MEK2_CAEEL
ID MEK2_CAEEL Reviewed; 387 AA.
AC Q10664;
DT 20-JUN-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 169.
DE RecName: Full=Dual specificity mitogen-activated protein kinase kinase mek-2;
DE Short=MAP kinase kinase mek-2;
DE EC=2.7.12.2;
GN Name=mek-2; ORFNames=Y54E10BL.6;
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 [MRNA], AND MUTAGENESIS OF PRO-237 AND GLU-238.
RX PubMed=7729690; DOI=10.1101/gad.9.6.742;
RA Wu Y., Han M., Guan K.-L.;
RT "MEK-2, a Caenorhabditis elegans MAP kinase kinase, functions in Ras-
RT mediated vulval induction and other developmental events.";
RL Genes Dev. 9:742-755(1995).
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 INTERACTION WITH KSR-1.
RX PubMed=10409742; DOI=10.1128/mcb.19.8.5523;
RA Stewart S., Sundaram M., Zhang Y., Lee J., Han M., Guan K.L.;
RT "Kinase suppressor of Ras forms a multiprotein signaling complex and
RT modulates MEK localization.";
RL Mol. Cell. Biol. 19:5523-5534(1999).
RN [4]
RP FUNCTION, AND MUTAGENESIS OF ASP-213.
RC STRAIN=Bristol N2;
RX PubMed=11689700; DOI=10.1128/mcb.21.23.8104-8116.2001;
RA Schutzman J.L., Borland C.Z., Newman J.C., Robinson M.K., Kokel M.,
RA Stern M.J.;
RT "The Caenorhabditis elegans EGL-15 signaling pathway implicates a DOS-like
RT multisubstrate adaptor protein in fibroblast growth factor signal
RT transduction.";
RL Mol. Cell. Biol. 21:8104-8116(2001).
RN [5]
RP FUNCTION, AND MUTAGENESIS OF SER-217; SER-223 AND SER-227.
RX PubMed=15268855; DOI=10.1016/j.cub.2004.07.022;
RA Nicholas H.R., Hodgkin J.;
RT "The ERK MAP kinase cascade mediates tail swelling and a protective
RT response to rectal infection in C. elegans.";
RL Curr. Biol. 14:1256-1261(2004).
RN [6]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=19826475; DOI=10.1371/journal.pone.0007450;
RA Schouest K.R., Kurasawa Y., Furuta T., Hisamoto N., Matsumoto K.,
RA Schumacher J.M.;
RT "The germinal center kinase GCK-1 is a negative regulator of MAP kinase
RT activation and apoptosis in the C. elegans germline.";
RL PLoS ONE 4:E7450-E7450(2009).
RN [7]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=20624915; DOI=10.1074/jbc.m110.146274;
RA Okuyama T., Inoue H., Ookuma S., Satoh T., Kano K., Honjoh S., Hisamoto N.,
RA Matsumoto K., Nishida E.;
RT "The ERK-MAPK pathway regulates longevity through SKN-1 and insulin-like
RT signaling in Caenorhabditis elegans.";
RL J. Biol. Chem. 285:30274-30281(2010).
CC -!- FUNCTION: Functions in the let-60 Ras signaling pathway; acts
CC downstream of lin-45 raf kinase, but before the sur-1/mpk-1 gene
CC product in controlling vulval cell differentiation (PubMed:7729690).
CC Required for progression of developing oocytes through the pachytene
CC stage (PubMed:19826475). Plays a role in responses to M.nematophilum-
CC mediated bacterial infection by promoting tail swelling and preventing
CC constipation (PubMed:15268855). Involved in fluid homeostasis
CC (PubMed:11689700). Positively regulates lifespan upstream of mpk-1
CC (PubMed:20624915). {ECO:0000269|PubMed:11689700,
CC ECO:0000269|PubMed:15268855, ECO:0000269|PubMed:19826475,
CC ECO:0000269|PubMed:20624915, ECO:0000269|PubMed:7729690}.
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=2.7.12.2;
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=2.7.12.2;
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-tyrosyl-[protein] = ADP + H(+) + O-phospho-L-tyrosyl-
CC [protein]; Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136, Rhea:RHEA-
CC COMP:10137, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:46858,
CC ChEBI:CHEBI:82620, ChEBI:CHEBI:456216; EC=2.7.12.2;
CC -!- ACTIVITY REGULATION: Activated by tyrosine and threonine
CC phosphorylation catalyzed by MAP kinase kinase kinases.
CC -!- SUBUNIT: Interacts with ksr-1. {ECO:0000269|PubMed:10409742}.
CC -!- DISRUPTION PHENOTYPE: RNAi-mediated knockdown causes a defect in
CC pachytene progression resulting in a proximal gonad devoid of nuclei.
CC The phenotype is more severe in gck-1 km15 mutant background
CC (PubMed:19826475). RNAi-mediated knockdown in adults decreases lifespan
CC (PubMed:20624915). {ECO:0000269|PubMed:19826475,
CC ECO:0000269|PubMed:20624915}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. STE Ser/Thr
CC protein kinase family. MAP kinase kinase subfamily. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; U21107; AAA85118.1; -; mRNA.
DR EMBL; FO081804; CCD73487.1; -; Genomic_DNA.
DR PIR; A56466; A56466.
DR RefSeq; NP_491087.1; NM_058686.4.
DR AlphaFoldDB; Q10664; -.
DR SMR; Q10664; -.
DR BioGRID; 37349; 16.
DR IntAct; Q10664; 3.
DR MINT; Q10664; -.
DR STRING; 6239.Y54E10BL.6; -.
DR iPTMnet; Q10664; -.
DR EPD; Q10664; -.
DR PaxDb; Q10664; -.
DR PeptideAtlas; Q10664; -.
DR PRIDE; Q10664; -.
DR EnsemblMetazoa; Y54E10BL.6.1; Y54E10BL.6.1; WBGene00003186.
DR GeneID; 171872; -.
DR KEGG; cel:CELE_Y54E10BL.6; -.
DR UCSC; Y54E10BL.6; c. elegans.
DR CTD; 171872; -.
DR WormBase; Y54E10BL.6; CE25437; WBGene00003186; mek-2.
DR eggNOG; KOG0581; Eukaryota.
DR GeneTree; ENSGT00940000153487; -.
DR HOGENOM; CLU_000288_63_23_1; -.
DR InParanoid; Q10664; -.
DR OMA; IAGWVCK; -.
DR OrthoDB; 688282at2759; -.
DR PhylomeDB; Q10664; -.
DR BRENDA; 2.7.12.2; 1045.
DR Reactome; R-CEL-110056; MAPK3 (ERK1) activation.
DR Reactome; R-CEL-112411; MAPK1 (ERK2) activation.
DR Reactome; R-CEL-170968; Frs2-mediated activation.
DR Reactome; R-CEL-445144; Signal transduction by L1.
DR Reactome; R-CEL-5674135; MAP2K and MAPK activation.
DR Reactome; R-CEL-5674499; Negative feedback regulation of MAPK pathway.
DR SignaLink; Q10664; -.
DR PRO; PR:Q10664; -.
DR Proteomes; UP000001940; Chromosome I.
DR Bgee; WBGene00003186; Expressed in pharyngeal muscle cell (C elegans) and 3 other tissues.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004708; F:MAP kinase kinase activity; IBA:GO_Central.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IEA:UniProtKB-KW.
DR GO; GO:0004712; F:protein serine/threonine/tyrosine kinase activity; IDA:WormBase.
DR GO; GO:0004713; F:protein tyrosine kinase activity; IEA:UniProtKB-KW.
DR GO; GO:0097110; F:scaffold protein binding; IPI:UniProtKB.
DR GO; GO:0050830; P:defense response to Gram-positive bacterium; IMP:UniProtKB.
DR GO; GO:0000165; P:MAPK cascade; IMP:UniProtKB.
DR GO; GO:0051321; P:meiotic cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0048477; P:oogenesis; IEA:UniProtKB-KW.
DR GO; GO:0006468; P:protein phosphorylation; IDA:WormBase.
DR GO; GO:0007265; P:Ras protein signal transduction; IGI:WormBase.
DR GO; GO:0040025; P:vulval development; IGI:WormBase.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR Pfam; PF00069; Pkinase; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
PE 1: Evidence at protein level;
KW ATP-binding; Developmental protein; Differentiation; Kinase; Meiosis;
KW Nucleotide-binding; Oogenesis; Phosphoprotein; Reference proteome;
KW Serine/threonine-protein kinase; Transferase; Tyrosine-protein kinase.
FT CHAIN 1..387
FT /note="Dual specificity mitogen-activated protein kinase
FT kinase mek-2"
FT /id="PRO_0000086322"
FT DOMAIN 73..360
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 1..37
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 14..29
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 195
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 79..87
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 102
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 223
FT /note="Phosphoserine"
FT /evidence="ECO:0000250"
FT MOD_RES 227
FT /note="Phosphoserine"
FT /evidence="ECO:0000250"
FT MUTAGEN 213
FT /note="D->N: In n2678; rescues fluid accumulation in crl-1
FT e1745ts mutant."
FT /evidence="ECO:0000269|PubMed:11689700"
FT MUTAGEN 217
FT /note="S->F: In n1989; severe constipation following
FT M.nematophilium infection."
FT /evidence="ECO:0000269|PubMed:15268855"
FT MUTAGEN 223
FT /note="S->E: Phosphomimetic mutant which, in a wild type
FT background, induces tail swelling; in association with D-
FT 227."
FT MUTAGEN 227
FT /note="S->D: Phosphomimetic mutant which, in a wild type
FT background, induces tail swelling; in association with E-
FT 223."
FT /evidence="ECO:0000269|PubMed:15268855"
FT MUTAGEN 237
FT /note="P->S: In KU114; 8% larval lethality."
FT /evidence="ECO:0000269|PubMed:7729690"
FT MUTAGEN 238
FT /note="E->K: In H294; 100% larval lethality."
FT /evidence="ECO:0000269|PubMed:7729690"
SQ SEQUENCE 387 AA; 42794 MW; 8FD8556236B6624B CRC64;
MSSGKRRNPL GLSLPPTVNE QSESGEATAE EATATVPLEE QLKKLGLTEP QTQRLSEFLQ
VKEGIKELSE DMLQTEGELG HGNGGVVNKC VHRKTGVIMA RKLVHLEIKP SVRQQIVKEL
AVLHKCNSPF IVGFYGAFVD NNDISICMEY MDGLSLDIVL KKVGRLPEKF VGRISVAVVR
GLTYLKDEIK ILHRDVKPSN MLVNSNGEIK LCDFGVSGML IDSMANSFVG TRSYMAPERL
TGSHYTISSD IWSFGLSLVE LLIGRYPVPA PSQAEYATMF NVAENEIELA DSLEEPNYHP
PSNPASMAIF EMLDYIVNGP PPTLPKRFFT DEVIGFVSKC LRKLPSERAT LKSLTADVFF
TQYADHDDQG EFAVFVKGTI NLPKLNP
