PMK3_CAEEL
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 03-AUG-2022, entry version 168.
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.F42G8.4.1; -.
DR iPTMnet; O44514; -.
DR EPD; O44514; -.
DR PaxDb; O44514; -.
DR PeptideAtlas; O44514; -.
DR PRIDE; 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 GeneID; 177610; -.
DR UCSC; F42G8.4.1; c. elegans.
DR CTD; 177610; -.
DR WormBase; F42G8.4a; CE29318; WBGene00004057; pmk-3.
DR eggNOG; KOG0660; Eukaryota.
DR InParanoid; O44514; -.
DR OMA; RADHIFD; -.
DR OrthoDB; 741207at2759; -.
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-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; O44514; -.
DR PRO; PR:O44514; -.
DR Proteomes; UP000001940; Chromosome IV.
DR Bgee; WBGene00004057; Expressed in pharyngeal muscle cell (C elegans) and 3 other 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; IBA:GO_Central.
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:0048691; P:positive regulation of axon extension involved in regeneration; IMP:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; IEA:InterPro.
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 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 Pfam; PF00069; Pkinase; 1.
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; 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
