ID   PMK3_CAEEL              Reviewed;         474 AA.
AC   O44514;
DT   30-APR-2003, integrated into UniProtKB/Swiss-Prot.
DT   01-DEC-2001, sequence version 2.
DT   24-JAN-2024, entry version 176.
DE   RecName: Full=Mitogen-activated protein kinase pmk-3;
DE            EC=2.7.11.24;
DE   AltName: Full=Stress-activated protein kinase pmk-3;
DE   AltName: Full=p38 MAP kinase 3;
GN   Name=pmk-3; ORFNames=F42G8.4;
OS   Caenorhabditis elegans.
OC   Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC   Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC   Caenorhabditis.
OX   NCBI_TaxID=6239;
RN   [1] {ECO:0000305}
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, TISSUE SPECIFICITY, AND
RP   SUBCELLULAR LOCATION.
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, AND INTERACTION WITH MAK-2.
RX   PubMed=19737525; DOI=10.1016/j.cell.2009.06.023;
RA   Yan D., Wu Z., Chisholm A.D., Jin Y.;
RT   "The DLK-1 kinase promotes mRNA stability and local translation in C.
RT   elegans synapses and axon regeneration.";
RL   Cell 138:1005-1018(2009).
RN   [4]
RP   FUNCTION, AND INTERACTION WITH VHP-1.
RX   PubMed=21670305; DOI=10.1073/pnas.1104830108;
RA   Nix P., Hisamoto N., Matsumoto K., Bastiani M.;
RT   "Axon regeneration requires coordinate activation of p38 and JNK MAPK
RT   pathways.";
RL   Proc. Natl. Acad. Sci. U.S.A. 108:10738-10743(2011).
RN   [5]
RP   INTERACTION WITH UEV-3.
RX   PubMed=20592265; DOI=10.1534/genetics.110.117341;
RA   Trujillo G., Nakata K., Yan D., Maruyama I.N., Jin Y.;
RT   "A ubiquitin E2 variant protein acts in axon termination and synaptogenesis
RT   in Caenorhabditis elegans.";
RL   Genetics 186:135-145(2010).
RN   [6]
RP   FUNCTION, AND SUBCELLULAR LOCATION.
RX   PubMed=26657059; DOI=10.1371/journal.pgen.1005733;
RA   van der Vaart A., Rademakers S., Jansen G.;
RT   "DLK-1/p38 MAP Kinase signaling controls cilium length by regulating RAB-5
RT   mediated endocytosis in Caenorhabditis elegans.";
RL   PLoS Genet. 11:E1005733-E1005733(2015).
RN   [7]
RP   FUNCTION, AND DISRUPTION PHENOTYPE.
RX   PubMed=27123983; DOI=10.1371/journal.pgen.1006010;
RA   D'Souza S.A., Rajendran L., Bagg R., Barbier L., van Pel D.M., Moshiri H.,
RA   Roy P.J.;
RT   "The MADD-3 LAMMER kinase interacts with a p38 MAP kinase pathway to
RT   regulate the display of the EVA-1 guidance receptor in Caenorhabditis
RT   elegans.";
RL   PLoS Genet. 12:E1006010-E1006010(2016).
CC   -!- FUNCTION: Responds to activation by environmental stress and pro-
CC       inflammatory cytokines by phosphorylating downstream targets
CC       (PubMed:11703092). Involved in axon regeneration after injury, probably
CC       downstream of dlk-1 and mkk-4 and upstream of mak-2 (PubMed:21670305,
CC       PubMed:19737525). May phosphorylate mak-2 (PubMed:19737525). Plays a
CC       role in cilium length regulation, possibly by reducing rab-5 mediated
CC       endocytosis (PubMed:26657059). Plays a role in the formation of muscle
CC       connections, also called muscle arm extensions, between the body wall
CC       and the motor axons in the dorsal and ventral cord (PubMed:27123983).
CC       {ECO:0000269|PubMed:11703092, ECO:0000269|PubMed:19737525,
CC       ECO:0000269|PubMed:21670305, ECO:0000269|PubMed:26657059,
CC       ECO:0000269|PubMed:27123983}.
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};
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   -!- COFACTOR:
CC       Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC         Evidence={ECO:0000269|PubMed:11703092};
CC   -!- ACTIVITY REGULATION: Activated by phosphorylation on threonine and
CC       tyrosine. {ECO:0000250|UniProtKB:Q16539}.
CC   -!- SUBUNIT: Interacts with mak-2 (PubMed:19737525). May interact with vhp-
CC       1 (PubMed:21670305). May interact with uev-3 (PubMed:20592265).
CC       {ECO:0000269|PubMed:19737525, ECO:0000269|PubMed:20592265,
CC       ECO:0000269|PubMed:21670305}.
CC   -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:11703092,
CC       ECO:0000269|PubMed:26657059}. Cytoplasm {ECO:0000269|PubMed:26657059}.
CC       Cell projection, axon {ECO:0000269|PubMed:26657059}. Cell projection,
CC       dendrite {ECO:0000269|PubMed:26657059}. Cell projection, cilium
CC       {ECO:0000269|PubMed:26657059}.
CC   -!- TISSUE SPECIFICITY: Expressed throughout the intestine.
CC       {ECO:0000269|PubMed:11703092}.
CC   -!- DOMAIN: The TXY motif contains the threonine and tyrosine residues
CC       whose phosphorylation activates the MAP kinases.
CC   -!- PTM: Dually phosphorylated on Thr-285 and Tyr-287, which activates the
CC       enzyme. {ECO:0000250}.
CC   -!- DISRUPTION PHENOTYPE: Weak defect in the extension of body wall muscle
CC       connections or arms towards the ventral nerve cord. Double knockout
CC       with madd-3 suppresses the muscle arm extension defects, eva-1 and rab-
CC       7 expression defects and restores the defect in the recruitment of
CC       madd-4 to the muscle membrane in the madd-3 single knockout. Triple
CC       knockout with madd-3 and unc-54 results in paralysis (as in the unc-54
CC       single knockout), and suppresses the lethality phenotype in the double
CC       madd-3 and unc-54 mutant. {ECO:0000269|PubMed:27123983}.
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; FO080126; CCD61404.1; -; Genomic_DNA.
DR   PIR; T32642; T32642.
DR   RefSeq; NP_501363.1; NM_068962.4.
DR   AlphaFoldDB; O44514; -.
DR   SMR; O44514; -.
DR   BioGRID; 42723; 5.
DR   DIP; DIP-59691N; -.
DR   IntAct; O44514; 1.
DR   STRING; 6239.F42G8.4a.1; -.
DR   iPTMnet; O44514; -.
DR   EPD; O44514; -.
DR   PaxDb; 6239-F42G8-4-1; -.
DR   PeptideAtlas; O44514; -.
DR   EnsemblMetazoa; F42G8.4a.1; F42G8.4a.1; WBGene00004057.
DR   EnsemblMetazoa; F42G8.4a.2; F42G8.4a.2; WBGene00004057.
DR   EnsemblMetazoa; F42G8.4a.3; F42G8.4a.3; WBGene00004057.
DR   UCSC; F42G8.4.1; c. elegans.
DR   AGR; WB:WBGene00004057; -.
DR   WormBase; F42G8.4a; CE29318; WBGene00004057; pmk-3.
DR   eggNOG; KOG0660; Eukaryota.
DR   InParanoid; O44514; -.
DR   OMA; RADHIFD; -.
DR   OrthoDB; 2873050at2759; -.
DR   PhylomeDB; O44514; -.
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-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   SignaLink; O44514; -.
DR   PRO; PR:O44514; -.
DR   Proteomes; UP000001940; Chromosome IV.
DR   Bgee; WBGene00004057; Expressed in pharyngeal muscle cell (C elegans) and 3 other cell types or tissues.
DR   ExpressionAtlas; O44514; baseline and differential.
DR   GO; GO:0030424; C:axon; IEA:UniProtKB-SubCell.
DR   GO; GO:0005929; C:cilium; IEA:UniProtKB-SubCell.
DR   GO; GO:0005737; C:cytoplasm; IDA:WormBase.
DR   GO; GO:0030425; C:dendrite; IEA:UniProtKB-SubCell.
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; IEA:UniProtKB-EC.
DR   GO; GO:0019901; F:protein kinase binding; IPI:UniProtKB.
DR   GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR   GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:UniProtKB.
DR   GO; GO:0031103; P:axon regeneration; IGI:UniProtKB.
DR   GO; GO:0035095; P:behavioral response to nicotine; IMP:UniProtKB.
DR   GO; GO:0035556; P:intracellular signal transduction; IBA:GO_Central.
DR   GO; GO:0000165; P:MAPK cascade; IMP:UniProtKB.
DR   GO; GO:0038066; P:p38MAPK cascade; IMP:UniProtKB.
DR   GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW.
DR   GO; GO:0048691; P:positive regulation of axon extension involved in regeneration; IMP:UniProtKB.
DR   GO; GO:1905868; P:regulation of 3'-UTR-mediated mRNA stabilization; IGI:UniProtKB.
DR   GO; GO:0048841; P:regulation of axon extension involved in axon guidance; IGI:UniProtKB.
DR   GO; GO:0050807; P:regulation of synapse organization; IGI:WormBase.
DR   GO; GO:0006970; P:response to osmotic stress; IDA:UniProtKB.
DR   CDD; cd07851; STKc_p38; 1.
DR   Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1.
DR   InterPro; IPR011009; Kinase-like_dom_sf.
DR   InterPro; IPR003527; MAP_kinase_CS.
DR   InterPro; IPR000719; Prot_kinase_dom.
DR   InterPro; IPR017441; Protein_kinase_ATP_BS.
DR   PANTHER; PTHR24055; MITOGEN-ACTIVATED PROTEIN KINASE; 1.
DR   PANTHER; PTHR24055:SF155; MITOGEN-ACTIVATED PROTEIN KINASE PMK-3; 1.
DR   Pfam; PF00069; Pkinase; 1.
DR   SMART; SM00220; S_TKc; 1.
DR   SUPFAM; SSF56112; Protein kinase-like (PK-like); 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; Cell projection; Cytoplasm; Kinase; Nucleotide-binding;
KW   Nucleus; Phosphoprotein; Reference proteome;
KW   Serine/threonine-protein kinase; Transferase.
FT   CHAIN           1..474
FT                   /note="Mitogen-activated protein kinase pmk-3"
FT                   /id="PRO_0000186305"
FT   DOMAIN          114..419
FT                   /note="Protein kinase"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT   REGION          1..90
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOTIF           285..287
FT                   /note="TXY"
FT   COMPBIAS        25..55
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   ACT_SITE        252
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT   BINDING         124..132
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT   BINDING         150
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT   MOD_RES         285
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0000250"
FT   MOD_RES         287
FT                   /note="Phosphotyrosine"
FT                   /evidence="ECO:0000250"
SQ   SEQUENCE   474 AA;  54894 MW;  E405C45FDCC6ABA9 CRC64;
     MASVPSSSSL PVSHVRRHED VSTPSAPPTK RSNNQSQPPE SYEPNTWLQQ QREQEQQKKL
     AAENIKKQSI EATGNNEMVG EEEEDILSKP CGPHKRRFQF VMIRNITFAI PEGYDVEPNS
     IEYLGGGSFG NVIKTSAVCR DGLRRYVAIK KMREPFFDPH HARRIFRETK LLQLMRHDNI
     ICALDIYTPD EENDFRDVYV VTEFAGRSLY QILKQQRDYG RRVLTDEHIK FIIYQIIRAL
     KYIHSANIIH RDLKPGNLAL TDDSDLMILD FGLARSLEKK DTSLTQYVQT RWYRSPEVIY
     WKIDSYTNLA DMWSLGCIAA ELLTGEPLFP GDEPNAQYQR ITQLCGSPDE ELLTKIENDN
     SSAIKAVIQS YTTHKRRNFR DVFSAHNPSE DFIDLLEKLL VLDPEKRITV EEAIQHPYLA
     EFSLPEDEPR ADHIFDLDDS QARTRFEWRD AVWKEIMNYK RLSSSPLIPG EADR
//