About Gene List

PF3D7_1223100 (PKAr)

Genome location: Pf3D7_12_v3:927,063..930,026(-)

Genome classification: Core

Function and Localization

Product Description: cAMP-dependent protein kinase regulatory subunit

SignalP Peptide: N/A

# Transmembrane Domains: 0

EC Numbers: 2.7.11.11 (cAMP-dependent protein kinase)

Curated GO (PlasmoDB):

Type GO Term Name
Component GO:0005952 cAMP-dependent protein kinase complex
Component GO:1903561 extracellular vesicle
Component GO:0005634 nucleus
Function GO:0071889 14-3-3 protein binding
Function GO:0003723 RNA binding
Function GO:0008603 cAMP-dependent protein kinase regulator activity
Function GO:0005515 protein binding

Expression by stage (LR - Le Roch et al., and MCA - Malaria Cell Atlas):

Stage LR class MCA mean MCA prop. zeros
Sporozoite expressed N/A N/A
Ring possibly expressed 0.47 0.82
Trophozoite expressed 0.74 0.61
Schizont expressed 2.73 0.08
Gametocyte expressed 0.97 0.50

More info:

Resistome Mutations

Old (Pf3D7v3) Gene ID: PF3D7_1223100

Resistome Missense Mutations: None

Resistome Compounds with Missense Mutations: None

Resistome # Samples with Disruptive Mutations: 0 (0 missense, 0 "interesting" missense)

Essentiality (ABS)

Zhang Phenotype: Non - Mutable in CDS

MIS: 0.399 | MFS: -2.62 | #Insertions: 0

PlasmoGEM Phenotype: N/A

RMgmDB ABS Phenotype: N/A

More info: PhenoPlasm Link

Binding Evidence

AlphaFill Uniprot ID: Q7KQK0

"Best" AlphaFill ligand hit: N2P (pentane-1,5-diamine, Local RMSD=0.02) with 4OFG (Global RMSD=2.04)

BRENDA EC Inhibitors:

EC # Name EC Inhibitors
2.7.11.11 cAMP-dependent protein kinase ADPH89PKIIP20KN-93KT5720HA1077U-73122KT-5720Rp-cAMPnaproxenimatinib...

Orthology to BindingDB Entries:

UniProt Protein Name Species Homology Source BindingDB Ligands
P00514 cAMP-dependent protein kinase type I-alpha regulatory subunit Bos taurus OMA, OrthoDB, OrthoMCL BLAST MLS000766286MLS000860011MLS001333136MLS001148197...
P31323 cAMP-dependent protein kinase type II-beta regulatory subunit Homo sapiens OrthoDB MLS000766286MLS000860011MLS001333136MLS001148197...

Orthology Information

Ortholog Group (OrthoMCL): OG6_100449

Most Similar Human Ortholog: C9JR00

TM-align score: 0.70 | RMSD: 2.92

Seq Identity: 0.32 | Length: 141 / 441

All Human Orthologs (OrthoMCL):

Gene ID Description
ENSG00000005249 protein kinase cAMP-dependent type II regulatory subunit beta
ENSG00000108946 protein kinase cAMP-dependent type I regulatory subunit alpha
ENSG00000114302 protein kinase cAMP-dependent type II regulatory subunit alpha
ENSG00000188191 protein kinase cAMP-dependent type I regulatory subunit beta
ENSG00000284096 protein kinase cAMP-dependent type II regulatory subunit beta

Protein Information

Protein Length: 441 | Molecular Weight (kDa): 50.833

UniProt ID(s): Q7KQK0, Q8T323

PDB ID(s): 5K8S, 5KBF, 5T3N

Isoelectric Point: 7.36

Protein Domain Annotations:

Source Family ID Description
InterPro IPR000595 Cyclic nucleotide-binding domain
InterPro IPR012198 cAMP-dependent protein kinase regulatory subunit
InterPro IPR018488 Cyclic nucleotide-binding, conserved site
InterPro IPR018490 Cyclic nucleotide-binding-like
PFam PF00027 Cyclic nucleotide-binding domain
Superfamily SSF51206 Cyclic nucleotide-binding-like

Genetic Variation

MalariaGEN Pf7 (worldwide samples) # unique SNV/indels:

Homozygous genotype calls only

variant type common rare doubleton singleton
synonymous 1 15 8 11
disruptive 4 15 9 27
missense 4 15 9 24

Any inclusion in genotype call

variant type common rare doubleton singleton
synonymous 5 27 5 18
disruptive 9 35 27 51
missense 8 26 22 36

PlasmoDB Total SNPs: 99

Non-coding: 87 | Synonymous: 5 | Nonsynonymous: 7 | Stop Codon: 0

Associated Publications

PMID Title Authors DOI/Link
12368864 Genome sequence of the human malaria parasite Plasmodium falciparum. Gardner MJ, Hall N, ..., Barrell B 10.1038/nature01097
16267556 A protein interaction network of the malaria parasite Plasmodium falciparum. LaCount DJ, Vignali M, ..., Hughes RE 10.1038/nature04104
18248092 Plasmodium falciparum regulatory subunit of cAMP-dependent PKA and anion channelconductance. Merckx A, Nivez MP, ..., Egee S 10.1371/journal.ppat.0040019
23181666 Organellar proteomics reveals hundreds of novel nuclear proteins in the malariaparasite Plasmodium falciparum. Oehring SC, Woodcroft BJ, ..., Voss TS 10.1186/gb-2012-13-11-r108
28680058 PfCDPK1 mediated signaling in erythrocytic stages of Plasmodium falciparum. Kumar S, Kumar M, ..., Sharma P 10.1038/s41467-017-00053-1
30794532 Phosphodiesterase beta is the master regulator of cAMP signalling during malariaparasite invasion. Flueck C, Drought LG, ..., Baker DA 10.1371/journal.pbio.3000154
32817103 Phosphorylation-Dependent Assembly of a 14-3-3 Mediated Signaling Complex during Red Blood Cell Invasion by Plasmodium falciparum Merozoites More KR, Kaur I, ..., Chitnis CE 10.1128/mBio.01287-20
33608523 20S proteasomes secreted by the malaria parasite promote its growth. Dekel E, Yaffe D, ..., Regev-Rudzki N 10.1038/s41467-021-21344-8
33906926 Functional Characterization of the m(6)A-Dependent Translational Modulator PfYTH Sinha A, Baumgarten S, ..., Scherf A 10.1128/mBio.00661-21
34063491 Development of Phosphodiesterase-Protein-Kinase Complexes as Novel Targets forDiscovery of Inhibitors with Enhanced Specificity Tulsian NK, Sin VJ, Koh HL, Anand GS 10.3390/ijms22105242
36941487 In silico evolutionary and structural analysis of cAMP response proteins (CARPs)from Leishmania major Bhakta S, Bhattacharya A 10.1007/s00203-023-03463-6
36431013 Functional Insights into Protein Kinase A (PKA) Signaling from C. elegans Sadeghian F, Castaneda PG, Amin MR, Cram EJ 10.3390/life12111878
33819633 The crystal structure of yeast regulatory subunit reveals key evolutionaryinsights into Protein Kinase A oligomerization Bardeci NG, Tofolon E, ..., Moreno S 10.1016/j.jsb.2021.107732
35199643 Complex effects of kinase localization revealed by compartment-specificregulation of protein kinase A activity LaCroix R, Lin B, Kang TY, Levchenko A 10.7554/eLife.66869
29449124 Investigating PKA-RII specificity using analogs of the PKA:AKAP peptide inhibitorSTAD-2 Bendzunas NG, Dorfler S, ..., Herberg FW 10.1016/j.bmc.2018.02.001