ID MKK4_CAEEL Reviewed; 363 AA.
AC Q20347; O01707;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 15-JUL-1998, sequence version 3.
DT 27-MAR-2024, entry version 172.
DE RecName: Full=MAP kinase kinase mkk-4;
DE EC=2.7.12.2;
GN Name=mkk-4; ORFNames=F42G10.2;
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 [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 [2]
RP TISSUE SPECIFICITY.
RX PubMed=11733138; DOI=10.1016/s0378-1119(01)00752-1;
RA Berman K.S., Hutchison M., Avery L., Cobb M.H.;
RT "kin-18, a C. elegans protein kinase involved in feeding.";
RL Gene 279:137-147(2001).
RN [3]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=15707898; DOI=10.1016/j.cell.2004.12.017;
RA Nakata K., Abrams B., Grill B., Goncharov A., Huang X., Chisholm A.D.,
RA Jin Y.;
RT "Regulation of a DLK-1 and p38 MAP kinase pathway by the ubiquitin ligase
RT RPM-1 is required for presynaptic development.";
RL Cell 120:407-420(2005).
RN [4]
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: Activity is required in presynaptic neurons, in a dose-
CC dependent manner, for normal presynaptic development and morphology
CC (PubMed:15707898). Plays a role in the formation of muscle connections,
CC also called muscle arm extensions, between the body wall and the motor
CC axons in the dorsal and ventral cord (PubMed:27123983).
CC {ECO:0000269|PubMed:15707898, 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=2.7.12.2;
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 -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:15707898}.
CC -!- TISSUE SPECIFICITY: Expressed in the pharynx, including the corpus,
CC isthmus and terminal bulb. {ECO:0000269|PubMed:11733138}.
CC -!- DISRUPTION PHENOTYPE: Defective extension of body wall muscle
CC connections or arms towards the ventral nerve cord. Double knockout
CC with madd-3 results in severe muscle arm extension defects.
CC {ECO:0000269|PubMed:27123983}.
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; Z48230; CAA88264.1; -; Genomic_DNA.
DR EMBL; Z95122; CAA88264.1; JOINED; Genomic_DNA.
DR PIR; T22107; T22107.
DR RefSeq; NP_509682.1; NM_077281.4.
DR AlphaFoldDB; Q20347; -.
DR SMR; Q20347; -.
DR BioGRID; 50442; 6.
DR DIP; DIP-25523N; -.
DR IntAct; Q20347; 3.
DR STRING; 6239.F42G10.2.1; -.
DR EPD; Q20347; -.
DR PaxDb; 6239-F42G10-2; -.
DR PeptideAtlas; Q20347; -.
DR EnsemblMetazoa; F42G10.2.1; F42G10.2.1; WBGene00003368.
DR GeneID; 185682; -.
DR KEGG; cel:CELE_F42G10.2; -.
DR UCSC; F42G10.2; c. elegans.
DR AGR; WB:WBGene00003368; -.
DR WormBase; F42G10.2; CE10328; WBGene00003368; mkk-4.
DR eggNOG; KOG1006; Eukaryota.
DR GeneTree; ENSGT00940000154744; -.
DR HOGENOM; CLU_000288_63_23_1; -.
DR InParanoid; Q20347; -.
DR OMA; PRLHTSY; -.
DR OrthoDB; 2900742at2759; -.
DR PhylomeDB; Q20347; -.
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; Q20347; -.
DR PRO; PR:Q20347; -.
DR Proteomes; UP000001940; Chromosome X.
DR Bgee; WBGene00003368; Expressed in pharyngeal muscle cell (C elegans) and 3 other cell types or tissues.
DR GO; GO:0005737; C:cytoplasm; IDA:WormBase.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0008545; F:JUN kinase kinase activity; IBA:GO_Central.
DR GO; GO:0031435; F:mitogen-activated protein kinase kinase kinase binding; IPI:WormBase.
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:RHEA.
DR GO; GO:0031103; P:axon regeneration; IGI:UniProtKB.
DR GO; GO:0000165; P:MAPK cascade; IMP:UniProtKB.
DR GO; GO:0038066; P:p38MAPK cascade; IMP:WormBase.
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:0050807; P:regulation of synapse organization; IMP:WormBase.
DR GO; GO:0008582; P:regulation of synaptic assembly at neuromuscular junction; IMP:UniProtKB.
DR CDD; cd06616; PKc_MKK4; 1.
DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1.
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 PANTHER; PTHR48013:SF35; DUAL SPECIFICITY MITOGEN-ACTIVATED PROTEIN KINASE KINASE 4; 1.
DR PANTHER; PTHR48013; DUAL SPECIFICITY MITOGEN-ACTIVATED PROTEIN KINASE KINASE 5-RELATED; 1.
DR Pfam; PF00069; Pkinase; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
PE 2: Evidence at transcript level;
KW ATP-binding; Cytoplasm; Kinase; Nucleotide-binding; Reference proteome;
KW Serine/threonine-protein kinase; Transferase.
FT CHAIN 1..363
FT /note="MAP kinase kinase mkk-4"
FT /id="PRO_0000086842"
FT DOMAIN 66..330
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 1..38
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 194
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 72..80
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 95
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
SQ SEQUENCE 363 AA; 41197 MW; 643A26A23329759A CRC64;
MVQEDDENLR NSMSLRPTSL STRPTSLSVN GNEKTLPEES VLRSLSTGTL KYPDDEHLYT
FSSANLQDLG AIGNGNFGTV YKMRHKETGK LIAVKRIRCN NIGHREQIRL LREHDTIVKS
EKGPNIVKFY GAIFSEGDCW ICMELMDISM DLLYKRVYMV KNSRLNENVV GHITVCTVDA
LDYLKKELKI IHRDVKPSNI LVDGTGAVKL CDFGICGQLE ESFAKTHDAG CQPYLAPERI
TSSDKYDVRS DVWSLGITLY EIATGKFPYQ EWNSLFDQIA TVVSGDPPIL HPDSDDFHYS
LPLVKFINTC LTKDRRHRPK YDTLKSFDFY RIYAVAGPEI EEAKRILGVE AIDTRNHPVD
HRG
//
