About Gene List

PF3D7_0520600 (Ap4AH)

Genome location: Pf3D7_05_v3:842,960..845,134(-)

Genome classification: Core

Function and Localization

Product Description: bis(5'-nucleosyl)-tetraphosphatase [asymmetrical]

SignalP Peptide: N/A

# Transmembrane Domains: 0

EC Numbers: 3.6.1.17 (Bis(5'-nucleosyl)-tetraphosphatase (asymmetrical))

Curated GO (PlasmoDB):

Type GO Term Name
Component GO:0033644 host cell membrane
Function GO:0004081 bis(5'-nucleosyl)-tetraphosphatase (asymmetrical) activity
Process GO:0006167 AMP biosynthetic process
Process GO:0006754 ATP biosynthetic process

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 expressed 0.73 0.66
Trophozoite expressed 0.50 0.72
Schizont expressed 0.08 0.95
Gametocyte possibly expressed 0.26 0.85

More info:

Resistome Mutations

Old (Pf3D7v3) Gene ID: PF3D7_0520600

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: Non - Mutable in CDS *tentative

MIS: 0.129 | MFS: -3.063 | #Insertions: 0

PlasmoGEM Phenotype: N/A

RMgmDB ABS Phenotype: N/A

More info: PhenoPlasm Link

Binding Evidence

AlphaFill Uniprot ID: C0H4F3

"Best" AlphaFill ligand hit: GPP (geranyl diphosphate, Local RMSD=2.19) with 6YPF (Global RMSD=5.22)

BRENDA EC Inhibitors:

EC # Name EC Inhibitors
3.6.1.17 bis(5'-nucleosyl)-tetraphosphatase (asymmetrical) BRENDA SOAP query unsuccessful

No evidence of orthology to BindingDB entries

Orthology Information

Ortholog Group (OrthoMCL): OG6_104771

Most Similar Human Ortholog: P50583

TM-align score: 0.91 | RMSD: 1.77

Seq Identity: 0.35 | Length: 146 / 152

All Human Orthologs (OrthoMCL):

Gene ID Description
ENSG00000164978 nudix hydrolase 2

Genetic Variation

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

Homozygous genotype calls only

variant type common rare doubleton singleton
synonymous 0 8 7 14
disruptive 3 13 5 22
missense 3 13 5 22

Any inclusion in genotype call

variant type common rare doubleton singleton
synonymous 0 23 4 13
disruptive 7 22 13 40
missense 7 20 13 31

PlasmoDB Total SNPs: 96

Non-coding: 84 | Synonymous: 8 | Nonsynonymous: 4 | Stop Codon: 0

Protein Information

Protein Length: 152 | Molecular Weight (kDa): 17.75

UniProt ID(s): C0H4F3

PDB ID(s): 5CFI, 5CFJ

Isoelectric Point: 5.69

Protein Domain Annotations:

Source Family ID Description
InterPro IPR000086 NUDIX hydrolase domain
InterPro IPR003565 Bis(5'-nucleosyl)-tetraphosphatase
InterPro IPR015797 NUDIX hydrolase-like domain superfamily
InterPro IPR020084 NUDIX hydrolase, conserved site
PFam PF00293 NUDIX hydrolase domain
Superfamily SSF55811 NUDIX hydrolase-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
22791172 Molecular characterization and mutational analysis of recombinant diadenosine5',5''-P(1),P(4)-tetraphosphate hydrolase from Plasmodium falciparum. Osman W, Endo S, ..., Kitade Y 10.1248/bpb.b12-00165
26829485 Structural and functional attributes of malaria parasite diadenosinetetraphosphate hydrolase. Sharma A, Yogavel M, Sharma A 10.1038/srep19981
30700216 Functional genetic evaluation of DNA house-cleaning enzymes in the malariaparasite: dUTPase and Ap4AH are essential in Plasmodium berghei but ITPase andNDH are dispensable Kumar H, Kehrer J, ..., Frischknecht F 10.1080/14728222.2019.1575810