CDPK1_PLAF7
ID CDPK1_PLAF7 Reviewed; 524 AA.
AC P62344; A0A143ZWW4; Q27731;
DT 05-JUL-2004, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 2.
DT 03-AUG-2022, entry version 131.
DE RecName: Full=Calcium-dependent protein kinase 1;
DE EC=2.7.11.1 {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};
DE AltName: Full=PfCDPK1 {ECO:0000303|PubMed:26149123};
GN Name=CDPK1 {ECO:0000303|PubMed:26149123}; Synonyms=CPK1;
GN ORFNames=PF3D7_0217500, PFB0815w;
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=9804551; DOI=10.1126/science.282.5391.1126;
RA Gardner M.J., Tettelin H., Carucci D.J., Cummings L.M., Aravind L.,
RA Koonin E.V., Shallom S.J., Mason T., Yu K., Fujii C., Pederson J., Shen K.,
RA Jing J., Aston C., Lai Z., Schwartz D.C., Pertea M., Salzberg S.L.,
RA Zhou L., Sutton G.G., Clayton R., White O., Smith H.O., Fraser C.M.,
RA Adams M.D., Venter J.C., Hoffman S.L.;
RT "Chromosome 2 sequence of the human malaria parasite Plasmodium
RT falciparum.";
RL Science 282:1126-1132(1998).
RN [2]
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 [3]
RP SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE, MOTIF, MYRISTOYLATION AT GLY-2,
RP PALMITOYLATION AT CYS-3, AND MUTAGENESIS OF GLY-2 AND 10-LYS--THR-20.
RX PubMed=15491359; DOI=10.1111/j.1365-2958.2004.04313.x;
RA Moeskes C., Burghaus P.A., Wernli B., Sauder U., Duerrenberger M.,
RA Kappes B.;
RT "Export of Plasmodium falciparum calcium-dependent protein kinase 1 to the
RT parasitophorous vacuole is dependent on three N-terminal membrane anchor
RT motifs.";
RL Mol. Microbiol. 54:676-691(2004).
RN [4]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, AND PHOSPHORYLATION.
RX PubMed=17123645; DOI=10.1016/j.molbiopara.2006.10.012;
RA Kugelstadt D., Winter D., Plueckhahn K., Lehmann W.D., Kappes B.;
RT "Raf kinase inhibitor protein affects activity of Plasmodium falciparum
RT calcium-dependent protein kinase 1.";
RL Mol. Biochem. Parasitol. 151:111-117(2007).
RN [5]
RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, ACTIVITY REGULATION,
RP BIOPHYSICOCHEMICAL PROPERTIES, SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE,
RP AND MUTAGENESIS OF ASP-191.
RX PubMed=18768477; DOI=10.1074/jbc.m803129200;
RA Green J.L., Rees-Channer R.R., Howell S.A., Martin S.R., Knuepfer E.,
RA Taylor H.M., Grainger M., Holder A.A.;
RT "The motor complex of Plasmodium falciparum: phosphorylation by a calcium-
RT dependent protein kinase.";
RL J. Biol. Chem. 283:30980-30989(2008).
RN [6]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, DOMAIN, MOTIF, AND
RP MUTAGENESIS OF 342-GLY--SER-524.
RX PubMed=19307175; DOI=10.1074/jbc.m900656200;
RA Ranjan R., Ahmed A., Gourinath S., Sharma P.;
RT "Dissection of mechanisms involved in the regulation of Plasmodium
RT falciparum calcium-dependent protein kinase 4.";
RL J. Biol. Chem. 284:15267-15276(2009).
RN [7]
RP FUNCTION, CATALYTIC ACTIVITY, PHOSPHORYLATION AT SER-17; SER-28; SER-64;
RP THR-100; SER-118; SER-217; SER-220; THR-231 AND SER-335, AND MUTAGENESIS OF
RP 2-GLY--THR-20; 2-GLY--ASN-30; 2-GLY--ASN-40; 2-GLY--GLY-50; LYS-27;
RP GLU-152; PHE-154; GLU-155; 157-ILE-ILE-158; THR-231; SER-335; THR-339;
RP MET-347; PHE-350; LYS-355; SER-366; 369-THR-THR-370 AND ARG-456.
RX PubMed=22539638; DOI=10.1096/fj.12-203877;
RA Ahmed A., Gaadhe K., Sharma G.P., Kumar N., Neculai M., Hui R., Mohanty D.,
RA Sharma P.;
RT "Novel insights into the regulation of malarial calcium-dependent protein
RT kinase 1.";
RL FASEB J. 26:3212-3221(2012).
RN [8]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, SUBCELLULAR LOCATION,
RP DEVELOPMENTAL STAGE, DOMAIN, PHOSPHORYLATION, AND MUTAGENESIS OF PHE-350;
RP SER-353; LEU-356 AND 363-PHE-ILE-364.
RX PubMed=23204525; DOI=10.1074/jbc.m112.411934;
RA Bansal A., Singh S., More K.R., Hans D., Nangalia K., Yogavel M.,
RA Sharma A., Chitnis C.E.;
RT "Characterization of Plasmodium falciparum calcium-dependent protein kinase
RT 1 (PfCDPK1) and its role in microneme secretion during erythrocyte
RT invasion.";
RL J. Biol. Chem. 288:1590-1602(2013).
RN [9]
RP CATALYTIC ACTIVITY, SUBUNIT, SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE,
RP IDENTIFICATION BY MASS SPECTROMETRY, PHOSPHORYLATION AT SER-64 AND THR-231,
RP AND MUTAGENESIS OF SER-64 AND ASP-191.
RX PubMed=26149123; DOI=10.1038/ncomms8285;
RA Alam M.M., Solyakov L., Bottrill A.R., Flueck C., Siddiqui F.A., Singh S.,
RA Mistry S., Viskaduraki M., Lee K., Hopp C.S., Chitnis C.E., Doerig C.,
RA Moon R.W., Green J.L., Holder A.A., Baker D.A., Tobin A.B.;
RT "Phosphoproteomics reveals malaria parasite Protein Kinase G as a
RT signalling hub regulating egress and invasion.";
RL Nat. Commun. 6:7285-7285(2015).
RN [10]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, INTERACTION WITH IMC1G
RP AND PKAR, SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=28680058; DOI=10.1038/s41467-017-00053-1;
RA Kumar S., Kumar M., Ekka R., Dvorin J.D., Paul A.S., Madugundu A.K.,
RA Gilberger T., Gowda H., Duraisingh M.T., Keshava Prasad T.S., Sharma P.;
RT "PfCDPK1 mediated signaling in erythrocytic stages of Plasmodium
RT falciparum.";
RL Nat. Commun. 8:63-63(2017).
RN [11]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, INTERACTION WITH SERA5
RP P50, SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RX PubMed=29716996; DOI=10.1074/jbc.ra117.001540;
RA Iyer G.R., Singh S., Kaur I., Agarwal S., Siddiqui M.A., Bansal A.,
RA Kumar G., Saini E., Paul G., Mohmmed A., Chitnis C.E., Malhotra P.;
RT "Calcium-dependent phosphorylation of Plasmodium falciparum serine repeat
RT antigen 5 triggers merozoite egress.";
RL J. Biol. Chem. 293:9736-9746(2018).
RN [12]
RP SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE, AND PALMITOYLATION AT CYS-3.
RX PubMed=32003970; DOI=10.1021/acsinfecdis.9b00321;
RA Siddiqui M.A., Singh S., Malhotra P., Chitnis C.E.;
RT "Protein S-Palmitoylation Is Responsive to External Signals and Plays a
RT Regulatory Role in Microneme Secretion in Plasmodium falciparum
RT Merozoites.";
RL ACS Infect. Dis. 6:379-392(2020).
RN [13]
RP CATALYTIC ACTIVITY, ACTIVITY REGULATION, INTERACTION WITH 14-3-3I,
RP SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE, AND PHOSPHORYLATION.
RX PubMed=32484216; DOI=10.1042/bcj20200145;
RA Jain R., Dey P., Gupta S., Pati S., Bhattacherjee A., Munde M., Singh S.;
RT "Molecular dynamics simulations and biochemical characterization of Pf14-3-
RT 3 and PfCDPK1 interaction towards its role in growth of human malaria
RT parasite.";
RL Biochem. J. 477:2153-2177(2020).
RN [14]
RP IDENTIFICATION IN A COMPLEX WITH PKAR AND 14-3-3I, INTERACTION WITH PKAR
RP AND 14-3-3I, DEVELOPMENTAL STAGE, IDENTIFICATION BY MASS SPECTROMETRY, AND
RP PHOSPHORYLATION AT SER-17; SER-28; SER-34; SER-64 AND SER-217.
RX PubMed=32817103; DOI=10.1128/mbio.01287-20;
RA More K.R., Kaur I., Giai Gianetto Q., Invergo B.M., Chaze T., Jain R.,
RA Huon C., Gutenbrunner P., Weisser H., Matondo M., Choudhary J.S.,
RA Langsley G., Singh S., Chitnis C.E.;
RT "Phosphorylation-Dependent Assembly of a 14-3-3 Mediated Signaling Complex
RT during Red Blood Cell Invasion by Plasmodium falciparum Merozoites.";
RL MBio 11:0-0(2020).
RN [15]
RP FUNCTION, CATALYTIC ACTIVITY, INTERACTION WITH RHOPH3, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=33024030; DOI=10.1128/mbio.00166-20;
RA Ekka R., Gupta A., Bhatnagar S., Malhotra P., Sharma P.;
RT "Phosphorylation of Rhoptry Protein RhopH3 Is Critical for Host Cell
RT Invasion by the Malaria Parasite.";
RL MBio 11:0-0(2020).
CC -!- FUNCTION: Calcium-dependent protein kinase which acts as a sensor and
CC effector of intracellular Ca(2+) levels probably in part downstream of
CC cGMP-activated PKG kinase (PubMed:18768477, PubMed:19307175,
CC PubMed:28680058, PubMed:29716996). By phosphorylating various proteins,
CC required for microneme secretion and thus merozoite egress from and
CC invasion of host erythrocytes (PubMed:23204525, PubMed:28680058,
CC PubMed:29716996). During gametogenesis, essential for the development
CC of both male and female gametes (By similarity). Phosphorylates SERA5
CC p50 which enhances SERA5 p50 protease activity; however, SERA5 p50
CC protease activity has been shown in other studies to be controversial
CC (PubMed:29716996). Probably by phosphorylating SERA5 p50, plays a role
CC in merozoite egress from host erythrocytes (PubMed:29716996). Probably
CC prior or during merozoite invasion of host erythrocytes, phosphorylates
CC rhoptry protein RhopH3 which is required for RhopH3 localization to
CC rhoptries and for its secretion (PubMed:33024030). Probably in late
CC schizonts, phosphorylates myosin A tail domain-interacting protein MTIP
CC and glideosome-associated protein 45 GAP45, both of which are
CC components of the motor complex that generates the force required by
CC the parasite to invade host cells (PubMed:18768477, PubMed:28680058,
CC PubMed:22539638). In late schizonts, phosphorylates inner membrane
CC complex protein IMC1g (PubMed:28680058). In late schizonts,
CC phosphorylates PKA regulatory subunit PKAr in a calcium-dependent
CC manner, which may contribute to the dissociation of regulatory PKAr and
CC catalytic PKAc subunits and promote the activation of PKAc
CC (PubMed:28680058). May phosphorylate raf kinase inhibitory protein RKIP
CC which in turn may regulate CDPK1 catalytic activity (PubMed:17123645).
CC May phosphorylate proteins of the host erythrocyte membranes (By
CC similarity). {ECO:0000250|UniProtKB:A0A2I0BVG8,
CC ECO:0000250|UniProtKB:P62343, ECO:0000269|PubMed:17123645,
CC ECO:0000269|PubMed:18768477, ECO:0000269|PubMed:19307175,
CC ECO:0000269|PubMed:22539638, ECO:0000269|PubMed:23204525,
CC ECO:0000269|PubMed:28680058, ECO:0000269|PubMed:29716996,
CC ECO:0000269|PubMed:33024030}.
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=2.7.11.1;
CC Evidence={ECO:0000269|PubMed:17123645, ECO:0000269|PubMed:18768477,
CC ECO:0000269|PubMed:19307175, ECO:0000269|PubMed:22539638,
CC ECO:0000269|PubMed:23204525, ECO:0000269|PubMed:26149123,
CC ECO:0000269|PubMed:28680058, ECO:0000269|PubMed:32484216,
CC ECO:0000269|PubMed:33024030};
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=2.7.11.1; Evidence={ECO:0000269|PubMed:19307175,
CC ECO:0000269|PubMed:22539638, ECO:0000269|PubMed:23204525,
CC ECO:0000269|PubMed:26149123, ECO:0000269|PubMed:28680058,
CC ECO:0000269|PubMed:29716996, ECO:0000269|PubMed:32484216};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:18768477};
CC -!- ACTIVITY REGULATION: Activated by calcium (PubMed:29716996,
CC PubMed:18768477, PubMed:23204525, PubMed:17123645, PubMed:32484216).
CC Upon calcium binding to the EF-hand domains, the C-terminus of the
CC junction domain (J domain) undergoes a conformational change which
CC results in the dissociation of the pseudo-substrate inhibitory motif
CC from the catalytic domain (Probable) (PubMed:23204525). This, in turn
CC may facilitate the autophosphorylation of the activation loop at Thr-
CC 231, which leads to the kinase activation (PubMed:19307175). May be
CC negatively regulated by PKA-mediated phosphorylation (PubMed:28680058).
CC Inhibited by purfalcamine (PubMed:23204525, PubMed:29716996).
CC {ECO:0000269|PubMed:17123645, ECO:0000269|PubMed:18768477,
CC ECO:0000269|PubMed:19307175, ECO:0000269|PubMed:23204525,
CC ECO:0000269|PubMed:28680058, ECO:0000269|PubMed:29716996,
CC ECO:0000269|PubMed:32484216, ECO:0000305|PubMed:19307175}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=9 uM for MTIP (at 30 degrees Celsius)
CC {ECO:0000269|PubMed:18768477};
CC KM=18 uM for GAP45 (at 30 degrees Celsius)
CC {ECO:0000269|PubMed:18768477};
CC KM=125 uM for ATP (with MTIP as substrate and at 30 degrees Celsius)
CC {ECO:0000269|PubMed:18768477};
CC KM=96 uM for ATP (with GAP45 as substrate and at 30 degrees Celsius)
CC {ECO:0000269|PubMed:18768477};
CC -!- SUBUNIT: Monomer (PubMed:26149123). Forms a high molecular weight (250
CC and 400 kDa) complex (PubMed:26149123). Forms a complex composed of
CC CDPK1, PKA regulatory subunit PKAr and 14-3-3I; the complex is formed
CC in merozoites in response to low extracellular level of K(+) and may
CC play a role in microneme secretion (PubMed:32817103). Interacts (when
CC phosphorylated) with 14-3-3I in a Ca(2+)-independent manner; the
CC interaction does not regulate CDPK1 catalytic activity but is required
CC for merozoite invasion of host erythrocytes (PubMed:32484216,
CC PubMed:32817103). Interacts with PKA regulatory subunit PKAr; in a
CC Ca(2+)-dependent manner (PubMed:28680058, PubMed:32817103). Interacts
CC with SERA5 p50 in the late schizont stage (PubMed:29716996). Interacts
CC with inner membrane complex protein IMC1g in late schizonts
CC (PubMed:28680058). Interacts with rhoptry protein RhopH3 in merozoites
CC (PubMed:33024030). {ECO:0000269|PubMed:26149123,
CC ECO:0000269|PubMed:28680058, ECO:0000269|PubMed:29716996,
CC ECO:0000269|PubMed:32484216, ECO:0000269|PubMed:32817103,
CC ECO:0000269|PubMed:33024030}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000269|PubMed:15491359,
CC ECO:0000269|PubMed:23204525, ECO:0000269|PubMed:28680058}; Lipid-anchor
CC {ECO:0000269|PubMed:15491359}. Cell membrane
CC {ECO:0000269|PubMed:15491359, ECO:0000269|PubMed:18768477,
CC ECO:0000269|PubMed:26149123, ECO:0000269|PubMed:32003970,
CC ECO:0000269|PubMed:32484216}; Lipid-anchor
CC {ECO:0000269|PubMed:15491359, ECO:0000269|PubMed:32003970}; Cytoplasmic
CC side {ECO:0000305}. Parasitophorous vacuole membrane
CC {ECO:0000269|PubMed:15491359, ECO:0000269|PubMed:23204525,
CC ECO:0000269|PubMed:29716996}; Lipid-anchor
CC {ECO:0000269|PubMed:15491359}. Cytoplasm
CC {ECO:0000250|UniProtKB:A0A2I0BVG8}. Cell projection, cilium, flagellum
CC {ECO:0000250|UniProtKB:A0A2I0BVG8}. Host cell membrane
CC {ECO:0000269|PubMed:23204525}; Lipid-anchor {ECO:0000305}.
CC Note=Localizes to the host erythrocytic membrane at low level (By
CC similarity). Localizes to the cell membrane in the nascent merozoites
CC contained within the late-stage schizonts and in free merozoites
CC (PubMed:26149123, PubMed:18768477). Colocalizes with MTIP around
CC developing merozoites in segmented schizonts, also localizes in
CC membranes around the mature food vacuole/residual body of the schizonts
CC (PubMed:18768477). Ser-64 phosphorylated form localizes at the apical
CC pole in punctate structures in merozoites within late schizonts in free
CC merozoites (PubMed:26149123). In trophozoites and schizonts, localizes
CC to the parasitophorous vacuole (PV) and in membranous systems derived
CC from the PV including intraparasitic vacuoles and the tubovesicular
CC system, an extension of the parasitophorous vacuole membrane into the
CC host cell cytoplasm (PubMed:15491359, PubMed:23204525). Localization to
CC the cytoplasm in trophozoite or schizonts is minimal (PubMed:15491359).
CC In female stage V gametocytes and gametes, localizes to the cell
CC membrane (By similarity). In stage V male gametocytes, localizes to the
CC cell membrane and in the cytoplasm (By similarity). In male gametes,
CC localizes to the residual body, cell membrane and in the flagella (By
CC similarity). Calcium and/or autophosphorylation does not affect
CC membrane localization (PubMed:15491359).
CC {ECO:0000250|UniProtKB:A0A2I0BVG8, ECO:0000250|UniProtKB:P62343,
CC ECO:0000269|PubMed:15491359, ECO:0000269|PubMed:18768477,
CC ECO:0000269|PubMed:23204525, ECO:0000269|PubMed:26149123}.
CC -!- DEVELOPMENTAL STAGE: Expressed during parasite asexual blood stages,
CC specifically at the ring and schizont stages, in free merozoites and to
CC a lesser extent in trophozoites (at protein level).
CC {ECO:0000269|PubMed:15491359, ECO:0000269|PubMed:18768477,
CC ECO:0000269|PubMed:23204525, ECO:0000269|PubMed:26149123,
CC ECO:0000269|PubMed:28680058, ECO:0000269|PubMed:29716996,
CC ECO:0000269|PubMed:32003970, ECO:0000269|PubMed:32484216,
CC ECO:0000269|PubMed:32817103}.
CC -!- DOMAIN: The junction domain (J domain) is composed of 2 motifs that
CC maintain the kinase inactive (PubMed:19307175). The N-terminal
CC autoinhibitory motif acts as a pseudosubstrate inhibiting the catalytic
CC domain while the C-terminal motif binds the EF-hand domains
CC (PubMed:19307175, PubMed:23204525). {ECO:0000269|PubMed:19307175,
CC ECO:0000269|PubMed:23204525}.
CC -!- PTM: Myristoylated (PubMed:15491359). Myristoylation, palmitoylation
CC and the basic cluster motif are required for the localization to the
CC parasitophorous vacuole membrane (PubMed:15491359).
CC {ECO:0000269|PubMed:15491359}.
CC -!- PTM: Palmitoylated (Probable) (PubMed:32003970). Palmitoylation
CC increases in merozoites in response to low level of extracellular K(+)
CC in the host blood (PubMed:32003970). Myristoylation, palmitoylation and
CC the basic cluster motif are required for the localization to the
CC parasitophorous vacuole membrane (PubMed:15491359).
CC {ECO:0000269|PubMed:15491359, ECO:0000269|PubMed:32003970,
CC ECO:0000305|PubMed:15491359}.
CC -!- PTM: Phosphorylation at Ser-64 occurs at late schizont stage and
CC regulates CDPK1 protein-protein interaction (PubMed:26149123).
CC Phosphorylated at Ser-28, Ser-34 and Ser-64 in merozoites in response
CC to low extracellular level of K(+) (PubMed:32817103). Phosphorylation
CC at Thr-231 may regulate CDPK1 kinase activity (PubMed:26149123).
CC Phosphorylation increases in response to an increase in intracellular
CC Ca(2+) levels (PubMed:32484216). Autophosphorylated in vitro
CC (PubMed:17123645, PubMed:22539638, PubMed:23204525, PubMed:26149123,
CC PubMed:32484216). Autophosphorylation does not affect membrane
CC localization in vitro (PubMed:15491359). {ECO:0000269|PubMed:15491359,
CC ECO:0000269|PubMed:17123645, ECO:0000269|PubMed:22539638,
CC ECO:0000269|PubMed:23204525, ECO:0000269|PubMed:26149123,
CC ECO:0000269|PubMed:32484216, ECO:0000269|PubMed:32817103}.
CC -!- DISRUPTION PHENOTYPE: Conditional knockdown at the ring stage produces
CC the development of mature schizonts and the subsequent release of
CC merozoites from the host erythrocytes; however, the invasion of new
CC erythrocytes by these merozoites is severely reduced due to a severe
CC defect in adhesion to the erythrocyte membrane (PubMed:28680058). In
CC merozoites, release of host glycophorin A/GYPA ligand EBA-175 from
CC micronemes is impaired but not AMA1 (PubMed:28680058). In late
CC schizont, phosphorylation of several proteins including GAP45, IMC1g
CC and PKAr is reduced (PubMed:28680058). Reduced PKA activity
CC (PubMed:28680058). Rhoptry protein RhopH3 phosphorylation and secretion
CC are reduced in merozoites (PubMed:33024030).
CC {ECO:0000269|PubMed:28680058, ECO:0000269|PubMed:33024030}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Ser/Thr protein
CC kinase family. CDPK subfamily. {ECO:0000255|PROSITE-ProRule:PRU00159}.
CC -!- CAUTION: Unlike P.berghei CDPK1, appears to be involved in the asexual
CC blood stage and in male gamete exflagellation prior host erythrocyte
CC membrane rupture. {ECO:0000305|PubMed:28680058}.
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DR EMBL; LN999943; CZT98189.1; -; Genomic_DNA.
DR PIR; A45472; A45472.
DR RefSeq; XP_001349680.1; XM_001349644.1.
DR AlphaFoldDB; P62344; -.
DR SMR; P62344; -.
DR BioGRID; 1208081; 9.
DR IntAct; P62344; 8.
DR STRING; 5833.PFB0815w; -.
DR ChEMBL; CHEMBL1908387; -.
DR DrugBank; DB12010; Fostamatinib.
DR DrugCentral; P62344; -.
DR SwissPalm; P62344; -.
DR PRIDE; P62344; -.
DR EnsemblProtists; CZT98189; CZT98189; PF3D7_0217500.
DR GeneID; 812762; -.
DR KEGG; pfa:PF3D7_0217500; -.
DR VEuPathDB; PlasmoDB:PF3D7_0217500; -.
DR HOGENOM; CLU_000288_37_4_1; -.
DR InParanoid; P62344; -.
DR OMA; KFDECDA; -.
DR PhylomeDB; P62344; -.
DR BRENDA; 2.7.11.1; 4889.
DR Reactome; R-PFA-5687128; MAPK6/MAPK4 signaling.
DR PRO; PR:P62344; -.
DR Proteomes; UP000001450; Chromosome 2.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0020002; C:host cell plasma membrane; IDA:UniProtKB.
DR GO; GO:0031224; C:intrinsic component of membrane; IDA:UniProtKB.
DR GO; GO:0031226; C:intrinsic component of plasma membrane; IDA:UniProtKB.
DR GO; GO:0031514; C:motile cilium; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; IDA:GeneDB.
DR GO; GO:0032991; C:protein-containing complex; IDA:UniProtKB.
DR GO; GO:0020004; C:symbiont-containing vacuolar space; IDA:UniProtKB.
DR GO; GO:0020005; C:symbiont-containing vacuole membrane; IDA:UniProtKB.
DR GO; GO:0071889; F:14-3-3 protein binding; IPI:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0009931; F:calcium-dependent protein serine/threonine kinase activity; IDA:UniProtKB.
DR GO; GO:0005516; F:calmodulin binding; IBA:GO_Central.
DR GO; GO:0004683; F:calmodulin-dependent protein kinase activity; IBA:GO_Central.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:UniProtKB.
DR GO; GO:0035556; P:intracellular signal transduction; IBA:GO_Central.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IDA:UniProtKB.
DR GO; GO:0018107; P:peptidyl-threonine phosphorylation; IDA:UniProtKB.
DR GO; GO:1903307; P:positive regulation of regulated secretory pathway; IDA:UniProtKB.
DR GO; GO:0046777; P:protein autophosphorylation; IDA:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; IDA:UniProtKB.
DR CDD; cd00051; EFh; 1.
DR InterPro; IPR011992; EF-hand-dom_pair.
DR InterPro; IPR018247; EF_Hand_1_Ca_BS.
DR InterPro; IPR002048; EF_hand_dom.
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; PF13499; EF-hand_7; 2.
DR Pfam; PF00069; Pkinase; 1.
DR SMART; SM00054; EFh; 4.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF47473; SSF47473; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS00018; EF_HAND_1; 4.
DR PROSITE; PS50222; EF_HAND_2; 4.
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; Calcium; Cell membrane; Cell projection; Cilium; Cytoplasm;
KW Flagellum; Host cell membrane; Host membrane; Kinase; Lipoprotein;
KW Magnesium; Membrane; Metal-binding; Myristate; Nucleotide-binding;
KW Palmitate; Phosphoprotein; Reference proteome; Repeat;
KW Serine/threonine-protein kinase; Transferase.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:15491359"
FT CHAIN 2..524
FT /note="Calcium-dependent protein kinase 1"
FT /id="PRO_0000085834"
FT DOMAIN 56..325
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT DOMAIN 372..407
FT /note="EF-hand 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DOMAIN 416..451
FT /note="EF-hand 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DOMAIN 452..487
FT /note="EF-hand 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DOMAIN 488..521
FT /note="EF-hand 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT REGION 1..34
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 346..364
FT /note="J domain"
FT /evidence="ECO:0000305|PubMed:19307175"
FT MOTIF 10..20
FT /note="Basic cluster involved in membrane binding"
FT /evidence="ECO:0000269|PubMed:15491359"
FT MOTIF 346..353
FT /note="J domain autoinhibitory motif"
FT /evidence="ECO:0000305|PubMed:19307175"
FT MOTIF 354..364
FT /note="J domain interacts with the EF-hand domains"
FT /evidence="ECO:0000269|PubMed:23204525,
FT ECO:0000305|PubMed:19307175"
FT COMPBIAS 18..34
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 191
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 62..70
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 85
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 385
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 387
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 389
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 391
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 396
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 429
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 431
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 433
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 435
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 440
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 465
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 467
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 469
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 471
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 476
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 499
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 501
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 503
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 505
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 510
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT MOD_RES 17
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:22539638,
FT ECO:0000269|PubMed:32817103"
FT MOD_RES 28
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:22539638,
FT ECO:0000269|PubMed:32817103"
FT MOD_RES 34
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:32817103"
FT MOD_RES 64
FT /note="Phosphoserine; by PKG; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:22539638,
FT ECO:0000269|PubMed:26149123, ECO:0000269|PubMed:32817103"
FT MOD_RES 100
FT /note="Phosphothreonine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:22539638"
FT MOD_RES 118
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:22539638"
FT MOD_RES 217
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:22539638,
FT ECO:0000269|PubMed:32817103"
FT MOD_RES 220
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:22539638"
FT MOD_RES 231
FT /note="Phosphothreonine; by PKG; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:22539638,
FT ECO:0000269|PubMed:26149123"
FT MOD_RES 335
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:22539638"
FT LIPID 2
FT /note="N-myristoyl glycine"
FT /evidence="ECO:0000269|PubMed:15491359"
FT LIPID 3
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000305|PubMed:15491359,
FT ECO:0000305|PubMed:32003970"
FT MUTAGEN 2..50
FT /note="Missing: Severe loss of catalytic activity."
FT /evidence="ECO:0000269|PubMed:22539638"
FT MUTAGEN 2..40
FT /note="Missing: Severe loss of catalytic activity."
FT /evidence="ECO:0000269|PubMed:22539638"
FT MUTAGEN 2..30
FT /note="Missing: Severe loss of catalytic activity."
FT /evidence="ECO:0000269|PubMed:22539638"
FT MUTAGEN 2..20
FT /note="Missing: No effect on catalytic activity."
FT /evidence="ECO:0000269|PubMed:22539638"
FT MUTAGEN 2
FT /note="G->V: Loss of myristoylation. Severe reduction in
FT membrane binding. Loss of membrane binding; when associated
FT with 10-K--T-20 DEL."
FT /evidence="ECO:0000269|PubMed:15491359"
FT MUTAGEN 10..20
FT /note="Missing: Does not affect myristoylation. Severe
FT reduction in membrane binding. Loss of membrane binding;
FT when associated with V-2."
FT /evidence="ECO:0000269|PubMed:15491359"
FT MUTAGEN 27
FT /note="K->A: Severe loss of ATP binding. Partial loss of
FT catalytic activity."
FT /evidence="ECO:0000269|PubMed:22539638"
FT MUTAGEN 64
FT /note="S->A: Loss of phosphorylation. No effect on
FT catalytic activity."
FT /evidence="ECO:0000269|PubMed:26149123"
FT MUTAGEN 152
FT /note="E->A: Severe loss of catalytic activity."
FT /evidence="ECO:0000269|PubMed:22539638"
FT MUTAGEN 154
FT /note="F->A: Severe loss of catalytic activity."
FT /evidence="ECO:0000269|PubMed:22539638"
FT MUTAGEN 155
FT /note="E->A: No effect on catalytic activity."
FT /evidence="ECO:0000269|PubMed:22539638"
FT MUTAGEN 157..158
FT /note="II->AA: Severe loss of catalytic activity."
FT /evidence="ECO:0000269|PubMed:22539638"
FT MUTAGEN 191
FT /note="D->N: Loss of catalytic activity."
FT /evidence="ECO:0000269|PubMed:18768477,
FT ECO:0000269|PubMed:26149123"
FT MUTAGEN 231
FT /note="T->A: Loss of catalytic activity."
FT /evidence="ECO:0000269|PubMed:22539638"
FT MUTAGEN 335
FT /note="S->A: Loss of phosphorylation. Loss of catalytic
FT activity."
FT /evidence="ECO:0000269|PubMed:22539638"
FT MUTAGEN 335
FT /note="S->D: Phospho-mimetic mutant.No effect on catalytic
FT activity."
FT /evidence="ECO:0000269|PubMed:22539638"
FT MUTAGEN 339
FT /note="T->D: No effect on catalytic activity."
FT /evidence="ECO:0000269|PubMed:22539638"
FT MUTAGEN 342..524
FT /note="Missing: Constitutively active."
FT /evidence="ECO:0000269|PubMed:19307175"
FT MUTAGEN 347
FT /note="M->A: Severe loss of catalytic activity."
FT /evidence="ECO:0000269|PubMed:22539638"
FT MUTAGEN 350
FT /note="F->A: Severe loss of catalytic activity."
FT /evidence="ECO:0000269|PubMed:22539638,
FT ECO:0000269|PubMed:23204525"
FT MUTAGEN 353
FT /note="S->A: No effect on catalytic activity."
FT /evidence="ECO:0000269|PubMed:23204525"
FT MUTAGEN 355
FT /note="K->A: No effect on catalytic activity."
FT /evidence="ECO:0000269|PubMed:22539638"
FT MUTAGEN 356
FT /note="L->A: Severe loss of catalytic activity."
FT /evidence="ECO:0000269|PubMed:23204525"
FT MUTAGEN 363..364
FT /note="FI->AA: Severe loss of catalytic activity."
FT /evidence="ECO:0000269|PubMed:23204525"
FT MUTAGEN 366
FT /note="S->A: Slight decrease in catalytic activity."
FT /evidence="ECO:0000269|PubMed:22539638"
FT MUTAGEN 369..370
FT /note="TT->AA: Slight decrease in catalytic activity."
FT /evidence="ECO:0000269|PubMed:22539638"
FT MUTAGEN 456
FT /note="R->A: Severe loss of catalytic activity."
FT /evidence="ECO:0000269|PubMed:22539638"
SQ SEQUENCE 524 AA; 60800 MW; D2A45E1579D2C951 CRC64;
MGCSQSSNVK DFKTRRSKFT NGNNYGKSGN NKNSEDLAIN PGMYVRKKEG KIGESYFKVR
KLGSGAYGEV LLCREKHGHG EKAIKVIKKS QFDKMKYSIT NKIECDDKIH EEIYNEISLL
KSLDHPNIIK LFDVFEDKKY FYLVTEFYEG GELFEQIINR HKFDECDAAN IMKQILSGIC
YLHKHNIVHR DIKPENILLE NKHSLLNIKI VDFGLSSFFS KDNKLRDRLG TAYYIAPEVL
RKKYNEKCDV WSCGVILYIL LCGYPPFGGQ NDQDIIKKVE KGKYYFDFND WKNISEEAKE
LIKLMLTYDY NKRITAKEAL NSKWIKKYAN NINKSDQKTL CGALSNMRKF EGSQKLAQAA
ILFIGSKLTT LEERKELTDI FKKLDKNGDG QLDKKELIEG YNILRSFKNE LGELKNVEEE
VDNILKEVDF DKNGYIEYSE FISVCMDKQI LFSEERLRDA FNLFDTDKSG KITKEELANL
FGLTSISEQM WNEVLGEADK NKDNMIDFDE FVNMMHKICD NKSS
