Protein: Calcium-dependent protein kinase 1 (EC 2.7.11.1) (PfCDPK1) (P62344)
Organism: Plasmodium falciparum (isolate 3D7)
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. By phosphorylating various proteins, required for microneme secretion and thus merozoite egress from and invasion of host erythrocytes. 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. Probably by phosphorylating SERA5 p50, plays a role in merozoite egress from host erythrocytes. 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. 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. In late schizonts, phosphorylates inner membrane complex protein IMC1g. 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. May phosphorylate raf kinase inhibitory protein RKIP which in turn may regulate CDPK1 catalytic activity. May phosphorylate proteins of the host erythrocyte membranes (By similarity).
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:18768477, PubMed:26149123). 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}.
Interaction partners:
- Myosin-A
- cAMP-dependent protein kinase catalytic subunit
- Calmodulin, putative
- Merozoite surface protein 9
- Putative E3 ubiquitin-protein ligase protein PFF1365c
- Coronin
Sequence:
MGCSQSSNVKDFKTRRSKFTNGNNYGKSGNNKNSEDLAINPGMYVRKKEGKIGESYFKVRKLGSGAYGEVLLCREKHGHGEKAIKVIKKSQFDKMKYSITNKIECDDKIHEEIYNEISLLKSLDHPNIIKLFDVFEDKKYFYLVTEFYEGGELFEQIINRHKFDECDAANIMKQILSGICYLHKHNIVHRDIKPENILLENKHSLLNIKIVDFGLSSFFSKDNKLRDRLGTAYYIAPEVLRKKYNEKCDVWSCGVILYILLCGYPPFGGQNDQDIIKKVEKGKYYFDFNDWKNISEEAKELIKLMLTYDYNKRITAKEALNSKWIKKYANNINKSDQKTLCGALSNMRKFEGSQKLAQAAILFIGSKLTTLEERKELTDIFKKLDKNGDGQLDKKELIEGYNILRSFKNELGELKNVEEEVDNILKEVDFDKNGYIEYSEFISVCMDKQILFSEERLRDAFNLFDTDKSGKITKEELANLFGLTSISEQMWNEVLGEADKNKDNMIDFDEFVNMMHKICDNKSS