Genome location: Pf3D7_13_v3:1,495,106..1,497,722(+)
Genome classification: Core
Product Description: protein kinase 6
SignalP Peptide: N/A
# Transmembrane Domains: 0
EC Numbers: 2.7.11.22 (Cyclin-dependent kinase)
Curated GO (PlasmoDB):
| Type | GO Term | Name |
|---|---|---|
| Component | GO:0000307 | cyclin-dependent protein kinase holoenzyme complex |
| Component | GO:0005737 | cytoplasm |
| Component | GO:0005634 | nucleus |
| Function | GO:0030332 | cyclin binding |
| Function | GO:0004693 | cyclin-dependent protein serine/threonine kinase activity |
| Process | GO:0000082 | G1/S transition of mitotic cell cycle |
| Process | GO:0008284 | positive regulation of cell population proliferation |
| Process | GO:0006468 | protein phosphorylation |
| Process | GO:0010389 | regulation of G2/M transition of mitotic cell cycle |
| Process | GO:0010468 | regulation of gene expression |
| Process | GO:0009410 | response to xenobiotic stimulus |
| 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 | expressed | N/A | N/A |
| Ring | expressed | 0.04 | 0.98 |
| Trophozoite | expressed | 0.21 | 0.88 |
| Schizont | expressed | 0.02 | 0.99 |
| Gametocyte | expressed | 0.20 | 0.88 |
More info:
Old (Pf3D7v3) Gene ID: PF3D7_1337100
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: 0.127 | MFS: -2.795 | #Insertions: 0
PlasmoGEM Phenotype: Essential (Pb ortholog: PBANKA_1350900)
RMgmDB ABS Phenotype: N/A
More info: PhenoPlasm Link
AlphaFill Uniprot ID: Q8IDW1
"Best" AlphaFill ligand hit: SGM (monothioglycerol, Local RMSD=0.26) with 3DOG (Global RMSD=3.60)
BRENDA EC Inhibitors:
| EC # | Name | EC Inhibitors |
|---|---|---|
| 2.7.11.22 | cyclin-dependent kinase | AMPDRBp16p18p21p27NMDATHZ1ICK1ICK2ICK3ICK4... |
Orthology to BindingDB Entries:
| UniProt | Protein Name | Species | Homology Source | BindingDB Ligands |
|---|---|---|---|---|
| P53779 | Mitogen-activated protein kinase 10 | Homo sapiens | HOGENOM | Pyrrole Carboxamide Analog 5bPyrrole Carboxamide Analog 5dPyrrole Carboxamide Analog 5gPyrrole Carboxamide Analog 5k... |
| P49187 | Mitogen-activated protein kinase 10 | Rattus norvegicus | HOGENOM | CHEMBL2376930Aminopyrazole inhibitor, 3576Aminopyrazole inhibitor, 3451CHEMBL571626... |
| P17157 | Cyclin-dependent protein kinase PHO85 | Saccharomyces cerevisiae | HOGENOM, OrthoDB | CHEMBL311228 |
| O96526 | Cell division related protein kinase 2 | Leishmania major | HOGENOM | CHEMBL2171518CHEMBL2171517CHEMBL2171516CHEMBL2171515... |
| Q00535 | Cyclin-dependent kinase 5 | Homo sapiens | HOGENOM, OrthoDB | Xanthen-9-one, 1.0Xanthen-9-one, 1.1Xanthen-9-one, 1.04-aminothiazole, 2.0... |
| Q00534 | Cyclin-dependent kinase 6 | Homo sapiens | HOGENOM, OrthoDB | Fisetin (14)acs.jmedchem.1c00409_ST.789cid_5281607Flavopiridol... |
| P28482 | Mitogen-activated protein kinase 1 | Homo sapiens | HOGENOM | Pyrrole Carboxamide Analog 1Pyrrole Carboxamide Analog 5aPyrrole Carboxamide Analog 5bPyrrole Carboxamide Analog 5c... |
| P00546 | Cyclin-dependent kinase 1 | Saccharomyces cerevisiae | HOGENOM, OrthoDB | aloisine ACHEMBL311228Purvalanol APurvalanol B |
| O15264 | Mitogen-activated protein kinase 13 | Homo sapiens | HOGENOM | Aminopyrazole inhibitor, 3451US9187470, 62US9187470, 61diaryl urea compound 10... |
| P27361 | Mitogen-activated protein kinase 3 | Homo sapiens | HOGENOM | US8546404, 6US9796700, Compound I-1US9796700, Compound I-2US9796700, Compound I-3... |
| Q9DGD3 | Cyclin-dependent kinase 1/G2/mitotic-specific cyclin-B | Marthasterias glacialis | HOGENOM, OrthoDB | NU2058CHEMBL115498NU2058O6-Cyclohexylmethylguanine deriv. 7... |
| Q15759 | Mitogen-activated protein kinase 11 | Homo sapiens | HOGENOM | US10266537, Compound 93HL-7CHEMBL340687CHEMBL128756... |
| Q02399 | Cyclin-dependent kinase 5 | HOGENOM, OrthoDB | Roscovitine | |
| P63086 | Mitogen-activated protein kinase 1 | Rattus norvegicus | HOGENOM | 1-Acyl-1H-[1,2,4]triazole-3,5-diamine Analogue 3c1-Acyl-1H-[1,2,4]triazole-3,5-diamine Analogue 3f1-Acyl-1H-[1,2,4]triazole-3,5-diamine Analogue 3nCHEMBL550658... |
| Q9WTU6 | Mitogen-activated protein kinase 9 | Mus musculus | HOGENOM | CHEMBL2037224CHEMBL2037220CHEMBL2037209CHEMBL2037211... |
| P24941 | Cyclin-dependent kinase 2/G1/S-specific cyclin-E1 | Homo sapiens | HOGENOM, OrthoDB | US8507510, 1.14US8507510, 1.15US8507510, 1.18US8507510, 1.21... |
| Q9Z1B7 | Mitogen-activated protein kinase 13 | HOGENOM | CHEMBL159932CHEMBL161197CHEMBL347592CHEMBL327632... | |
| Q5MAI5 | Cyclin-dependent kinase-like 4 | HOGENOM, OrthoDB | CHEMBL5190023 | |
| Q9WUI1 | Mitogen-activated protein kinase 11 | Mus musculus | HOGENOM | 2-arylpyridazin-3-one, 152-arylpyridazin-3-one, 182-arylpyridazin-3-one, 192-arylpyridazin-3-one, 20... |
| P63085 | Mitogen-activated protein kinase 1 | Mus musculus | HOGENOM | US8546404, 479US8546404, 459US8546404, 336US8546404, 469... |
| P50750 | Cyclin-dependent kinase 9 | Homo sapiens | HOGENOM, OrthoDB | CDK Inhibitor, 1CDK Inhibitor, 2CDK Inhibitor, 3CDK Inhibitor, 4... |
| P45984 | Mitogen-activated protein kinase 9 | Homo sapiens | HOGENOM | 9-hydroxy pyrazoloquinolinone 19-hydroxy pyrazoloquinolinone 22-pyridinecarboxamide deriv. 32-pyridinecarboxamide deriv. 8a... |
| P21127 | Cyclin-dependent kinase 11B | Homo sapiens | OrthoDB | CHEMBL4101411Indirubin derivative, 1 |
| P06493 | Cyclin-dependent kinase 1 | Homo sapiens | OrthoDB | 4-(Phenylamino)pyrazolo[3,4-d]pyrimidine deriv. 124-(Phenylamino)pyrazolo[3,4-d]pyrimidine deriv. 144-(Phenylamino)pyrazolo[3,4-d]pyrimidine deriv. 154-(Phenylamino)pyrazolo[3,4-d]pyrimidine deriv. 18... |
| O94921 | Cyclin-dependent kinase 14 | Homo sapiens | OrthoDB | CHEMBL4281048CHEMBL4554744CHEMBL4534124CHEMBL4555069... |
| Q9UQ88 | Cyclin-dependent kinase 11A | Homo sapiens | OrthoDB | CHEMBL1989043CHEMBL5206282CHEMBL5169674CHEMBL5185655... |
| P11440 | Cyclin-dependent kinase 1 | Mus musculus | OrthoDB | Staurosporine, 8CHEMBL359486CHEMBL178945CHEMBL360304... |
| Q92772 | Cyclin-dependent kinase-like 2 | OrthoDB | CHEMBL5190023 | |
| Q00536 | Cyclin-Y/Cyclin-dependent kinase 16 | OrthoDB | US9163013, 1CHEMBL4281048Staurosporine, 8CHEMBL4580787... | |
| P11802 | Cyclin-dependent kinase 4/G1/S-specific cyclin-D1 | Homo sapiens | OrthoDB | Indenopyrazole 5aIndenopyrazole 5bIndenopyrazole 5cIndenopyrazole 5d... |
| Q00526 | Cyclin-dependent kinase 3 | OrthoDB | US9067888, 33US9067888, 34Staurosporine, 8CHEMBL489833... | |
| Q07002 | Cyclin-dependent kinase 18 | OrthoDB | Staurosporine, 8Staurosporine, 8 | |
| Q00537 | Cyclin-Y/Cyclin-dependent kinase 17 | OrthoDB | Staurosporine, 8Staurosporine, 8 | |
| Q00532 | Cyclin-dependent kinase-like 1 | OrthoDB | CHEMBL455428 | |
| P50613 | Cyclin-dependent kinase 7 | Homo sapiens | OrthoDB | MLS000665974CDK Inhibitor, 1CDK Inhibitor, 2CDK Inhibitor, 3... |
Protein Length: 305 | Molecular Weight (kDa): 35.844
UniProt ID(s): O44022, O77239, Q8IDW1
PDB ID(s): 8U2O
Isoelectric Point: 6.17
Protein Domain Annotations:
| Source | Family ID | Description |
|---|---|---|
| InterPro | IPR000719 | Protein kinase domain |
| 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 | 5 | 10 | 11 | 19 |
| disruptive | 2 | 27 | 16 | 52 |
| missense | 2 | 26 | 16 | 47 |
Any inclusion in genotype call
| variant type | common | rare | doubleton | singleton |
|---|---|---|---|---|
| synonymous | 6 | 21 | 24 | 16 |
| disruptive | 6 | 65 | 39 | 53 |
| missense | 6 | 55 | 35 | 36 |
PlasmoDB Total SNPs: 199
Non-coding: 188 | Synonymous: 4 | Nonsynonymous: 7 | Stop Codon: 0
| PMID | Title | Authors | DOI/Link |
|---|---|---|---|
| 10727426 | PfPK6, a novel cyclin-dependent kinase/mitogen-activated protein kinase-relatedprotein kinase from Plasmodium falciparum. | Bracchi-Ricard V, Barik S, ..., Chakrabarti D | https://pubmed.ncbi.nlm.nih.gov/10727426/ |
| 16096806 | Molecular models of protein kinase 6 from Plasmodium falciparum. | Manhani KK, Arcuri HA, ..., Canduri F | 10.1007/s00894-005-0002-1 |
| 30929936 | Molecular characterization and phylogenetic analysis of Trypanosoma evansi fromNorthern India based on 18S ribosomal gene | Kumar R, Sarkhel SP, ..., Tripathi BN | 10.1016/j.vprsr.2018.100259 |
| 12556199 | Cyclin-dependent protein kinases as therapeutic drug targets for antimalarialdrug development | Waters NC, Geyer JA | 10.1517/14728222.7.1.7 |
| 31824917 | Integrative Multi-Kinase Approach for the Identification of Potent AntiplasmodialHits | Lima MNN, Cassiano GC, ..., Andrade CH | 10.3389/fchem.2019.00773 |
| 11700040 | Influence of human p16(INK4) and p21(CIP1) on the in vitro activity ofrecombinant Plasmodium falciparum cyclin-dependent protein kinases | Li Z, Le Roch K, ..., Waters NC | 10.1006/bbrc.2001.5920 |
| 26934697 | Biochemical Screening of Five Protein Kinases from Plasmodium falciparum against14,000 Cell-Active Compounds | Crowther GJ, Hillesland HK, ..., Ojo KK | 10.1371/journal.pone.0149996 |
| 28615873 | Molecular characterization of internal transcribed spacer 1 (ITS 1) region ofdifferent Trypanosoma evansi isolates of India | Sarkhel SP, Gupta SK, ..., Kumar R | 10.1007/s12639-016-0843-9 |