bacterium Source: WormBase
  • determination of adult lifespan Source: UniProtKB
  • hyperosmotic response Source: WormBase
  • innate immune response Source: UniProtKB
  • intracellular signal transduction Source: UniProtKB
  • MAPK cascade Source: WormBase
  • negative regulation of neuron death Source: ParkinsonsUK-UCL
  • p38MAPK cascade Source: WormBase
  • peptidyl-serine phosphorylation Source: CACAO
  • positive regulation of defense response to bacterium Source: UniProtKB
  • positive regulation of protein localization to nucleus Source: WormBase
  • positive regulation of transcription from RNA polymerase II promoter Source: WormBase
  • positive regulation of transcription from RNA polymerase II promoter involved in defense response to Gram-negative bacterium Source: WormBase
  • programmed cell death Source: WormBase
  • protein phosphorylation Source: WormBase
  • response to nematicide Source: UniProtKB
  • response to osmotic stress Source: UniProtKB
  • response to reactive oxygen species Source: WormBase
  • response to superoxide Source: WormBase
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Biological processi

Stress response

Keywords - Ligandi

ATP-binding, Magnesium, Manganese, Metal-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiR-CEL-168638. NOD1/2 Signaling Pathway.
R-CEL-171007. p38MAPK events.
R-CEL-198753. ERK/MAPK targets.
R-CEL-2559580. Oxidative Stress Induced Senescence.
R-CEL-375170. CDO in myogenesis.
R-CEL-418592. ADP signalling through P2Y purinoceptor 1.
R-CEL-432142. Platelet sensitization by LDL.
R-CEL-4420097. VEGFA-VEGFR2 Pathway.
R-CEL-450302. activated TAK1 mediates p38 MAPK activation.
SignaLinkiQ17446.

Names & Taxonomyi

Protein namesi
Recommended name:
Mitogen-activated protein kinase pmk-1 (EC:2.7.11.243 Publications)
Alternative name(s):
Stress-activated protein kinase pmk-1
p38 MAP kinase 1
Gene namesi
Name:pmk-1
ORF Names:B0218.3
OrganismiCaenorhabditis elegans
Taxonomic identifieri6239 [NCBI]
Taxonomic lineageiEukaryotaMetazoaEcdysozoaNematodaChromadoreaRhabditidaRhabditoideaRhabditidaePeloderinaeCaenorhabditis
Proteomesi
  • UP000001940 Componenti: Chromosome IV

Organism-specific databases

WormBaseiB0218.3; CE06686; WBGene00004055; pmk-1.

Subcellular locationi

GO - Cellular componenti

  • cytosol Source: WormBase
  • nucleus Source: WormBase
Complete GO annotation...

Pathology & Biotechi

Disruption phenotypei

Upon infection by P.aeruginosa or E.faecalis, RNAi-mediated knockdown results in a decrease in survival rate and in a reduced up-regulation of gst-4 and gcs-1 expression (PubMed:12142542, PubMed:22216003). Causes a severe reduction in rnt-1 accumulation in the intestine during oxidative stress mediated by paraquat (PubMed:22308034).3 Publications

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi64 – 641K → R: Loss of kinase activity. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 377377Mitogen-activated protein kinase pmk-1PRO_0000186303Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei191 – 1911Phosphothreonine2 Publications
Modified residuei193 – 1931Phosphotyrosine2 Publications

Post-translational modificationi

Dually phosphorylated on Thr-191 and Tyr-193, probably by sek-1, which activates the enzyme.3 Publications

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ17446.
PaxDbiQ17446.
PRIDEiQ17446.

PTM databases

iPTMnetiQ17446.

Interactioni

GO - Molecular functioni

  • transcription factor binding Source: WormBase

Protein-protein interaction databases

BioGridi56238. 22 interactions.
DIPiDIP-26892N.
IntActiQ17446. 17 interactions.
MINTiMINT-1037719.
STRINGi6239.B0218.3.

Structurei

3D structure databases

ProteinModelPortaliQ17446.
SMRiQ17446. Positions 16-359.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini35 – 319285Protein kinasePROSITE-ProRule annotationAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi191 – 1933TXY

Domaini

The TXY motif contains the threonine and tyrosine residues whose phosphorylation activates the MAP kinases.

Sequence similaritiesi

Contains 1 protein kinase domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG0660. Eukaryota.
ENOG410XNY0. LUCA.
GeneTreeiENSGT00550000074271.
HOGENOMiHOG000233024.
InParanoidiQ17446.
KOiK04441.
OMAiFQKNVAF.
OrthoDBiEOG7PCJGV.
PhylomeDBiQ17446.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR003527. MAP_kinase_CS.
IPR008352. MAPK_p38.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
[Graphical view]
PfamiPF00069. Pkinase. 1 hit.
[Graphical view]
PRINTSiPR01773. P38MAPKINASE.
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS01351. MAPK. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q17446-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MFPQTTMDHI LHPTPREGYY VVELNRSVWV VPNYYINLTP IGTGAYGTVC
60 70 80 90 100
AAECTRSGTR VAIKKFNRPF QSIIHARRTY RELRLLRCMC HENIIDLLDV
110 120 130 140 150
FTPNENVNDI EDVYFVSMLM GADLSNILKI QRLNDDHIQF LVYQILRGLK
160 170 180 190 200
YIHSADIIHR DLKPSNIAVN EDCELKILDF GLARQTDSEM TGYVATRWYR
210 220 230 240 250
APEIMLNWMH YTQTVDVWSV GCILAELITG KTLFPGSDHI DQLTRIMSVT
260 270 280 290 300
GTPDEEFLKK ISSEEARNYI RNLPKMTRRD FKRLFAQATP QAIDLLEKML
310 320 330 340 350
HLDPDRRPTA KEAMEHEYLA AYHDETDEPI AEEMDLNDDV RADTIDEWKK
360 370
IIWEEISDFQ KNVAFADEEE DEEKMES
Length:377
Mass (Da):43,919
Last modified:November 1, 1996 - v1
Checksum:iF20BC395B38EFD03
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
FO080124 Genomic DNA. Translation: CCD61386.1.
PIRiT29750.
RefSeqiNP_501365.1. NM_068964.3.
UniGeneiCel.12534.

Genome annotation databases

EnsemblMetazoaiB0218.3; B0218.3; WBGene00004055.
GeneIDi191743.
KEGGicel:CELE_B0218.3.
UCSCiB0218.3. c. elegans.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
FO080124 Genomic DNA. Translation: CCD61386.1.
PIRiT29750.
RefSeqiNP_501365.1. NM_068964.3.
UniGeneiCel.12534.

3D structure databases

ProteinModelPortaliQ17446.
SMRiQ17446. Positions 16-359.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi56238. 22 interactions.
DIPiDIP-26892N.
IntActiQ17446. 17 interactions.
MINTiMINT-1037719.
STRINGi6239.B0218.3.

PTM databases

iPTMnetiQ17446.

Proteomic databases

EPDiQ17446.
PaxDbiQ17446.
PRIDEiQ17446.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsemblMetazoaiB0218.3; B0218.3; WBGene00004055.
GeneIDi191743.
KEGGicel:CELE_B0218.3.
UCSCiB0218.3. c. elegans.

Organism-specific databases

CTDi191743.
WormBaseiB0218.3; CE06686; WBGene00004055; pmk-1.

Phylogenomic databases

eggNOGiKOG0660. Eukaryota.
ENOG410XNY0. LUCA.
GeneTreeiENSGT00550000074271.
HOGENOMiHOG000233024.
InParanoidiQ17446.
KOiK04441.
OMAiFQKNVAF.
OrthoDBiEOG7PCJGV.
PhylomeDBiQ17446.

Enzyme and pathway databases

ReactomeiR-CEL-168638. NOD1/2 Signaling Pathway.
R-CEL-171007. p38MAPK events.
R-CEL-198753. ERK/MAPK targets.
R-CEL-2559580. Oxidative Stress Induced Senescence.
R-CEL-375170. CDO in myogenesis.
R-CEL-418592. ADP signalling through P2Y purinoceptor 1.
R-CEL-432142. Platelet sensitization by LDL.
R-CEL-4420097. VEGFA-VEGFR2 Pathway.
R-CEL-450302. activated TAK1 mediates p38 MAPK activation.
SignaLinkiQ17446.

Miscellaneous databases

PROiQ17446.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR003527. MAP_kinase_CS.
IPR008352. MAPK_p38.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
[Graphical view]
PfamiPF00069. Pkinase. 1 hit.
[Graphical view]
PRINTSiPR01773. P38MAPKINASE.
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS01351. MAPK. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Isolation and characterization of pmk-(1-3): three p38 homologs in Caenorhabditis elegans."
    Berman K., McKay J., Avery L., Cobb M.
    Mol. Cell Biol. Res. Commun. 4:337-344(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, CATALYTIC ACTIVITY, COFACTOR, ENZYME REGULATION.
    Strain: Bristol N2.
  2. "Genome sequence of the nematode C. elegans: a platform for investigating biology."
    The C. elegans sequencing consortium
    Science 282:2012-2018(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: Bristol N2.
  3. Cited for: FUNCTION, PHOSPHORYLATION AT THR-191 AND TYR-193, DISRUPTION PHENOTYPE.
    Strain: Bristol N2.
  4. "The C. elegans p38 MAPK pathway regulates nuclear localization of the transcription factor SKN-1 in oxidative stress response."
    Inoue H., Hisamoto N., An J.H., Oliveira R.P., Nishida E., Blackwell T.K., Matsumoto K.
    Genes Dev. 19:2278-2283(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, CATALYTIC ACTIVITY, PHOSPHORYLATION AT THR-191 AND TYR-193, MUTAGENESIS OF LYS-64.
  5. "Distinct innate immune responses to infection and wounding in the C. elegans epidermis."
    Pujol N., Cypowyj S., Ziegler K., Millet A., Astrain A., Goncharov A., Jin Y., Chisholm A.D., Ewbank J.J.
    Curr. Biol. 18:481-489(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  6. "Copper-induced germline apoptosis in Caenorhabditis elegans: the independent roles of DNA damage response signaling and the dependent roles of MAPK cascades."
    Wang S., Wu L., Wang Y., Luo X., Lu Y.
    Chem. Biol. Interact. 180:151-157(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  7. "Regulation of anoxic death in Caenorhabditis elegans by mammalian apoptosis signal-regulating kinase (ASK) family proteins."
    Hayakawa T., Kato K., Hayakawa R., Hisamoto N., Matsumoto K., Takeda K., Ichijo H.
    Genetics 187:785-792(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, PHOSPHORYLATION AT THR-191 AND TYR-193.
  8. "Ce-Duox1/BLI-3 generated reactive oxygen species trigger protective SKN-1 activity via p38 MAPK signaling during infection in C. elegans."
    Hoeven R.V., McCallum K.C., Cruz M.R., Garsin D.A.
    PLoS Pathog. 7:E1002453-E1002453(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, DISRUPTION PHENOTYPE.
  9. "Stabilization of RNT-1 protein, runt-related transcription factor (RUNX) protein homolog of Caenorhabditis elegans, by oxidative stress through mitogen-activated protein kinase pathway."
    Lee K., Shim J., Bae J., Kim Y.J., Lee J.
    J. Biol. Chem. 287:10444-10452(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, CATALYTIC ACTIVITY, COFACTOR, DISRUPTION PHENOTYPE.

Entry informationi

Entry nameiPMK1_CAEEL
AccessioniPrimary (citable) accession number: Q17446
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 30, 2003
Last sequence update: November 1, 1996
Last modified: June 8, 2016
This is version 144 of the entry and version 1 of the sequence. [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

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.