Product Description: cdc2-related protein kinase 3
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:0005634 | nucleus |
| Function | GO:0008353 | RNA polymerase II CTD heptapeptide repeat kinase activity |
| Function | GO:0004693 | cyclin-dependent protein serine/threonine kinase activity |
| Function | GO:0004407 | histone deacetylase activity |
| Function | GO:0004672 | protein kinase activity |
| Process | GO:0070816 | phosphorylation of RNA polymerase II C-terminal domain |
| Process | GO:0032968 | positive regulation of transcription elongation from RNA polymerase II promoter |
| Process | GO:0006468 | protein phosphorylation |
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 | 0.89 | 0.60 |
| Trophozoite | expressed | 0.98 | 0.50 |
| Schizont | expressed | 0.29 | 0.83 |
| Gametocyte | expressed | 0.99 | 0.49 |
More info:
Old (Pf3D7v3) Gene ID: PF3D7_0415300
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: 0.138 | MFS: -2.825 | #Insertions: 0
PlasmoGEM Phenotype: Essential (Pb ortholog: PBANKA_0717300)
RMgmDB ABS Phenotype: N/A
More info: PhenoPlasm Link
AlphaFill Uniprot ID: Q8I1T4
"Best" AlphaFill ligand hit: AMP (adenosine monophosphate, Local RMSD=0.36) with 4IMY (Global RMSD=1.95)
BRENDA EC Inhibitors:
| EC # | Name | EC Inhibitors |
|---|---|---|
| 2.7.11.22 | cyclin-dependent kinase | AMPDRBp16p18p21p27NMDATHZ1ICK1ICK2ICK3ICK4... |
No evidence of orthology to BindingDB entries
MalariaGEN Pf7 (worldwide samples) # unique SNV/indels:
Homozygous genotype calls only
| variant type | common | rare | doubleton | singleton |
|---|---|---|---|---|
| synonymous | 38 | 59 | 28 | 45 |
| disruptive | 102 | 163 | 71 | 188 |
| missense | 37 | 88 | 52 | 129 |
Any inclusion in genotype call
| variant type | common | rare | doubleton | singleton |
|---|---|---|---|---|
| synonymous | 48 | 93 | 44 | 66 |
| disruptive | 149 | 292 | 122 | 262 |
| missense | 57 | 175 | 89 | 148 |
PlasmoDB Total SNPs: 286
Non-coding: 62 | Synonymous: 155 | Nonsynonymous: 68 | Stop Codon: 1
Protein Length: 1339 | Molecular Weight (kDa): 159.559
UniProt ID(s): Q8I1T4
PDB ID(s): None
Isoelectric Point: 9.5
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 |
| PMID | Title | Authors | DOI/Link |
|---|---|---|---|
| 12368867 | Sequence of Plasmodium falciparum chromosomes 1, 3-9 and 13. | Hall N, Pain A, ..., Barrell BG | 10.1038/nature01095 |
| 16267556 | A protein interaction network of the malaria parasite Plasmodium falciparum. | LaCount DJ, Vignali M, ..., Hughes RE | 10.1038/nature04104 |
| 20305001 | A Plasmodium falciparum transcriptional cyclin-dependent kinase-related kinasewith a crucial role in parasite proliferation associates with histone deacetylaseactivity. | Halbert J, Ayong L, ..., Doerig C | 10.1128/EC.00005-10 |
| 24447365 | Novel fragment-based QSAR modeling and combinatorial design of pyrazole-derived CRK3 inhibitors as potent antileishmanials | Goyal S, Dhanjal JK, ..., Grover A | 10.1111/cbdd.12290 |
| 23104649 | Leishmania mexicana: expression; characterization and activity assessment of E.coli-expressed recombinant CRK3 | Ali NO, Ibrahim ME, Grant KM, Mottram JC | https://pubmed.ncbi.nlm.nih.gov/23104649/ |
| 33378956 | Unveiling six potent and highly selective antileishmanial agents via the opensource compound collection 'Pathogen Box' against antimony-sensitive and-resistant Leishmania braziliensis | Souza Silva JA, Tunes LG, ..., Monte-Neto RL | 10.1016/j.biopha.2020.111049 |
| 21483720 | High throughput screens yield small molecule inhibitors of Leishmania CRK3:CYC6cyclin-dependent kinase | Walker RG, Thomson G, ..., Mottram JC | 10.1371/journal.pntd.0001033 |
| 26991545 | Conditional gene deletion with DiCre demonstrates an essential role for CRK3 inLeishmania mexicana cell cycle regulation | Duncan SM, Myburgh E, ..., Mottram JC | 10.1111/mmi.13375 |
| 25969537 | Members of the Plant CRK Superfamily Are Capable of Trans- andAutophosphorylation of Tyrosine Residues | Nemoto K, Takemori N, ..., Sawasaki T | 10.1074/jbc.M114.617274 |
| 19649663 | Homology modeling and atomic level binding study of Leishmania MAPK withinhibitors | Awale M, Kumar V, Saravanan P, Mohan CG | 10.1007/s00894-009-0565-3 |
| 21913331 | Identification of inhibitors of the Leishmania cdc2-related protein kinase CRK3 | Cleghorn LA, Woodland A, ..., Wyatt PG | 10.1002/cmdc.201100344 |
| 25937014 | 2,6,9-Trisubstituted purines as CRK3 kinase inhibitors with antileishmanialactivity in vitro | Reznickova E, Popa A, ..., Strnad M | 10.1016/j.bmcl.2015.04.030 |
| 21850927 | Molecular cloning, characterization and overexpression of a novel cyclin fromLeishmania mexicana | Ali NO, Ibrahim ME, Grant KM, Mottram JC | 10.3923/pjbs.2010.775.784 |
| 21708149 | Identification of substrates of an S-phase cell cycle kinase from Leishmania donovani | Maity AK, Goswami A, Saha P | 10.1016/j.febslet.2011.06.017 |
| 20338198 | Recombinant Leishmania mexicana CRK3:CYCA has protein kinase activity in theabsence of phosphorylation on the T-loop residue Thr178 | Gomes FC, Ali NO, ..., Mottram JC | 10.1016/j.molbiopara.2010.03.002 |
| 21683592 | Anti-leishmanial activity of disubstituted purines and relatedpyrazolo[4,3-d]pyrimidines | Jorda R, Sacerdoti-Sierra N, ..., Jaffe CL | 10.1016/j.bmcl.2011.05.076 |
| 26991431 | Joining forces: first application of a rapamycin-induced dimerizable Cre systemfor conditional null mutant analysis in Leishmania | Spath GF, Clos J | 10.1111/mmi.13374 |
| 23805309 | Identification and Functional Characterisation of CRK12:CYC9, a NovelCyclin-Dependent Kinase (CDK)-Cyclin Complex in Trypanosoma brucei | Monnerat S, Almeida Costa CI, ..., Hammarton TC | 10.1371/journal.pone.0067327 |