UniProtKB - Q8I719 (KGP_PLAF7)
cGMP-dependent protein kinase
PKG
Functioni
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 Ca2+ from intracellular stores by regulating phosphoinositide biosynthesis (PubMed:24594931).
Ca2+ 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 crescent-shaped form to the spherical form (PubMed:18532880).
Required for the gliding motility of ookinetes to reach and penetrate the midgut epithelium by promoting Ca2+-mediated activation of CDPK1 and CDPK4 (By similarity).
Also required for microneme secretion in ookinete by promoting Ca2+-mediated activation of CDPK3 (By similarity).
By similarity8 PublicationsCatalytic activityi
Cofactori
Activity regulationi
pH dependencei
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 113 | 3',5'-cGMP 1; allosteric activatorCombined sources1 Publication | 1 | |
Binding sitei | 122 | 3',5'-cGMP 1; via amide nitrogen; allosteric activatorCombined sources1 Publication | 1 | |
Binding sitei | 123 | 3',5'-cGMP 1; allosteric activatorCombined sources1 Publication | 1 | |
Binding sitei | 125 | 3',5'-cGMP 1; via amide nitrogen; allosteric activatorCombined sources1 Publication | 1 | |
Binding sitei | 132 | 3',5'-cGMP 1; allosteric activatorCombined sources1 Publication | 1 | |
Binding sitei | 133 | 3',5'-cGMP 1; allosteric activatorCombined sources1 Publication | 1 | |
Binding sitei | 473 | 3',5'-cGMP 2; allosteric activatorCombined sources1 Publication | 1 | |
Binding sitei | 482 | 3',5'-cGMP 2; via amide nitrogen; allosteric activatorCombined sources1 Publication | 1 | |
Binding sitei | 483 | 3',5'-cGMP 2; allosteric activatorCombined sources1 Publication | 1 | |
Sitei | 484 | Part of a catalytic triad required for cGMP binding and cGMP-dependent kinase activity1 Publication | 1 | |
Binding sitei | 485 | 3',5'-cGMP 2; via amide nitrogen; allosteric activatorCombined sources1 Publication | 1 | |
Binding sitei | 492 | 3',5'-cGMP 2; allosteric activatorCombined sources1 Publication | 1 | |
Binding sitei | 493 | 3',5'-cGMP 2; allosteric activatorCombined sources1 Publication | 1 | |
Sitei | 532 | Part of a catalytic triad required for cGMP binding and cGMP-dependent kinase activity1 Publication | 1 | |
Sitei | 533 | Part of a catalytic triad required for cGMP binding and cGMP-dependent kinase activity1 Publication | 1 | |
Binding sitei | 570 | ATPPROSITE-ProRule annotation | 1 | |
Active sitei | 664 | Proton acceptorPROSITE-ProRule annotation | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Nucleotide bindingi | 547 – 555 | ATPPROSITE-ProRule annotation | 9 |
GO - Molecular functioni
- ATP binding Source: UniProtKB-KW
- cAMP-dependent protein kinase activity Source: GO_Central
- cGMP binding Source: UniProtKB-KW
- cGMP-dependent protein kinase activity Source: UniProtKB
- metal ion binding Source: UniProtKB-KW
- protein serine/threonine/tyrosine kinase activity Source: RHEA
- protein serine kinase activity Source: RHEA
GO - Biological processi
- gamete generation Source: UniProtKB
- peptidyl-serine phosphorylation Source: GO_Central
- protein phosphorylation Source: UniProtKB
- signal transduction Source: GO_Central
Keywordsi
Molecular function | Kinase, Serine/threonine-protein kinase, Transferase |
Ligand | ATP-binding, cGMP, cGMP-binding, Magnesium, Metal-binding, Nucleotide-binding |
Names & Taxonomyi
Protein namesi | Recommended name: cGMP-dependent protein kinase1 Publication (EC:2.7.11.127 Publications)Alternative name(s): PfPKG1 Publication |
Gene namesi | Name:PKG1 Publication ORF Names:PF3D7_1436600Imported |
Organismi | Plasmodium falciparum (isolate 3D7)Imported |
Taxonomic identifieri | 36329 [NCBI] |
Taxonomic lineagei | Eukaryota › Sar › Alveolata › Apicomplexa › Aconoidasida › Haemosporida › Plasmodiidae › Plasmodium › Plasmodium (Laverania) › |
Proteomesi |
|
Organism-specific databases
VEuPathDBi | PlasmoDB:PF3D7_1436600 |
Subcellular locationi
Endoplasmic reticulum
- Endoplasmic reticulum membrane 1 Publication; Peripheral membrane protein 1 Publication; Cytoplasmic side 1 Publication
Cytoplasm and Cytosol
- Cytoplasm 3 Publications
Note: Predominantly localizes to the cytoplasm during schizogony.1 Publication
Endoplasmic reticulum
- endoplasmic reticulum Source: GeneDB
- endoplasmic reticulum membrane Source: UniProtKB-SubCell
Other locations
- cAMP-dependent protein kinase complex Source: GO_Central
- cytoplasm Source: GeneDB
- extrinsic component of membrane Source: GeneDB
Keywords - Cellular componenti
Cytoplasm, Endoplasmic reticulum, MembranePathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 2 – 518 | Missing : Loss of catalytic activity and irresponsive to cGMP, with peptides as substrates. 1 PublicationAdd BLAST | 517 | |
Mutagenesisi | 2 – 434 | Missing : Loss of catalytic activity. 1 PublicationAdd BLAST | 433 | |
Mutagenesisi | 2 – 400 | Missing : Low basal catalytic activity. Normal increase in catalytic activity in presence of cGMP. 1 PublicationAdd BLAST | 399 | |
Mutagenesisi | 2 – 274 | Missing : Low basal catalytic activity. Normal increase in catalytic activity in presence of cGMP. 1 PublicationAdd BLAST | 273 | |
Mutagenesisi | 2 – 157 | Missing : Low basal catalytic activity. Normal increase in catalytic activity in presence of cGMP. 1 PublicationAdd BLAST | 156 | |
Mutagenesisi | 2 – 114 | Missing : Has low catalytic activity in absence of cGMP. Normal increase in catalytic activity in presence of cGMP. 1 PublicationAdd BLAST | 113 | |
Mutagenesisi | 2 – 31 | Missing : Has low catalytic activity in absence of cGMP. cGMP binding is still required for full activation. 1 PublicationAdd BLAST | 30 | |
Mutagenesisi | 2 – 29 | Missing : Has low catalytic activity in absence of cGMP. 1 PublicationAdd BLAST | 28 | |
Mutagenesisi | 133 | S → A: No effect on cGMP-mediated catalytic activity. Slight reduction in cGMP-mediated catalytic activity; when associated with A-251. Severe loss of cGMP-mediated catalytic activity; when associated with A-493 or A-251 and A-493. 1 Publication | 1 | |
Mutagenesisi | 251 | S → A: 12% reduction in cGMP-mediated catalytic activity. Slight reduction in cGMP-mediated catalytic activity; when associated with A-133. Severe loss of cGMP-mediated catalytic activity; when associated with A-493 or A-133 and A-493. 1 Publication | 1 | |
Mutagenesisi | 360 | G → E: 55% loss in cGMP-mediated catalytic activity. 1 Publication | 1 | |
Mutagenesisi | 484 | R → A: Reduces affinity for cGMP and severe loss of kinase activity. 1 Publication | 1 | |
Mutagenesisi | 493 | T → A: 42% reduction in cGMP-mediated catalytic activity. Severe loss of cGMP-mediated catalytic activity; when associated with A-133, A-251 or A-133 and A-251. 1 Publication | 1 | |
Mutagenesisi | 532 | Q → A: Reduces affinity for cGMP and severe loss of kinase activity. 1 Publication | 1 | |
Mutagenesisi | 533 | D → A: Reduces affinity for cGMP and severe loss of kinase activity. 1 Publication | 1 | |
Mutagenesisi | 618 | T → Q: 4.5-fold reduction in affinity for ATP. No defect in schizogony during host erythrocyte invasion. However, Ca(2+) increase in response to cGMP is reduced in schizonts. Does not affect merozoite egress from host erythrocytes. Resistant to trisubstituted pyrrole compound 1 (C1) and imidazopyridine-based compound 2 (C2) inhibitors. 4 Publications | 1 |
Chemistry databases
GuidetoPHARMACOLOGYi | 3013 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000451908 | 1 – 853 | cGMP-dependent protein kinaseAdd BLAST | 853 |
Post-translational modificationi
Keywords - PTMi
PhosphoproteinProteomic databases
PRIDEi | Q8I719 |
Expressioni
Developmental stagei
Interactioni
Subunit structurei
Monomer.
2 PublicationsProtein-protein interaction databases
STRINGi | 5833.PF14_0346 |
Structurei
Secondary structure
3D structure databases
AlphaFoldDBi | Q8I719 |
SMRi | Q8I719 |
ModBasei | Search... |
PDBe-KBi | Search... |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 541 – 798 | Protein kinasePROSITE-ProRule annotationAdd BLAST | 258 | |
Domaini | 799 – 853 | AGC-kinase C-terminalPROSITE-ProRule annotationAdd BLAST | 55 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 1 – 29 | Autoinhibitory segment1 PublicationAdd BLAST | 29 | |
Regioni | 58 – 173 | cNMP-binding domain 1PROSITE-ProRule annotationAdd BLAST | 116 | |
Regioni | 176 – 275 | cNMP-binding domain 2PROSITE-ProRule annotationAdd BLAST | 100 | |
Regioni | 295 – 398 | cNMP-binding domain 3PROSITE-ProRule annotationAdd BLAST | 104 | |
Regioni | 418 – 517 | cNMP-binding domain 4PROSITE-ProRule annotationAdd BLAST | 100 | |
Regioni | 827 – 853 | DisorderedSequence analysisAdd BLAST | 27 |
Domaini
Sequence similaritiesi
Phylogenomic databases
HOGENOMi | CLU_000288_73_2_1 |
InParanoidi | Q8I719 |
OMAi | SKNPDGH |
PhylomeDBi | Q8I719 |
Family and domain databases
CDDi | cd00038, CAP_ED, 4 hits cd05572, STKc_cGK, 1 hit |
Gene3Di | 2.60.120.10, 4 hits |
InterProi | View protein in InterPro IPR000961, AGC-kinase_C IPR002374, cGMP_dep_kinase IPR018490, cNMP-bd-like IPR018488, cNMP-bd_CS IPR000595, cNMP-bd_dom IPR011009, Kinase-like_dom_sf IPR000719, Prot_kinase_dom IPR017441, Protein_kinase_ATP_BS IPR014710, RmlC-like_jellyroll IPR008271, Ser/Thr_kinase_AS IPR035014, STKc_cGK |
Pfami | View protein in Pfam PF00027, cNMP_binding, 3 hits PF00069, Pkinase, 1 hit |
PIRSFi | PIRSF000559, cGMP-dep_kinase, 1 hit |
SMARTi | View protein in SMART SM00100, cNMP, 4 hits SM00220, S_TKc, 1 hit |
SUPFAMi | SSF51206, SSF51206, 4 hits SSF56112, SSF56112, 1 hit |
PROSITEi | View protein in PROSITE PS51285, AGC_KINASE_CTER, 1 hit PS00888, CNMP_BINDING_1, 3 hits PS00889, CNMP_BINDING_2, 3 hits PS50042, CNMP_BINDING_3, 4 hits PS00107, PROTEIN_KINASE_ATP, 1 hit PS50011, PROTEIN_KINASE_DOM, 1 hit PS00108, PROTEIN_KINASE_ST, 1 hit |
i Sequence
Sequence statusi: Complete.
10 20 30 40 50
MEEDDNLKKG NERNKKKAIF SNDDFTGEDS LMEDHLELRE KLSEDIDMIK
60 70 80 90 100
TSLKNNLVCS TLNDNEILTL SNYMQFFVFK SGNLVIKQGE KGSYFFIINS
110 120 130 140 150
GKFDVYVNDK KVKTMGKGSS FGEAALIHNT QRSATIIAET DGTLWGVQRS
160 170 180 190 200
TFRATLKQLS NRNFNENRTF IDSVSVFDML TEAQKNMITN ACVIQNFKSG
210 220 230 240 250
ETIVKQGDYG DVLYILKEGK ATVYINDEEI RVLEKGSYFG ERALLYDEPR
260 270 280 290 300
SATIIAKEPT ACASICRKLL NIVLGNLQVV LFRNIMTEAL QQSEIFKQFS
310 320 330 340 350
GDQLNDLADT AIVRDYPANY NILHKDKVKS VKYIIVLEGK VELFLDDTSI
360 370 380 390 400
GILSRGMSFG DQYVLNQKQP FKHTIKSLEV CKIALITETC LADCLGNNNI
410 420 430 440 450
DASIDYNNKK SIIKKMYIFR YLTDKQCNLL IEAFRTTRYE EGDYIIQEGE
460 470 480 490 500
VGSRFYIIKN GEVEIVKNKK RLRTLGKNDY FGERALLYDE PRTASVISKV
510 520 530 540 550
NNVECWFVDK SVFLQIIQGP MLAHLEERIK MQDTKVEMDE LETERIIGRG
560 570 580 590 600
TFGTVKLVHH KPTKIRYALK CVSKRSIINL NQQNNIKLER EITAENDHPF
610 620 630 640 650
IIRLVRTFKD SKYFYFLTEL VTGGELYDAI RKLGLLSKSQ AQFYLGSIIL
660 670 680 690 700
AIEYLHERNI VYRDLKPENI LLDKQGYVKL IDFGCAKKVQ GRAYTLVGTP
710 720 730 740 750
HYMAPEVILG KGYGCTVDIW ALGICLYEFI CGPLPFGNDE EDQLEIFRDI
760 770 780 790 800
LTGQLTFPDY VTDTDSINLM KRLLCRLPQG RIGCSINGFK DIKDHPFFSN
810 820 830 840 850
FNWDKLAGRL LDPPLVSKSE TYAEDIDIKQ IEEEDAEDDE EPLNDEDNWD
IDF
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | LN999946 Genomic DNA Translation: CZU00064.1 |
RefSeqi | XP_001348520.1, XM_001348484.1 |
Genome annotation databases
EnsemblProtistsi | CZU00064; CZU00064; PF3D7_1436600 |
GeneIDi | 811928 |
KEGGi | pfa:PF3D7_1436600 |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | LN999946 Genomic DNA Translation: CZU00064.1 |
RefSeqi | XP_001348520.1, XM_001348484.1 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
4OFF | X-ray | 1.89 | A | 401-542 | [»] | |
4OFG | X-ray | 2.00 | A | 401-542 | [»] | |
5DYK | X-ray | 2.45 | A | 1-853 | [»] | |
5E16 | X-ray | 1.65 | A | 21-162 | [»] | |
AlphaFoldDBi | Q8I719 | |||||
SMRi | Q8I719 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
STRINGi | 5833.PF14_0346 |
Chemistry databases
GuidetoPHARMACOLOGYi | 3013 |
Proteomic databases
PRIDEi | Q8I719 |
Genome annotation databases
EnsemblProtistsi | CZU00064; CZU00064; PF3D7_1436600 |
GeneIDi | 811928 |
KEGGi | pfa:PF3D7_1436600 |
Organism-specific databases
VEuPathDBi | PlasmoDB:PF3D7_1436600 |
Phylogenomic databases
HOGENOMi | CLU_000288_73_2_1 |
InParanoidi | Q8I719 |
OMAi | SKNPDGH |
PhylomeDBi | Q8I719 |
Family and domain databases
CDDi | cd00038, CAP_ED, 4 hits cd05572, STKc_cGK, 1 hit |
Gene3Di | 2.60.120.10, 4 hits |
InterProi | View protein in InterPro IPR000961, AGC-kinase_C IPR002374, cGMP_dep_kinase IPR018490, cNMP-bd-like IPR018488, cNMP-bd_CS IPR000595, cNMP-bd_dom IPR011009, Kinase-like_dom_sf IPR000719, Prot_kinase_dom IPR017441, Protein_kinase_ATP_BS IPR014710, RmlC-like_jellyroll IPR008271, Ser/Thr_kinase_AS IPR035014, STKc_cGK |
Pfami | View protein in Pfam PF00027, cNMP_binding, 3 hits PF00069, Pkinase, 1 hit |
PIRSFi | PIRSF000559, cGMP-dep_kinase, 1 hit |
SMARTi | View protein in SMART SM00100, cNMP, 4 hits SM00220, S_TKc, 1 hit |
SUPFAMi | SSF51206, SSF51206, 4 hits SSF56112, SSF56112, 1 hit |
PROSITEi | View protein in PROSITE PS51285, AGC_KINASE_CTER, 1 hit PS00888, CNMP_BINDING_1, 3 hits PS00889, CNMP_BINDING_2, 3 hits PS50042, CNMP_BINDING_3, 4 hits PS00107, PROTEIN_KINASE_ATP, 1 hit PS50011, PROTEIN_KINASE_DOM, 1 hit PS00108, PROTEIN_KINASE_ST, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | KGP_PLAF7 | |
Accessioni | Q8I719Primary (citable) accession number: Q8I719 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | February 10, 2021 |
Last sequence update: | March 1, 2003 | |
Last modified: | May 25, 2022 | |
This is version 149 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) |
Miscellaneousi
Keywords - Technical termi
3D-structure, Reference proteomeDocuments
- PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families