CDK2H_PLAF7
ID CDK2H_PLAF7 Reviewed; 288 AA.
AC P61075;
DT 26-APR-2004, integrated into UniProtKB/Swiss-Prot.
DT 26-APR-2004, sequence version 1.
DT 03-AUG-2022, entry version 115.
DE RecName: Full=Cyclin-dependent kinase 2 homolog {ECO:0000305};
DE EC=2.7.11.22 {ECO:0000269|PubMed:10722743, ECO:0000269|PubMed:12869562, ECO:0000269|PubMed:26094711};
DE EC=2.7.11.23 {ECO:0000269|PubMed:12869562};
DE AltName: Full=Cell division control protein 2 homolog {ECO:0000305|PubMed:10722743};
DE AltName: Full=Protein kinase 5 {ECO:0000303|PubMed:10722743};
DE Short=PfPK5 {ECO:0000303|PubMed:10722743};
DE AltName: Full=cdc2-related kinase 2 {ECO:0000250|UniProtKB:O96821};
GN Name=CRK2 {ECO:0000250|UniProtKB:O96821};
GN Synonyms=PK5 {ECO:0000303|PubMed:10722743};
GN ORFNames=MAL13P1.279, PF3D7_1356900;
OS Plasmodium falciparum (isolate 3D7).
OC Eukaryota; Sar; Alveolata; Apicomplexa; Aconoidasida; Haemosporida;
OC Plasmodiidae; Plasmodium; Plasmodium (Laverania).
OX NCBI_TaxID=36329;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=3D7;
RX PubMed=12368864; DOI=10.1038/nature01097;
RA Gardner M.J., Hall N., Fung E., White O., Berriman M., Hyman R.W.,
RA Carlton J.M., Pain A., Nelson K.E., Bowman S., Paulsen I.T., James K.D.,
RA Eisen J.A., Rutherford K.M., Salzberg S.L., Craig A., Kyes S., Chan M.-S.,
RA Nene V., Shallom S.J., Suh B., Peterson J., Angiuoli S., Pertea M.,
RA Allen J., Selengut J., Haft D., Mather M.W., Vaidya A.B., Martin D.M.A.,
RA Fairlamb A.H., Fraunholz M.J., Roos D.S., Ralph S.A., McFadden G.I.,
RA Cummings L.M., Subramanian G.M., Mungall C., Venter J.C., Carucci D.J.,
RA Hoffman S.L., Newbold C., Davis R.W., Fraser C.M., Barrell B.G.;
RT "Genome sequence of the human malaria parasite Plasmodium falciparum.";
RL Nature 419:498-511(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=3D7;
RX PubMed=12368867; DOI=10.1038/nature01095;
RA Hall N., Pain A., Berriman M., Churcher C.M., Harris B., Harris D.,
RA Mungall K.L., Bowman S., Atkin R., Baker S., Barron A., Brooks K.,
RA Buckee C.O., Burrows C., Cherevach I., Chillingworth C., Chillingworth T.,
RA Christodoulou Z., Clark L., Clark R., Corton C., Cronin A., Davies R.M.,
RA Davis P., Dear P., Dearden F., Doggett J., Feltwell T., Goble A.,
RA Goodhead I., Gwilliam R., Hamlin N., Hance Z., Harper D., Hauser H.,
RA Hornsby T., Holroyd S., Horrocks P., Humphray S., Jagels K., James K.D.,
RA Johnson D., Kerhornou A., Knights A., Konfortov B., Kyes S., Larke N.,
RA Lawson D., Lennard N., Line A., Maddison M., Mclean J., Mooney P.,
RA Moule S., Murphy L., Oliver K., Ormond D., Price C., Quail M.A.,
RA Rabbinowitsch E., Rajandream M.A., Rutter S., Rutherford K.M., Sanders M.,
RA Simmonds M., Seeger K., Sharp S., Smith R., Squares R., Squares S.,
RA Stevens K., Taylor K., Tivey A., Unwin L., Whitehead S., Woodward J.R.,
RA Sulston J.E., Craig A., Newbold C., Barrell B.G.;
RT "Sequence of Plasmodium falciparum chromosomes 1, 3-9 and 13.";
RL Nature 419:527-531(2002).
RN [3]
RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, ACTIVITY REGULATION, AND
RP PHOSPHORYLATION.
RX PubMed=10722743; DOI=10.1074/jbc.275.12.8952;
RA Le Roch K., Sestier C., Dorin D., Waters N., Kappes B., Chakrabarti D.,
RA Meijer L., Doerig C.;
RT "Activation of a Plasmodium falciparum cdc2-related kinase by heterologous
RT p25 and cyclin H. Functional characterization of a P. falciparum cyclin
RT homologue.";
RL J. Biol. Chem. 275:8952-8958(2000).
RN [4]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, SUBUNIT, DEVELOPMENTAL
RP STAGE, AND PHOSPHORYLATION.
RX PubMed=12869562; DOI=10.1074/jbc.m301625200;
RA Merckx A., Le Roch K., Nivez M.P., Dorin D., Alano P., Gutierrez G.J.,
RA Nebreda A.R., Goldring D., Whittle C., Patterson S., Chakrabarti D.,
RA Doerig C.;
RT "Identification and initial characterization of three novel cyclin-related
RT proteins of the human malaria parasite Plasmodium falciparum.";
RL J. Biol. Chem. 278:39839-39850(2003).
RN [5]
RP FUNCTION, CATALYTIC ACTIVITY, AND DEVELOPMENTAL STAGE.
RX PubMed=26094711; DOI=10.1111/mmi.13099;
RA Deshmukh A.S., Agarwal M., Mehra P., Gupta A., Gupta N., Doerig C.D.,
RA Dhar S.K.;
RT "Regulation of Plasmodium falciparum Origin Recognition Complex subunit 1
RT (PfORC1) function through phosphorylation mediated by CDK-like kinase
RT PK5.";
RL Mol. Microbiol. 98:17-33(2015).
CC -!- FUNCTION: Serine/threonine-protein kinase (PubMed:10722743,
CC PubMed:12869562, PubMed:26094711). Involved in the control of the cell
CC cycle (By similarity). Required for entry into S-phase and mitosis (By
CC similarity). Probable component of the kinase complex that
CC phosphorylates the repetitive C-terminus of RNA polymerase II
CC (PubMed:12869562). In schizonts, phosphorylates ORC1 resulting in its
CC dissociation from DNA, relocalization to the cytoplasm and likely its
CC degradation (PubMed:26094711). {ECO:0000250|UniProtKB:P04551,
CC ECO:0000269|PubMed:10722743, ECO:0000269|PubMed:12869562,
CC ECO:0000269|PubMed:26094711}.
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=2.7.11.22;
CC Evidence={ECO:0000269|PubMed:10722743, ECO:0000269|PubMed:12869562,
CC ECO:0000269|PubMed:26094711};
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=2.7.11.22; Evidence={ECO:0000269|PubMed:10722743,
CC ECO:0000269|PubMed:12869562, ECO:0000269|PubMed:26094711};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=[DNA-directed RNA polymerase] + ATP = ADP + H(+) + phospho-
CC [DNA-directed RNA polymerase]; Xref=Rhea:RHEA:10216, Rhea:RHEA-
CC COMP:11321, Rhea:RHEA-COMP:11322, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:43176, ChEBI:CHEBI:68546,
CC ChEBI:CHEBI:456216; EC=2.7.11.23;
CC Evidence={ECO:0000269|PubMed:12869562};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:10722743};
CC -!- ACTIVITY REGULATION: Phosphorylation at Thr-14 or Tyr-15 inactivates
CC the enzyme, while phosphorylation at Thr-158 activates it (By
CC similarity). Activated by cyclin cyc-1 in vitro (PubMed:10722743,
CC PubMed:12869562). Activated by cyclin cyc-3 in vitro (PubMed:12869562).
CC {ECO:0000250|UniProtKB:P24941, ECO:0000269|PubMed:10722743,
CC ECO:0000269|PubMed:12869562}.
CC -!- SUBUNIT: May form a complex composed of at least the catalytic subunit
CC CRK2 and a cyclin. {ECO:0000305|PubMed:12869562}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:P04551}.
CC -!- DEVELOPMENTAL STAGE: Expressed during the asexual blood stage;
CC expression is low at the ring stage and peaks in trophozoites and
CC schizonts (at protein level). {ECO:0000269|PubMed:12869562,
CC ECO:0000269|PubMed:26094711}.
CC -!- PTM: Autophosphorylates in presence of cyclin cyc-1 but not in presence
CC of cyclin cyc-3. {ECO:0000269|PubMed:10722743,
CC ECO:0000269|PubMed:12869562}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CMGC Ser/Thr
CC protein kinase family. CDC2/CDKX subfamily. {ECO:0000305}.
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DR EMBL; AL844509; CAD52689.1; -; Genomic_DNA.
DR RefSeq; XP_001350280.1; XM_001350244.1.
DR AlphaFoldDB; P61075; -.
DR SMR; P61075; -.
DR STRING; 5833.MAL13P1.279; -.
DR BindingDB; P61075; -.
DR ChEMBL; CHEMBL1908388; -.
DR SwissPalm; P61075; -.
DR PRIDE; P61075; -.
DR EnsemblProtists; CAD52689; CAD52689; PF3D7_1356900.
DR GeneID; 813841; -.
DR KEGG; pfa:PF3D7_1356900; -.
DR VEuPathDB; PlasmoDB:PF3D7_1356900; -.
DR HOGENOM; CLU_000288_181_1_1; -.
DR InParanoid; P61075; -.
DR OMA; NNDVWPE; -.
DR PhylomeDB; P61075; -.
DR PRO; PR:P61075; -.
DR Proteomes; UP000001450; Chromosome 13.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005634; C:nucleus; IDA:GeneDB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004693; F:cyclin-dependent protein serine/threonine kinase activity; IDA:GeneDB.
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:0008353; F:RNA polymerase II CTD heptapeptide repeat kinase activity; IEA:UniProtKB-EC.
DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:0006468; P:protein phosphorylation; ISS:GeneDB.
DR GO; GO:0000083; P:regulation of transcription involved in G1/S transition of mitotic cell cycle; IBA:GO_Central.
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; Cell cycle; Cell division; Cytoplasm; Kinase; Magnesium;
KW Metal-binding; Mitosis; Nucleotide-binding; Phosphoprotein;
KW Reference proteome; Serine/threonine-protein kinase; Transferase.
FT CHAIN 1..288
FT /note="Cyclin-dependent kinase 2 homolog"
FT /id="PRO_0000085741"
FT DOMAIN 4..284
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT ACT_SITE 125
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 10..18
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 32
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 14
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P24941"
FT MOD_RES 15
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P24941"
FT MOD_RES 158
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P24941"
SQ SEQUENCE 288 AA; 32996 MW; BF8C2935F872F6F0 CRC64;
MEKYHGLEKI GEGTYGVVYK AQNNYGETFA LKKIRLEKED EGIPSTTIRE ISILKELKHS
NIVKLYDVIH TKKRLVLVFE HLDQDLKKLL DVCEGGLESV TAKSFLLQLL NGIAYCHDRR
VLHRDLKPQN LLINREGELK IADFGLARAF GIPVRKYTHE VVTLWYRAPD VLMGSKKYST
TIDIWSVGCI FAEMVNGTPL FPGVSEADQL MRIFRILGTP NSKNWPNVTE LPKYDPNFTV
YEPLPWESFL KGLDESGIDL LSKMLKLDPN QRITAKQALE HAYFKENN
