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phosphatidylinositol 4-kinase alpha

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Target id: 2148

Nomenclature: phosphatidylinositol 4-kinase alpha

Abbreviated Name: PI4KIIIα/PIK4CA

Family: 1-phosphatidylinositol 4-kinase family, Phosphatidylinositol kinases

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 2102 22q11.21 PI4KA phosphatidylinositol 4-kinase alpha
Mouse - 2044 16 A3 Pi4ka phosphatidylinositol 4-kinase alpha
Rat - 2041 11 q23 Pi4ka phosphatidylinositol 4-kinase alpha
Previous and Unofficial Names Click here for help
phosphatidylinositol 4-kinase, catalytic, alpha | leuserpin 2 | PI4K-alpha | PtdIns-4-kinase alpha
Database Links Click here for help
Alphafold P42356 (Hs)
BRENDA 2.7.1.67
CATH/Gene3D 1.10.1070.11, 1.25.10.10
ChEMBL Target CHEMBL3667 (Hs)
Ensembl Gene ENSG00000241973 (Hs), ENSMUSG00000041720 (Mm), ENSRNOG00000060045 (Rn)
Entrez Gene 5297 (Hs), 224020 (Mm), 64161 (Rn)
Human Protein Atlas ENSG00000241973 (Hs)
KEGG Enzyme 2.7.1.67
KEGG Gene hsa:5297 (Hs), mmu:224020 (Mm), rno:64161 (Rn)
OMIM 600286 (Hs)
Pharos P42356 (Hs)
RefSeq Nucleotide NM_058004 (Hs), NM_001001983 (Mm), NM_022301 (Rn)
RefSeq Protein NP_477352 (Hs), NP_001001983 (Mm), NP_071637 (Rn)
UniProtKB P42356 (Hs)
Wikipedia PI4KA (Hs)
Enzyme Reaction Click here for help
EC Number: 2.7.1.67

Download all structure-activity data for this target as a CSV file go icon to follow link

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
wortmannin Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 6.7 – 6.8 pIC50 3,5
⤷ pIC50 6.7 – 6.8 [3,5]
phenylarsine oxide Small molecule or natural product Ligand has a PDB structure Hs Inhibition - - 1
⤷ [1]
DiscoveRx KINOMEscan® screen Click here for help
A screen of 72 inhibitors against 456 human kinases. Quantitative data were derived using DiscoveRx KINOMEscan® platform.
http://www.discoverx.com/services/drug-discovery-development-services/kinase-profiling/kinomescan
Reference: 2,6
Key to terms and symbols Click column headers to sort
Target used in screen: PIK4CB
Ligand Sp. Type Action Value Parameter
MLN-120B Small molecule or natural product Immunopharmacology Ligand Hs Inhibitor Inhibition 6.6 pKd
lestaurtinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 6.5 pKd
TG-100-115 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 6.4 pKd
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 6.3 pKd
NVP-TAE684 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 6.1 pKd
tamatinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 6.0 pKd
PP-242 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 6.0 pKd
lapatinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 6.0 pKd
pazopanib Small molecule or natural product Approved drug Hs Inhibitor Inhibition 6.0 pKd
PLX-4720 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 5.9 pKd
Displaying the top 10 most potent ligands  View all ligands in screen »
Tissue Distribution Click here for help
Intracellular membranes, with prominent co-localization with early endosomes and recycling endosomes but not with the Golgi.
Species:  Human
Technique:  Immunocytochemistry and confocal microscopy using epitope-tagged and green fluorescent protein-tagged enzyme expressed in COS-7 cells.
References:  1
Physiological Functions Click here for help
PI4KIIα is required for trafficking LIMP-2 (a receptor for transport of β-glucocerebrosidase into lysosomes) at a post-Golgi compartment (endocytic transport), leading to accumulation of LIMP-2 in enlarged endosomal vesicles. β-glucocerebrosidase (GBA) is the Gaucher disease enzyme.
Species:  Human
Tissue:  COS-7 cells transfected with a fluorescent LIMP-2.
References:  4

References

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1. Balla A, Tuymetova G, Barshishat M, Geiszt M, Balla T. (2002) Characterization of type II phosphatidylinositol 4-kinase isoforms reveals association of the enzymes with endosomal vesicular compartments. J Biol Chem, 277 (22): 20041-50. [PMID:11923287]

2. Davis MI, Hunt JP, Herrgard S, Ciceri P, Wodicka LM, Pallares G, Hocker M, Treiber DK, Zarrinkar PP. (2011) Comprehensive analysis of kinase inhibitor selectivity. Nat Biotechnol, 29 (11): 1046-51. [PMID:22037378]

3. Gehrmann T, Gülkan H, Suer S, Herberg FW, Balla A, Vereb G, Mayr GW, Heilmeyer Jr LM. (1999) Functional expression and characterisation of a new human phosphatidylinositol 4-kinase PI4K230. Biochim Biophys Acta, 1437 (3): 341-56. [PMID:10101268]

4. Jović M, Kean MJ, Szentpetery Z, Polevoy G, Gingras AC, Brill JA, Balla T. (2012) Two phosphatidylinositol 4-kinases control lysosomal delivery of the Gaucher disease enzyme, β-glucocerebrosidase. Mol Biol Cell, 23 (8): 1533-45. [PMID:22337770]

5. Meyers R, Cantley LC. (1997) Cloning and characterization of a wortmannin-sensitive human phosphatidylinositol 4-kinase. J Biol Chem, 272 (7): 4384-90. [PMID:9020160]

6. Wodicka LM, Ciceri P, Davis MI, Hunt JP, Floyd M, Salerno S, Hua XH, Ford JM, Armstrong RC, Zarrinkar PP et al.. (2010) Activation state-dependent binding of small molecule kinase inhibitors: structural insights from biochemistry. Chem Biol, 17 (11): 1241-9. [PMID:21095574]

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