MKK4_LEIME
ID MKK4_LEIME Reviewed; 350 AA.
AC Q9GRT1;
DT 17-JUN-2020, integrated into UniProtKB/Swiss-Prot.
DT 04-APR-2006, sequence version 2.
DT 03-AUG-2022, entry version 85.
DE RecName: Full=Putative mitogen-activated protein kinase kinase 4 {ECO:0000303|PubMed:15882412};
DE EC=2.7.12.2 {ECO:0000305|PubMed:15882412};
DE AltName: Full=LmxPK4 {ECO:0000303|PubMed:15882412};
GN Name=MKK4 {ECO:0000312|EMBL:CAC07968.2};
OS Leishmania mexicana.
OC Eukaryota; Discoba; Euglenozoa; Kinetoplastea; Metakinetoplastina;
OC Trypanosomatida; Trypanosomatidae; Leishmaniinae; Leishmania.
OX NCBI_TaxID=5665;
RN [1] {ECO:0000312|EMBL:CAC07968.2}
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, CATALYTIC ACTIVITY, COFACTOR,
RP BIOPHYSICOCHEMICAL PROPERTIES, SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE,
RP DISRUPTION PHENOTYPE, ACTIVE SITE, AND MUTAGENESIS OF LYS-102 AND
RP 2-PRO--VAL-64.
RC STRAIN=MNYC/BZ/62/M379 {ECO:0000312|EMBL:CAC07968.2};
RX PubMed=15882412; DOI=10.1111/j.1365-2958.2005.04614.x;
RA Kuhn D., Wiese M.;
RT "LmxPK4, a mitogen-activated protein kinase kinase homologue of Leishmania
RT mexicana with a potential role in parasite differentiation.";
RL Mol. Microbiol. 56:1169-1182(2005).
CC -!- FUNCTION: Protein kinase which regulates promastigote proliferation in
CC host macrophages, thereby playing an essential role in parasite
CC virulence. {ECO:0000269|PubMed:15882412}.
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:0000305|PubMed:15882412};
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:0000305|PubMed:15882412};
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:0000305|PubMed:15882412};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:15882412};
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:15882412};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Temperature dependence:
CC Active between 21 and 40 degrees Celsius.
CC {ECO:0000269|PubMed:15882412};
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:15882412}.
CC Cell projection, cilium, flagellum {ECO:0000269|PubMed:15882412}.
CC Nucleus {ECO:0000269|PubMed:15882412}.
CC -!- DEVELOPMENTAL STAGE: Expressed at promastigote stage but not in lesion-
CC derived amastigotes (at protein level). Expressed during the
CC differentiation of promastigotes to amastigotes in vitro.
CC {ECO:0000269|PubMed:15882412}.
CC -!- DISRUPTION PHENOTYPE: Homozygous deletion mutants grow slightly slower,
CC but have no significant morphological abnormalities. In BALB/c mice,
CC has reduced infectivity, which is characterized by a delayed and
CC decelerated development of footpad lesions.
CC {ECO:0000269|PubMed:15882412}.
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; AJ293292; CAC07968.2; -; Genomic_DNA.
DR AlphaFoldDB; Q9GRT1; -.
DR SMR; Q9GRT1; -.
DR VEuPathDB; TriTrypDB:LmxM.24.2320; -.
DR OMA; NHEETVR; -.
DR BRENDA; 2.7.12.2; 2951.
DR GO; GO:0005929; C:cilium; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0031514; C:motile cilium; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004708; F:MAP kinase kinase activity; IEA:UniProtKB-EC.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004672; F:protein kinase activity; IDA:UniProtKB.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004713; F:protein tyrosine kinase activity; IEA:RHEA.
DR GO; GO:0006468; P:protein phosphorylation; IDA:UniProtKB.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
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 ATP-binding; Cell projection; Cilium; Cytoplasm; Flagellum; Kinase;
KW Magnesium; Metal-binding; Nucleotide-binding; Nucleus; Transferase.
FT CHAIN 1..350
FT /note="Putative mitogen-activated protein kinase kinase 4"
FT /id="PRO_0000450210"
FT DOMAIN 73..331
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT ACT_SITE 196
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
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 ECO:0000305|PubMed:15882412"
FT MUTAGEN 2..64
FT /note="Missing: No loss of catalytic activity. In BALB/c
FT mice, has reduced infectivity which is characterized by a
FT delayed and decelerated development of footpad lesions.
FT Complete loss of catalytic activity; when associated with
FT R-102."
FT /evidence="ECO:0000269|PubMed:15882412"
FT MUTAGEN 102
FT /note="K->R: Severe loss of catalytic activity. In BALB/c
FT mice, has reduced infectivity which is characterized by a
FT delayed and decelerated development of footpad lesions.
FT Complete loss of catalytic activity; when associated with
FT 2-P--V-64 DEL."
FT /evidence="ECO:0000269|PubMed:15882412"
SQ SEQUENCE 350 AA; 38920 MW; 67B8FA3A2A5D4E6B CRC64;
MPPKRPQALE KLHVEPHDKG VSITDTMTLV VKGEGGVEMR VKQTGIAQGP GSSSAGGQPK
SDAVMNKIKF EDLRIGSELG KGSQGKVRVA QHKLTGEKYA MKYIAFDGDS DDMRSALEAE
LRQVAAVKHH NVVSSYEAFF RDGRLYIVLE YMDCGTMNNL IDRHPEGFSE DMLAYIAREL
FKGLEFLHHL NMIHRDIKPA NVLANTKGEI KISDFGVAKT LSGGDLQTLS AQGSVPYMSP
ERIQSKPYSF NSDIWSAGLT IAECAFREYP FASLKPKLFE LCQAIASGTA KINWDDRETK
FSDEFKEFIE LCLRPEATRP SATEMLSHSL IQKASNVNPL EAGRWMSRKK
