PF3D7_1363200 (PNKP)

Genome location: Pf3D7_13_v3:2,539,355..2,541,896(-)

Genome classification: Core

Function and Localization

Product Description: bifunctional polynucleotide phosphatase/kinase

SignalP Peptide: N/A

# Transmembrane Domains: 0

EC Numbers: 2.7.1.78 (Polynucleotide 5'-hydroxyl-kinase);3.1.3.32 (Polynucleotide 3'-phosphatase)

Curated GO (PlasmoDB):

Type	GO Term	Name
Function	GO:0003684	damaged DNA binding
Function	GO:0003690	double-stranded DNA binding
Function	GO:0046404	polydeoxyribonucleotide 5'-hydroxyl-kinase activity
Function	GO:0046403	polynucleotide 3'-phosphatase activity
Process	GO:0006281	DNA repair
Process	GO:0006974	cellular response to DNA damage stimulus
Process	GO:0046939	nucleotide phosphorylation

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	0.22	0.89
Trophozoite	expressed	0.47	0.72
Schizont	not expressed	0.07	0.96
Gametocyte	not expressed	0.39	0.78

More info:

Resistome Mutations

Old (Pf3D7v3) Gene ID: PF3D7_1363200

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: -0.753 | #Insertions: 4

PlasmoGEM Phenotype: N/A

RMgmDB ABS Phenotype: N/A

More info: PhenoPlasm Link

Binding Evidence

AlphaFill Uniprot ID: Q8ID74

"Best" AlphaFill ligand hit: ADP (adenosine-5'-diphosphate, Local RMSD=1.29) with 3ZVM (Global RMSD=2.66)

BRENDA EC Inhibitors:

EC #	Name	EC Inhibitors
2.7.1.78	polynucleotide 5'-hydroxyl-kinase	ADPGTPCTPUTPKClEDTANH4+dATPdTTPdCTPdGTPAgNO3...
3.1.3.32	polynucleotide 3'-phosphatase	EDTASO42-PO43-heparindiphosphate2-(1-hydroxyundecyl)-1-(4-nitrophenylamino)-6-phenyl-6,7a-dihydro-1H-pyrrolo[3,4-b]pyridine-5,7(2H,4aH)-dione2-(hydroxy(phenyl)methyl)-1-(4-nitrophenylamino)-6-phenyl-6,7a-dihydro-1H-pyrrolo[3,4-b]pyridine-5,7(2H,4aH)-dione2-(hydroxy(thiophen-2-yl)methyl)-6-methyl-1-(phenylamino)-6,7a-dihydro-1H-pyrrolo[3,4-b]pyridine-5,7(2H,4aH)-dionetert-butyl 2-(1-hydroxy-2,2-diphenylethyl)-6-methyl-5,7-dioxo-2,4a,5,6,7,7a-hexahydro-1H-pyrrolo[3,4-b]pyridin-1-ylcarbamate2-(hydroxy(3,4,5-trimethoxyphenyl)methyl)-1-(4-nitrophenylamino)-6-phenyl-6,7a-dihydro-1H-pyrrolo[3,4-b]pyridine-5,7(2H,4aH)-dione

Orthology to BindingDB Entries:

UniProt	Protein Name	Species	Homology Source	BindingDB Ligands
Q96T60	Bifunctional polynucleotide phosphatase/kinase		OMA, OrthoDB, OrthoMCL BLAST	US11325905, Compound A77B4C3US11325905, Compound A89B4C3US11325905, Compound A12B4C10US11325905, Compound A12B4C15...

Orthology Information

Ortholog Group (OrthoMCL): OG6_102580

Most Similar Human Ortholog: M0R097

TM-align score: 0.84 | RMSD: 1.34

Seq Identity: 0.20 | Length: 56 / 462

All Human Orthologs (OrthoMCL):

Gene ID	Description
ENSG00000039650	polynucleotide kinase 3-phosphatase

Protein Information

Protein Length: 462 | Molecular Weight (kDa): 55.334

UniProt ID(s): Q8ID74

PDB ID(s): None

Isoelectric Point: 9.36

Protein Domain Annotations:

Source	Family ID	Description
InterPro	IPR006549	HAD-superfamily hydrolase,subfamily IIIA
InterPro	IPR013954	Polynucleotide kinase 3 phosphatase
InterPro	IPR027417	P-loop containing nucleoside triphosphate hydrolase
InterPro	IPR036412	HAD-like superfamily
PFam	PF08645	Polynucleotide kinase 3 phosphatase
Superfamily	SSF52540	P-loop containing nucleoside triphosphate hydrolase
Superfamily	SSF56784	HAD-like superfamily

Genetic Variation

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

Homozygous genotype calls only

variant type	common	rare	doubleton	singleton
synonymous	4	27	10	28
disruptive	3	33	31	67
missense	3	32	30	63

Any inclusion in genotype call

variant type	common	rare	doubleton	singleton
synonymous	7	46	20	34
disruptive	8	84	55	111
missense	7	70	49	90

PlasmoDB Total SNPs: 152

Non-coding: 129 | Synonymous: 15 | Nonsynonymous: 6 | Stop Codon: 2