About Gene List

PF3D7_1219600 (ATP2)

Genome location: Pf3D7_12_v3:785,247..791,068(-)

Genome classification: Core

Function and Localization

Product Description: phospholipid-transporting ATPase 2

SignalP Peptide: N/A

# Transmembrane Domains: 10

EC Numbers: 3.6.3.1 (Transferred entry: 7.6.2.1);7.6.2.1 (P-type phospholipid transporter)

Curated GO (PlasmoDB):

Type GO Term Name
Component GO:0016021 integral component of membrane
Component GO:0005886 plasma membrane
Function GO:0016887 ATP hydrolysis activity
Function GO:0140326 ATPase-coupled intramembrane lipid transporter activity
Function GO:0005515 protein binding
Process GO:0045332 phospholipid translocation
Process GO:0015914 phospholipid transport
Process GO:0009410 response to xenobiotic stimulus

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 0.61 0.71
Trophozoite expressed 1.03 0.47
Schizont expressed 0.98 0.46
Gametocyte expressed 0.51 0.71

More info:

Resistome Mutations

Old (Pf3D7v3) Gene ID: PF3D7_1219600

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

MIS: 0.119 | MFS: -3.033 | #Insertions: 0

PlasmoGEM Phenotype: Essential (Pb ortholog: PBANKA_1434800)

  • Relative Growth Rate: 0.10 ± 0.28
  • Confidence: 1.00

RMgmDB ABS Phenotype: Different from wild type (Pb ortholog: PBANKA_1434800)

Modification: Tagged | RMgm-1405

More info: PhenoPlasm Link

Binding Evidence

AlphaFill Uniprot ID: Q8I5L4

"Best" AlphaFill ligand hit: PCW ((z,z)-4-hydroxy-n,n,n-trimethyl-10-oxo-7-[(1-oxo-9-octadecenyl)oxy]-3,5,9-trioxa-4-phosphaheptacos-18-en-1-aminium-4-oxide, Local RMSD=0.04) with 7W48 (Global RMSD=2.88)

BRENDA EC Inhibitors:

EC # Name EC Inhibitors
3.6.3.1 phospholipid-translocating ATPase No BRENDA inhibitors
7.6.2.1 P-type phospholipid transporter NEMNaFEDTADTNBazideBcl-2Kes1psuraminDiamideAMP-PNPlipid Aeosin Y...

No evidence of orthology to BindingDB entries

Orthology Information

Ortholog Group (OrthoMCL): OG6_100089

Most Similar Human Ortholog: H7C4E6

TM-align score: 0.95 | RMSD: 1.46

Seq Identity: 0.35 | Length: 237 / 1555

All Human Orthologs (OrthoMCL):

Gene ID Description
ENSG00000058063 ATPase phospholipid transporting 11B (putative)
ENSG00000068650 ATPase phospholipid transporting 11A
ENSG00000081923 ATPase phospholipid transporting 8B1
ENSG00000101974 ATPase phospholipid transporting 11C
ENSG00000104043 ATPase phospholipid transporting 8B4 (putative)
ENSG00000124406 ATPase phospholipid transporting 8A1
ENSG00000130270 ATPase phospholipid transporting 8B3
ENSG00000132932 ATPase phospholipid transporting 8A2
ENSG00000143515 ATPase phospholipid transporting 8B2

Genetic Variation

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

Homozygous genotype calls only

variant type common rare doubleton singleton
synonymous 17 58 27 84
disruptive 20 51 46 101
missense 14 46 38 88

Any inclusion in genotype call

variant type common rare doubleton singleton
synonymous 32 90 49 80
disruptive 35 137 59 190
missense 21 102 49 143

PlasmoDB Total SNPs: 144

Non-coding: 64 | Synonymous: 60 | Nonsynonymous: 20 | Stop Codon: 0

Protein Information

Protein Length: 1555 | Molecular Weight (kDa): 179.135

UniProt ID(s): Q27720, Q27728, Q8I5L4, Q9U421

PDB ID(s): None

Isoelectric Point: 7.07

Protein Domain Annotations:

Source Family ID Description
InterPro IPR001757 P-type ATPase
InterPro IPR006539 P-type ATPase, subfamily IV
InterPro IPR008250 P-type ATPase, A domain superfamily
InterPro IPR018303 P-type ATPase, phosphorylation site
InterPro IPR023298 P-type ATPase, transmembrane domain superfamily
InterPro IPR023299 P-type ATPase, cytoplasmic domain N
InterPro IPR026871 Phospholipid-transporting P-type ATPase
InterPro IPR032630 P-type ATPase, C-terminal
InterPro IPR032631 P-type ATPase, N-terminal
InterPro IPR036412 HAD-like superfamily
PFam PF16209 P-type ATPase, N-terminal
PFam PF16212 P-type ATPase, C-terminal
Superfamily SSF56784 HAD-like superfamily
Superfamily SSF81653 P-type ATPase, A domain superfamily
Superfamily SSF81660 P-type ATPase, cytoplasmic domain N
Superfamily SSF81665 P-type ATPase, transmembrane domain superfamily

Associated Publications

PMID Title Authors DOI/Link
11152613 Predicting transmembrane protein topology with a hidden Markov model: applicationto complete genomes. Krogh A, Larsson B, von Heijne G, Sonnhammer EL 10.1006/jmbi.2000.4315
12368864 Genome sequence of the human malaria parasite Plasmodium falciparum. Gardner MJ, Hall N, ..., Barrell B 10.1038/nature01097
29326268 Mapping the malaria parasite druggable genome by using in vitro evolution andchemogenomics. Cowell AN, Istvan ES, ..., Winzeler EA 10.1126/science.aan4472
33372863 ATP2, The essential P4-ATPase of malaria parasites, catalyzes lipid-stimulatedATP hydrolysis in complex with a Cdc50 beta-subunit. Lamy A, Macarini-Bruzaferro E, ..., Vazquez-Ibar JL https://pubmed.ncbi.nlm.nih.gov/33372863/
35862778 CDC50 Orthologues in Plasmodium falciparum Have Distinct Roles in MerozoiteEgress and Trophozoite Maturation. Patel A, Nofal SD, Blackman MJ, Baker DA 10.1128/mbio.01635-22
35877905 In Silico Assessment of the Lipid Fingerprint Signature of ATP2, the EssentialP4-ATPase of Malaria Parasites Lopez-Martin M, Renault P, ..., Peralvarez-Marin A 10.3390/membranes12070702