CDK2H_PLAFK
ID CDK2H_PLAFK Reviewed; 288 AA.
AC Q07785;
DT 01-OCT-1994, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1994, sequence version 1.
DT 03-AUG-2022, entry version 124.
DE RecName: Full=Cyclin-dependent kinase 2 homolog {ECO:0000305};
DE EC=2.7.11.22 {ECO:0000269|PubMed:14604523, ECO:0000269|PubMed:8844681};
DE EC=2.7.11.23 {ECO:0000250|UniProtKB:P61075};
DE AltName: Full=Cell division control protein 2 homolog {ECO:0000303|PubMed:8143724};
DE AltName: Full=Protein kinase 5 {ECO:0000303|PubMed:8143724};
DE Short=PfPK5 {ECO:0000303|PubMed:8143724};
DE AltName: Full=cdc2-related kinase 2 {ECO:0000250|UniProtKB:O96821};
GN Name=CRK2 {ECO:0000250|UniProtKB:O96821};
GN Synonyms=PK5 {ECO:0000303|PubMed:8143724};
OS Plasmodium falciparum (isolate K1 / Thailand).
OC Eukaryota; Sar; Alveolata; Apicomplexa; Aconoidasida; Haemosporida;
OC Plasmodiidae; Plasmodium; Plasmodium (Laverania).
OX NCBI_TaxID=5839;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND DEVELOPMENTAL STAGE.
RX PubMed=8143724; DOI=10.1111/j.1432-1033.1994.tb18670.x;
RA Ross-Macdonald P.B., Graeser R., Kappes B., Franklin R., Williamson D.H.;
RT "Isolation and expression of a gene specifying a cdc2-like protein kinase
RT from the human malaria parasite Plasmodium falciparum.";
RL Eur. J. Biochem. 220:693-701(1994).
RN [2]
RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, AND MUTAGENESIS OF LYS-32 AND
RP THR-158.
RX PubMed=8844681; DOI=10.1016/0166-6851(96)02643-6;
RA Graeser R., Franklin R.M., Kappes B.;
RT "Mechanisms of activation of the cdc2-related kinase PfPK5 from Plasmodium
RT falciparum.";
RL Mol. Biochem. Parasitol. 79:125-127(1996).
RN [3] {ECO:0007744|PDB:1OB3, ECO:0007744|PDB:1V0B, ECO:0007744|PDB:1V0O, ECO:0007744|PDB:1V0P}
RP X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) IN COMPLEX WITH INHIBITORS,
RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF THR-158.
RX PubMed=14604523; DOI=10.1016/j.str.2003.09.020;
RA Holton S., Merckx A., Burgess D., Doerig C., Noble M., Endicott J.;
RT "Structures of P. falciparum PfPK5 test the CDK regulation paradigm and
RT suggest mechanisms of small molecule inhibition.";
RL Structure 11:1329-1337(2003).
CC -!- FUNCTION: Serine/threonine-protein kinase (PubMed:8844681,
CC PubMed:14604523). Involved in the control of the cell cycle (By
CC 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 (By
CC similarity). In schizonts, phosphorylates ORC1 resulting in its
CC dissociation from DNA, relocalization to the cytoplasm and likely its
CC degradation (By similarity). {ECO:0000250|UniProtKB:P04551,
CC ECO:0000269|PubMed:14604523, ECO:0000269|PubMed:8844681}.
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:14604523, ECO:0000269|PubMed:8844681};
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:14604523,
CC ECO:0000269|PubMed:8844681};
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:0000250|UniProtKB:P61075};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:8844681};
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 (By similarity).
CC Activated by cyclin cyc-3 in vitro (By similarity).
CC {ECO:0000250|UniProtKB:P24941, ECO:0000250|UniProtKB:P61075}.
CC -!- SUBUNIT: May form a complex composed of at least the catalytic subunit
CC CRK2 and a cyclin. {ECO:0000250|UniProtKB:P61075}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:P04551}.
CC -!- DEVELOPMENTAL STAGE: Expressed during the asexual blood stage including
CC in trophozoites and schizonts. {ECO:0000269|PubMed:8143724}.
CC -!- PTM: Autophosphorylates in presence of cyclin cyc-1 but not in presence
CC of cyclin cyc-3. {ECO:0000250|UniProtKB:P61075}.
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; X61921; CAA43923.1; -; Genomic_DNA.
DR PIR; S42566; S42566.
DR PDB; 1OB3; X-ray; 1.90 A; A/B=1-288.
DR PDB; 1V0B; X-ray; 2.20 A; A/B=1-288.
DR PDB; 1V0O; X-ray; 1.90 A; A/B=1-288.
DR PDB; 1V0P; X-ray; 2.00 A; A/B=1-288.
DR PDBsum; 1OB3; -.
DR PDBsum; 1V0B; -.
DR PDBsum; 1V0O; -.
DR PDBsum; 1V0P; -.
DR AlphaFoldDB; Q07785; -.
DR SMR; Q07785; -.
DR ChEMBL; CHEMBL2189145; -.
DR DrugBank; DB02519; Indirubin-5-sulphonate.
DR DrugBank; DB02733; Purvalanol.
DR BRENDA; 2.7.11.22; 4889.
DR EvolutionaryTrace; Q07785; -.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004693; F:cyclin-dependent protein serine/threonine kinase activity; IEA:UniProtKB-EC.
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; IEA:InterPro.
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 3D-structure; ATP-binding; Cell cycle; Cell division; Cytoplasm; Kinase;
KW Magnesium; Metal-binding; Mitosis; Nucleotide-binding; Phosphoprotein;
KW Serine/threonine-protein kinase; Transferase.
FT CHAIN 1..288
FT /note="Cyclin-dependent kinase 2 homolog"
FT /id="PRO_0000085742"
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"
FT MUTAGEN 32
FT /note="K->R: Loss of catalytic activity."
FT /evidence="ECO:0000269|PubMed:8844681"
FT MUTAGEN 158
FT /note="T->A: Abolishes phosphorylation. No effect on
FT catalytic activity."
FT /evidence="ECO:0000269|PubMed:14604523"
FT MUTAGEN 158
FT /note="T->D: Phosphomimetic mutant. Increases catalytic
FT activity."
FT /evidence="ECO:0000269|PubMed:8844681"
FT MUTAGEN 158
FT /note="T->V: Abolishes phosphorylation. Loss of catalytic
FT activity."
FT /evidence="ECO:0000269|PubMed:8844681"
FT STRAND 3..13
FT /evidence="ECO:0007829|PDB:1OB3"
FT STRAND 16..23
FT /evidence="ECO:0007829|PDB:1OB3"
FT STRAND 28..34
FT /evidence="ECO:0007829|PDB:1OB3"
FT HELIX 39..41
FT /evidence="ECO:0007829|PDB:1OB3"
FT HELIX 45..52
FT /evidence="ECO:0007829|PDB:1OB3"
FT HELIX 53..56
FT /evidence="ECO:0007829|PDB:1OB3"
FT STRAND 65..70
FT /evidence="ECO:0007829|PDB:1OB3"
FT STRAND 75..80
FT /evidence="ECO:0007829|PDB:1OB3"
FT STRAND 83..85
FT /evidence="ECO:0007829|PDB:1OB3"
FT HELIX 86..91
FT /evidence="ECO:0007829|PDB:1OB3"
FT STRAND 93..96
FT /evidence="ECO:0007829|PDB:1V0O"
FT HELIX 99..118
FT /evidence="ECO:0007829|PDB:1OB3"
FT HELIX 128..130
FT /evidence="ECO:0007829|PDB:1OB3"
FT STRAND 131..133
FT /evidence="ECO:0007829|PDB:1OB3"
FT STRAND 139..141
FT /evidence="ECO:0007829|PDB:1OB3"
FT HELIX 146..150
FT /evidence="ECO:0007829|PDB:1OB3"
FT STRAND 152..155
FT /evidence="ECO:0007829|PDB:1V0O"
FT TURN 159..161
FT /evidence="ECO:0007829|PDB:1V0O"
FT HELIX 169..172
FT /evidence="ECO:0007829|PDB:1OB3"
FT HELIX 181..196
FT /evidence="ECO:0007829|PDB:1OB3"
FT HELIX 206..217
FT /evidence="ECO:0007829|PDB:1OB3"
FT TURN 222..224
FT /evidence="ECO:0007829|PDB:1OB3"
FT HELIX 228..230
FT /evidence="ECO:0007829|PDB:1OB3"
FT HELIX 246..248
FT /evidence="ECO:0007829|PDB:1OB3"
FT HELIX 255..264
FT /evidence="ECO:0007829|PDB:1OB3"
FT TURN 269..271
FT /evidence="ECO:0007829|PDB:1OB3"
FT HELIX 275..279
FT /evidence="ECO:0007829|PDB:1OB3"
FT HELIX 282..285
FT /evidence="ECO:0007829|PDB:1OB3"
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
