ID PMK2_CAEEL Reviewed; 419 AA.
AC Q8MXI4; Q8MXI3;
DT 30-APR-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2002, sequence version 1.
DT 27-MAR-2024, entry version 172.
DE RecName: Full=Mitogen-activated protein kinase pmk-2;
DE EC=2.7.11.24;
DE AltName: Full=Stress-activated protein kinase pmk-2;
DE AltName: Full=p38 MAP kinase 2;
GN Name=pmk-2; ORFNames=F42G8.3;
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239;
RN [1] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM A), FUNCTION, SUBCELLULAR
RP LOCATION, AND ACTIVITY REGULATION.
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], AND ALTERNATIVE SPLICING.
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).
CC -!- FUNCTION: Responds to activation by environmental stress and pro-
CC inflammatory cytokines by phosphorylating downstream targets.
CC {ECO:0000269|PubMed:11703092}.
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. Inhibited by pyridinyl-imidazole related compounds.
CC {ECO:0000269|PubMed:11703092}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:11703092}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=a {ECO:0000305};
CC IsoId=Q8MXI4-1; Sequence=Displayed;
CC Name=b {ECO:0000305};
CC IsoId=Q8MXI4-2; Sequence=VSP_009272, VSP_050273;
CC -!- DOMAIN: The TXY motif contains the threonine and tyrosine residues
CC whose phosphorylation activates the MAP kinases.
CC -!- PTM: Dually phosphorylated on Thr-222 and Tyr-224, which activates the
CC enzyme. {ECO:0000250}.
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; CCD61402.1; -; Genomic_DNA.
DR EMBL; FO080126; CCD61403.1; -; Genomic_DNA.
DR RefSeq; NP_741457.2; NM_171392.5.
DR RefSeq; NP_741458.2; NM_171913.4. [Q8MXI4-2]
DR AlphaFoldDB; Q8MXI4; -.
DR SMR; Q8MXI4; -.
DR BioGRID; 42724; 3.
DR DIP; DIP-24927N; -.
DR IntAct; Q8MXI4; 1.
DR STRING; 6239.F42G8.3a.1; -.
DR PaxDb; 6239-F42G8-3a; -.
DR PeptideAtlas; Q8MXI4; -.
DR EnsemblMetazoa; F42G8.3a.1; F42G8.3a.1; WBGene00004056.
DR EnsemblMetazoa; F42G8.3b.1; F42G8.3b.1; WBGene00004056. [Q8MXI4-2]
DR GeneID; 177611; -.
DR KEGG; cel:CELE_F42G8.3; -.
DR UCSC; F42G8.3a; c. elegans. [Q8MXI4-1]
DR AGR; WB:WBGene00004056; -.
DR WormBase; F42G8.3a; CE49565; WBGene00004056; pmk-2.
DR WormBase; F42G8.3b; CE34862; WBGene00004056; pmk-2. [Q8MXI4-2]
DR eggNOG; KOG0660; Eukaryota.
DR HOGENOM; CLU_000288_181_1_1; -.
DR InParanoid; Q8MXI4; -.
DR OrthoDB; 158564at2759; -.
DR PhylomeDB; Q8MXI4; -.
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 PRO; PR:Q8MXI4; -.
DR Proteomes; UP000001940; Chromosome IV.
DR Bgee; WBGene00004056; Expressed in embryo and 3 other cell types or tissues.
DR ExpressionAtlas; Q8MXI4; baseline and differential.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004707; F:MAP kinase activity; IDA:UniProtKB.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IBA:GO_Central.
DR GO; GO:0035556; P:intracellular signal transduction; IDA:UniProtKB.
DR GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW.
DR GO; GO:0006970; P:response to osmotic stress; IDA:UniProtKB.
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; IPR008352; MAPK_p38-like.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR PANTHER; PTHR24055; MITOGEN-ACTIVATED PROTEIN KINASE; 1.
DR PANTHER; PTHR24055:SF158; MITOGEN-ACTIVATED PROTEIN KINASE P38A-RELATED; 1.
DR Pfam; PF00069; Pkinase; 1.
DR PRINTS; PR01773; P38MAPKINASE.
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 3: Inferred from homology;
KW Alternative splicing; ATP-binding; Cytoplasm; Kinase; Nucleotide-binding;
KW Phosphoprotein; Reference proteome; Serine/threonine-protein kinase;
KW Transferase.
FT CHAIN 1..419
FT /note="Mitogen-activated protein kinase pmk-2"
FT /id="PRO_0000186304"
FT DOMAIN 49..350
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOTIF 222..224
FT /note="TXY"
FT ACT_SITE 210
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 55..63
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 78
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 222
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250"
FT MOD_RES 224
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250"
FT VAR_SEQ 190..206
FT /note="Missing (in isoform b)"
FT /evidence="ECO:0000305"
FT /id="VSP_009272"
FT VAR_SEQ 366..370
FT /note="Missing (in isoform b)"
FT /evidence="ECO:0000305"
FT /id="VSP_050273"
SQ SEQUENCE 419 AA; 48026 MW; 621C52BFAB7EF37B CRC64;
MGMSATMGDS ASIPGVFFAD FGPAPPEITP EGYHEVELNK TKWVLPQWYN SLKPLGEGAY
GVVCTAEYEP TGDRVAIKKF FRPFQSTIHA KRTYRELKLL RTLQHDNVLE MIDVFTPDPD
ASSLNNVYFV SVLMGSDLQN IMKIQRLTDE QIQLLIYQVL RGLKYIHSAG IIHRDLKPSN
IAVNERCEVK VFLSFSQLSF LILSFFKILD FGLARAQDAE MTGYVATRWY RAPEIMLNWM
HYTQTVDVWS VGCILAELVS GRPLFPGDDH IDQLTKIMSV VGTPKEEFWS KIQSEEARNY
IKNRSPIIRQ DFVTLFPMAS PYALELLEMM LILDPDRRIS VSSALRHDYL REYSVPNDEP
VAMDTVINSI VTIDPAEERA TTLSDWRELI WNEIRLFQNS ARRLSFVSCT DTEEEPMKI
//
