Protein: cGMP-dependent protein kinase (EC 2.7.11.12) (PfPKG) (Q8I719)
Organism: Plasmodium falciparum (isolate 3D7)
Function: Serine/threonine protein kinase which acts as a downstream effector of the second messenger cGMP. Controls the release of Ca(2+) from intracellular stores by regulating phosphoinositide biosynthesis. 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. 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. Regulates merozoite egress by promoting the release of exonemes and micronemes which contain proteins essential for egress. 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. Phosphorylates MyoA at 'Ser-19'. In the mosquito vector, required for the initiation of gametogenesis induced by xanthurenic acid, specifically the gametocyte differentiation from the crescent-shaped form to the spherical form. 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).
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}.
Interaction partners:
- cAMP-dependent protein kinase catalytic subunit
- Protein phosphatase PPM5, putative
- Potassium channel K1
- Glutamine synthetase, putative
- glutamate synthase
- NADPH:adrenodoxin oxidoreductase, mitochondrial
- Aquaporin, putative
- DNA-directed RNA polymerases I, II, and III subunit RPABC2, putative
- Ribosomal protein L16, mitochondrial, putative
- cAMP-dependent protein kinase regulatory subunit
Sequence:
MEEDDNLKKGNERNKKKAIFSNDDFTGEDSLMEDHLELREKLSEDIDMIKTSLKNNLVCSTLNDNEILTLSNYMQFFVFKSGNLVIKQGEKGSYFFIINSGKFDVYVNDKKVKTMGKGSSFGEAALIHNTQRSATIIAETDGTLWGVQRSTFRATLKQLSNRNFNENRTFIDSVSVFDMLTEAQKNMITNACVIQNFKSGETIVKQGDYGDVLYILKEGKATVYINDEEIRVLEKGSYFGERALLYDEPRSATIIAKEPTACASICRKLLNIVLGNLQVVLFRNIMTEALQQSEIFKQFSGDQLNDLADTAIVRDYPANYNILHKDKVKSVKYIIVLEGKVELFLDDTSIGILSRGMSFGDQYVLNQKQPFKHTIKSLEVCKIALITETCLADCLGNNNIDASIDYNNKKSIIKKMYIFRYLTDKQCNLLIEAFRTTRYEEGDYIIQEGEVGSRFYIIKNGEVEIVKNKKRLRTLGKNDYFGERALLYDEPRTASVISKVNNVECWFVDKSVFLQIIQGPMLAHLEERIKMQDTKVEMDELETERIIGRGTFGTVKLVHHKPTKIRYALKCVSKRSIINLNQQNNIKLEREITAENDHPFIIRLVRTFKDSKYFYFLTELVTGGELYDAIRKLGLLSKSQAQFYLGSIILAIEYLHERNIVYRDLKPENILLDKQGYVKLIDFGCAKKVQGRAYTLVGTPHYMAPEVILGKGYGCTVDIWALGICLYEFICGPLPFGNDEEDQLEIFRDILTGQLTFPDYVTDTDSINLMKRLLCRLPQGRIGCSINGFKDIKDHPFFSNFNWDKLAGRLLDPPLVSKSETYAEDIDIKQIEEEDAEDDEEPLNDEDNWDIDF