About Gene List

PF3D7_0515300 (PI3K)

Genome location: Pf3D7_05_v3:628,784..635,412(+)

Genome classification: Core

Function and Localization

Product Description: phosphatidylinositol 3-kinase

SignalP Peptide: N/A

# Transmembrane Domains: 0

EC Numbers: 2.7.1.137 (Phosphatidylinositol 3-kinase);2.7.1.150 (1-phosphatidylinositol-3-phosphate 5-kinase)

Curated GO (PlasmoDB):

Type GO Term Name
Component GO:0005737 cytoplasm
Component GO:0031410 cytoplasmic vesicle
Component GO:0005768 endosome
Component GO:0020020 food vacuole
Component GO:0043656 host intracellular region
Component GO:0016020 membrane
Component GO:0005777 peroxisome
Component GO:0000407 phagophore assembly site
Component GO:0034271 phosphatidylinositol 3-kinase complex, class III, type I
Component GO:0034272 phosphatidylinositol 3-kinase complex, class III, type II
Function GO:0016303 1-phosphatidylinositol-3-kinase activity
Function GO:0030492 hemoglobin binding
Function GO:0052742 phosphatidylinositol kinase activity
Function GO:0005515 protein binding
Process GO:0000045 autophagosome assembly
Process GO:0030242 autophagy of peroxisome
Process GO:0006897 endocytosis
Process GO:0046907 intracellular transport
Process GO:0046854 phosphatidylinositol phosphate biosynthetic process
Process GO:0036092 phosphatidylinositol-3-phosphate biosynthetic process
Process GO:0048015 phosphatidylinositol-mediated signaling
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 possibly expressed N/A N/A
Ring expressed 0.42 0.81
Trophozoite expressed 1.48 0.34
Schizont expressed 0.91 0.56
Gametocyte expressed 1.03 0.49

More info:

Resistome Mutations

Old (Pf3D7v3) Gene ID: PF3D7_0515300

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: 0.242 | MFS: -2.674 | #Insertions: 0

PlasmoGEM Phenotype: Essential (Pb ortholog: PBANKA_1114900)

  • Relative Growth Rate: 0.08 ± 0.11
  • Confidence: 5.77

RMgmDB ABS Phenotype: N/A

More info: PhenoPlasm Link

Binding Evidence

AlphaFill Uniprot ID: Q8I3V5

"Best" AlphaFill ligand hit: BHO (benzhydroxamic acid, Local RMSD=0.06) with 5SXJ (Global RMSD=4.03)

BRENDA EC Inhibitors:

EC # Name EC Inhibitors
2.7.1.137 phosphatidylinositol 3-kinase BRENDA SOAP query unsuccessful
2.7.1.150 1-phosphatidylinositol-3-phosphate 5-kinase YM201636apilimodvacuolin-1

Orthology to BindingDB Entries:

UniProt Protein Name Species Homology Source BindingDB Ligands
P42336 Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform Homo sapiens OrthoDB LY294002imidazopyridine derivative, 3imidazopyridine derivative, 4imidazopyridine derivative, 7a...
P42338 Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform Homo sapiens OrthoDB 17-Hydroxywortmannin Analogue, 13LY294002PIK-75, 1CHEMBL541643...
Q9Z1L0 Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform OrthoDB US10202371, Example 1US10202371, Example 2US10202371, Example 3US10202371, Example 4...
O00329 Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform Homo sapiens OrthoDB US9828378, # 1CID24905148CID24905149PIK293...
O75747 Phosphatidylinositol 3-kinase C2 domain-containing subunit gamma Homo sapiens OrthoDB US11091472, Compound S-1US11091472, Compound S-160US11091472, Compound S-231US11091472, Compound S-261...
P32871 Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform Bos taurus OrthoDB CHEMBL3589320CHEMBL3589321CHEMBL3589322CHEMBL3589323...
Q8NEB9 Phosphatidylinositol 3-kinase catalytic subunit type 3 Homo sapiens OrthoDB STK16-IN-1US10112926, Example 4US10112926, Example 4.1US10112926, Example 9...
Q9JHG7 Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform OrthoDB GS-9820Cyclosporine ACHEMBL3753671CHEMBL3752369...
D3ZFJ0 Phosphatidylinositol-4,5-bisphosphate 3-kinase OrthoDB CHEMBL4126773
O00443 Phosphatidylinositol 4-phosphate 3-kinase C2 domain-containing subunit alpha OrthoDB STK16-IN-1CHEMBL4166144CHEMBL4160104CHEMBL4167351...
P48736 Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform Homo sapiens OrthoDB LY294002med.21724, Compound 4Myricetin (Myr)Staurosporine, 8...
Q8BTI9 Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform OrthoDB GS-9820
P42337 Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform OrthoDB US9156831, 1US9156831, 3US9156831, 4US9156831, 5...
O35904 Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform OrthoDB GS-9820US10202371, Example 1US10202371, Example 2US10202371, Example 3...
A0A0G2K344 Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform OrthoDB US10202371, Example 1US10202371, Example 2US10202371, Example 3US10202371, Example 4...
O00750 Phosphatidylinositol 4-phosphate 3-kinase C2 domain-containing subunit beta Homo sapiens OrthoDB GDC-0941LY294002PIK-75, 1CHEMBL541643...

Orthology Information

Ortholog Group (OrthoMCL): OG6_101850

Most Similar Human Ortholog: A0A0B4J2B1

TM-align score: 0.95 | RMSD: 1.08

Seq Identity: 0.42 | Length: 104 / 2133

All Human Orthologs (OrthoMCL):

Gene ID Description
ENSG00000078142 phosphatidylinositol 3-kinase catalytic subunit type 3

Protein Information

Protein Length: 2133 | Molecular Weight (kDa): 255.921

UniProt ID(s): Q8I3V5

PDB ID(s): None

Isoelectric Point: 9.63

Protein Domain Annotations:

Source Family ID Description
InterPro IPR000403 Phosphatidylinositol 3-/4-kinase, catalytic domain
InterPro IPR001263 Phosphoinositide 3-kinase, accessory (PIK) domain
InterPro IPR011009 Protein kinase-like domain superfamily
InterPro IPR015433 Phosphatidylinositol kinase
InterPro IPR016024 Armadillo-type fold
InterPro IPR018936 Phosphatidylinositol 3/4-kinase, conserved site
PFam PF00454 Phosphatidylinositol 3-/4-kinase, catalytic domain
PFam PF00613 Phosphoinositide 3-kinase, accessory (PIK) domain
Superfamily SSF48371 Armadillo-type fold
Superfamily SSF56112 Protein kinase-like domain superfamily

Genetic Variation

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

Homozygous genotype calls only

variant type common rare doubleton singleton
synonymous 23 79 29 91
disruptive 93 245 132 315
missense 48 154 107 239

Any inclusion in genotype call

variant type common rare doubleton singleton
synonymous 39 126 57 122
disruptive 150 466 235 433
missense 63 325 163 300

PlasmoDB Total SNPs: 338

Non-coding: 21 | Synonymous: 169 | Nonsynonymous: 148 | Stop Codon: 0

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
20093402 PfPI3K, a phosphatidylinositol-3 kinase from Plasmodium falciparum, is exportedto the host erythrocyte and is involved in hemoglobin trafficking. Vaid A, Ranjan R, ..., Sharma P 10.1182/blood-2009-08-238972
25874676 A molecular mechanism of artemisinin resistance in Plasmodium falciparum malaria. Mbengue A, Bhattacharjee S, ..., Haldar K 10.1038/nature14412
32543181 Heterologous Expression, Purification, and Functional Analysis of the Plasmodiumfalciparum Phosphatidylinositol 4-Kinase IIIbeta. Sternberg AR, Roepe PD 10.1021/acs.biochem.0c00259