| IED ID | IndEnz0002001973 |
| Enzyme Type ID | protease001973 |
| Protein Name |
Calcium-dependent protein kinase 1 EC 2.7.11.1 PfCDPK1 |
| Gene Name | CDPK1 CPK1 PF3D7_0217500 PFB0815w |
| Organism | Plasmodium falciparum (isolate 3D7) |
| Taxonomic Lineage | cellular organisms Eukaryota Sar Alveolata Apicomplexa Aconoidasida Haemosporida (haemosporidians) Plasmodiidae Plasmodium Plasmodium (Laverania) Plasmodium falciparum Plasmodium falciparum (isolate 3D7) |
| Enzyme Sequence | MGCSQSSNVKDFKTRRSKFTNGNNYGKSGNNKNSEDLAINPGMYVRKKEGKIGESYFKVRKLGSGAYGEVLLCREKHGHGEKAIKVIKKSQFDKMKYSITNKIECDDKIHEEIYNEISLLKSLDHPNIIKLFDVFEDKKYFYLVTEFYEGGELFEQIINRHKFDECDAANIMKQILSGICYLHKHNIVHRDIKPENILLENKHSLLNIKIVDFGLSSFFSKDNKLRDRLGTAYYIAPEVLRKKYNEKCDVWSCGVILYILLCGYPPFGGQNDQDIIKKVEKGKYYFDFNDWKNISEEAKELIKLMLTYDYNKRITAKEALNSKWIKKYANNINKSDQKTLCGALSNMRKFEGSQKLAQAAILFIGSKLTTLEERKELTDIFKKLDKNGDGQLDKKELIEGYNILRSFKNELGELKNVEEEVDNILKEVDFDKNGYIEYSEFISVCMDKQILFSEERLRDAFNLFDTDKSGKITKEELANLFGLTSISEQMWNEVLGEADKNKDNMIDFDEFVNMMHKICDNKSS |
| Enzyme Length | 524 |
| Uniprot Accession Number | P62344 |
| Absorption | |
| Active Site | ACT_SITE 191; /note="Proton acceptor"; /evidence="ECO:0000255|PROSITE-ProRule:PRU00159, ECO:0000255|PROSITE-ProRule:PRU10027" |
| Activity Regulation | ACTIVITY REGULATION: Activated by calcium (PubMed:29716996, PubMed:18768477, PubMed:23204525, PubMed:17123645, PubMed:32484216). Upon calcium binding to the EF-hand domains, the C-terminus of the junction domain (J domain) undergoes a conformational change which results in the dissociation of the pseudo-substrate inhibitory motif from the catalytic domain (Probable) (PubMed:23204525). This, in turn may facilitate the autophosphorylation of the activation loop at Thr-231, which leads to the kinase activation (PubMed:19307175). May be negatively regulated by PKA-mediated phosphorylation (PubMed:28680058). Inhibited by purfalcamine (PubMed:23204525, PubMed:29716996). {ECO:0000269|PubMed:17123645, ECO:0000269|PubMed:18768477, ECO:0000269|PubMed:19307175, ECO:0000269|PubMed:23204525, ECO:0000269|PubMed:28680058, ECO:0000269|PubMed:29716996, ECO:0000269|PubMed:32484216, ECO:0000305|PubMed:19307175}. |
| Binding Site | BINDING 85; /note=ATP; /evidence=ECO:0000255|PROSITE-ProRule:PRU00159 |
| Calcium Binding | |
| catalytic Activity | CATALYTIC ACTIVITY: Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-[protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616, ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1; Evidence={ECO:0000269|PubMed:17123645, ECO:0000269|PubMed:18768477, ECO:0000269|PubMed:19307175, ECO:0000269|PubMed:22539638, ECO:0000269|PubMed:23204525, ECO:0000269|PubMed:26149123, ECO:0000269|PubMed:28680058, ECO:0000269|PubMed:32484216, ECO:0000269|PubMed:33024030}; CATALYTIC ACTIVITY: Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060, Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013, ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216; EC=2.7.11.1; Evidence={ECO:0000269|PubMed:19307175, ECO:0000269|PubMed:22539638, ECO:0000269|PubMed:23204525, ECO:0000269|PubMed:26149123, ECO:0000269|PubMed:28680058, ECO:0000269|PubMed:29716996, ECO:0000269|PubMed:32484216}; |
| DNA Binding | |
| EC Number | 2.7.11.1 |
| Enzyme Function | FUNCTION: Calcium-dependent protein kinase which acts as a sensor and effector of intracellular Ca(2+) levels probably in part downstream of cGMP-activated PKG kinase (PubMed:18768477, PubMed:19307175, PubMed:28680058, PubMed:29716996). By phosphorylating various proteins, required for microneme secretion and thus merozoite egress from and invasion of host erythrocytes (PubMed:23204525, PubMed:28680058, PubMed:29716996). During gametogenesis, essential for the development of both male and female gametes (By similarity). Phosphorylates SERA5 p50 which enhances SERA5 p50 protease activity; however, SERA5 p50 protease activity has been shown in other studies to be controversial (PubMed:29716996). Probably by phosphorylating SERA5 p50, plays a role in merozoite egress from host erythrocytes (PubMed:29716996). Probably prior or during merozoite invasion of host erythrocytes, phosphorylates rhoptry protein RhopH3 which is required for RhopH3 localization to rhoptries and for its secretion (PubMed:33024030). Probably in late schizonts, phosphorylates myosin A tail domain-interacting protein MTIP and glideosome-associated protein 45 GAP45, both of which are components of the motor complex that generates the force required by the parasite to invade host cells (PubMed:18768477, PubMed:28680058, PubMed:22539638). In late schizonts, phosphorylates inner membrane complex protein IMC1g (PubMed:28680058). In late schizonts, phosphorylates PKA regulatory subunit PKAr in a calcium-dependent manner, which may contribute to the dissociation of regulatory PKAr and catalytic PKAc subunits and promote the activation of PKAc (PubMed:28680058). May phosphorylate raf kinase inhibitory protein RKIP which in turn may regulate CDPK1 catalytic activity (PubMed:17123645). May phosphorylate proteins of the host erythrocyte membranes (By similarity). {ECO:0000250|UniProtKB:A0A2I0BVG8, ECO:0000250|UniProtKB:P62343, ECO:0000269|PubMed:17123645, ECO:0000269|PubMed:18768477, ECO:0000269|PubMed:19307175, ECO:0000269|PubMed:22539638, ECO:0000269|PubMed:23204525, ECO:0000269|PubMed:28680058, ECO:0000269|PubMed:29716996, ECO:0000269|PubMed:33024030}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | NP_BIND 62..70; /note=ATP; /evidence=ECO:0000255|PROSITE-ProRule:PRU00159 |
| Features | Active site (1); Binding site (1); Chain (1); Compositional bias (1); Domain (5); Initiator methionine (1); Lipidation (2); Metal binding (20); Modified residue (10); Motif (3); Mutagenesis (27); Nucleotide binding (1); Region (2) |
| Keywords | ATP-binding;Calcium;Cell membrane;Cell projection;Cilium;Cytoplasm;Flagellum;Host cell membrane;Host membrane;Kinase;Lipoprotein;Magnesium;Membrane;Metal-binding;Myristate;Nucleotide-binding;Palmitate;Phosphoprotein;Reference proteome;Repeat;Serine/threonine-protein kinase;Transferase |
| Interact With | |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: Membrane {ECO:0000269|PubMed:15491359, ECO:0000269|PubMed:23204525, ECO:0000269|PubMed:28680058}; Lipid-anchor {ECO:0000269|PubMed:15491359}. Cell membrane {ECO:0000269|PubMed:15491359, ECO:0000269|PubMed:18768477, ECO:0000269|PubMed:26149123, ECO:0000269|PubMed:32003970, ECO:0000269|PubMed:32484216}; Lipid-anchor {ECO:0000269|PubMed:15491359, ECO:0000269|PubMed:32003970}; Cytoplasmic side {ECO:0000305}. Parasitophorous vacuole membrane {ECO:0000269|PubMed:15491359, ECO:0000269|PubMed:23204525, ECO:0000269|PubMed:29716996}; Lipid-anchor {ECO:0000269|PubMed:15491359}. Cytoplasm {ECO:0000250|UniProtKB:A0A2I0BVG8}. Cell projection, cilium, flagellum {ECO:0000250|UniProtKB:A0A2I0BVG8}. Host cell membrane {ECO:0000269|PubMed:23204525}; Lipid-anchor {ECO:0000305}. Note=Localizes to the host erythrocytic membrane at low level (By similarity). Localizes to the cell membrane in the nascent merozoites contained within the late-stage schizonts and in free merozoites (PubMed:26149123, PubMed:18768477). Colocalizes with MTIP around developing merozoites in segmented schizonts, also localizes in membranes around the mature food vacuole/residual body of the schizonts (PubMed:18768477). Ser-64 phosphorylated form localizes at the apical pole in punctate structures in merozoites within late schizonts in free merozoites (PubMed:26149123). In trophozoites and schizonts, localizes to the parasitophorous vacuole (PV) and in membranous systems derived from the PV including intraparasitic vacuoles and the tubovesicular system, an extension of the parasitophorous vacuole membrane into the host cell cytoplasm (PubMed:15491359, PubMed:23204525). Localization to the cytoplasm in trophozoite or schizonts is minimal (PubMed:15491359). In female stage V gametocytes and gametes, localizes to the cell membrane (By similarity). In stage V male gametocytes, localizes to the cell membrane and in the cytoplasm (By similarity). In male gametes, localizes to the residual body, cell membrane and in the flagella (By similarity). Calcium and/or autophosphorylation does not affect membrane localization (PubMed:15491359). {ECO:0000250|UniProtKB:A0A2I0BVG8, ECO:0000250|UniProtKB:P62343, ECO:0000269|PubMed:15491359, ECO:0000269|PubMed:18768477, ECO:0000269|PubMed:23204525, ECO:0000269|PubMed:26149123}. |
| Modified Residue | MOD_RES 17; /note="Phosphoserine; by autocatalysis"; /evidence="ECO:0000269|PubMed:22539638, ECO:0000269|PubMed:32817103"; MOD_RES 28; /note="Phosphoserine; by autocatalysis"; /evidence="ECO:0000269|PubMed:22539638, ECO:0000269|PubMed:32817103"; MOD_RES 34; /note="Phosphoserine; by autocatalysis"; /evidence="ECO:0000269|PubMed:32817103"; MOD_RES 64; /note="Phosphoserine; by PKG; by autocatalysis"; /evidence="ECO:0000269|PubMed:22539638, ECO:0000269|PubMed:26149123, ECO:0000269|PubMed:32817103"; MOD_RES 100; /note="Phosphothreonine; by autocatalysis"; /evidence="ECO:0000269|PubMed:22539638"; MOD_RES 118; /note="Phosphoserine; by autocatalysis"; /evidence="ECO:0000269|PubMed:22539638"; MOD_RES 217; /note="Phosphoserine"; /evidence="ECO:0000269|PubMed:22539638, ECO:0000269|PubMed:32817103"; MOD_RES 220; /note="Phosphoserine; by autocatalysis"; /evidence="ECO:0000269|PubMed:22539638"; MOD_RES 231; /note="Phosphothreonine; by PKG; by autocatalysis"; /evidence="ECO:0000269|PubMed:22539638, ECO:0000269|PubMed:26149123"; MOD_RES 335; /note="Phosphoserine; by autocatalysis"; /evidence="ECO:0000269|PubMed:22539638" |
| Post Translational Modification | PTM: Myristoylated (PubMed:15491359). Myristoylation, palmitoylation and the basic cluster motif are required for the localization to the parasitophorous vacuole membrane (PubMed:15491359). {ECO:0000269|PubMed:15491359}.; PTM: Palmitoylated (Probable) (PubMed:32003970). Palmitoylation increases in merozoites in response to low level of extracellular K(+) in the host blood (PubMed:32003970). Myristoylation, palmitoylation and the basic cluster motif are required for the localization to the parasitophorous vacuole membrane (PubMed:15491359). {ECO:0000269|PubMed:15491359, ECO:0000269|PubMed:32003970, ECO:0000305|PubMed:15491359}.; PTM: Phosphorylation at Ser-64 occurs at late schizont stage and regulates CDPK1 protein-protein interaction (PubMed:26149123). Phosphorylated at Ser-28, Ser-34 and Ser-64 in merozoites in response to low extracellular level of K(+) (PubMed:32817103). Phosphorylation at Thr-231 may regulate CDPK1 kinase activity (PubMed:26149123). Phosphorylation increases in response to an increase in intracellular Ca(2+) levels (PubMed:32484216). Autophosphorylated in vitro (PubMed:17123645, PubMed:22539638, PubMed:23204525, PubMed:26149123, PubMed:32484216). Autophosphorylation does not affect membrane localization in vitro (PubMed:15491359). {ECO:0000269|PubMed:15491359, ECO:0000269|PubMed:17123645, ECO:0000269|PubMed:22539638, ECO:0000269|PubMed:23204525, ECO:0000269|PubMed:26149123, ECO:0000269|PubMed:32484216, ECO:0000269|PubMed:32817103}. |
| Signal Peptide | |
| Structure 3D | |
| Cross Reference PDB | - |
| Mapped Pubmed ID | 16267556; |
| Motif | MOTIF 10..20; /note="Basic cluster involved in membrane binding"; /evidence="ECO:0000269|PubMed:15491359"; MOTIF 346..353; /note="J domain autoinhibitory motif"; /evidence="ECO:0000305|PubMed:19307175"; MOTIF 354..364; /note="J domain interacts with the EF-hand domains"; /evidence="ECO:0000269|PubMed:23204525, ECO:0000305|PubMed:19307175" |
| Gene Encoded By | |
| Mass | 60,800 |
| Kinetics | BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=9 uM for MTIP (at 30 degrees Celsius) {ECO:0000269|PubMed:18768477}; KM=18 uM for GAP45 (at 30 degrees Celsius) {ECO:0000269|PubMed:18768477}; KM=125 uM for ATP (with MTIP as substrate and at 30 degrees Celsius) {ECO:0000269|PubMed:18768477}; KM=96 uM for ATP (with GAP45 as substrate and at 30 degrees Celsius) {ECO:0000269|PubMed:18768477}; |
| Metal Binding | METAL 385; /note=Calcium 1; /evidence=ECO:0000255|PROSITE-ProRule:PRU00448; METAL 387; /note=Calcium 1; /evidence=ECO:0000255|PROSITE-ProRule:PRU00448; METAL 389; /note=Calcium 1; /evidence=ECO:0000255|PROSITE-ProRule:PRU00448; METAL 391; /note=Calcium 1; /evidence=ECO:0000255|PROSITE-ProRule:PRU00448; METAL 396; /note=Calcium 1; /evidence=ECO:0000255|PROSITE-ProRule:PRU00448; METAL 429; /note=Calcium 2; /evidence=ECO:0000255|PROSITE-ProRule:PRU00448; METAL 431; /note=Calcium 2; /evidence=ECO:0000255|PROSITE-ProRule:PRU00448; METAL 433; /note=Calcium 2; /evidence=ECO:0000255|PROSITE-ProRule:PRU00448; METAL 435; /note=Calcium 2; /evidence=ECO:0000255|PROSITE-ProRule:PRU00448; METAL 440; /note=Calcium 2; /evidence=ECO:0000255|PROSITE-ProRule:PRU00448; METAL 465; /note=Calcium 3; /evidence=ECO:0000255|PROSITE-ProRule:PRU00448; METAL 467; /note=Calcium 3; /evidence=ECO:0000255|PROSITE-ProRule:PRU00448; METAL 469; /note=Calcium 3; /evidence=ECO:0000255|PROSITE-ProRule:PRU00448; METAL 471; /note=Calcium 3; /evidence=ECO:0000255|PROSITE-ProRule:PRU00448; METAL 476; /note=Calcium 3; /evidence=ECO:0000255|PROSITE-ProRule:PRU00448; METAL 499; /note=Calcium 4; /evidence=ECO:0000255|PROSITE-ProRule:PRU00448; METAL 501; /note=Calcium 4; /evidence=ECO:0000255|PROSITE-ProRule:PRU00448; METAL 503; /note=Calcium 4; /evidence=ECO:0000255|PROSITE-ProRule:PRU00448; METAL 505; /note=Calcium 4; /evidence=ECO:0000255|PROSITE-ProRule:PRU00448; METAL 510; /note=Calcium 4; /evidence=ECO:0000255|PROSITE-ProRule:PRU00448 |
| Rhea ID | RHEA:17989; RHEA:46608 |
| Cross Reference Brenda | 2.7.11.1; |