UniProt functional annotation for Q8IBS5



	UniProt functional annotation for Q8IBS5

UniProt code: Q8IBS5.

Organism: Plasmodium falciparum (isolate 3D7).

Taxonomy: Eukaryota; Sar; Alveolata; Apicomplexa; Aconoidasida; Haemosporida; Plasmodiidae; Plasmodium; Plasmodium (Laverania).

Function: Calcium-dependent protein kinase which acts as a sensor and effector of intracellular Ca(2+) levels probably in part downstream of cGMP-activated PKG kinase (PubMed:19307175, PubMed:19666141). Plays a central role in the host erythrocytes and hepatocytes infection cycles, sexual reproduction and mosquito transmission of the parasite. During the liver stage, involved in sporozoite motility and thus in sporozoite invasion of host hepatocytes, probably together with CDPK1 and CDPK5. Involved in merosome egress from host hepatocytes, probably together with CDPK5. During the asexual blood stage, involved in merozoite invasion of host erythrocytes and motility by stabilizing the inner membrane complex, a structure below the plasma membrane which acts as an anchor for the glidosome, an acto-myosin motor. Required for cell cycle progression in the male gametocyte. During male gametogenesis in the mosquito gut, required to initiate the first round of DNA replication, probably by facilitating the assembly of the pre- replicative MCM complex, to assemble the first mitotic spindle and, at the end of gametogenesis, to initiate axoneme motility, cytokinesis and subsequent exflagellation. For each of these steps, may phosphorylate SOC1, SOC2 and SOC3, respectively. Together with CDPK1, regulates ookinete gliding in the mosquito host midgut (By similarity). {ECO:0000250|UniProtKB:P62345, ECO:0000269|PubMed:19307175, ECO:0000269|PubMed:19666141}.

Catalytic activity: Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl- [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA- COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616, ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1; Evidence={ECO:0000269|PubMed:19307175, ECO:0000269|PubMed:19666141};

Catalytic activity: Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L- threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060, Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013, ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216; EC=2.7.11.1; Evidence={ECO:0000269|PubMed:19307175, ECO:0000269|PubMed:19666141};

Cofactor: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000269|PubMed:19666141};

Activity regulation: Activated by calcium (PubMed:19307175, PubMed:19666141). Upon calcium binding to the EF-hand domains, the C- terminus of the junction domain (J domain) undergoes a conformational change which results in the dissociation of the pseudo-substrate inhibitory motif from the catalytic domain (PubMed:19307175). This, in turn, may facilitate the autophosphorylation of the activation loop at Thr-234, which leads to the kinase activation (PubMed:19307175). Intracellular calcium increase is triggered by xanthurenic acid (XA), a small mosquito molecule that induces the differentiation of specialized transmission stages, the gametocytes, into male and female gametes (Probable). Activated by a decrease in temperature (20 degrees Celsius) and an increase in pH (7.6) occurring when the parasite is ingested by in the mosquito (PubMed:19666141). {ECO:0000269|PubMed:19307175, ECO:0000269|PubMed:19666141, ECO:0000305|PubMed:19666141}.

Biophysicochemical properties: pH dependence: Optimum pH is 7.5-8 (at 20 degrees Celsius). {ECO:0000269|PubMed:19666141}; Temperature dependence: Optimum temperature is 20-30 degrees Celsius (at pH 7.6). {ECO:0000269|PubMed:19666141};

Subunit: May interact with the pre-replication MCM complex prior male gametogenesis activation. {ECO:0000250|UniProtKB:P62345}.

Subcellular location: Cytoplasm {ECO:0000250|UniProtKB:P62345}. Cell membrane {ECO:0000269|PubMed:19307175}; Lipid-anchor {ECO:0000303|PubMed:19307175}.

Developmental stage: Expressed in gametocytes (at protein level). {ECO:0000269|PubMed:12368870, ECO:0000269|PubMed:19307175, ECO:0000269|PubMed:19666141}.

Induction: Induced by xanthurenic acid (XA) and human serum. {ECO:0000269|PubMed:19666141}.

Domain: The junction domain (J domain) is composed of 2 motifs that maintain the kinase inactive (PubMed:19307175). The N-terminal autoinhibitory motif acts as a pseudosubstrate inhibiting the catalytic domain while the C-terminal motif binds the EF-hand domains (PubMed:19307175). {ECO:0000269|PubMed:19307175}.

Ptm: Myristoylated; myristoylation may target it to different subcellular compartments. During male gametogenesis, myristoylation is required to initiate DNA replication but not for mitotic spindle assembly or axoneme activation. {ECO:0000250|UniProtKB:P62345}.

Ptm: Not palmitoylated. {ECO:0000250|UniProtKB:P62345}.

Ptm: May be autophosphorylated on Thr-234 in vitro. {ECO:0000269|PubMed:19307175, ECO:0000269|PubMed:19666141}.

Disruption phenotype: Replication in host erythrocytes is normal. {ECO:0000269|PubMed:20466936}.

Similarity: Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. CDPK subfamily. {ECO:0000255|PROSITE-ProRule:PRU00159}.

Annotations taken from UniProtKB at the EBI.


Organism:		Plasmodium falciparum (isolate 3D7).
Taxonomy:		Eukaryota; Sar; Alveolata; Apicomplexa; Aconoidasida; Haemosporida; Plasmodiidae; Plasmodium; Plasmodium (Laverania).



Function:		Calcium-dependent protein kinase which acts as a sensor and effector of intracellular Ca(2+) levels probably in part downstream of cGMP-activated PKG kinase (PubMed:19307175, PubMed:19666141). Plays a central role in the host erythrocytes and hepatocytes infection cycles, sexual reproduction and mosquito transmission of the parasite. During the liver stage, involved in sporozoite motility and thus in sporozoite invasion of host hepatocytes, probably together with CDPK1 and CDPK5. Involved in merosome egress from host hepatocytes, probably together with CDPK5. During the asexual blood stage, involved in merozoite invasion of host erythrocytes and motility by stabilizing the inner membrane complex, a structure below the plasma membrane which acts as an anchor for the glidosome, an acto-myosin motor. Required for cell cycle progression in the male gametocyte. During male gametogenesis in the mosquito gut, required to initiate the first round of DNA replication, probably by facilitating the assembly of the pre- replicative MCM complex, to assemble the first mitotic spindle and, at the end of gametogenesis, to initiate axoneme motility, cytokinesis and subsequent exflagellation. For each of these steps, may phosphorylate SOC1, SOC2 and SOC3, respectively. Together with CDPK1, regulates ookinete gliding in the mosquito host midgut (By similarity). {ECO:0000250\|UniProtKB:P62345, ECO:0000269\|PubMed:19307175, ECO:0000269\|PubMed:19666141}.


Catalytic activity:		Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl- [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA- COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616, ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1; Evidence={ECO:0000269\|PubMed:19307175, ECO:0000269\|PubMed:19666141};
Catalytic activity:		Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L- threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060, Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013, ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216; EC=2.7.11.1; Evidence={ECO:0000269\|PubMed:19307175, ECO:0000269\|PubMed:19666141};
Cofactor:		Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000269\|PubMed:19666141};
Activity regulation:		Activated by calcium (PubMed:19307175, PubMed:19666141). Upon calcium binding to the EF-hand domains, the C- terminus of the junction domain (J domain) undergoes a conformational change which results in the dissociation of the pseudo-substrate inhibitory motif from the catalytic domain (PubMed:19307175). This, in turn, may facilitate the autophosphorylation of the activation loop at Thr-234, which leads to the kinase activation (PubMed:19307175). Intracellular calcium increase is triggered by xanthurenic acid (XA), a small mosquito molecule that induces the differentiation of specialized transmission stages, the gametocytes, into male and female gametes (Probable). Activated by a decrease in temperature (20 degrees Celsius) and an increase in pH (7.6) occurring when the parasite is ingested by in the mosquito (PubMed:19666141). {ECO:0000269\|PubMed:19307175, ECO:0000269\|PubMed:19666141, ECO:0000305\|PubMed:19666141}.
Biophysicochemical properties:		pH dependence: Optimum pH is 7.5-8 (at 20 degrees Celsius). {ECO:0000269\|PubMed:19666141}; Temperature dependence: Optimum temperature is 20-30 degrees Celsius (at pH 7.6). {ECO:0000269\|PubMed:19666141};
Subunit:		May interact with the pre-replication MCM complex prior male gametogenesis activation. {ECO:0000250\|UniProtKB:P62345}.
Subcellular location:		Cytoplasm {ECO:0000250\|UniProtKB:P62345}. Cell membrane {ECO:0000269\|PubMed:19307175}; Lipid-anchor {ECO:0000303\|PubMed:19307175}.
Developmental stage:		Expressed in gametocytes (at protein level). {ECO:0000269\|PubMed:12368870, ECO:0000269\|PubMed:19307175, ECO:0000269\|PubMed:19666141}.
Induction:		Induced by xanthurenic acid (XA) and human serum. {ECO:0000269\|PubMed:19666141}.
Domain:		The junction domain (J domain) is composed of 2 motifs that maintain the kinase inactive (PubMed:19307175). The N-terminal autoinhibitory motif acts as a pseudosubstrate inhibiting the catalytic domain while the C-terminal motif binds the EF-hand domains (PubMed:19307175). {ECO:0000269\|PubMed:19307175}.
Ptm:		Myristoylated; myristoylation may target it to different subcellular compartments. During male gametogenesis, myristoylation is required to initiate DNA replication but not for mitotic spindle assembly or axoneme activation. {ECO:0000250\|UniProtKB:P62345}.
Ptm:		Not palmitoylated. {ECO:0000250\|UniProtKB:P62345}.
Ptm:		May be autophosphorylated on Thr-234 in vitro. {ECO:0000269\|PubMed:19307175, ECO:0000269\|PubMed:19666141}.
Disruption phenotype:		Replication in host erythrocytes is normal. {ECO:0000269\|PubMed:20466936}.
Similarity:		Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. CDPK subfamily. {ECO:0000255\|PROSITE-ProRule:PRU00159}.