MEK1_CAEEL
ID MEK1_CAEEL Reviewed; 347 AA.
AC Q21307; Q7Z1P1;
DT 22-JUL-2015, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2002, sequence version 2.
DT 03-AUG-2022, entry version 177.
DE RecName: Full=Dual specificity mitogen-activated protein kinase kinase mek-1 {ECO:0000250|UniProtKB:O14733};
DE EC=2.7.12.2 {ECO:0000269|PubMed:15116070};
GN Name=mek-1 {ECO:0000312|WormBase:K08A8.1a};
GN ORFNames=K08A8.1 {ECO:0000312|WormBase:K08A8.1a};
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239 {ECO:0000312|Proteomes:UP000001940};
RN [1] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A), FUNCTION, TISSUE SPECIFICITY,
RP DEVELOPMENTAL STAGE, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF SER-221 AND
RP SER-225.
RX PubMed=11013217; DOI=10.1093/emboj/19.19.5148;
RA Koga M., Zwaal R., Guan K.L., Avery L., Ohshima Y.;
RT "A Caenorhabditis elegans MAP kinase kinase, MEK-1, is involved in stress
RT responses.";
RL EMBO J. 19:5148-5156(2000).
RN [2] {ECO:0000312|Proteomes:UP000001940}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Bristol N2 {ECO:0000312|Proteomes:UP000001940};
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] {ECO:0000305}
RP FUNCTION, CATALYTIC ACTIVITY, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF
RP LYS-99.
RX PubMed=15116070; DOI=10.1038/sj.emboj.7600226;
RA Mizuno T., Hisamoto N., Terada T., Kondo T., Adachi M., Nishida E.,
RA Kim D.H., Ausubel F.M., Matsumoto K.;
RT "The Caenorhabditis elegans MAPK phosphatase VHP-1 mediates a novel JNK-
RT like signaling pathway in stress response.";
RL EMBO J. 23:2226-2234(2004).
RN [4] {ECO:0000305}
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=15256594; DOI=10.1073/pnas.0403546101;
RA Kim D.H., Liberati N.T., Mizuno T., Inoue H., Hisamoto N., Matsumoto K.,
RA Ausubel F.M.;
RT "Integration of Caenorhabditis elegans MAPK pathways mediating immunity and
RT stress resistance by MEK-1 MAPK kinase and VHP-1 MAPK phosphatase.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:10990-10994(2004).
RN [5]
RP FUNCTION.
RX PubMed=16729024; DOI=10.1038/sj.cdd.4401976;
RA Salinas L.S., Maldonado E., Navarro R.E.;
RT "Stress-induced germ cell apoptosis by a p53 independent pathway in
RT Caenorhabditis elegans.";
RL Cell Death Differ. 13:2129-2139(2006).
RN [6]
RP FUNCTION, AND INTERACTION WITH SHC-1.
RX PubMed=18832074; DOI=10.1101/gad.478408;
RA Neumann-Haefelin E., Qi W., Finkbeiner E., Walz G., Baumeister R.,
RA Hertweck M.;
RT "SHC-1/p52Shc targets the insulin/IGF-1 and JNK signaling pathways to
RT modulate life span and stress response in C. elegans.";
RL Genes Dev. 22:2721-2735(2008).
RN [7]
RP FUNCTION, ACTIVITY REGULATION, INTERACTION WITH SHC-1, TISSUE SPECIFICITY,
RP AND MUTAGENESIS OF LYS-99.
RX PubMed=18809575; DOI=10.1128/mcb.00938-08;
RA Mizuno T., Fujiki K., Sasakawa A., Hisamoto N., Matsumoto K.;
RT "Role of the Caenorhabditis elegans Shc adaptor protein in the c-Jun N-
RT terminal kinase signaling pathway.";
RL Mol. Cell. Biol. 28:7041-7049(2008).
RN [8]
RP FUNCTION, DISRUPTION PHENOTYPE, PHOSPHORYLATION AT SER-221 AND SER-225, AND
RP MUTAGENESIS OF LYS-99; SER-221 AND SER-225.
RX PubMed=20008556; DOI=10.1128/mcb.01131-09;
RA Fujiki K., Mizuno T., Hisamoto N., Matsumoto K.;
RT "The Caenorhabditis elegans Ste20-related kinase and Rac-type small GTPase
RT regulate the c-Jun N-terminal kinase signaling pathway mediating the stress
RT response.";
RL Mol. Cell. Biol. 30:995-1003(2010).
RN [9]
RP FUNCTION.
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).
CC -!- FUNCTION: Dual specificity protein kinase which may phosphorylate kgb-1
CC and thereby is an essential component of the JNK pathway composed of
CC mlk-1, mek-1 and kgb-1 (PubMed:15116070, PubMed:18809575,
CC PubMed:20008556). May also have a synergistic role with sek-1 in
CC phosphorylating pmk-1 (PubMed:15256594, PubMed:18809575). Involved in
CC the response to environmental stress including heavy metal ions (Cu(2+)
CC and Cd(2+)), oxidative stress and starvation (PubMed:11013217,
CC PubMed:15116070, PubMed:18832074, PubMed:18809575). In association with
CC sek-1, regulates germline cell apoptosis in response to oxidative,
CC osmotic and heat shock stresses (PubMed:16729024). Involved in
CC resistance to pathogenic bacteria infection (PubMed:15256594). Involved
CC in axon regeneration after injury (PubMed:21670305).
CC {ECO:0000269|PubMed:11013217, ECO:0000269|PubMed:15116070,
CC ECO:0000269|PubMed:15256594, ECO:0000269|PubMed:16729024,
CC ECO:0000269|PubMed:18809575, ECO:0000269|PubMed:18832074,
CC ECO:0000269|PubMed:20008556, ECO:0000269|PubMed:21670305}.
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 Evidence={ECO:0000269|PubMed:15116070};
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; Evidence={ECO:0000269|PubMed:15116070};
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 Evidence={ECO:0000269|PubMed:15116070};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:Q8CE90};
CC -!- ACTIVITY REGULATION: May be activated by phosphorylation at Ser-221 and
CC Ser-225. {ECO:0000269|PubMed:18809575}.
CC -!- SUBUNIT: Interacts with shc-1; the interaction is independent of mek-1
CC catalytic activity, is constitutive and may facilitate mlk-1-mediated
CC phosphorylation by bringing mlk-1 and mek-1 together.
CC {ECO:0000269|PubMed:18809575, ECO:0000269|PubMed:18832074}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=a {ECO:0000312|WormBase:K08A8.1a};
CC IsoId=Q21307-1; Sequence=Displayed;
CC Name=b {ECO:0000312|WormBase:K08A8.1b};
CC IsoId=Q21307-2; Sequence=VSP_057796, VSP_057797;
CC -!- TISSUE SPECIFICITY: Expressed in pharyngeal muscles, uterine
CC endothelial cells, intestine and in neurons of ring ganglia, ventral
CC ganglion and ganglia around anus (PubMed:11013217, PubMed:18809575).
CC Expressed also in hypodermis and body muscles (PubMed:18809575).
CC {ECO:0000269|PubMed:11013217, ECO:0000269|PubMed:18809575}.
CC -!- DEVELOPMENTAL STAGE: Expressed at the embryonic stage.
CC {ECO:0000269|PubMed:11013217}.
CC -!- PTM: May be phosphorylated at Ser-221 and/or Ser-225 by mlk-1.
CC {ECO:0000269|PubMed:20008556}.
CC -!- DISRUPTION PHENOTYPE: Loss of kgb-1 activation (PubMed:15116070,
CC PubMed:20008556). Hypersensitivity to high concentrations of copper (>
CC 50 microM) and cadmium (>5 microM) and to food starvation which is
CC characterized by a failure for most animals to reach adulthood. The few
CC surviving adults appear starved and are defective in egg laying and are
CC infertile (PubMed:11013217, PubMed:15116070). In addition, have
CC moderate susceptibility to pathogenic bacteria infection characterized
CC by a shorter lifespan and a substantial decrease in pmk-1
CC phosphorylation (PubMed:15256594). In absence of stress, animals have
CC no obvious phenotype (PubMed:11013217, PubMed:15116070).
CC {ECO:0000269|PubMed:11013217, ECO:0000269|PubMed:15116070,
CC ECO:0000269|PubMed:15256594, ECO:0000269|PubMed:20008556}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. STE Ser/Thr
CC protein kinase family. MAP kinase kinase subfamily. {ECO:0000305}.
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DR EMBL; BX284606; CCD62387.1; -; Genomic_DNA.
DR EMBL; BX284606; CCD62388.1; -; Genomic_DNA.
DR PIR; T16583; T16583.
DR RefSeq; NP_001024771.1; NM_001029600.4. [Q21307-1]
DR AlphaFoldDB; Q21307; -.
DR SMR; Q21307; -.
DR DIP; DIP-24753N; -.
DR IntAct; Q21307; 5.
DR STRING; 6239.K08A8.1a; -.
DR iPTMnet; Q21307; -.
DR EPD; Q21307; -.
DR PaxDb; Q21307; -.
DR PeptideAtlas; Q21307; -.
DR EnsemblMetazoa; K08A8.1a.1; K08A8.1a.1; WBGene00003185. [Q21307-1]
DR GeneID; 181004; -.
DR KEGG; cel:CELE_K08A8.1; -.
DR UCSC; K08A8.1b; c. elegans.
DR CTD; 181004; -.
DR WormBase; K08A8.1a; CE30816; WBGene00003185; mek-1.
DR WormBase; K08A8.1b; CE34335; WBGene00003185; mek-1.
DR eggNOG; KOG0983; Eukaryota.
DR GeneTree; ENSGT00940000158914; -.
DR InParanoid; Q21307; -.
DR OMA; CFGYFIT; -.
DR OrthoDB; 688282at2759; -.
DR PhylomeDB; Q21307; -.
DR Reactome; R-CEL-2559580; Oxidative Stress Induced Senescence.
DR Reactome; R-CEL-2871796; FCERI mediated MAPK activation.
DR Reactome; R-CEL-450321; JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1.
DR SignaLink; Q21307; -.
DR PRO; PR:Q21307; -.
DR Proteomes; UP000001940; Chromosome X.
DR Bgee; WBGene00003185; Expressed in germ line (C elegans) and 4 other tissues.
DR GO; GO:0005737; C:cytoplasm; IC:WormBase.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0008545; F:JUN kinase kinase activity; IDA:WormBase.
DR GO; GO:0004708; F:MAP kinase kinase activity; IDA:WormBase.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
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:0004713; F:protein tyrosine kinase activity; IEA:UniProtKB-KW.
DR GO; GO:0042169; F:SH2 domain binding; IPI:WormBase.
DR GO; GO:0008340; P:determination of adult lifespan; IMP:UniProtKB.
DR GO; GO:0007254; P:JNK cascade; IMP:UniProtKB.
DR GO; GO:0007140; P:male meiotic nuclear division; IMP:WormBase.
DR GO; GO:0000165; P:MAPK cascade; IDA:WormBase.
DR GO; GO:0048599; P:oocyte development; IMP:WormBase.
DR GO; GO:0038066; P:p38MAPK cascade; IMP:WormBase.
DR GO; GO:0048691; P:positive regulation of axon extension involved in regeneration; IMP:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; IMP:WormBase.
DR GO; GO:0040009; P:regulation of growth rate; IGI:WormBase.
DR GO; GO:0000003; P:reproduction; IMP:WormBase.
DR GO; GO:0046686; P:response to cadmium ion; IMP:WormBase.
DR GO; GO:0046688; P:response to copper ion; IMP:WormBase.
DR GO; GO:0042594; P:response to starvation; IMP:UniProtKB.
DR GO; GO:0009266; P:response to temperature stimulus; IMP:WormBase.
DR GO; GO:1990169; P:stress response to copper ion; IMP:WormBase.
DR GO; GO:0051403; P:stress-activated MAPK cascade; IBA:GO_Central.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
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; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; ATP-binding; Kinase; Magnesium; Metal-binding;
KW Nucleotide-binding; Phosphoprotein; Reference proteome;
KW Serine/threonine-protein kinase; Stress response; Transferase;
KW Tyrosine-protein kinase.
FT CHAIN 1..347
FT /note="Dual specificity mitogen-activated protein kinase
FT kinase mek-1"
FT /evidence="ECO:0000305"
FT /id="PRO_0000433509"
FT DOMAIN 72..325
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 1..42
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 193
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 78..86
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 99
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 221
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:20008556"
FT MOD_RES 225
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:20008556"
FT VAR_SEQ 292..300
FT /note="AKFSPDFCQ -> VCALRKKFI (in isoform b)"
FT /evidence="ECO:0000305"
FT /id="VSP_057796"
FT VAR_SEQ 301..347
FT /note="Missing (in isoform b)"
FT /evidence="ECO:0000305"
FT /id="VSP_057797"
FT MUTAGEN 99
FT /note="K->R: Loss of kinase activity. Loss of kgb-1
FT activation. No effect on the interaction with shc-1. No
FT effect on phosphorylation by mlk-1."
FT /evidence="ECO:0000269|PubMed:15116070,
FT ECO:0000269|PubMed:18809575, ECO:0000269|PubMed:20008556"
FT MUTAGEN 221
FT /note="S->A: Abolishes phosphorylation by mlk-1; when
FT associated with A-225."
FT /evidence="ECO:0000269|PubMed:20008556"
FT MUTAGEN 221
FT /note="S->E: Phosphomimetic mutant which probably causes
FT constitutive kinase activation. Loss of pharyngeal muscle
FT contraction and egg laying. Formation of vacuoles in the
FT pharynx and uterus lumen; when associated with E-225."
FT /evidence="ECO:0000269|PubMed:11013217"
FT MUTAGEN 225
FT /note="S->A: Abolishes phosphorylation by mlk-1; when
FT associated with A-221."
FT /evidence="ECO:0000269|PubMed:20008556"
FT MUTAGEN 225
FT /note="S->E: Phosphomimetic mutant which probably causes
FT constitutive kinase activation. Loss of pharyngeal muscle
FT contraction and egg laying. Formation of vacuoles in the
FT pharynx and uterus lumen; when associated with E-221."
FT /evidence="ECO:0000269|PubMed:11013217"
SQ SEQUENCE 347 AA; 39422 MW; 997701F253FCB2C9 CRC64;
MERDFDLGMG RPGGLGGLGG EPIMQQMPQP APHHPSRSSN DHNVKNLMKQ AEENSGYLTL
QGNRRKADLK ELQFVEDIGH GSCGTVTKCR YKSVIMAVKT MPRTSNSYEM SRILMDLDVI
CLSFDCPYIV RCFGYFITNF DVRVCMECMA TCLDRLLIRI KQPIPERIIG KLSVSIIKAL
HYLKTKHQIM HRDVKPSNIL LDWSGVIKLC DFGIAGRLIE SRAHSKQAGC PLYMGPERLD
PNNFDSYDIR SDVWSFGVTL VELATGQYPY AGTEFDMMSK ILNDEPPRLD PAKFSPDFCQ
LVESCLQRDP TMRPNYDMLL QHPFVVHHEK IETDVEEWFA DVMGECG
