UniProt functional annotation for Q8I719



	UniProt functional annotation for Q8I719

UniProt code: Q8I719.

Organism: Plasmodium falciparum (isolate 3D7).

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

Function: Serine/threonine protein kinase which acts as a downstream effector of the second messenger cGMP (PubMed:12068803, PubMed:12817987, PubMed:26149123). Controls the release of Ca(2+) from intracellular stores by regulating phosphoinositide biosynthesis (PubMed:24594931). Ca(2+) signals are essential for merozoite and sporozoite invasion and egress from host hepatocytes and erythrocytes, and, in the mosquito vector, for gametocyte activation, and ookinete and sporozoite motility (PubMed:24594931). During the host liver stage, regulates the initial invasion of host hepatocytes by sporozoites by regulating sporozoite motility and microneme exocytosis (By similarity). Following parasite development in the hepatocytes, required for the release of merosomes, a vesicle containing the mature merozoites (By similarity). During the asexual blood stage, required for the progression from schizont to the ring stage following merozoite invasion of host erythrocytes and for merozoite egress (PubMed:19915077, PubMed:26149123, PubMed:25646845). Regulates merozoite egress by promoting the release of exonemes and micronemes which contain proteins essential for egress (PubMed:23675297). Phosphorylates CDPK1 predominantly at the late schizont stage; phosphorylation at 'Ser-64' regulates CDPK1 protein-protein interaction and phosphorylation at 'Thr-231' may regulate CDPK1 kinase activity (PubMed:26149123). Phosphorylates MyoA at 'Ser-19' (PubMed:26149123). In the mosquito vector, required for the initiation of gametogenesis induced by xanthurenic acid, specifically the gametocyte differentiation from the crecsent-shaped form to the spherical form (PubMed:18532880). Required for the gliding motility of ookinetes to reach and penetrate the midgut epithelium by promoting Ca(2+)-mediated activation of CDPK1 and CDPK4 (By similarity). Also required for microneme secretion in ookinete by promoting Ca(2+)-mediated activation of CDPK3 (By similarity). {ECO:0000250|UniProtKB:A0A509AKL0, ECO:0000269|PubMed:12068803, ECO:0000269|PubMed:12817987, ECO:0000269|PubMed:18532880, ECO:0000269|PubMed:19915077, ECO:0000269|PubMed:23675297, ECO:0000269|PubMed:24594931, ECO:0000269|PubMed:25646845, ECO:0000269|PubMed:26149123}.

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=2.7.11.12; Evidence={ECO:0000269|PubMed:12068803, ECO:0000269|PubMed:12817987, ECO:0000269|PubMed:25646845, ECO:0000269|PubMed:26149123, ECO:0000269|PubMed:29251493, ECO:0000269|PubMed:30315162, ECO:0000269|PubMed:31239348};

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=2.7.11.12; Evidence={ECO:0000269|PubMed:12068803, ECO:0000269|PubMed:12817987, ECO:0000269|PubMed:25646845, ECO:0000269|PubMed:26149123, ECO:0000269|PubMed:29251493, ECO:0000269|PubMed:30315162, ECO:0000269|PubMed:31239348};

Cofactor: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000269|PubMed:25646845};

Activity regulation: Activated by cGMP (PubMed:12068803, PubMed:12817987, PubMed:26149123, PubMed:29251493, PubMed:25646845, PubMed:31239348). Not activated by cAMP (PubMed:12068803, PubMed:12817987). cGMP binding allosterically triggers a conformational change at the alpha C-helix of cGMP-binding domain 4, which bridges the regulatory and catalytic domains, causing the capping triad, composed of Arg-484, Gln-532 and Asp-533, to form and stabilize the active conformation (PubMed:29251493, PubMed:25646845). The cGMP-binding domains acts cooperatively to activate PKG (PubMed:29251493, PubMed:12817987). {ECO:0000269|PubMed:12068803, ECO:0000269|PubMed:12817987, ECO:0000269|PubMed:25646845, ECO:0000269|PubMed:26149123, ECO:0000269|PubMed:29251493, ECO:0000269|PubMed:31239348}.

Biophysicochemical properties: pH dependence: Optimum pH is 7.0. {ECO:0000269|PubMed:12068803};

Subunit: Monomer. {ECO:0000269|PubMed:26149123, ECO:0000269|PubMed:31239348}.

Subcellular location: Cytoplasm {ECO:0000269|PubMed:19915077, ECO:0000269|PubMed:23139764, ECO:0000269|PubMed:31239348}. Endoplasmic reticulum membrane {ECO:0000269|PubMed:23139764}; Peripheral membrane protein {ECO:0000269|PubMed:23139764}; Cytoplasmic side {ECO:0000269|PubMed:23139764}. Note=Predominantly localizes to the cytoplasm during schizogony. {ECO:0000269|PubMed:23139764}.

Developmental stage: Expressed during the parasite blood stage, expression is low at the ring stage and in early trophozoites, then increases during the parasite maturation to peak at the late schizont stage (at protein level) (PubMed:31239348, PubMed:19915077, PubMed:23139764, PubMed:12068803). Expression is low in gametocytes (at protein level) (PubMed:23139764). {ECO:0000269|PubMed:12068803, ECO:0000269|PubMed:19915077, ECO:0000269|PubMed:23139764, ECO:0000269|PubMed:31239348}.

Domain: The cGMP-binding domains 1, 2 and 4 bind preferentially cGMP (PubMed:25646845). The cGMP-binding domain 4 binds cGMP with the highest affinity and is highly selective for cGMP (PubMed:29251493, PubMed:25646845, PubMed:31239348). The cGMP-binding domain 3 does not bind cGMP but is required for cGMP-dependent catalytic activity (PubMed:12817987). The cGMP-binding domains 1, 2 and 4 can bind cAMP but with less affinity (PubMed:25646845). {ECO:0000269|PubMed:12817987, ECO:0000269|PubMed:25646845, ECO:0000269|PubMed:29251493, ECO:0000269|PubMed:31239348}.

Domain: The autoinhibitory segment (AIS) interacts with the active site and inhibits catalytic activity. {ECO:0000269|PubMed:31239348}.

Ptm: Autophosphorylated. {ECO:0000269|PubMed:12068803, ECO:0000269|PubMed:12817987}.

Similarity: Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. cGMP subfamily. {ECO:0000305}.

Annotations taken from UniProtKB at the EBI.


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



Function:		Serine/threonine protein kinase which acts as a downstream effector of the second messenger cGMP (PubMed:12068803, PubMed:12817987, PubMed:26149123). Controls the release of Ca(2+) from intracellular stores by regulating phosphoinositide biosynthesis (PubMed:24594931). Ca(2+) signals are essential for merozoite and sporozoite invasion and egress from host hepatocytes and erythrocytes, and, in the mosquito vector, for gametocyte activation, and ookinete and sporozoite motility (PubMed:24594931). During the host liver stage, regulates the initial invasion of host hepatocytes by sporozoites by regulating sporozoite motility and microneme exocytosis (By similarity). Following parasite development in the hepatocytes, required for the release of merosomes, a vesicle containing the mature merozoites (By similarity). During the asexual blood stage, required for the progression from schizont to the ring stage following merozoite invasion of host erythrocytes and for merozoite egress (PubMed:19915077, PubMed:26149123, PubMed:25646845). Regulates merozoite egress by promoting the release of exonemes and micronemes which contain proteins essential for egress (PubMed:23675297). Phosphorylates CDPK1 predominantly at the late schizont stage; phosphorylation at 'Ser-64' regulates CDPK1 protein-protein interaction and phosphorylation at 'Thr-231' may regulate CDPK1 kinase activity (PubMed:26149123). Phosphorylates MyoA at 'Ser-19' (PubMed:26149123). In the mosquito vector, required for the initiation of gametogenesis induced by xanthurenic acid, specifically the gametocyte differentiation from the crecsent-shaped form to the spherical form (PubMed:18532880). Required for the gliding motility of ookinetes to reach and penetrate the midgut epithelium by promoting Ca(2+)-mediated activation of CDPK1 and CDPK4 (By similarity). Also required for microneme secretion in ookinete by promoting Ca(2+)-mediated activation of CDPK3 (By similarity). {ECO:0000250\|UniProtKB:A0A509AKL0, ECO:0000269\|PubMed:12068803, ECO:0000269\|PubMed:12817987, ECO:0000269\|PubMed:18532880, ECO:0000269\|PubMed:19915077, ECO:0000269\|PubMed:23675297, ECO:0000269\|PubMed:24594931, ECO:0000269\|PubMed:25646845, ECO:0000269\|PubMed:26149123}.


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=2.7.11.12; Evidence={ECO:0000269\|PubMed:12068803, ECO:0000269\|PubMed:12817987, ECO:0000269\|PubMed:25646845, ECO:0000269\|PubMed:26149123, ECO:0000269\|PubMed:29251493, ECO:0000269\|PubMed:30315162, ECO:0000269\|PubMed:31239348};
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=2.7.11.12; Evidence={ECO:0000269\|PubMed:12068803, ECO:0000269\|PubMed:12817987, ECO:0000269\|PubMed:25646845, ECO:0000269\|PubMed:26149123, ECO:0000269\|PubMed:29251493, ECO:0000269\|PubMed:30315162, ECO:0000269\|PubMed:31239348};
Cofactor:		Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000269\|PubMed:25646845};
Activity regulation:		Activated by cGMP (PubMed:12068803, PubMed:12817987, PubMed:26149123, PubMed:29251493, PubMed:25646845, PubMed:31239348). Not activated by cAMP (PubMed:12068803, PubMed:12817987). cGMP binding allosterically triggers a conformational change at the alpha C-helix of cGMP-binding domain 4, which bridges the regulatory and catalytic domains, causing the capping triad, composed of Arg-484, Gln-532 and Asp-533, to form and stabilize the active conformation (PubMed:29251493, PubMed:25646845). The cGMP-binding domains acts cooperatively to activate PKG (PubMed:29251493, PubMed:12817987). {ECO:0000269\|PubMed:12068803, ECO:0000269\|PubMed:12817987, ECO:0000269\|PubMed:25646845, ECO:0000269\|PubMed:26149123, ECO:0000269\|PubMed:29251493, ECO:0000269\|PubMed:31239348}.
Biophysicochemical properties:		pH dependence: Optimum pH is 7.0. {ECO:0000269\|PubMed:12068803};
Subunit:		Monomer. {ECO:0000269\|PubMed:26149123, ECO:0000269\|PubMed:31239348}.
Subcellular location:		Cytoplasm {ECO:0000269\|PubMed:19915077, ECO:0000269\|PubMed:23139764, ECO:0000269\|PubMed:31239348}. Endoplasmic reticulum membrane {ECO:0000269\|PubMed:23139764}; Peripheral membrane protein {ECO:0000269\|PubMed:23139764}; Cytoplasmic side {ECO:0000269\|PubMed:23139764}. Note=Predominantly localizes to the cytoplasm during schizogony. {ECO:0000269\|PubMed:23139764}.
Developmental stage:		Expressed during the parasite blood stage, expression is low at the ring stage and in early trophozoites, then increases during the parasite maturation to peak at the late schizont stage (at protein level) (PubMed:31239348, PubMed:19915077, PubMed:23139764, PubMed:12068803). Expression is low in gametocytes (at protein level) (PubMed:23139764). {ECO:0000269\|PubMed:12068803, ECO:0000269\|PubMed:19915077, ECO:0000269\|PubMed:23139764, ECO:0000269\|PubMed:31239348}.
Domain:		The cGMP-binding domains 1, 2 and 4 bind preferentially cGMP (PubMed:25646845). The cGMP-binding domain 4 binds cGMP with the highest affinity and is highly selective for cGMP (PubMed:29251493, PubMed:25646845, PubMed:31239348). The cGMP-binding domain 3 does not bind cGMP but is required for cGMP-dependent catalytic activity (PubMed:12817987). The cGMP-binding domains 1, 2 and 4 can bind cAMP but with less affinity (PubMed:25646845). {ECO:0000269\|PubMed:12817987, ECO:0000269\|PubMed:25646845, ECO:0000269\|PubMed:29251493, ECO:0000269\|PubMed:31239348}.
Domain:		The autoinhibitory segment (AIS) interacts with the active site and inhibits catalytic activity. {ECO:0000269\|PubMed:31239348}.
Ptm:		Autophosphorylated. {ECO:0000269\|PubMed:12068803, ECO:0000269\|PubMed:12817987}.
Similarity:		Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. cGMP subfamily. {ECO:0000305}.