Genome location: Pf3D7_09_v3:1,360,721..1,364,051(+)
Genome classification: Core
Product Description: cAMP-dependent protein kinase catalytic 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:0005634 | nucleus |
| Function | GO:0004691 | cAMP-dependent protein kinase activity |
| Function | GO:0005515 | protein binding |
| Process | GO:0030154 | cell differentiation |
| Process | GO:0044409 | entry into host |
| Process | GO:0018105 | peptidyl-serine phosphorylation |
| 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 | possibly expressed | 0.08 | 0.96 |
| Trophozoite | expressed | 0.16 | 0.90 |
| Schizont | expressed | 2.21 | 0.14 |
| Gametocyte | expressed | 0.11 | 0.93 |
More info:
Old (Pf3D7v3) Gene ID: PF3D7_0934800
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: 0.202 | MFS: -2.607 | #Insertions: 0
PlasmoGEM Phenotype: Essential (Pb ortholog: PBANKA_0835600)
RMgmDB ABS Phenotype: Different from wild type (Pb ortholog: PY17X_0839000)
Modification: Mutated | RMgm-5084
More info: PhenoPlasm Link
AlphaFill Uniprot ID: Q7K6A0
"Best" AlphaFill ligand hit: NTN (isonicotinamidine, Local RMSD=0.12) with 6ZN0 (Global RMSD=1.03)
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 |
|---|---|---|---|---|
| Q86UX6 | Serine/threonine-protein kinase 32C | Homo sapiens | HOGENOM | Staurosporine, 8Staurosporine, 8 |
| Q05513 | Protein kinase C zeta type | Homo sapiens | HOGENOM | Acyclic Balanol Analog (-)-1pyridine-base inhibitor 1bStaurosporine, 8pyridine-base inhibitor 13a... |
| P68182 | cAMP-dependent protein kinase catalytic subunit beta | Rattus | HOGENOM, OrthoDB | CAS_140663-38-3HT-89 (H-89)Fasudil (HA-1077) |
| P05132 | cAMP-dependent protein kinase catalytic subunit alpha | Mus musculus | HOGENOM, OMA, OrthoDB | Fasudil (HA-1077)HydroxyfasudilH-1152PHT-89 (H-89)... |
| P00517 | cAMP-dependent protein kinase catalytic subunit alpha | Bos taurus | HOGENOM, OMA, OrthoDB | Bisindolylmaleimide deriv. 28Bisindolylmaleimide deriv. 5Bisindolylmaleimide deriv. 8Bisindolyl deriv. 10... |
| P22694 | cAMP-dependent protein kinase catalytic subunit beta | Homo sapiens | HOGENOM, OrthoDB | Staurosporine, 8Staurosporine, 8Staurosporine, 8 |
| P23443 | Ribosomal protein S6 kinase beta-1 | Homo sapiens | HOGENOM | US8637532, 2US8637532, 3US8637532, 5US8637532, 6... |
| P51817 | cAMP-dependent protein kinase catalytic subunit PRKX | Homo sapiens | HOGENOM, OrthoDB | CHEMBL1667967CHEMBL1667963Staurosporine, 8Staurosporine, 8... |
| Q9NY57 | Serine/threonine-protein kinase 32B | Homo sapiens | HOGENOM | Staurosporine, 8Staurosporine, 8 |
| Q9UBS0 | Ribosomal protein S6 kinase beta-2 | Homo sapiens | HOGENOM | CHEMBL364499CHEMBL193162CHEMBL193172CHEMBL193232... |
| P22612 | cAMP-dependent protein kinase catalytic subunit gamma | HOGENOM, OrthoDB | Staurosporine, 8UCN-01Staurosporine, 8UCN-01... | |
| O14578 | Citron Rho-interacting kinase | Homo sapiens | HOGENOM | CHEBI:90705CHEMBL4248525CHEMBL4245242CHEMBL4249925... |
| O00141 | Serine/threonine-protein kinase Sgk1 | Homo sapiens | HOGENOM | Indirubin-3 -monoximeUS9174993, 1US9174993, 2US9174993, 3... |
| P17612 | cAMP-dependent protein kinase catalytic subunit alpha | Homo sapiens | OMA, OrthoDB | Debromohymenialdisine (DBH)pyridine-thiazole, 1pyridine-phenyl, 2pyrazole-phenyl, 3... |
| Q95J97 | cAMP-dependent protein kinase | Oryctolagus cuniculus | OrthoDB | 4'',6''-Dideoxybalanol, 65'-Deoxybalanol, 7CHEMBL19369714''-Decarboxybalanol hydrochloride, 5... |
| Q13976 | cGMP-dependent protein kinase 1 | Homo sapiens | OrthoDB | CAS_140663-38-3HT-89 (H-89)Fasudil (HA-1077)H-88... |
| Q13237 | cGMP-dependent protein kinase 2 | Homo sapiens | OrthoDB | Cyclic GMP analogs8-Br-cGMPCyclic GMP analogsPET-cGMP... |
Ortholog Group (OrthoMCL): OG6_100326
Most Similar Human Ortholog: A0A7I2V5J4
TM-align score: 0.97 | RMSD: 1.35
Seq Identity: 0.48 | Length: 293 / 342
All Human Orthologs (OrthoMCL):
| Gene ID | Description |
|---|---|
| ENSG00000072062 | protein kinase cAMP-activated catalytic subunit alpha |
| ENSG00000142875 | protein kinase cAMP-activated catalytic subunit beta |
| ENSG00000165059 | protein kinase cAMP-activated catalytic subunit gamma |
| ENSG00000183943 | protein kinase X-linked |
| ENSG00000288516 | protein kinase cAMP-activated catalytic subunit alpha |
Protein Length: 342 | Molecular Weight (kDa): 40.196
UniProt ID(s): O15906, O44020, Q7K6A0
PDB ID(s): None
Isoelectric Point: 9.08
Protein Domain Annotations:
| Source | Family ID | Description |
|---|---|---|
| InterPro | IPR000719 | Protein kinase domain |
| InterPro | IPR000961 | AGC-kinase, C-terminal |
| InterPro | IPR008271 | Serine/threonine-protein kinase, active site |
| InterPro | IPR011009 | Protein kinase-like domain superfamily |
| InterPro | IPR017441 | Protein kinase, ATP binding site |
| PFam | PF00069 | Protein kinase domain |
| 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 | 0 | 18 | 7 | 27 |
| disruptive | 1 | 5 | 2 | 10 |
| missense | 1 | 5 | 2 | 8 |
Any inclusion in genotype call
| variant type | common | rare | doubleton | singleton |
|---|---|---|---|---|
| synonymous | 0 | 36 | 12 | 23 |
| disruptive | 2 | 12 | 13 | 45 |
| missense | 2 | 7 | 10 | 24 |
PlasmoDB Total SNPs: 202
Non-coding: 198 | Synonymous: 4 | Nonsynonymous: 0 | Stop Codon: 0
| PMID | Title | Authors | DOI/Link |
|---|---|---|---|
| 10960174 | Isolation and characterisation of a cAMP-dependent protein kinase catalyticsubunit gene from Plasmodium falciparum. | Li J, Cox LS | 10.1016/s0166-6851(00)00242-5 |
| 12368867 | Sequence of Plasmodium falciparum chromosomes 1, 3-9 and 13. | Hall N, Pain A, ..., Barrell BG | 10.1038/nature01095 |
| 22188458 | Construction of a Plasmodium falciparum Rab-interactome identifies CK1 and PKA asRab-effector kinases in malaria parasites. | Rached FB, Ndjembo-Ezougou C, ..., Langsley G | 10.1111/boc.201100081 |
| 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 |
| 31594816 | Protein Kinase A Is Essential for Invasion of Plasmodium falciparum into Human Erythrocytes | Wilde ML, Triglia T, ..., Tonkin CJ | 10.1128/mBio.01972-19 |
| 38030378 | Glucocorticoid receptor (GR) activation is associated with increased cAMP/PKAsignaling in castrate-resistant prostate cancer | Bennett L, Jaiswal PK, ..., Conzen SD | 10.1158/1535-7163.MCT-22-0479 |
| 37214942 | GRK2 Kinases in the Primary Cilium Initiate SMOOTHENED-PKA Signaling in the Hedgehog Cascade | Walker MF, Zhang J, ..., Myers BR | 10.1101/2023.05.10.540226 |
| 36692000 | Oncogenic PKA signaling increases c-MYC protein expression through multiple targetable mechanisms | Chan GKL, Maisel S, ..., Gordan JD | 10.7554/eLife.69521 |
| 37745542 | The alphaC-beta4 loop controls the allosteric cooperativity between nucleotide and substrate in the catalytic subunit of protein kinase A | Olivieri C, Wang Y, ..., Veglia G | 10.1101/2023.09.12.557419 |
| 37775785 | Retraction Note: Effect of hCMSCs and liraglutide combination in ALI through cAMP/PKAc/beta-catenin signaling pathway | Feng Y, Wang L, ..., Song Y | 10.1186/s13287-023-03474-6 |
| 36431013 | Functional Insights into Protein Kinase A (PKA) Signaling from C. elegans | Sadeghian F, Castaneda PG, Amin MR, Cram EJ | 10.3390/life12111878 |
| 36892429 | An NMR portrait of functional and dysfunctional allosteric cooperativity in cAMP-dependent protein kinase A | Olivieri C, Walker C, ..., Veglia G | 10.1002/1873-3468.14610 |