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 27-MAR-2024, entry version 123. 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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AL844509; CAD52689.1; -; Genomic_DNA. DR RefSeq; XP_001350280.1; XM_001350244.1. DR AlphaFoldDB; P61075; -. DR SMR; P61075; -. DR STRING; 36329.P61075; -. DR BindingDB; P61075; -. DR ChEMBL; CHEMBL1908388; -. DR SwissPalm; P61075; -. DR PaxDb; 5833-MAL13P1-279; -. 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; YLYQITR; -. DR OrthoDB; 244018at2759; -. 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:0007049; P:cell cycle; IEA:UniProtKB-KW. DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW. DR GO; GO:0006468; P:protein phosphorylation; ISS:GeneDB. DR CDD; cd07829; STKc_CDK_like; 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; PTHR24056; CELL DIVISION PROTEIN KINASE; 1. DR PANTHER; PTHR24056:SF46; CYCLIN-DEPENDENT KINASE 5; 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 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 //