Calcium-dependent protein kinase 1 (CDPK1) of Plasmodium falciparum is a serine/threonine protein kinase of the plant/alveolate CDPK family. It fuses an N-terminal kinase domain to a junction (autoinhibitory) domain and a C-terminal calmodulin-like domain carrying four EF-hand Ca2+-binding sites, so the enzyme is a self-contained calcium sensor-effector that is activated by Ca2+ alone, without exogenous calmodulin: Ca2+ binding releases the junction domain from the catalytic cleft and permits autophosphorylation and substrate phosphorylation. An N-terminal myristoylation/palmitoylation signal plus a basic cluster anchor CDPK1 peripherally to membranes, chiefly the parasite plasma membrane and inner membrane complex of schizonts and merozoites, with additional pools at the parasitophorous vacuole membrane and tubovesicular network. CDPK1 is highly expressed in asexual blood stages and is required for erythrocyte invasion: downstream of cGMP/PKG and a rise in cytosolic Ca2+, it phosphorylates components of the glideosome motor complex (MTIP, GAP45) and inner membrane complex, the PKA regulatory subunit, the rhoptry protein RhopH3 and the protease SERA5, driving microneme discharge during invasion and egress. Phosphorylated CDPK1 is bound by 14-3-3I, which scaffolds a CDPK1/PKA complex. CDPK1 is also essential for male and female gametogenesis and mosquito transmission, and is an actively pursued antimalarial drug target.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0004672 protein kinase activity | IEA GO_REF:0000002 | MODIFY | Summary: CDPK1 is a Ser/Thr protein kinase whose activity depends on Ca2+ binding to its own C-terminal calmodulin-like domain (CLD); this generic kinase term is correct but less specific than the evidence supports. Reason: Correct but general. Recombinant CDPK1 phosphorylates MTIP, GAP45, PKAr, SERA5, RhopH3 and RKIP in vitro, and activation requires Ca2+ binding to EF hands of its CLD. The gene already carries the specific descendant GO:0009931 by multiple IDA rows, so that term is proposed as the replacement. Proposed replacements: calcium-dependent protein serine/threonine kinase activity Supporting Evidence: PMID:18768477 we demonstrate that both proteins can be efficiently phosphorylated by CDPK1 in vitro. PMID:8142371 The kinase can be activated by Ca2+ alone and associates with 45Ca2+. PMID:23204525 we provide direct evidence for the binding of the CamLD with the P3 region (Leu(356) to Thr(370)) of the JD in the presence of calcium (Ca(2+)) |
| GO:0004674 protein serine/threonine kinase activity | IDA PMID:17123645 Raf kinase inhibitor protein affects activity of Plasmodium ... | MODIFY | Summary: CDPK1 is a Ser/Thr protein kinase whose activity depends on Ca2+ binding to its own C-terminal calmodulin-like domain (CLD); this generic kinase term is correct but less specific than the evidence supports. Reason: Correct but general. Recombinant CDPK1 phosphorylates MTIP, GAP45, PKAr, SERA5, RhopH3 and RKIP in vitro, and activation requires Ca2+ binding to EF hands of its CLD. The gene already carries the specific descendant GO:0009931 by multiple IDA rows, so that term is proposed as the replacement. Proposed replacements: calcium-dependent protein serine/threonine kinase activity Supporting Evidence: PMID:18768477 we demonstrate that both proteins can be efficiently phosphorylated by CDPK1 in vitro. PMID:8142371 The kinase can be activated by Ca2+ alone and associates with 45Ca2+. PMID:23204525 we provide direct evidence for the binding of the CamLD with the P3 region (Leu(356) to Thr(370)) of the JD in the presence of calcium (Ca(2+)) |
| GO:0004674 protein serine/threonine kinase activity | IDA PMID:18768477 The motor complex of Plasmodium falciparum: phosphorylation ... | MODIFY | Summary: CDPK1 is a Ser/Thr protein kinase whose activity depends on Ca2+ binding to its own C-terminal calmodulin-like domain (CLD); this generic kinase term is correct but less specific than the evidence supports. Reason: Correct but general. Recombinant CDPK1 phosphorylates MTIP, GAP45, PKAr, SERA5, RhopH3 and RKIP in vitro, and activation requires Ca2+ binding to EF hands of its CLD. The gene already carries the specific descendant GO:0009931 by multiple IDA rows, so that term is proposed as the replacement. Proposed replacements: calcium-dependent protein serine/threonine kinase activity Supporting Evidence: PMID:18768477 we demonstrate that both proteins can be efficiently phosphorylated by CDPK1 in vitro. PMID:8142371 The kinase can be activated by Ca2+ alone and associates with 45Ca2+. PMID:23204525 we provide direct evidence for the binding of the CamLD with the P3 region (Leu(356) to Thr(370)) of the JD in the presence of calcium (Ca(2+)) |
| GO:0004674 protein serine/threonine kinase activity | IDA PMID:22539638 Novel insights into the regulation of malarial calcium-depen... | MODIFY | Summary: CDPK1 is a Ser/Thr protein kinase whose activity depends on Ca2+ binding to its own C-terminal calmodulin-like domain (CLD); this generic kinase term is correct but less specific than the evidence supports. Reason: Correct but general. Recombinant CDPK1 phosphorylates MTIP, GAP45, PKAr, SERA5, RhopH3 and RKIP in vitro, and activation requires Ca2+ binding to EF hands of its CLD. The gene already carries the specific descendant GO:0009931 by multiple IDA rows, so that term is proposed as the replacement. Proposed replacements: calcium-dependent protein serine/threonine kinase activity Supporting Evidence: PMID:18768477 we demonstrate that both proteins can be efficiently phosphorylated by CDPK1 in vitro. PMID:8142371 The kinase can be activated by Ca2+ alone and associates with 45Ca2+. PMID:23204525 we provide direct evidence for the binding of the CamLD with the P3 region (Leu(356) to Thr(370)) of the JD in the presence of calcium (Ca(2+)) |
| GO:0004674 protein serine/threonine kinase activity | IEA GO_REF:0000003 | MODIFY | Summary: CDPK1 is a Ser/Thr protein kinase whose activity depends on Ca2+ binding to its own C-terminal calmodulin-like domain (CLD); this generic kinase term is correct but less specific than the evidence supports. Reason: Correct but general. Recombinant CDPK1 phosphorylates MTIP, GAP45, PKAr, SERA5, RhopH3 and RKIP in vitro, and activation requires Ca2+ binding to EF hands of its CLD. The gene already carries the specific descendant GO:0009931 by multiple IDA rows, so that term is proposed as the replacement. Proposed replacements: calcium-dependent protein serine/threonine kinase activity Supporting Evidence: PMID:18768477 we demonstrate that both proteins can be efficiently phosphorylated by CDPK1 in vitro. PMID:8142371 The kinase can be activated by Ca2+ alone and associates with 45Ca2+. PMID:23204525 we provide direct evidence for the binding of the CamLD with the P3 region (Leu(356) to Thr(370)) of the JD in the presence of calcium (Ca(2+)) |
| GO:0004674 protein serine/threonine kinase activity | ISS PMID:12368867 Sequence of Plasmodium falciparum chromosomes 1, 3-9 and 13. | MODIFY | Summary: CDPK1 is a Ser/Thr protein kinase whose activity depends on Ca2+ binding to its own C-terminal calmodulin-like domain (CLD); this generic kinase term is correct but less specific than the evidence supports. Reason: Correct but general. Recombinant CDPK1 phosphorylates MTIP, GAP45, PKAr, SERA5, RhopH3 and RKIP in vitro, and activation requires Ca2+ binding to EF hands of its CLD. The gene already carries the specific descendant GO:0009931 by multiple IDA rows, so that term is proposed as the replacement. Proposed replacements: calcium-dependent protein serine/threonine kinase activity Supporting Evidence: PMID:18768477 we demonstrate that both proteins can be efficiently phosphorylated by CDPK1 in vitro. PMID:8142371 The kinase can be activated by Ca2+ alone and associates with 45Ca2+. PMID:23204525 we provide direct evidence for the binding of the CamLD with the P3 region (Leu(356) to Thr(370)) of the JD in the presence of calcium (Ca(2+)) |
| GO:0004683 calcium/calmodulin-dependent protein kinase activity | IBA GO_REF:0000033 | MODIFY | Summary: IBA from a PANTHER node spanning CaMKs and CDPKs. CDPK1 is Ca2+-regulated but does not need calmodulin; Ca2+ alone activates it through its fused calmodulin-like domain. Reason: The core of the claim (a Ca2+-regulated Ser/Thr kinase) is right, but 'calcium/calmodulin-dependent' implies dependence on separate calmodulin, which is not how CDPKs work. CDPK1 binds 45Ca2+ and Ca2+ alone activates it (PMID:8142371). Replace with GO:0009931, which the gene already carries by IDA. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: PANTHER:PTN000681419 SUPPORTS SOURCE BUT NOT TARGET Node spans CaMKs and CDPKs; the Ca2+/calmodulin-dependent wording fits the CaMK donors but not CDPKs, which carry their own calmodulin-like domain. Refined to GO:0009931. Proposed replacements: calcium-dependent protein serine/threonine kinase activity Supporting Evidence: PMID:8142371 The kinase can be activated by Ca2+ alone and associates with 45Ca2+. PMID:23204525 we provide direct evidence for the binding of the CamLD with the P3 region (Leu(356) to Thr(370)) of the JD in the presence of calcium (Ca(2+)) |
| GO:0005509 calcium ion binding | IEA GO_REF:0000002 | ACCEPT | Summary: CDPK1 has four EF-hand Ca2+-binding sites in its C-terminal CLD. Direct 45Ca2+ binding and site mutagenesis show that sites I and II are needed for activation. Reason: The InterPro EF-hand mapping is confirmed experimentally. Calcium binding is the sensor half of the CDPK mechanism. Supporting Evidence: PMID:8142371 As predicted from the cDNA sequence, the kinase has four EF-hand calcium-binding sites in the C-terminal domain. PMID:8142371 The kinase can be activated by Ca2+ alone and associates with 45Ca2+. |
| GO:0005515 protein binding | IPI PMID:28680058 PfCDPK1 mediated signaling in erythrocytic stages of Plasmod... | REMOVE | Summary: Interactions with the PKA regulatory subunit (Q7KQK0) and IMC1g (Q8I3K7), both identified as CDPK1 substrates in late schizonts. Reason: Generic 'protein binding' is uninformative. The interaction is real, but it is a kinase-substrate association that the kinase activity core function (GO:0009931) already captures. Removing the row does not mean the interaction is false. Supporting Evidence: PMID:28680058 PfCDPK1 phosphorylates PfPKA regulatory subunit (PfPKA-R) and regulates PfPKA activity in the parasite, which may be relevant for the process of invasion. PMID:28680058 We identify substrates of PfCDPK1, which includes proteins of Inner Membrane Complex and glideosome-actomyosin motor assembly. |
| GO:0005515 protein binding | IPI PMID:29716996 Calcium-dependent phosphorylation of Plasmodium falciparum s... | REMOVE | Summary: Co-immunoprecipitation and co-sedimentation of CDPK1 with its substrate SERA5 (Q9TY95) in schizonts. Reason: Generic 'protein binding' is uninformative. The interaction is real, but it is a kinase-substrate association that the kinase activity core function (GO:0009931) already captures. Removing the row does not mean the interaction is false. Supporting Evidence: PMID:29716996 Association of PfSERA5 with PfCDPK1 was corroborated by co-sedimentation, co-immunoprecipitation, and co-immunolocalization analyses. |
| GO:0005515 protein binding | IPI PMID:32817103 Phosphorylation-Dependent Assembly of a 14-3-3 Mediated Sign... | MODIFY | Summary: Phosphorylated CDPK1 binds 14-3-3I (C0H4V6) and associates with PKAr in a 14-3-3I-scaffolded complex in merozoites. Reason: The 14-3-3I interaction is better captured by GO:0071889 14-3-3 protein binding, which the gene already carries by IPI from PMID:32484216. Proposed replacements: 14-3-3 protein binding Supporting Evidence: PMID:32817103 Pf14-3-3I binds phosphorylated PfPKAr and PfCDPK1 to mediate the assembly of a multiprotein complex in P. falciparum merozoites. PMID:32484216 The 14-3-3I/CDPK1 interaction was validated in vitro with ELISA and SPR, which confirmed that the interaction is phosphorylation dependent, with binding affinity constant of 670 ± 3.6 nM. |
| GO:0005516 calmodulin binding | IBA GO_REF:0000033 | REMOVE | Summary: IBA calmodulin binding, propagated from a PANTHER node whose donors include CDPK-related kinases (CRKs) that bind calmodulin. No calmodulin binding has been reported for PfCDPK1. Reason: CDPKs carry their own calmodulin-like domain, and Ca2+ alone activates PfCDPK1 without calmodulin (PMID:8142371). The CLD binds the kinase's own junction domain (PMID:23204525), which is an intramolecular contact, not calmodulin binding. Calmodulin binding belongs to the CaMK/CRK branches, not to the CDPK clade that contains CDPK1. Propagation Review Root cause: PROPAGATION BAD Failure modes: FUNCTIONAL DIVERGENCE Sources checked: PANTHER:PTN000681419 SUPPORTS SOURCE BUT NOT TARGET Calmodulin binding is a property of the CaMK/CRK donors at this node; CDPK1 is activated by Ca2+ alone via its fused calmodulin-like domain and does not bind exogenous calmodulin. Supporting Evidence: PMID:8142371 The kinase can be activated by Ca2+ alone and associates with 45Ca2+. PMID:23204525 we provide direct evidence for the binding of the CamLD with the P3 region (Leu(356) to Thr(370)) of the JD in the presence of calcium (Ca(2+)) |
| GO:0005524 ATP binding | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: ATP binding by the protein kinase domain. Inhibitor potency depends on ATP concentration and on the gatekeeper residue of the ATP pocket. Reason: True but implied by kinase activity; not informative as a core function. Supporting Evidence: PMID:25070106 enzyme inhibition by these compounds was found to be sensitive to both the ATP concentration and substitution of the amino acid residue present at the "gatekeeper" position at the ATP-binding site of the enzyme. |
| GO:0005634 nucleus | IBA GO_REF:0000033 | MARK AS OVER ANNOTATED | Summary: IBA nucleus from a broad CAMK-family node. PfCDPK1 is N-myristoylated and palmitoylated and is consistently found at the parasite plasma membrane, PV/PVM and the periphery of gametes; no nuclear localization has been reported. Reason: Target-specific divergence. The N-terminal acylation and basic motif target CDPK1 to membranes, and independent localization studies (IFA, GFP tagging, immuno-EM) never place it in the nucleus. The nucleus assertion likely reflects nuclear-acting mammalian CaMKs and plant CPKs at the node. Propagation Review Root cause: PROPAGATION BAD Failure modes: COMPARTMENT OR COMPLEX MISMATCH Sources checked: PANTHER:PTN000681419 SUPPORTS SOURCE BUT NOT TARGET Nuclear localization reflects nuclear-acting mammalian CaMKs and plant CPKs at the node; PfCDPK1 is an N-acylated membrane kinase never detected in the nucleus. Supporting Evidence: PMID:15491359 The supposed membrane attachment function of the basic cluster was experimentally verified and shown to participate together with N-myristoylation in membrane anchoring of the kinase. PMID:23548171 CDPK1 localizes to the parasite plasma membrane of replicating and invasive forms as well as very young intracellular parasites and does not appear to be exported into RBCs. |
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: CDPK1 is a peripheral membrane protein acting on the cytoplasmic face of the plasma membrane and IMC; soluble cytoplasmic pools are minor. Reason: Cytoplasm is not wrong for a cytosolically synthesized, peripherally attached kinase, but the functional location is the plasma membrane. Kept as non-core. Supporting Evidence: PMID:18768477 CDPK1 localizes to the periphery of P. falciparum merozoites and is therefore suitably located to act on MTIP and GAP45 at the inner membrane complex. PMID:15491359 The supposed membrane attachment function of the basic cluster was experimentally verified and shown to participate together with N-myristoylation in membrane anchoring of the kinase. |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: CDPK1 is a peripheral membrane protein acting on the cytoplasmic face of the plasma membrane and IMC; soluble cytoplasmic pools are minor. Reason: Cytoplasm is not wrong for a cytosolically synthesized, peripherally attached kinase, but the functional location is the plasma membrane. Kept as non-core. Supporting Evidence: PMID:18768477 CDPK1 localizes to the periphery of P. falciparum merozoites and is therefore suitably located to act on MTIP and GAP45 at the inner membrane complex. PMID:15491359 The supposed membrane attachment function of the basic cluster was experimentally verified and shown to participate together with N-myristoylation in membrane anchoring of the kinase. |
| GO:0005737 cytoplasm | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: CDPK1 is a peripheral membrane protein acting on the cytoplasmic face of the plasma membrane and IMC; soluble cytoplasmic pools are minor. Reason: Cytoplasm is not wrong for a cytosolically synthesized, peripherally attached kinase, but the functional location is the plasma membrane. Kept as non-core. Supporting Evidence: PMID:18768477 CDPK1 localizes to the periphery of P. falciparum merozoites and is therefore suitably located to act on MTIP and GAP45 at the inner membrane complex. PMID:15491359 The supposed membrane attachment function of the basic cluster was experimentally verified and shown to participate together with N-myristoylation in membrane anchoring of the kinase. |
| GO:0005886 plasma membrane | EXP PMID:26149123 Phosphoproteomics reveals malaria parasite Protein Kinase G ... | ACCEPT | Summary: CDPK1 localizes to the parasite plasma membrane of schizonts, merozoites and young rings, anchored by N-myristoylation, palmitoylation and a basic cluster; this is the most reproducible localization across laboratories. Reason: Consistent IFA, GFP-tagging, HA-tagging and palmitoylation data place CDPK1 at the merozoite plasma membrane, where it phosphorylates IMC/glideosome substrates. Supporting Evidence: PMID:23548171 CDPK1 localizes to the parasite plasma membrane of replicating and invasive forms as well as very young intracellular parasites and does not appear to be exported into RBCs. PMID:18768477 CDPK1 localizes to the periphery of P. falciparum merozoites and is therefore suitably located to act on MTIP and GAP45 at the inner membrane complex. PMID:23204525 In merozoites, PfCDPK1 was found primarily at the boundary of the merozoite at the merozoite plasma membrane ( Fig. 2 B ). PMID:32003970 undergoes dynamic palmitoylation and localizes to the merozoite membrane. |
| GO:0005886 plasma membrane | IDA PMID:15491359 Export of Plasmodium falciparum calcium-dependent protein ki... | ACCEPT | Summary: CDPK1 localizes to the parasite plasma membrane of schizonts, merozoites and young rings, anchored by N-myristoylation, palmitoylation and a basic cluster; this is the most reproducible localization across laboratories. Reason: Consistent IFA, GFP-tagging, HA-tagging and palmitoylation data place CDPK1 at the merozoite plasma membrane, where it phosphorylates IMC/glideosome substrates. Supporting Evidence: PMID:23548171 CDPK1 localizes to the parasite plasma membrane of replicating and invasive forms as well as very young intracellular parasites and does not appear to be exported into RBCs. PMID:18768477 CDPK1 localizes to the periphery of P. falciparum merozoites and is therefore suitably located to act on MTIP and GAP45 at the inner membrane complex. PMID:23204525 In merozoites, PfCDPK1 was found primarily at the boundary of the merozoite at the merozoite plasma membrane ( Fig. 2 B ). PMID:32003970 undergoes dynamic palmitoylation and localizes to the merozoite membrane. |
| GO:0005886 plasma membrane | IDA PMID:18768477 The motor complex of Plasmodium falciparum: phosphorylation ... | ACCEPT | Summary: CDPK1 localizes to the parasite plasma membrane of schizonts, merozoites and young rings, anchored by N-myristoylation, palmitoylation and a basic cluster; this is the most reproducible localization across laboratories. Reason: Consistent IFA, GFP-tagging, HA-tagging and palmitoylation data place CDPK1 at the merozoite plasma membrane, where it phosphorylates IMC/glideosome substrates. Supporting Evidence: PMID:23548171 CDPK1 localizes to the parasite plasma membrane of replicating and invasive forms as well as very young intracellular parasites and does not appear to be exported into RBCs. PMID:18768477 CDPK1 localizes to the periphery of P. falciparum merozoites and is therefore suitably located to act on MTIP and GAP45 at the inner membrane complex. PMID:23204525 In merozoites, PfCDPK1 was found primarily at the boundary of the merozoite at the merozoite plasma membrane ( Fig. 2 B ). PMID:32003970 undergoes dynamic palmitoylation and localizes to the merozoite membrane. |
| GO:0005886 plasma membrane | IDA PMID:23204525 Characterization of Plasmodium falciparum calcium-dependent ... | ACCEPT | Summary: CDPK1 localizes to the parasite plasma membrane of schizonts, merozoites and young rings, anchored by N-myristoylation, palmitoylation and a basic cluster; this is the most reproducible localization across laboratories. Reason: Consistent IFA, GFP-tagging, HA-tagging and palmitoylation data place CDPK1 at the merozoite plasma membrane, where it phosphorylates IMC/glideosome substrates. Supporting Evidence: PMID:23548171 CDPK1 localizes to the parasite plasma membrane of replicating and invasive forms as well as very young intracellular parasites and does not appear to be exported into RBCs. PMID:18768477 CDPK1 localizes to the periphery of P. falciparum merozoites and is therefore suitably located to act on MTIP and GAP45 at the inner membrane complex. PMID:23204525 In merozoites, PfCDPK1 was found primarily at the boundary of the merozoite at the merozoite plasma membrane ( Fig. 2 B ). PMID:32003970 undergoes dynamic palmitoylation and localizes to the merozoite membrane. |
| GO:0005886 plasma membrane | IDA PMID:23548171 Inhibition of Plasmodium falciparum CDPK1 by conditional exp... | ACCEPT | Summary: CDPK1 localizes to the parasite plasma membrane of schizonts, merozoites and young rings, anchored by N-myristoylation, palmitoylation and a basic cluster; this is the most reproducible localization across laboratories. Reason: Consistent IFA, GFP-tagging, HA-tagging and palmitoylation data place CDPK1 at the merozoite plasma membrane, where it phosphorylates IMC/glideosome substrates. Supporting Evidence: PMID:23548171 CDPK1 localizes to the parasite plasma membrane of replicating and invasive forms as well as very young intracellular parasites and does not appear to be exported into RBCs. PMID:18768477 CDPK1 localizes to the periphery of P. falciparum merozoites and is therefore suitably located to act on MTIP and GAP45 at the inner membrane complex. PMID:23204525 In merozoites, PfCDPK1 was found primarily at the boundary of the merozoite at the merozoite plasma membrane ( Fig. 2 B ). PMID:32003970 undergoes dynamic palmitoylation and localizes to the merozoite membrane. |
| GO:0005886 plasma membrane | IDA PMID:32003970 Protein S-Palmitoylation Is Responsive to External Signals a... | ACCEPT | Summary: CDPK1 localizes to the parasite plasma membrane of schizonts, merozoites and young rings, anchored by N-myristoylation, palmitoylation and a basic cluster; this is the most reproducible localization across laboratories. Reason: Consistent IFA, GFP-tagging, HA-tagging and palmitoylation data place CDPK1 at the merozoite plasma membrane, where it phosphorylates IMC/glideosome substrates. Supporting Evidence: PMID:23548171 CDPK1 localizes to the parasite plasma membrane of replicating and invasive forms as well as very young intracellular parasites and does not appear to be exported into RBCs. PMID:18768477 CDPK1 localizes to the periphery of P. falciparum merozoites and is therefore suitably located to act on MTIP and GAP45 at the inner membrane complex. PMID:23204525 In merozoites, PfCDPK1 was found primarily at the boundary of the merozoite at the merozoite plasma membrane ( Fig. 2 B ). PMID:32003970 undergoes dynamic palmitoylation and localizes to the merozoite membrane. |
| GO:0005886 plasma membrane | IDA PMID:32484216 Molecular dynamics simulations and biochemical characterizat... | ACCEPT | Summary: CDPK1 localizes to the parasite plasma membrane of schizonts, merozoites and young rings, anchored by N-myristoylation, palmitoylation and a basic cluster; this is the most reproducible localization across laboratories. Reason: Consistent IFA, GFP-tagging, HA-tagging and palmitoylation data place CDPK1 at the merozoite plasma membrane, where it phosphorylates IMC/glideosome substrates. Supporting Evidence: PMID:23548171 CDPK1 localizes to the parasite plasma membrane of replicating and invasive forms as well as very young intracellular parasites and does not appear to be exported into RBCs. PMID:18768477 CDPK1 localizes to the periphery of P. falciparum merozoites and is therefore suitably located to act on MTIP and GAP45 at the inner membrane complex. PMID:23204525 In merozoites, PfCDPK1 was found primarily at the boundary of the merozoite at the merozoite plasma membrane ( Fig. 2 B ). PMID:32003970 undergoes dynamic palmitoylation and localizes to the merozoite membrane. |
| GO:0005886 plasma membrane | IEA GO_REF:0000044 | ACCEPT | Summary: CDPK1 localizes to the parasite plasma membrane of schizonts, merozoites and young rings, anchored by N-myristoylation, palmitoylation and a basic cluster; this is the most reproducible localization across laboratories. Reason: Consistent IFA, GFP-tagging, HA-tagging and palmitoylation data place CDPK1 at the merozoite plasma membrane, where it phosphorylates IMC/glideosome substrates. Supporting Evidence: PMID:23548171 CDPK1 localizes to the parasite plasma membrane of replicating and invasive forms as well as very young intracellular parasites and does not appear to be exported into RBCs. PMID:18768477 CDPK1 localizes to the periphery of P. falciparum merozoites and is therefore suitably located to act on MTIP and GAP45 at the inner membrane complex. PMID:23204525 In merozoites, PfCDPK1 was found primarily at the boundary of the merozoite at the merozoite plasma membrane ( Fig. 2 B ). PMID:32003970 undergoes dynamic palmitoylation and localizes to the merozoite membrane. |
| GO:0006468 protein phosphorylation | IDA PMID:17123645 Raf kinase inhibitor protein affects activity of Plasmodium ... | ACCEPT | Summary: CDPK1 phosphorylates many parasite proteins (MTIP, GAP45, IMC proteins, PKAr, SERA5, RhopH3, RKIP) in vitro and, by phosphoproteomics after knockdown, in the parasite. Reason: Direct biochemical evidence of protein phosphorylation by CDPK1; the appropriate process term for a protein kinase. Supporting Evidence: PMID:18768477 we demonstrate that both proteins can be efficiently phosphorylated by CDPK1 in vitro. PMID:22479457 We show that GAP45 is phosphorylated by calcium dependent protein kinase 1 (CDPK1), and identify the modified serine residues. PMID:28680058 We identify substrates of PfCDPK1, which includes proteins of Inner Membrane Complex and glideosome-actomyosin motor assembly. |
| GO:0006468 protein phosphorylation | IDA PMID:19307175 Dissection of mechanisms involved in the regulation of Plasm... | ACCEPT | Summary: CDPK1 phosphorylates many parasite proteins (MTIP, GAP45, IMC proteins, PKAr, SERA5, RhopH3, RKIP) in vitro and, by phosphoproteomics after knockdown, in the parasite. Reason: Direct biochemical evidence of protein phosphorylation by CDPK1; the appropriate process term for a protein kinase. Supporting Evidence: PMID:18768477 we demonstrate that both proteins can be efficiently phosphorylated by CDPK1 in vitro. PMID:22479457 We show that GAP45 is phosphorylated by calcium dependent protein kinase 1 (CDPK1), and identify the modified serine residues. PMID:28680058 We identify substrates of PfCDPK1, which includes proteins of Inner Membrane Complex and glideosome-actomyosin motor assembly. |
| GO:0006468 protein phosphorylation | IDA PMID:22479457 Subcellular location, phosphorylation and assembly into the ... | ACCEPT | Summary: CDPK1 phosphorylates many parasite proteins (MTIP, GAP45, IMC proteins, PKAr, SERA5, RhopH3, RKIP) in vitro and, by phosphoproteomics after knockdown, in the parasite. Reason: Direct biochemical evidence of protein phosphorylation by CDPK1; the appropriate process term for a protein kinase. Supporting Evidence: PMID:18768477 we demonstrate that both proteins can be efficiently phosphorylated by CDPK1 in vitro. PMID:22479457 We show that GAP45 is phosphorylated by calcium dependent protein kinase 1 (CDPK1), and identify the modified serine residues. PMID:28680058 We identify substrates of PfCDPK1, which includes proteins of Inner Membrane Complex and glideosome-actomyosin motor assembly. |
| GO:0006468 protein phosphorylation | IDA PMID:23204525 Characterization of Plasmodium falciparum calcium-dependent ... | ACCEPT | Summary: CDPK1 phosphorylates many parasite proteins (MTIP, GAP45, IMC proteins, PKAr, SERA5, RhopH3, RKIP) in vitro and, by phosphoproteomics after knockdown, in the parasite. Reason: Direct biochemical evidence of protein phosphorylation by CDPK1; the appropriate process term for a protein kinase. Supporting Evidence: PMID:18768477 we demonstrate that both proteins can be efficiently phosphorylated by CDPK1 in vitro. PMID:22479457 We show that GAP45 is phosphorylated by calcium dependent protein kinase 1 (CDPK1), and identify the modified serine residues. PMID:28680058 We identify substrates of PfCDPK1, which includes proteins of Inner Membrane Complex and glideosome-actomyosin motor assembly. |
| GO:0006468 protein phosphorylation | IDA PMID:32484216 Molecular dynamics simulations and biochemical characterizat... | ACCEPT | Summary: CDPK1 phosphorylates many parasite proteins (MTIP, GAP45, IMC proteins, PKAr, SERA5, RhopH3, RKIP) in vitro and, by phosphoproteomics after knockdown, in the parasite. Reason: Direct biochemical evidence of protein phosphorylation by CDPK1; the appropriate process term for a protein kinase. Supporting Evidence: PMID:18768477 we demonstrate that both proteins can be efficiently phosphorylated by CDPK1 in vitro. PMID:22479457 We show that GAP45 is phosphorylated by calcium dependent protein kinase 1 (CDPK1), and identify the modified serine residues. PMID:28680058 We identify substrates of PfCDPK1, which includes proteins of Inner Membrane Complex and glideosome-actomyosin motor assembly. |
| GO:0009410 response to xenobiotic stimulus | IDA PMID:25070106 Biochemical and antiparasitic properties of inhibitors of th... | REMOVE | Summary: Derived from a high-throughput inhibitor screen and medicinal-chemistry campaign against recombinant CDPK1. Reason: Sensitivity of an enzyme to synthetic inhibitors in vitro is not a biological process in which the gene product participates. 'Response to xenobiotic stimulus' describes a cellular program responding to a foreign compound, which this study does not demonstrate; the authors even note biochemical inhibition did not correlate with growth inhibition. Supporting Evidence: PMID:25070106 we were unable to correlate biochemical inhibition with parasite growth inhibition for this series overall. |
| GO:0009931 calcium-dependent protein serine/threonine kinase activity | IBA GO_REF:0000033 | ACCEPT | Summary: Core activity is Ca2+-activated Ser/Thr protein kinase. Ca2+ binding to the CLD EF hands releases the autoinhibitory junction domain. Substrates include MTIP, GAP45, PKAr, SERA5 and RhopH3. Reason: Several independent biochemical studies show Ca2+-dependent phosphorylation of protein substrates. Removing the junction domain and CLD gives Ca2+-independent activity, which confirms the autoinhibitory mechanism. Supporting Evidence: PMID:8142371 The kinase can be activated by Ca2+ alone and associates with 45Ca2+. PMID:23204525 we provide direct evidence for the binding of the CamLD with the P3 region (Leu(356) to Thr(370)) of the JD in the presence of calcium (Ca(2+)) PMID:18768477 we demonstrate that both proteins can be efficiently phosphorylated by CDPK1 in vitro. PMID:29716996 PfCDPK1 phosphorylated PfSERA5 in vitro in the presence of Ca2+ and enhanced its proteolytic activity. PMID:19307175 this PfCDPK1 truncation was also active both in the presence and the absence of calcium (not shown here). |
| GO:0009931 calcium-dependent protein serine/threonine kinase activity | IDA PMID:19307175 Dissection of mechanisms involved in the regulation of Plasm... | ACCEPT | Summary: Core activity is Ca2+-activated Ser/Thr protein kinase. Ca2+ binding to the CLD EF hands releases the autoinhibitory junction domain. Substrates include MTIP, GAP45, PKAr, SERA5 and RhopH3. Reason: Several independent biochemical studies show Ca2+-dependent phosphorylation of protein substrates. Removing the junction domain and CLD gives Ca2+-independent activity, which confirms the autoinhibitory mechanism. Supporting Evidence: PMID:8142371 The kinase can be activated by Ca2+ alone and associates with 45Ca2+. PMID:23204525 we provide direct evidence for the binding of the CamLD with the P3 region (Leu(356) to Thr(370)) of the JD in the presence of calcium (Ca(2+)) PMID:18768477 we demonstrate that both proteins can be efficiently phosphorylated by CDPK1 in vitro. PMID:29716996 PfCDPK1 phosphorylated PfSERA5 in vitro in the presence of Ca2+ and enhanced its proteolytic activity. PMID:19307175 this PfCDPK1 truncation was also active both in the presence and the absence of calcium (not shown here). |
| GO:0009931 calcium-dependent protein serine/threonine kinase activity | IDA PMID:23204525 Characterization of Plasmodium falciparum calcium-dependent ... | ACCEPT | Summary: Core activity is Ca2+-activated Ser/Thr protein kinase. Ca2+ binding to the CLD EF hands releases the autoinhibitory junction domain. Substrates include MTIP, GAP45, PKAr, SERA5 and RhopH3. Reason: Several independent biochemical studies show Ca2+-dependent phosphorylation of protein substrates. Removing the junction domain and CLD gives Ca2+-independent activity, which confirms the autoinhibitory mechanism. Supporting Evidence: PMID:8142371 The kinase can be activated by Ca2+ alone and associates with 45Ca2+. PMID:23204525 we provide direct evidence for the binding of the CamLD with the P3 region (Leu(356) to Thr(370)) of the JD in the presence of calcium (Ca(2+)) PMID:18768477 we demonstrate that both proteins can be efficiently phosphorylated by CDPK1 in vitro. PMID:29716996 PfCDPK1 phosphorylated PfSERA5 in vitro in the presence of Ca2+ and enhanced its proteolytic activity. PMID:19307175 this PfCDPK1 truncation was also active both in the presence and the absence of calcium (not shown here). |
| GO:0009931 calcium-dependent protein serine/threonine kinase activity | IDA PMID:28680058 PfCDPK1 mediated signaling in erythrocytic stages of Plasmod... | ACCEPT | Summary: Core activity is Ca2+-activated Ser/Thr protein kinase. Ca2+ binding to the CLD EF hands releases the autoinhibitory junction domain. Substrates include MTIP, GAP45, PKAr, SERA5 and RhopH3. Reason: Several independent biochemical studies show Ca2+-dependent phosphorylation of protein substrates. Removing the junction domain and CLD gives Ca2+-independent activity, which confirms the autoinhibitory mechanism. Supporting Evidence: PMID:8142371 The kinase can be activated by Ca2+ alone and associates with 45Ca2+. PMID:23204525 we provide direct evidence for the binding of the CamLD with the P3 region (Leu(356) to Thr(370)) of the JD in the presence of calcium (Ca(2+)) PMID:18768477 we demonstrate that both proteins can be efficiently phosphorylated by CDPK1 in vitro. PMID:29716996 PfCDPK1 phosphorylated PfSERA5 in vitro in the presence of Ca2+ and enhanced its proteolytic activity. PMID:19307175 this PfCDPK1 truncation was also active both in the presence and the absence of calcium (not shown here). |
| GO:0009931 calcium-dependent protein serine/threonine kinase activity | IDA PMID:29716996 Calcium-dependent phosphorylation of Plasmodium falciparum s... | ACCEPT | Summary: Core activity is Ca2+-activated Ser/Thr protein kinase. Ca2+ binding to the CLD EF hands releases the autoinhibitory junction domain. Substrates include MTIP, GAP45, PKAr, SERA5 and RhopH3. Reason: Several independent biochemical studies show Ca2+-dependent phosphorylation of protein substrates. Removing the junction domain and CLD gives Ca2+-independent activity, which confirms the autoinhibitory mechanism. Supporting Evidence: PMID:8142371 The kinase can be activated by Ca2+ alone and associates with 45Ca2+. PMID:23204525 we provide direct evidence for the binding of the CamLD with the P3 region (Leu(356) to Thr(370)) of the JD in the presence of calcium (Ca(2+)) PMID:18768477 we demonstrate that both proteins can be efficiently phosphorylated by CDPK1 in vitro. PMID:29716996 PfCDPK1 phosphorylated PfSERA5 in vitro in the presence of Ca2+ and enhanced its proteolytic activity. PMID:19307175 this PfCDPK1 truncation was also active both in the presence and the absence of calcium (not shown here). |
| GO:0009931 calcium-dependent protein serine/threonine kinase activity | IDA PMID:32484216 Molecular dynamics simulations and biochemical characterizat... | ACCEPT | Summary: Core activity is Ca2+-activated Ser/Thr protein kinase. Ca2+ binding to the CLD EF hands releases the autoinhibitory junction domain. Substrates include MTIP, GAP45, PKAr, SERA5 and RhopH3. Reason: Several independent biochemical studies show Ca2+-dependent phosphorylation of protein substrates. Removing the junction domain and CLD gives Ca2+-independent activity, which confirms the autoinhibitory mechanism. Supporting Evidence: PMID:8142371 The kinase can be activated by Ca2+ alone and associates with 45Ca2+. PMID:23204525 we provide direct evidence for the binding of the CamLD with the P3 region (Leu(356) to Thr(370)) of the JD in the presence of calcium (Ca(2+)) PMID:18768477 we demonstrate that both proteins can be efficiently phosphorylated by CDPK1 in vitro. PMID:29716996 PfCDPK1 phosphorylated PfSERA5 in vitro in the presence of Ca2+ and enhanced its proteolytic activity. PMID:19307175 this PfCDPK1 truncation was also active both in the presence and the absence of calcium (not shown here). |
| GO:0009931 calcium-dependent protein serine/threonine kinase activity | IDA PMID:8142371 Calcium-binding properties of a calcium-dependent protein ki... | ACCEPT | Summary: Core activity is Ca2+-activated Ser/Thr protein kinase. Ca2+ binding to the CLD EF hands releases the autoinhibitory junction domain. Substrates include MTIP, GAP45, PKAr, SERA5 and RhopH3. Reason: Several independent biochemical studies show Ca2+-dependent phosphorylation of protein substrates. Removing the junction domain and CLD gives Ca2+-independent activity, which confirms the autoinhibitory mechanism. Supporting Evidence: PMID:8142371 The kinase can be activated by Ca2+ alone and associates with 45Ca2+. PMID:23204525 we provide direct evidence for the binding of the CamLD with the P3 region (Leu(356) to Thr(370)) of the JD in the presence of calcium (Ca(2+)) PMID:18768477 we demonstrate that both proteins can be efficiently phosphorylated by CDPK1 in vitro. PMID:29716996 PfCDPK1 phosphorylated PfSERA5 in vitro in the presence of Ca2+ and enhanced its proteolytic activity. PMID:19307175 this PfCDPK1 truncation was also active both in the presence and the absence of calcium (not shown here). |
| GO:0016020 membrane | EXP PMID:15491359 Export of Plasmodium falciparum calcium-dependent protein ki... | MODIFY | Summary: CDPK1 is lipid-anchored to membranes; the specific compartments determined experimentally are the parasite plasma membrane and the parasitophorous (symbiont-containing) vacuole membrane. Reason: Correct but general. The more specific supported locations are already annotated to the gene (plasma membrane; symbiont-containing vacuole membrane), so 'membrane' should be refined to those descendants. Proposed replacements: plasma membrane symbiont-containing vacuole membrane Supporting Evidence: PMID:23548171 CDPK1 localizes to the parasite plasma membrane of replicating and invasive forms as well as very young intracellular parasites and does not appear to be exported into RBCs. PMID:15491359 Using immunogold electron microscopy, the protein was detected in the parasitophorous vacuole and the tubovesicular system of the parasite. |
| GO:0016020 membrane | EXP PMID:23204525 Characterization of Plasmodium falciparum calcium-dependent ... | MODIFY | Summary: CDPK1 is lipid-anchored to membranes; the specific compartments determined experimentally are the parasite plasma membrane and the parasitophorous (symbiont-containing) vacuole membrane. Reason: Correct but general. The more specific supported locations are already annotated to the gene (plasma membrane; symbiont-containing vacuole membrane), so 'membrane' should be refined to those descendants. Proposed replacements: plasma membrane symbiont-containing vacuole membrane Supporting Evidence: PMID:23548171 CDPK1 localizes to the parasite plasma membrane of replicating and invasive forms as well as very young intracellular parasites and does not appear to be exported into RBCs. PMID:15491359 Using immunogold electron microscopy, the protein was detected in the parasitophorous vacuole and the tubovesicular system of the parasite. |
| GO:0016020 membrane | IDA PMID:28680058 PfCDPK1 mediated signaling in erythrocytic stages of Plasmod... | MODIFY | Summary: CDPK1 is lipid-anchored to membranes; the specific compartments determined experimentally are the parasite plasma membrane and the parasitophorous (symbiont-containing) vacuole membrane. Reason: Correct but general. The more specific supported locations are already annotated to the gene (plasma membrane; symbiont-containing vacuole membrane), so 'membrane' should be refined to those descendants. Proposed replacements: plasma membrane symbiont-containing vacuole membrane Supporting Evidence: PMID:23548171 CDPK1 localizes to the parasite plasma membrane of replicating and invasive forms as well as very young intracellular parasites and does not appear to be exported into RBCs. PMID:15491359 Using immunogold electron microscopy, the protein was detected in the parasitophorous vacuole and the tubovesicular system of the parasite. |
| GO:0016020 membrane | IEA GO_REF:0000120 | MODIFY | Summary: CDPK1 is lipid-anchored to membranes; the specific compartments determined experimentally are the parasite plasma membrane and the parasitophorous (symbiont-containing) vacuole membrane. Reason: Correct but general. The more specific supported locations are already annotated to the gene (plasma membrane; symbiont-containing vacuole membrane), so 'membrane' should be refined to those descendants. Proposed replacements: plasma membrane symbiont-containing vacuole membrane Supporting Evidence: PMID:23548171 CDPK1 localizes to the parasite plasma membrane of replicating and invasive forms as well as very young intracellular parasites and does not appear to be exported into RBCs. PMID:15491359 Using immunogold electron microscopy, the protein was detected in the parasitophorous vacuole and the tubovesicular system of the parasite. |
| GO:0018105 peptidyl-serine phosphorylation | IDA PMID:18768477 The motor complex of Plasmodium falciparum: phosphorylation ... | ACCEPT | Summary: CDPK1 phosphorylates serine residues on substrate proteins (e.g. MTIP S47, SERA5, RhopH3 S804) and autophosphorylates on serines. Reason: Direct evidence of peptidyl-serine phosphorylation activity on identified sites. Supporting Evidence: PMID:18768477 A primary phosphorylation of MTIP occurs at serine 47, whereas GAP45 is phosphorylated at two sites, one of which could also be detected in phosphopeptides purified from parasite lysates. PMID:33024030 First, we tested if PfCDPK1 can directly phosphorylate RhopH3 by performing in vitro kinase assays. |
| GO:0018105 peptidyl-serine phosphorylation | IDA PMID:22539638 Novel insights into the regulation of malarial calcium-depen... | ACCEPT | Summary: CDPK1 phosphorylates serine residues on substrate proteins (e.g. MTIP S47, SERA5, RhopH3 S804) and autophosphorylates on serines. Reason: Direct evidence of peptidyl-serine phosphorylation activity on identified sites. Supporting Evidence: PMID:18768477 A primary phosphorylation of MTIP occurs at serine 47, whereas GAP45 is phosphorylated at two sites, one of which could also be detected in phosphopeptides purified from parasite lysates. PMID:33024030 First, we tested if PfCDPK1 can directly phosphorylate RhopH3 by performing in vitro kinase assays. |
| GO:0018105 peptidyl-serine phosphorylation | IDA PMID:28680058 PfCDPK1 mediated signaling in erythrocytic stages of Plasmod... | ACCEPT | Summary: CDPK1 phosphorylates serine residues on substrate proteins (e.g. MTIP S47, SERA5, RhopH3 S804) and autophosphorylates on serines. Reason: Direct evidence of peptidyl-serine phosphorylation activity on identified sites. Supporting Evidence: PMID:18768477 A primary phosphorylation of MTIP occurs at serine 47, whereas GAP45 is phosphorylated at two sites, one of which could also be detected in phosphopeptides purified from parasite lysates. PMID:33024030 First, we tested if PfCDPK1 can directly phosphorylate RhopH3 by performing in vitro kinase assays. |
| GO:0018105 peptidyl-serine phosphorylation | IDA PMID:29716996 Calcium-dependent phosphorylation of Plasmodium falciparum s... | ACCEPT | Summary: CDPK1 phosphorylates serine residues on substrate proteins (e.g. MTIP S47, SERA5, RhopH3 S804) and autophosphorylates on serines. Reason: Direct evidence of peptidyl-serine phosphorylation activity on identified sites. Supporting Evidence: PMID:18768477 A primary phosphorylation of MTIP occurs at serine 47, whereas GAP45 is phosphorylated at two sites, one of which could also be detected in phosphopeptides purified from parasite lysates. PMID:33024030 First, we tested if PfCDPK1 can directly phosphorylate RhopH3 by performing in vitro kinase assays. |
| GO:0018107 peptidyl-threonine phosphorylation | IDA PMID:22539638 Novel insights into the regulation of malarial calcium-depen... | ACCEPT | Summary: CDPK1 also phosphorylates threonine residues; in vitro it phosphorylates protein substrates on both Ser and Thr, consistent with its dual catalytic-activity annotations. Reason: CDPK1 has documented protein-threonine kinase activity (UniProt catalytic activity EC 2.7.11.1 Thr reaction; autophosphorylation at Thr-231 activation loop). Supporting Evidence: file:PLAF7/CDPK1/CDPK1-uniprot.txt Reaction=L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] PMID:22539638 Mass spectrometry revealed that PfCDPK1 was autophosphorylated at several sites; some of these were placed at strategic locations and therefore were found to be critical for kinase activation. |
| GO:0018107 peptidyl-threonine phosphorylation | IDA PMID:28680058 PfCDPK1 mediated signaling in erythrocytic stages of Plasmod... | ACCEPT | Summary: CDPK1 also phosphorylates threonine residues; in vitro it phosphorylates protein substrates on both Ser and Thr, consistent with its dual catalytic-activity annotations. Reason: CDPK1 has documented protein-threonine kinase activity (UniProt catalytic activity EC 2.7.11.1 Thr reaction; autophosphorylation at Thr-231 activation loop). Supporting Evidence: file:PLAF7/CDPK1/CDPK1-uniprot.txt Reaction=L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] PMID:22539638 Mass spectrometry revealed that PfCDPK1 was autophosphorylated at several sites; some of these were placed at strategic locations and therefore were found to be critical for kinase activation. |
| GO:0020002 host cell plasma membrane | IDA PMID:23204525 Characterization of Plasmodium falciparum calcium-dependent ... | KEEP AS NON CORE | Summary: By IFA, CDPK1 was reported at the rim of the infected erythrocyte in rings and trophozoites, consistent with low-level export to the host erythrocyte membrane. Reason: A minor, non-core localization reported in one study and not seen with endogenous GFP tagging; kept as non-core rather than removed since the host-membrane pool is independently proposed in UniProt. Supporting Evidence: PMID:23204525 PfCDPK1 localized to the rim of the infected erythrocyte and appeared to be associated with the erythrocyte membrane in rings and trophozoites ( Fig. 2B ). |
| GO:0020002 host cell plasma membrane | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: By IFA, CDPK1 was reported at the rim of the infected erythrocyte in rings and trophozoites, consistent with low-level export to the host erythrocyte membrane. Reason: A minor, non-core localization reported in one study and not seen with endogenous GFP tagging; kept as non-core rather than removed since the host-membrane pool is independently proposed in UniProt. Supporting Evidence: PMID:23204525 PfCDPK1 localized to the rim of the infected erythrocyte and appeared to be associated with the erythrocyte membrane in rings and trophozoites ( Fig. 2B ). |
| GO:0020004 symbiont-containing vacuolar space | IDA PMID:29716996 Calcium-dependent phosphorylation of Plasmodium falciparum s... | KEEP AS NON CORE | Summary: CDPK1 is present in the parasitophorous (symbiont-containing) vacuole and co-localizes with the PV protein SERA5 in trophozoites. Reason: A documented non-core localization (PV lumen/space) reached by the non-classical acylation-dependent export pathway; secondary to the plasma-membrane pool. Supporting Evidence: PMID:23204525 PfCDPK1 was found in the parasitophorous vacuole (PV) and co-localized with SERA5, a known PV protein ( 26 , 27 ), in trophozoites ( Fig. 2 B ). PMID:15491359 Using immunogold electron microscopy, the protein was detected in the parasitophorous vacuole and the tubovesicular system of the parasite. |
| GO:0020005 symbiont-containing vacuole membrane | EXP PMID:29716996 Calcium-dependent phosphorylation of Plasmodium falciparum s... | KEEP AS NON CORE | Summary: CDPK1 is lipid-anchored to the parasitophorous (symbiont-containing) vacuole membrane and the tubovesicular system derived from it. Reason: Immuno-EM and fractionation place a pool of CDPK1 at the PVM; this is a genuine non-core compartment secondary to the merozoite plasma membrane. Supporting Evidence: PMID:15491359 Using immunogold electron microscopy, the protein was detected in the parasitophorous vacuole and the tubovesicular system of the parasite. PMID:15491359 The supposed membrane attachment function of the basic cluster was experimentally verified and shown to participate together with N-myristoylation in membrane anchoring of the kinase. |
| GO:0020005 symbiont-containing vacuole membrane | IDA PMID:15491359 Export of Plasmodium falciparum calcium-dependent protein ki... | KEEP AS NON CORE | Summary: CDPK1 is lipid-anchored to the parasitophorous (symbiont-containing) vacuole membrane and the tubovesicular system derived from it. Reason: Immuno-EM and fractionation place a pool of CDPK1 at the PVM; this is a genuine non-core compartment secondary to the merozoite plasma membrane. Supporting Evidence: PMID:15491359 Using immunogold electron microscopy, the protein was detected in the parasitophorous vacuole and the tubovesicular system of the parasite. PMID:15491359 The supposed membrane attachment function of the basic cluster was experimentally verified and shown to participate together with N-myristoylation in membrane anchoring of the kinase. |
| GO:0020005 symbiont-containing vacuole membrane | IDA PMID:23204525 Characterization of Plasmodium falciparum calcium-dependent ... | KEEP AS NON CORE | Summary: CDPK1 is lipid-anchored to the parasitophorous (symbiont-containing) vacuole membrane and the tubovesicular system derived from it. Reason: Immuno-EM and fractionation place a pool of CDPK1 at the PVM; this is a genuine non-core compartment secondary to the merozoite plasma membrane. Supporting Evidence: PMID:15491359 Using immunogold electron microscopy, the protein was detected in the parasitophorous vacuole and the tubovesicular system of the parasite. PMID:15491359 The supposed membrane attachment function of the basic cluster was experimentally verified and shown to participate together with N-myristoylation in membrane anchoring of the kinase. |
| GO:0020005 symbiont-containing vacuole membrane | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: CDPK1 is lipid-anchored to the parasitophorous (symbiont-containing) vacuole membrane and the tubovesicular system derived from it. Reason: Immuno-EM and fractionation place a pool of CDPK1 at the PVM; this is a genuine non-core compartment secondary to the merozoite plasma membrane. Supporting Evidence: PMID:15491359 Using immunogold electron microscopy, the protein was detected in the parasitophorous vacuole and the tubovesicular system of the parasite. PMID:15491359 The supposed membrane attachment function of the basic cluster was experimentally verified and shown to participate together with N-myristoylation in membrane anchoring of the kinase. |
| GO:0031514 motile cilium | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: UniProt subcellular-location mapping (flagellum/cilium) from the By-similarity statement that CDPK1 localizes to the flagella of male gametes. Reason: The gene product does localize to the male-gamete flagellum by similarity, so the term is not wrong, but it is a sexual-stage, non-core location transferred electronically; kept as non-core. Supporting Evidence: file:PLAF7/CDPK1/CDPK1-uniprot.txt In male gametes, localizes to the residual body, cell membrane and in the flagella PMID:29311293 As in the asexual stages, CDPK1 shows peripheral localization in the gametocytes and gametes, suggesting the association of CDPK1 with the inner membrane complex due to the presence of N-terminal motifs that were critical for membrane association (1). |
| GO:0032991 protein-containing complex | IDA PMID:32817103 Phosphorylation-Dependent Assembly of a 14-3-3 Mediated Sign... | ACCEPT | Summary: CDPK1 is part of a high-molecular-weight 14-3-3I-scaffolded complex (CDPK1, PKAr, PKAc, 14-3-3I) formed in merozoites in response to low extracellular K+. Reason: Gel filtration and co-immunoprecipitation demonstrate CDPK1 in a multiprotein complex; part_of protein-containing complex is appropriate. Supporting Evidence: PMID:32817103 Pf14-3-3I binds phosphorylated PfPKAr and PfCDPK1 to mediate the assembly of a multiprotein complex in P. falciparum merozoites. |
| GO:0035556 intracellular signal transduction | IBA GO_REF:0000033 | ACCEPT | Summary: CDPK1 is a Ca2+ sensor/effector acting downstream of the PKG/cGMP and Ca2+ second-messenger cascades, relaying the signal to glideosome, IMC and PKA components. Reason: CDPK1 is phosphorylated by PKG and in turn phosphorylates PKAr to modulate PKA activity, placing it within an intracellular signalling relay; the IBA term is apt for a Ca2+-dependent kinase. Supporting Evidence: PMID:28680058 PfCDPK1 phosphorylates PfPKA regulatory subunit (PfPKA-R) and regulates PfPKA activity in the parasite, which may be relevant for the process of invasion. PMID:26149123 revealed the peripheral (membrane) localization of PfCDPK1 in the nascent merozoites contained within the late-stage schizonts or free merozoites, in agreement with previous studies3940 (Fig. 6b). |
| GO:0046777 protein autophosphorylation | IDA PMID:32484216 Molecular dynamics simulations and biochemical characterizat... | ACCEPT | Summary: CDPK1 autophosphorylates at several residues, including S64 and the activation-loop Thr-231, and autophosphorylation contributes to kinase activation. Reason: Mass-spectrometry mapping of CDPK1 autophosphorylation sites and functional mutagenesis support this. Supporting Evidence: PMID:22539638 Mass spectrometry revealed that PfCDPK1 was autophosphorylated at several sites; some of these were placed at strategic locations and therefore were found to be critical for kinase activation. PMID:26149123 We found that purified recombinant PfCDPK1 was highly active and able to auto-phosphorylate on many residues including S64. |
| GO:0071889 14-3-3 protein binding | IPI PMID:32484216 Molecular dynamics simulations and biochemical characterizat... | KEEP AS NON CORE | Summary: CDPK1 phosphorylated at S64 (a PKG site) binds 14-3-3I through a canonical mode I motif, in a phosphorylation-dependent manner. Reason: Well-supported interaction (ELISA, SPR, modelling) that scaffolds a signalling complex. It is a regulatory property rather than the kinase's core activity, so it is kept as non-core. Supporting Evidence: PMID:32484216 The 14-3-3I/CDPK1 interaction was validated in vitro with ELISA and SPR, which confirmed that the interaction is phosphorylation dependent, with binding affinity constant of 670 ± 3.6 nM. PMID:32484216 CDPK1 polypeptide sequence (61KLGpS64) behaves as canonical Mode I-type (RXXpS/pT) consensus 14-3-3 binding motif, mediating the interaction. |
| GO:0106310 protein serine kinase activity | EXP PMID:17123645 Raf kinase inhibitor protein affects activity of Plasmodium ... | ACCEPT | Summary: CDPK1 phosphorylates serine residues of protein substrates, for example MTIP S47, GAP45 serines and RhopH3 S804, and autophosphorylates on serines including S64. Reason: Direct experimental evidence of protein-serine phosphorylation by recombinant CDPK1 from several laboratories. Supporting Evidence: PMID:18768477 A primary phosphorylation of MTIP occurs at serine 47, whereas GAP45 is phosphorylated at two sites, one of which could also be detected in phosphopeptides purified from parasite lysates. PMID:22479457 We show that GAP45 is phosphorylated by calcium dependent protein kinase 1 (CDPK1), and identify the modified serine residues. PMID:33024030 First, we tested if PfCDPK1 can directly phosphorylate RhopH3 by performing in vitro kinase assays. PMID:26149123 We found that purified recombinant PfCDPK1 was highly active and able to auto-phosphorylate on many residues including S64. |
| GO:0106310 protein serine kinase activity | EXP PMID:18768477 The motor complex of Plasmodium falciparum: phosphorylation ... | ACCEPT | Summary: CDPK1 phosphorylates serine residues of protein substrates, for example MTIP S47, GAP45 serines and RhopH3 S804, and autophosphorylates on serines including S64. Reason: Direct experimental evidence of protein-serine phosphorylation by recombinant CDPK1 from several laboratories. Supporting Evidence: PMID:18768477 A primary phosphorylation of MTIP occurs at serine 47, whereas GAP45 is phosphorylated at two sites, one of which could also be detected in phosphopeptides purified from parasite lysates. PMID:22479457 We show that GAP45 is phosphorylated by calcium dependent protein kinase 1 (CDPK1), and identify the modified serine residues. PMID:33024030 First, we tested if PfCDPK1 can directly phosphorylate RhopH3 by performing in vitro kinase assays. PMID:26149123 We found that purified recombinant PfCDPK1 was highly active and able to auto-phosphorylate on many residues including S64. |
| GO:0106310 protein serine kinase activity | EXP PMID:19307175 Dissection of mechanisms involved in the regulation of Plasm... | ACCEPT | Summary: CDPK1 phosphorylates serine residues of protein substrates, for example MTIP S47, GAP45 serines and RhopH3 S804, and autophosphorylates on serines including S64. Reason: Direct experimental evidence of protein-serine phosphorylation by recombinant CDPK1 from several laboratories. Supporting Evidence: PMID:18768477 A primary phosphorylation of MTIP occurs at serine 47, whereas GAP45 is phosphorylated at two sites, one of which could also be detected in phosphopeptides purified from parasite lysates. PMID:22479457 We show that GAP45 is phosphorylated by calcium dependent protein kinase 1 (CDPK1), and identify the modified serine residues. PMID:33024030 First, we tested if PfCDPK1 can directly phosphorylate RhopH3 by performing in vitro kinase assays. PMID:26149123 We found that purified recombinant PfCDPK1 was highly active and able to auto-phosphorylate on many residues including S64. |
| GO:0106310 protein serine kinase activity | EXP PMID:22539638 Novel insights into the regulation of malarial calcium-depen... | ACCEPT | Summary: CDPK1 phosphorylates serine residues of protein substrates, for example MTIP S47, GAP45 serines and RhopH3 S804, and autophosphorylates on serines including S64. Reason: Direct experimental evidence of protein-serine phosphorylation by recombinant CDPK1 from several laboratories. Supporting Evidence: PMID:18768477 A primary phosphorylation of MTIP occurs at serine 47, whereas GAP45 is phosphorylated at two sites, one of which could also be detected in phosphopeptides purified from parasite lysates. PMID:22479457 We show that GAP45 is phosphorylated by calcium dependent protein kinase 1 (CDPK1), and identify the modified serine residues. PMID:33024030 First, we tested if PfCDPK1 can directly phosphorylate RhopH3 by performing in vitro kinase assays. PMID:26149123 We found that purified recombinant PfCDPK1 was highly active and able to auto-phosphorylate on many residues including S64. |
| GO:0106310 protein serine kinase activity | EXP PMID:23204525 Characterization of Plasmodium falciparum calcium-dependent ... | ACCEPT | Summary: CDPK1 phosphorylates serine residues of protein substrates, for example MTIP S47, GAP45 serines and RhopH3 S804, and autophosphorylates on serines including S64. Reason: Direct experimental evidence of protein-serine phosphorylation by recombinant CDPK1 from several laboratories. Supporting Evidence: PMID:18768477 A primary phosphorylation of MTIP occurs at serine 47, whereas GAP45 is phosphorylated at two sites, one of which could also be detected in phosphopeptides purified from parasite lysates. PMID:22479457 We show that GAP45 is phosphorylated by calcium dependent protein kinase 1 (CDPK1), and identify the modified serine residues. PMID:33024030 First, we tested if PfCDPK1 can directly phosphorylate RhopH3 by performing in vitro kinase assays. PMID:26149123 We found that purified recombinant PfCDPK1 was highly active and able to auto-phosphorylate on many residues including S64. |
| GO:0106310 protein serine kinase activity | EXP PMID:26149123 Phosphoproteomics reveals malaria parasite Protein Kinase G ... | ACCEPT | Summary: CDPK1 phosphorylates serine residues of protein substrates, for example MTIP S47, GAP45 serines and RhopH3 S804, and autophosphorylates on serines including S64. Reason: Direct experimental evidence of protein-serine phosphorylation by recombinant CDPK1 from several laboratories. Supporting Evidence: PMID:18768477 A primary phosphorylation of MTIP occurs at serine 47, whereas GAP45 is phosphorylated at two sites, one of which could also be detected in phosphopeptides purified from parasite lysates. PMID:22479457 We show that GAP45 is phosphorylated by calcium dependent protein kinase 1 (CDPK1), and identify the modified serine residues. PMID:33024030 First, we tested if PfCDPK1 can directly phosphorylate RhopH3 by performing in vitro kinase assays. PMID:26149123 We found that purified recombinant PfCDPK1 was highly active and able to auto-phosphorylate on many residues including S64. |
| GO:0106310 protein serine kinase activity | EXP PMID:28680058 PfCDPK1 mediated signaling in erythrocytic stages of Plasmod... | ACCEPT | Summary: CDPK1 phosphorylates serine residues of protein substrates, for example MTIP S47, GAP45 serines and RhopH3 S804, and autophosphorylates on serines including S64. Reason: Direct experimental evidence of protein-serine phosphorylation by recombinant CDPK1 from several laboratories. Supporting Evidence: PMID:18768477 A primary phosphorylation of MTIP occurs at serine 47, whereas GAP45 is phosphorylated at two sites, one of which could also be detected in phosphopeptides purified from parasite lysates. PMID:22479457 We show that GAP45 is phosphorylated by calcium dependent protein kinase 1 (CDPK1), and identify the modified serine residues. PMID:33024030 First, we tested if PfCDPK1 can directly phosphorylate RhopH3 by performing in vitro kinase assays. PMID:26149123 We found that purified recombinant PfCDPK1 was highly active and able to auto-phosphorylate on many residues including S64. |
| GO:0106310 protein serine kinase activity | EXP PMID:32484216 Molecular dynamics simulations and biochemical characterizat... | ACCEPT | Summary: CDPK1 phosphorylates serine residues of protein substrates, for example MTIP S47, GAP45 serines and RhopH3 S804, and autophosphorylates on serines including S64. Reason: Direct experimental evidence of protein-serine phosphorylation by recombinant CDPK1 from several laboratories. Supporting Evidence: PMID:18768477 A primary phosphorylation of MTIP occurs at serine 47, whereas GAP45 is phosphorylated at two sites, one of which could also be detected in phosphopeptides purified from parasite lysates. PMID:22479457 We show that GAP45 is phosphorylated by calcium dependent protein kinase 1 (CDPK1), and identify the modified serine residues. PMID:33024030 First, we tested if PfCDPK1 can directly phosphorylate RhopH3 by performing in vitro kinase assays. PMID:26149123 We found that purified recombinant PfCDPK1 was highly active and able to auto-phosphorylate on many residues including S64. |
| GO:0106310 protein serine kinase activity | EXP PMID:33024030 Phosphorylation of Rhoptry Protein RhopH3 Is Critical for Ho... | ACCEPT | Summary: CDPK1 phosphorylates serine residues of protein substrates, for example MTIP S47, GAP45 serines and RhopH3 S804, and autophosphorylates on serines including S64. Reason: Direct experimental evidence of protein-serine phosphorylation by recombinant CDPK1 from several laboratories. Supporting Evidence: PMID:18768477 A primary phosphorylation of MTIP occurs at serine 47, whereas GAP45 is phosphorylated at two sites, one of which could also be detected in phosphopeptides purified from parasite lysates. PMID:22479457 We show that GAP45 is phosphorylated by calcium dependent protein kinase 1 (CDPK1), and identify the modified serine residues. PMID:33024030 First, we tested if PfCDPK1 can directly phosphorylate RhopH3 by performing in vitro kinase assays. PMID:26149123 We found that purified recombinant PfCDPK1 was highly active and able to auto-phosphorylate on many residues including S64. |
| GO:0106310 protein serine kinase activity | IEA GO_REF:0000120 | ACCEPT | Summary: CDPK1 phosphorylates serine residues of protein substrates, for example MTIP S47, GAP45 serines and RhopH3 S804, and autophosphorylates on serines including S64. Reason: Direct experimental evidence of protein-serine phosphorylation by recombinant CDPK1 from several laboratories. Supporting Evidence: PMID:18768477 A primary phosphorylation of MTIP occurs at serine 47, whereas GAP45 is phosphorylated at two sites, one of which could also be detected in phosphopeptides purified from parasite lysates. PMID:22479457 We show that GAP45 is phosphorylated by calcium dependent protein kinase 1 (CDPK1), and identify the modified serine residues. PMID:33024030 First, we tested if PfCDPK1 can directly phosphorylate RhopH3 by performing in vitro kinase assays. PMID:26149123 We found that purified recombinant PfCDPK1 was highly active and able to auto-phosphorylate on many residues including S64. |
| GO:1903307 positive regulation of regulated secretory pathway | IDA PMID:23204525 Characterization of Plasmodium falciparum calcium-dependent ... | ACCEPT | Summary: CDPK1 activity is required for the Ca2+-triggered discharge of micronemes during erythrocyte invasion; inhibition by purfalcamine or the P3 peptide blocks microneme secretion. Reason: Best available GO term for a positive role in a regulated secretory (microneme discharge) process; pharmacological and peptide inhibition of CDPK1 block microneme secretion. Supporting Evidence: PMID:23204525 Purfalcamine, a previously identified specific inhibitor of PfCDPK1, also inhibits microneme discharge and erythrocyte invasion, confirming a role for PfCDPK1 in this process. PMID:23204525 The P3 peptide, which specifically inhibits the functional activity of PfCDPK1, blocks microneme discharge and erythrocyte invasion by P. falciparum merozoites. |
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Download this section (compressed HTML)Q: Is the apparent host-erythrocyte-membrane pool of CDPK1 a genuine export event, given that endogenous GFP-tagged CDPK1 is not detected in the RBC, or does it reflect PV/tubovesicular membrane continuous with the host cytosol?
Q: Which of the many in vitro CDPK1 substrates (MTIP, GAP45, PKAr, SERA5, RhopH3, IMC proteins) are the physiologically rate-limiting targets for microneme discharge versus for gametogenesis?
Experiment: Rapid conditional inactivation of CDPK1 (e.g. knocksideways or a chemical-genetic analogue-sensitive allele) in synchronized schizonts, combined with quantitative microneme-discharge and invasion assays, to separate CDPK1's catalytic role in invasion from indirect effects of slow depletion.
Hypothesis: Acute loss of CDPK1 catalytic activity blocks Ca2+-triggered microneme discharge and erythrocyte invasion without affecting earlier schizont development.
Experiment: Stage-specific phosphoproteomics of CDPK1 knockout versus wild-type gametocytes/gametes to identify the CDPK1-dependent phosphosites underlying the male and female gametogenesis defect.
Hypothesis: CDPK1 phosphorylates a distinct set of cytoskeletal/IMC substrates in gametocytes that are required for gamete egress and flagellum formation.
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