PMK1_CAEEL
ID PMK1_CAEEL Reviewed; 377 AA.
AC Q17446;
DT 30-APR-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 180.
DE RecName: Full=Mitogen-activated protein kinase pmk-1;
DE EC=2.7.11.24 {ECO:0000269|PubMed:11703092, ECO:0000269|PubMed:16166371, ECO:0000269|PubMed:22308034};
DE AltName: Full=Stress-activated protein kinase pmk-1;
DE AltName: Full=p38 MAP kinase 1;
GN Name=pmk-1 {ECO:0000312|WormBase:B0218.3};
GN ORFNames=B0218.3 {ECO:0000312|WormBase:B0218.3};
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 [GENOMIC DNA], FUNCTION, CATALYTIC ACTIVITY, COFACTOR,
RP ACTIVITY REGULATION, AND DOMAIN.
RC STRAIN=Bristol N2;
RX PubMed=11703092; DOI=10.1006/mcbr.2001.0300;
RA Berman K., McKay J., Avery L., Cobb M.;
RT "Isolation and characterization of pmk-(1-3): three p38 homologs in
RT Caenorhabditis elegans.";
RL Mol. Cell Biol. Res. Commun. 4:337-344(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]
RP FUNCTION, PHOSPHORYLATION AT THR-191 AND TYR-193, AND DISRUPTION PHENOTYPE.
RC STRAIN=Bristol N2;
RX PubMed=12142542; DOI=10.1126/science.1073759;
RA Kim D.H., Feinbaum R., Alloing G., Emerson F.E., Garsin D.A., Inoue H.,
RA Tanaka-Hino M., Hisamoto N., Matsumoto K., Tan M.-W., Ausubel F.M.;
RT "A conserved p38 MAP kinase pathway in Caenorhabditis elegans innate
RT immunity.";
RL Science 297:623-626(2002).
RN [4]
RP FUNCTION, CATALYTIC ACTIVITY, PHOSPHORYLATION AT THR-191 AND TYR-193, AND
RP MUTAGENESIS OF LYS-64.
RX PubMed=16166371; DOI=10.1101/gad.1324805;
RA Inoue H., Hisamoto N., An J.H., Oliveira R.P., Nishida E., Blackwell T.K.,
RA Matsumoto K.;
RT "The C. elegans p38 MAPK pathway regulates nuclear localization of the
RT transcription factor SKN-1 in oxidative stress response.";
RL Genes Dev. 19:2278-2283(2005).
RN [5]
RP FUNCTION.
RX PubMed=18394898; DOI=10.1016/j.cub.2008.02.079;
RA Pujol N., Cypowyj S., Ziegler K., Millet A., Astrain A., Goncharov A.,
RA Jin Y., Chisholm A.D., Ewbank J.J.;
RT "Distinct innate immune responses to infection and wounding in the C.
RT elegans epidermis.";
RL Curr. Biol. 18:481-489(2008).
RN [6]
RP FUNCTION.
RX PubMed=19497412; DOI=10.1016/j.cbi.2009.03.012;
RA Wang S., Wu L., Wang Y., Luo X., Lu Y.;
RT "Copper-induced germline apoptosis in Caenorhabditis elegans: the
RT independent roles of DNA damage response signaling and the dependent roles
RT of MAPK cascades.";
RL Chem. Biol. Interact. 180:151-157(2009).
RN [7] {ECO:0000305}
RP FUNCTION, AND INTERACTION WITH ATF-7.
RX PubMed=20369020; DOI=10.1371/journal.pgen.1000892;
RA Shivers R.P., Pagano D.J., Kooistra T., Richardson C.E., Reddy K.C.,
RA Whitney J.K., Kamanzi O., Matsumoto K., Hisamoto N., Kim D.H.;
RT "Phosphorylation of the conserved transcription factor ATF-7 by PMK-1 p38
RT MAPK regulates innate immunity in Caenorhabditis elegans.";
RL PLoS Genet. 6:e1000892-e1000892(2010).
RN [8]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=20062796; DOI=10.1371/journal.ppat.1000717;
RA Butschi A., Titz A., Waelti M.A., Olieric V., Paschinger K., Noebauer K.,
RA Guo X., Seeberger P.H., Wilson I.B., Aebi M., Hengartner M.O., Kuenzler M.;
RT "Caenorhabditis elegans N-glycan core beta-galactoside confers sensitivity
RT towards nematotoxic fungal galectin CGL2.";
RL PLoS Pathog. 6:E1000717-E1000717(2010).
RN [9]
RP FUNCTION, AND PHOSPHORYLATION AT THR-191 AND TYR-193.
RX PubMed=21212236; DOI=10.1534/genetics.110.124883;
RA Hayakawa T., Kato K., Hayakawa R., Hisamoto N., Matsumoto K., Takeda K.,
RA Ichijo H.;
RT "Regulation of anoxic death in Caenorhabditis elegans by mammalian
RT apoptosis signal-regulating kinase (ASK) family proteins.";
RL Genetics 187:785-792(2011).
RN [10]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=22216003; DOI=10.1371/journal.ppat.1002453;
RA Hoeven R.V., McCallum K.C., Cruz M.R., Garsin D.A.;
RT "Ce-Duox1/BLI-3 generated reactive oxygen species trigger protective SKN-1
RT activity via p38 MAPK signaling during infection in C. elegans.";
RL PLoS Pathog. 7:E1002453-E1002453(2011).
RN [11]
RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, AND DISRUPTION PHENOTYPE.
RX PubMed=22308034; DOI=10.1074/jbc.m111.314146;
RA Lee K., Shim J., Bae J., Kim Y.J., Lee J.;
RT "Stabilization of RNT-1 protein, runt-related transcription factor (RUNX)
RT protein homolog of Caenorhabditis elegans, by oxidative stress through
RT mitogen-activated protein kinase pathway.";
RL J. Biol. Chem. 287:10444-10452(2012).
RN [12]
RP FUNCTION, AND PHOSPHORYLATION.
RX PubMed=25204677; DOI=10.1186/s12915-014-0064-6;
RA Crook-McMahon H.M., Olahova M., Button E.L., Winter J.J., Veal E.A.;
RT "Genome-wide screening identifies new genes required for stress-induced
RT phase 2 detoxification gene expression in animals.";
RL BMC Biol. 12:64-64(2014).
RN [13]
RP FUNCTION, DISRUPTION PHENOTYPE, AND PHOSPHORYLATION.
RX PubMed=29748542; DOI=10.1038/s41598-018-25333-8;
RA Park M.R., Ryu S., Maburutse B.E., Oh N.S., Kim S.H., Oh S., Jeong S.Y.,
RA Jeong D.Y., Oh S., Kim Y.;
RT "Probiotic Lactobacillus fermentum strain JDFM216 stimulates the longevity
RT and immune response of Caenorhabditis elegans through a nuclear hormone
RT receptor.";
RL Sci. Rep. 8:7441-7441(2018).
CC -!- FUNCTION: Serine/threonine kinase which responds to activation by
CC environmental stress and pro-inflammatory cytokines by phosphorylating
CC downstream targets (PubMed:11703092, PubMed:12142542, PubMed:16166371,
CC PubMed:18394898, PubMed:22308034, PubMed:20369020). As part of a MAP
CC kinase signaling pathway, plays a role in modulation of lifespan and
CC immunity (PubMed:29748542, PubMed:12142542, PubMed:20369020,
CC PubMed:22216003). Phosphorylates skn-1 which probably regulates skn-1
CC nuclear translocation in response to oxidative stress
CC (PubMed:16166371). Probably by activating skn-1, involved in the up-
CC regulation of gcs-1 and glutathione-S-transferase gst-4 expression upon
CC bacteria infection (PubMed:22216003). Up-regulates expression of gcs-1
CC in intestinal cells upon arsenite treatment (PubMed:16166371,
CC PubMed:25204677). Functions downstream of the MAPKK sek-1 and the
CC MAPKKK nsy-1 as the MAP kinase which regulates pathogen resistance and
CC responses to oxidative stress (PubMed:11703092, PubMed:12142542,
CC PubMed:16166371, PubMed:18394898). Required for expression of
CC antimicrobial peptide nlp-29 in response to fungal infection or
CC physical injury (PubMed:18394898). Involved in resistance to the
CC nematotoxic C.cinerea galectin (Cgl2) (PubMed:20062796). May play a
CC redundant role with other MAP kinases in susceptibility to anoxia,
CC downstream of tir-1/nsy-1 (PubMed:21212236). Phosphorylates
CC transcription factor rnt-1 during oxidative stress which results in
CC rnt-1 stabilization in the intestine (PubMed:22308034). Phosphorylates
CC transcription factor atf-7 during pathogen infection resulting in
CC modulation of target genes (PubMed:20369020). Probably downstream of
CC nsy-1 and sek-1, involved in germline apoptosis induced by heavy
CC metals, such as Cu(2+) (PubMed:19497412). {ECO:0000269|PubMed:11703092,
CC ECO:0000269|PubMed:12142542, ECO:0000269|PubMed:16166371,
CC ECO:0000269|PubMed:18394898, ECO:0000269|PubMed:19497412,
CC ECO:0000269|PubMed:20062796, ECO:0000269|PubMed:20369020,
CC ECO:0000269|PubMed:21212236, ECO:0000269|PubMed:22216003,
CC ECO:0000269|PubMed:22308034, ECO:0000269|PubMed:25204677,
CC ECO:0000269|PubMed:29748542}.
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=2.7.11.24;
CC Evidence={ECO:0000269|PubMed:11703092, ECO:0000269|PubMed:16166371,
CC ECO:0000269|PubMed:22308034};
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=2.7.11.24; Evidence={ECO:0000269|PubMed:11703092,
CC ECO:0000269|PubMed:16166371, ECO:0000269|PubMed:22308034};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:11703092, ECO:0000269|PubMed:22308034};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000269|PubMed:22308034};
CC Note=Divalent cations such as magnesium or manganese.
CC {ECO:0000269|PubMed:22308034};
CC -!- ACTIVITY REGULATION: Activated by phosphorylation on threonine and
CC tyrosine. Inhibited by pyridinyl-imidazole related compounds.
CC {ECO:0000269|PubMed:11703092}.
CC -!- SUBUNIT: Interacts with transcription factor atf-7; perhaps in a manner
CC dependent on dual specificity protein kinase sek-1.
CC {ECO:0000269|PubMed:20369020}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:20369020}.
CC Note=Accumulates in nucleus in response to heavy metals, such as
CC cadmium. {ECO:0000269|PubMed:20369020}.
CC -!- TISSUE SPECIFICITY: Expressed in intestinal cells.
CC {ECO:0000269|PubMed:20369020}.
CC -!- DOMAIN: The TXY motif contains the threonine and tyrosine residues
CC whose phosphorylation activates the MAP kinases.
CC {ECO:0000269|PubMed:11703092}.
CC -!- PTM: Dually phosphorylated on Thr-191 and Tyr-193, probably by sek-1,
CC which activates the enzyme (PubMed:16166371, PubMed:21212236).
CC Increased phosphorylation in response to the heavy metal arsenite
CC (PubMed:25204677). Increased phosphorylation in response to intestinal
CC colonization by probiotic Lactobacillus fermentum strain JDFM216
CC (PubMed:29748542). {ECO:0000269|PubMed:16166371,
CC ECO:0000269|PubMed:21212236, ECO:0000269|PubMed:25204677,
CC ECO:0000269|PubMed:29748542}.
CC -!- DISRUPTION PHENOTYPE: Knockout causes reduction in adult lifespan
CC (PubMed:29748542). Upon infection by P.aeruginosa or E.faecalis, RNAi-
CC mediated knockdown results in a decrease in survival rate and in a
CC reduced up-regulation of gst-4 and gcs-1 expression (PubMed:12142542,
CC PubMed:22216003). Causes a severe reduction in rnt-1 accumulation in
CC the intestine during oxidative stress mediated by paraquat
CC (PubMed:22308034). Upon exposure to C.cinerea galectin Cgl2, adults
CC show reduced survival and larvae do not develop (PubMed:20062796).
CC Larval development is partially restored in a bre-1, fut-8, gly-13,
CC galt-1 or ger-1 mutant background (PubMed:20062796).
CC {ECO:0000269|PubMed:12142542, ECO:0000269|PubMed:20062796,
CC ECO:0000269|PubMed:22216003, ECO:0000269|PubMed:22308034,
CC ECO:0000269|PubMed:29748542}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CMGC Ser/Thr
CC protein kinase family. MAP kinase subfamily. {ECO:0000305}.
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DR EMBL; BX284604; CCD61386.1; -; Genomic_DNA.
DR PIR; T29750; T29750.
DR RefSeq; NP_501365.1; NM_068964.3.
DR AlphaFoldDB; Q17446; -.
DR SMR; Q17446; -.
DR BioGRID; 56238; 32.
DR DIP; DIP-26892N; -.
DR IntAct; Q17446; 17.
DR STRING; 6239.B0218.3; -.
DR iPTMnet; Q17446; -.
DR EPD; Q17446; -.
DR PaxDb; Q17446; -.
DR PeptideAtlas; Q17446; -.
DR EnsemblMetazoa; B0218.3.1; B0218.3.1; WBGene00004055.
DR GeneID; 191743; -.
DR KEGG; cel:CELE_B0218.3; -.
DR UCSC; B0218.3; c. elegans.
DR CTD; 191743; -.
DR WormBase; B0218.3; CE06686; WBGene00004055; pmk-1.
DR eggNOG; KOG0660; Eukaryota.
DR GeneTree; ENSGT00970000196450; -.
DR HOGENOM; CLU_000288_181_1_1; -.
DR InParanoid; Q17446; -.
DR OMA; YTDLNPV; -.
DR OrthoDB; 683132at2759; -.
DR PhylomeDB; Q17446; -.
DR BRENDA; 2.7.11.24; 1045.
DR Reactome; R-CEL-168638; NOD1/2 Signaling Pathway.
DR Reactome; R-CEL-171007; p38MAPK events.
DR Reactome; R-CEL-198753; ERK/MAPK targets.
DR Reactome; R-CEL-2559580; Oxidative Stress Induced Senescence.
DR Reactome; R-CEL-376172; DSCAM interactions.
DR Reactome; R-CEL-418592; ADP signalling through P2Y purinoceptor 1.
DR Reactome; R-CEL-432142; Platelet sensitization by LDL.
DR Reactome; R-CEL-4420097; VEGFA-VEGFR2 Pathway.
DR Reactome; R-CEL-450302; activated TAK1 mediates p38 MAPK activation.
DR Reactome; R-CEL-450341; Activation of the AP-1 family of transcription factors.
DR Reactome; R-CEL-525793; Myogenesis.
DR Reactome; R-CEL-5675221; Negative regulation of MAPK pathway.
DR Reactome; R-CEL-6798695; Neutrophil degranulation.
DR SignaLink; Q17446; -.
DR PRO; PR:Q17446; -.
DR Proteomes; UP000001940; Chromosome IV.
DR Bgee; WBGene00004055; Expressed in pharyngeal muscle cell (C elegans) and 4 other tissues.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; IDA:WormBase.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004707; F:MAP kinase activity; IDA:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004672; F:protein kinase activity; IDA:WormBase.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:WormBase.
DR GO; GO:0008134; F:transcription factor binding; IPI:WormBase.
DR GO; GO:0035095; P:behavioral response to nicotine; IMP:UniProtKB.
DR GO; GO:0071248; P:cellular response to metal ion; IMP:UniProtKB.
DR GO; GO:0050832; P:defense response to fungus; IMP:UniProtKB.
DR GO; GO:0050829; P:defense response to Gram-negative bacterium; IMP:UniProtKB.
DR GO; GO:0050830; P:defense response to Gram-positive bacterium; IMP:UniProtKB.
DR GO; GO:0006972; P:hyperosmotic response; IGI:WormBase.
DR GO; GO:0045087; P:innate immune response; IMP:WormBase.
DR GO; GO:0035556; P:intracellular signal transduction; IDA:UniProtKB.
DR GO; GO:0000165; P:MAPK cascade; IGI:WormBase.
DR GO; GO:1901215; P:negative regulation of neuron death; IMP:ParkinsonsUK-UCL.
DR GO; GO:0038066; P:p38MAPK cascade; IMP:WormBase.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IDA:WormBase.
DR GO; GO:1900426; P:positive regulation of defense response to bacterium; IGI:UniProtKB.
DR GO; GO:0010628; P:positive regulation of gene expression; IMP:UniProtKB.
DR GO; GO:1900182; P:positive regulation of protein localization to nucleus; IMP:WormBase.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IMP:WormBase.
DR GO; GO:1902097; P:positive regulation of transcription from RNA polymerase II promoter involved in defense response to Gram-negative bacterium; IMP:UniProtKB.
DR GO; GO:0012501; P:programmed cell death; IMP:WormBase.
DR GO; GO:0006468; P:protein phosphorylation; IDA:WormBase.
DR GO; GO:0034976; P:response to endoplasmic reticulum stress; IMP:UniProtKB.
DR GO; GO:0009408; P:response to heat; IMP:UniProtKB.
DR GO; GO:0093002; P:response to nematicide; IMP:UniProtKB.
DR GO; GO:0006970; P:response to osmotic stress; IDA:UniProtKB.
DR GO; GO:0006979; P:response to oxidative stress; IMP:UniProtKB.
DR GO; GO:0000302; P:response to reactive oxygen species; IEP:WormBase.
DR GO; GO:0000303; P:response to superoxide; IEP:WormBase.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR003527; MAP_kinase_CS.
DR InterPro; IPR008352; MAPK_p38-like.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR Pfam; PF00069; Pkinase; 1.
DR PRINTS; PR01773; P38MAPKINASE.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS01351; MAPK; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
PE 1: Evidence at protein level;
KW ATP-binding; Kinase; Magnesium; Manganese; Metal-binding;
KW Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome;
KW Serine/threonine-protein kinase; Stress response; Transferase.
FT CHAIN 1..377
FT /note="Mitogen-activated protein kinase pmk-1"
FT /id="PRO_0000186303"
FT DOMAIN 35..319
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOTIF 191..193
FT /note="TXY"
FT ACT_SITE 179
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 41..49
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 64
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 191
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:16166371,
FT ECO:0000269|PubMed:21212236"
FT MOD_RES 193
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:16166371,
FT ECO:0000269|PubMed:21212236"
FT MUTAGEN 64
FT /note="K->R: Loss of kinase activity."
FT /evidence="ECO:0000269|PubMed:16166371"
SQ SEQUENCE 377 AA; 43919 MW; F20BC395B38EFD03 CRC64;
MFPQTTMDHI LHPTPREGYY VVELNRSVWV VPNYYINLTP IGTGAYGTVC AAECTRSGTR
VAIKKFNRPF QSIIHARRTY RELRLLRCMC HENIIDLLDV FTPNENVNDI EDVYFVSMLM
GADLSNILKI QRLNDDHIQF LVYQILRGLK YIHSADIIHR DLKPSNIAVN EDCELKILDF
GLARQTDSEM TGYVATRWYR APEIMLNWMH YTQTVDVWSV GCILAELITG KTLFPGSDHI
DQLTRIMSVT GTPDEEFLKK ISSEEARNYI RNLPKMTRRD FKRLFAQATP QAIDLLEKML
HLDPDRRPTA KEAMEHEYLA AYHDETDEPI AEEMDLNDDV RADTIDEWKK IIWEEISDFQ
KNVAFADEEE DEEKMES
