MPK4_LEIME
ID MPK4_LEIME Reviewed; 363 AA.
AC Q9GRU1;
DT 22-APR-2020, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 03-AUG-2022, entry version 101.
DE RecName: Full=Mitogen-activated protein kinase 4 {ECO:0000303|PubMed:14636673};
DE EC=2.7.11.24 {ECO:0000269|PubMed:16384531, ECO:0000269|PubMed:20178803};
DE AltName: Full=LmxMPK4 {ECO:0000303|PubMed:14636673};
GN Name=MPK4 {ECO:0000303|PubMed:14636673};
OS Leishmania mexicana.
OC Eukaryota; Discoba; Euglenozoa; Kinetoplastea; Metakinetoplastina;
OC Trypanosomatida; Trypanosomatidae; Leishmaniinae; Leishmania.
OX NCBI_TaxID=5665 {ECO:0000312|EMBL:CAC07958.1};
RN [1] {ECO:0000312|EMBL:CAC07958.1}
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND DEVELOPMENTAL STAGE.
RC STRAIN=MNYC/BZ/62/M379 {ECO:0000312|EMBL:CAC07958.1};
RX PubMed=14636673; DOI=10.1016/s0020-7519(03)00252-2;
RA Wiese M., Wang Q., Gorcke I.;
RT "Identification of mitogen-activated protein kinase homologues from
RT Leishmania mexicana.";
RL Int. J. Parasitol. 33:1577-1587(2003).
RN [2] {ECO:0000305}
RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, BIOPHYSICOCHEMICAL PROPERTIES,
RP DEVELOPMENTAL STAGE, AND MUTAGENESIS OF LYS-59.
RX PubMed=16384531; DOI=10.1186/1475-9292-4-6;
RA Wang Q., Melzer I.M., Kruse M., Sander-Juelch C., Wiese M.;
RT "LmxMPK4, a mitogen-activated protein (MAP) kinase homologue essential for
RT promastigotes and amastigotes of Leishmania mexicana.";
RL Kinetoplastid Biol. Dis. 4:6-6(2005).
RN [3] {ECO:0000305}
RP CATALYTIC ACTIVITY, PHOSPHORYLATION AT SER-186; SER-187; THR-190 AND
RP TYR-192, AND MUTAGENESIS OF LYS-59.
RX PubMed=20178803; DOI=10.1016/j.ijpara.2010.02.004;
RA von Freyend S.J., Rosenqvist H., Fink A., Melzer I.M., Clos J.,
RA Jensen O.N., Wiese M.;
RT "LmxMPK4, an essential mitogen-activated protein kinase of Leishmania
RT mexicana is phosphorylated and activated by the STE7-like protein kinase
RT LmxMKK5.";
RL Int. J. Parasitol. 40:969-978(2010).
CC -!- FUNCTION: Essential for the two main proliferating life stages, the
CC promastigotes and amastigotes, of the parasite.
CC {ECO:0000269|PubMed:16384531}.
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:16384531, ECO:0000269|PubMed:20178803};
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:16384531,
CC ECO:0000269|PubMed:20178803};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:16384531};
CC Note=Can use both Mg(2+) and Mn(2+) in vitro and shows higher activity
CC with Mn(2+) but Mg(2+) is likely to be the in vivo cofactor.
CC {ECO:0000269|PubMed:16384531};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC pH dependence:
CC Optimum pH is 6-7. {ECO:0000269|PubMed:16384531};
CC -!- DEVELOPMENTAL STAGE: Expressed in promastigotes and to a lower extent
CC in axenic amastigotes (at protein level) (PubMed:14636673,
CC PubMed:16384531). Low expression levels in lesion-derived amastigotes
CC (at protein level) (PubMed:14636673, PubMed:16384531).
CC {ECO:0000269|PubMed:14636673, ECO:0000269|PubMed:16384531}.
CC -!- DOMAIN: The TXY motif contains the threonine and tyrosine residues
CC whose phosphorylation activates the MAP kinases.
CC {ECO:0000269|PubMed:20178803}.
CC -!- PTM: Dually phosphorylated on Thr-190 and Tyr-192, which activates the
CC enzyme. {ECO:0000269|PubMed:20178803}.
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; AJ293282; CAC07958.1; -; Genomic_DNA.
DR AlphaFoldDB; Q9GRU1; -.
DR SMR; Q9GRU1; -.
DR VEuPathDB; TriTrypDB:LmxM.19.1440; -.
DR OMA; HSCMCRC; -.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004707; F:MAP kinase activity; IDA:UniProtKB.
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; IDA:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; IEA:InterPro.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR003527; MAP_kinase_CS.
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; PS01351; MAPK; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
PE 1: Evidence at protein level;
KW ATP-binding; Kinase; Magnesium; Metal-binding; Nucleotide-binding;
KW Phosphoprotein; Serine/threonine-protein kinase; Transferase.
FT CHAIN 1..363
FT /note="Mitogen-activated protein kinase 4"
FT /id="PRO_0000449293"
FT DOMAIN 30..318
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOTIF 190..192
FT /note="TQY"
FT /evidence="ECO:0000269|PubMed:20178803"
FT ACT_SITE 156
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 36..44
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 59
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 186
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:20178803"
FT MOD_RES 187
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:20178803"
FT MOD_RES 190
FT /note="Phosphothreonine; by MKK5"
FT /evidence="ECO:0000269|PubMed:20178803"
FT MOD_RES 192
FT /note="Phosphotyrosine; by MKK5"
FT /evidence="ECO:0000269|PubMed:20178803"
FT MUTAGEN 59
FT /note="K->M: Loss of catalytic activity."
FT /evidence="ECO:0000269|PubMed:16384531,
FT ECO:0000269|PubMed:20178803"
SQ SEQUENCE 363 AA; 41548 MW; D320FBF13B3A87D6 CRC64;
MTQLVPLAEL PSGKKIYSVR GQRFEVDRQY DLVKVVGFGA CGTVCSAVVN GSGERVAIKR
LSRVFGDLRE GKRILREMEI MTSLKHNNLI RLHHFMRPQS KETFEDIYLV MDLYDTDLNR
IIRSRQKLTD EHLQYFMIQA FRGLHYLHSA KVMHRDLKPS NLLVNADCAL AICDFGLARD
DQVMSSSDLT QYVVTRWYRP PEVLGMGSNQ YTSAVDVWSL GLIFAELMVG RALLPGTDYI
GQLVMIVNLL GSPSIDDMEF LSSEAKAFIL SQPHRPALSF RDLFPMATEE ATDLLSKLLV
FHPARRLTAK QVMEHPYFSK YRDAAEEADA PDPFVWNHSH IETKEQLRED LWRVVEAHSQ
LNE
