PF3D7_0417800 (CRK1)

Genome location: Pf3D7_04_v3:786,700..790,000(-)

Genome classification: Core

Function and Localization

Product Description: cdc2-related protein kinase 1

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:0005634	nucleus
Function	GO:0004693	cyclin-dependent protein serine/threonine kinase activity
Function	GO:0004672	protein kinase activity
Process	GO:0006468	protein phosphorylation
Process	GO:0010468	regulation of gene expression
Process	GO:0007346	regulation of mitotic cell cycle

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	0.11	0.95
Trophozoite	expressed	0.68	0.62
Schizont	expressed	0.16	0.89
Gametocyte	expressed	0.48	0.73

More info:

Resistome Mutations

Old (Pf3D7v3) Gene ID: PF3D7_0417800

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: Mutable in CDS

MIS: 1 | MFS: -2.585 | #Insertions: 3

PlasmoGEM Phenotype: N/A

RMgmDB ABS Phenotype: N/A

More info: PhenoPlasm Link

Binding Evidence

AlphaFill Uniprot ID: Q8I1Q9

"Best" AlphaFill ligand hit: 2AN (8-anilino-1-naphthalene sulfonate, Local RMSD=0.04) with 3PXF (Global RMSD=6.96)

BRENDA EC Inhibitors:

EC #	Name	EC Inhibitors
2.7.11.22	cyclin-dependent kinase	AMPDRBp16p18p21p27NMDATHZ1ICK1ICK2ICK3ICK4...

No evidence of orthology to BindingDB entries

Orthology Information

Ortholog Group (OrthoMCL): OG6_102464

Most Similar Human Ortholog: Q5QPQ9

TM-align score: 0.67 | RMSD: 1.72

Seq Identity: 0.06 | Length: 33 / 699

All Human Orthologs (OrthoMCL):

Gene ID	Description
ENSG00000008128	cyclin dependent kinase 11A
ENSG00000248333	cyclin dependent kinase 11B

Genetic Variation

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

Homozygous genotype calls only

variant type	common	rare	doubleton	singleton
synonymous	11	23	12	37
disruptive	19	60	35	112
missense	12	54	32	93

Any inclusion in genotype call

variant type	common	rare	doubleton	singleton
synonymous	17	58	17	41
disruptive	35	167	73	150
missense	20	140	60	112

PlasmoDB Total SNPs: 210

Non-coding: 135 | Synonymous: 53 | Nonsynonymous: 22 | Stop Codon: 0

Protein Information

Protein Length: 699 | Molecular Weight (kDa): 83.504

UniProt ID(s): Q25826, Q8I1Q9

PDB ID(s): None

Isoelectric Point: 9.69

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
PFam	PF00069	Protein kinase domain
Superfamily	SSF56112	Protein kinase-like domain superfamily

Associated Publications

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
23909752	The cooperative roles of PHO80-like cyclins in regulating the G1/S transition andposterior cytoskeletal morphogenesis in Trypanosoma brucei	Liu Y, Hu H, Li Z	10.1111/mmi.12352
37398039	The protein phosphatase PPKL is a key regulator of daughter parasite developmentin Toxoplasma gondii	Yang C, Doud EH, Sampson E, Arrizabalaga G	10.1101/2023.06.13.544803
27252375	The G1 Cyclin-dependent Kinase CRK1 in Trypanosoma brucei Regulates AnterogradeProtein Transport by Phosphorylating the COPII Subunit Sec31	Hu H, Gourguechon S, Wang CC, Li Z	10.1074/jbc.M116.715185
37877735	The protein phosphatase PPKL is a key regulator of daughter parasite developmentin Toxoplasma gondii	Yang C, Doud EH, Sampson E, Arrizabalaga G	10.1128/mbio.02254-23
36275617	Distinct mRNA and protein interactomes highlight functional differentiation ofmajor eIF4F-like complexes from Trypanosoma brucei	Bezerra MJR, Moura DMN, ..., de Melo Neto OP	10.3389/fmolb.2022.971811