Genome location: Pf3D7_14_v3:1,490,321..1,494,453(-)
Genome classification: Core
Product Description: cGMP-dependent protein kinase
SignalP Peptide: N/A
# Transmembrane Domains: 0
EC Numbers: 2.7.11.12 (cGMP-dependent protein kinase)
Curated GO (PlasmoDB):
| Type | GO Term | Name |
|---|---|---|
| Component | GO:0005952 | cAMP-dependent protein kinase complex |
| Component | GO:0005737 | cytoplasm |
| Component | GO:0005783 | endoplasmic reticulum |
| Component | GO:0019898 | extrinsic component of membrane |
| Function | GO:0004691 | cAMP-dependent protein kinase activity |
| Function | GO:0004692 | cGMP-dependent protein kinase activity |
| Function | GO:0005515 | protein binding |
| Process | GO:0044409 | entry into host |
| Process | GO:0035890 | exit from host |
| Process | GO:0018105 | peptidyl-serine phosphorylation |
| Process | GO:0006468 | protein phosphorylation |
| Process | GO:0009410 | response to xenobiotic stimulus |
| Process | GO:0020014 | schizogony |
| Process | GO:0007165 | signal transduction |
Expression by stage (LR - Le Roch et al., and MCA - Malaria Cell Atlas):
| Stage | LR class | MCA mean | MCA prop. zeros |
|---|---|---|---|
| Sporozoite | not expressed | N/A | N/A |
| Ring | not expressed | 0.08 | 0.96 |
| Trophozoite | possibly expressed | 0.16 | 0.90 |
| Schizont | expressed | 1.17 | 0.41 |
| Gametocyte | expressed | 0.29 | 0.83 |
More info:
Old (Pf3D7v3) Gene ID: PF3D7_1436600
Resistome Missense Mutations: None
Resistome Compounds with Missense Mutations: None
Resistome # Samples with Disruptive Mutations: 0 (0 missense, 0 "interesting" missense)
Zhang Phenotype: Non - Mutable in CDS
MIS: 0.179 | MFS: -2.721 | #Insertions: 0
PlasmoGEM Phenotype: N/A
RMgmDB ABS Phenotype: Different from wild type (Pb ortholog: PBANKA_1008200)
Modification: Tagged | RMgm-4552
More info: PhenoPlasm Link
AlphaFill Uniprot ID: Q8I719
"Best" AlphaFill ligand hit: N2P (pentane-1,5-diamine, Local RMSD=0.05) with 4OFG (Global RMSD=3.86)
BRENDA EC Inhibitors:
| EC # | Name | EC Inhibitors |
|---|---|---|
| 2.7.11.12 | cGMP-dependent protein kinase | DT3KT5823KT5926KT-5823terferolLRKKKKKHD-glucoseangiotensin8-bromo-cGMPDT-2 peptideRp-8-Br-cGMPstaurosporine... |
Orthology to BindingDB Entries:
| UniProt | Protein Name | Species | Homology Source | BindingDB Ligands |
|---|---|---|---|---|
| Q13976 | cGMP-dependent protein kinase 1 | Homo sapiens | HOGENOM | CAS_140663-38-3HT-89 (H-89)Fasudil (HA-1077)H-88... |
| Q13237 | cGMP-dependent protein kinase 2 | Homo sapiens | HOGENOM, OMA | Cyclic GMP analogs8-Br-cGMPCyclic GMP analogsPET-cGMP... |
| Q8MMZ4 | cGMP-dependent protein kinase | Plasmodium falciparum | OrthoMCL, OrthoMCL BLAST | CHEMBL3770802CHEMBL3108913CHEMBL3108997CHEMBL3109011... |
| Q8MMZ8 | cGMP-dependent protein kinase | Eimeria tenella | OrthoMCL BLAST | Tenellone BCHEMBL370248CHEMBL193163CHEMBL370263... |
| Q8MMZ7 | cGMP-dependent protein kinase | OrthoMCL BLAST | CHEMBL2069954CHEMBL1784959CHEMBL1784960CHEMBL1784961... |
Ortholog Group (OrthoMCL): OG6_100630
Most Similar Human Ortholog: B7ZA25
TM-align score: 0.90 | RMSD: 1.81
Seq Identity: 0.39 | Length: 327 / 853
All Human Orthologs (OrthoMCL):
| Gene ID | Description |
|---|---|
| ENSG00000138669 | protein kinase cGMP-dependent 2 |
| ENSG00000185532 | protein kinase cGMP-dependent 1 |
Protein Length: 853 | Molecular Weight (kDa): 97.694
Isoelectric Point: 5.22
Protein Domain Annotations:
| Source | Family ID | Description |
|---|---|---|
| InterPro | IPR000595 | Cyclic nucleotide-binding domain |
| InterPro | IPR000719 | Protein kinase domain |
| InterPro | IPR002374 | cGMP-dependent kinase |
| InterPro | IPR008271 | Serine/threonine-protein kinase, active site |
| InterPro | IPR011009 | Protein kinase-like domain superfamily |
| InterPro | IPR017441 | Protein kinase, ATP binding site |
| InterPro | IPR018488 | Cyclic nucleotide-binding, conserved site |
| InterPro | IPR018490 | Cyclic nucleotide-binding-like |
| InterPro | IPR035014 | cGMP-dependent protein kinase, catalytic domain |
| PFam | PF00027 | Cyclic nucleotide-binding domain |
| PFam | PF00069 | Protein kinase domain |
| Superfamily | SSF51206 | Cyclic nucleotide-binding-like |
| Superfamily | SSF56112 | Protein kinase-like domain superfamily |
MalariaGEN Pf7 (worldwide samples) # unique SNV/indels:
Homozygous genotype calls only
| variant type | common | rare | doubleton | singleton |
|---|---|---|---|---|
| synonymous | 8 | 45 | 30 | 72 |
| disruptive | 4 | 16 | 13 | 41 |
| missense | 1 | 12 | 12 | 38 |
Any inclusion in genotype call
| variant type | common | rare | doubleton | singleton |
|---|---|---|---|---|
| synonymous | 16 | 113 | 46 | 61 |
| disruptive | 7 | 53 | 40 | 106 |
| missense | 2 | 41 | 38 | 80 |
PlasmoDB Total SNPs: 158
Non-coding: 129 | Synonymous: 27 | Nonsynonymous: 2 | Stop Codon: 0
| PMID | Title | Authors | DOI/Link |
|---|---|---|---|
| 12068803 | A novel cyclic GMP-dependent protein kinase is expressed in the ring stage of thePlasmodium falciparum life cycle. | Deng W, Baker DA | 10.1046/j.1365-2958.2002.02948.x |
| 12368864 | Genome sequence of the human malaria parasite Plasmodium falciparum. | Gardner MJ, Hall N, ..., Barrell B | 10.1038/nature01097 |
| 19915077 | The malaria parasite cyclic GMP-dependent protein kinase plays a central role inblood-stage schizogony. | Taylor HM, McRobert L, ..., Baker DA | 10.1128/EC.00186-09 |
| 23139764 | Spatiotemporal and functional characterisation of the Plasmodium falciparumcGMP-dependent protein kinase. | Hopp CS, Flueck C, ..., Baker DA | 10.1371/journal.pone.0048206 |
| 24805991 | Development of a transgenic Plasmodium berghei line (Pb pfpkg) expressing the P.falciparum cGMP-dependent protein kinase, a novel antimalarial drug target. | Tewari R, Patzewitz EM, ..., Baker DA | 10.1371/journal.pone.0096923 |
| 26149123 | Phosphoproteomics reveals malaria parasite Protein Kinase G as a signalling hubregulating egress and invasion. | Alam MM, Solyakov L, ..., Tobin AB | 10.1038/ncomms8285 |
| 28874661 | A potent series targeting the malarial cGMP-dependent protein kinase clearsinfection and blocks transmission. | Baker DA, Stewart LB, ..., Osborne SA | 10.1038/s41467-017-00572-x |
| 29251493 | cGMP Binding Domain D Mediates a Unique Activation Mechanism in Plasmodiumfalciparum PKG. | Franz E, Knape MJ, Herberg FW | 10.1021/acsinfecdis.7b00222 |
| 30174152 | Trisubstituted thiazoles as potent and selective inhibitors of Plasmodiumfalciparum protein kinase G (PfPKG). | Tsagris DJ, Birchall K, ..., Osborne SA | 10.1016/j.bmcl.2018.08.028 |
| 30323024 | Plasmodium falciparum Cyclic G MP-Dependent Protein Kinase Interacts with a Subunit of the Parasite Proteasome | Govindasamy K, Khan R, ..., Bhanot P | 10.1128/IAI.00523-18 |
| 31065005 | High-throughput screening of the Plasmodium falciparum cGMP-dependent proteinkinase identified a thiazole scaffold which kills erythrocytic and sexual stageparasites. | Penzo M, de Las Heras-Duena L, ..., Baker DA | 10.1038/s41598-019-42801-x |
| 31239348 | Structures of the cGMP-dependent protein kinase in malaria parasites reveal aunique structural relay mechanism for activation. | El Bakkouri M, Kouidmi I, ..., Hui R | 10.1073/pnas.1905558116 |
| 32317283 | Mechanism of allosteric inhibition in the Plasmodium falciparum cGMP-dependentprotein kinase. | Byun JA, Van K, ..., Melacini G | 10.1074/jbc.RA120.013070 |
| 32359426 | Inhibition of Resistance-Refractory P. falciparum Kinase PKG DeliversProphylactic, Blood Stage, and Transmission-Blocking Antiplasmodial Activity. | Vanaerschot M, Murithi JM, ..., Fidock DA | 10.1016/j.chembiol.2020.04.001 |
| 33271627 | Cyclic nucleotide selectivity of protein kinase G isozymes. | Kim C, Sharma R | 10.1002/pro.4008 |
| 33762339 | Ca(2+) signals critical for egress and gametogenesis in malaria parasites dependon a multipass membrane protein that interacts with P KG | Balestra AC, Koussis K, ..., Brochet M | 10.1126/sciadv.abe5396 |
| 38254010 | Comprehensive analysis of m6A modification in lipopolysaccharide-induced acutelung injury in mice | Xu C, Song C, ..., Geng Q | 10.1186/s10020-024-00782-2 |
| 38382669 | Regulation of Calcium entry by cyclic GMP signaling in Toxoplasma gondii | Hortua Triana MA, Marquez-Nogueras KM, ..., Moreno SNJ | 10.1016/j.jbc.2024.105771 |
| 38372781 | Structure-Activity Relationship of a Pyrrole Based Series of PfPKG Inhibitors asAnti-Malarials | Gilleran JA, Ashraf K, ..., Bhanot P | 10.1021/acs.jmedchem.3c01795 |