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phosphatidylinositol 4-kinase beta

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Target id: 2149

Nomenclature: phosphatidylinositol 4-kinase beta

Abbreviated Name: PI4KIIIβ/PIK4CB

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

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 816 1q21.3 PI4KB phosphatidylinositol 4-kinase beta
Mouse - 816 3 F2.1 Pi4kb phosphatidylinositol 4-kinase beta
Rat - 816 2q34 Pi4kb phosphatidylinositol 4-kinase beta
Gene and Protein Information Comments
The Antimalarial targets family provides information about P. falciparum phosphatidylinositol-4 kinase.
Previous and Unofficial Names Click here for help
phosphatidylinositol 4-kinase, catalytic, beta | phosphatidylinositol 4-kinase, catalytic, beta polypeptide | PI4Kbeta | ptdIns 4-kinase beta
Database Links Click here for help
Alphafold
BRENDA
CATH/Gene3D
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Enzyme
KEGG Gene
OMIM
Pharos
RefSeq Nucleotide
RefSeq Protein
SynPHARM
UniProtKB
Wikipedia
Enzyme Reaction Click here for help
EC Number: 2.7.1.67
Endogenous activation
PKD-mediated phosphorylation  [4]

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
torin 2 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.7 pIC50 7
pIC50 7.7 (IC50 1.83x10-8 M) [7]
PIK-93 Small molecule or natural product Primary target of this compound Ligand has a PDB structure Hs Inhibition 7.7 pIC50 1,6
pIC50 7.7 (IC50 1.9x10-8 M) [1,6]
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 3,8
pIC50 6.7 – 6.8 [3,8]
Immuno Process Associations
Immuno Process:  Antigen presentation
GO Annotations:  Associated to 1 GO processes
GO:0006898 receptor-mediated endocytosis TAS
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:  2
Physiological Functions Click here for help
PI4KIIIβ is responsible for controlling the exit of LIMP-2 from the Golgi. LIMP-2 is a receptor for transport of β-glucocerebrosidase into lysosomes. β-glucocerebrosidase (GBA) is the Gaucher disease enzyme.
Species:  Human
Tissue:  COS-7 cells transfected with photoactivatable LIMP-2
References:  5

References

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1. Balla A, Kim YJ, Varnai P, Szentpetery Z, Knight Z, Shokat KM, Balla T. (2008) Maintenance of hormone-sensitive phosphoinositide pools in the plasma membrane requires phosphatidylinositol 4-kinase IIIalpha. Mol Biol Cell, 19 (2): 711-21. [PMID:18077555]

2. 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]

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. Hausser A, Storz P, Märtens S, Link G, Toker A, Pfizenmaier K. (2005) Protein kinase D regulates vesicular transport by phosphorylating and activating phosphatidylinositol-4 kinase IIIbeta at the Golgi complex. Nat Cell Biol, 7 (9): 880-6. [PMID:16100512]

5. 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]

6. Knight ZA, Gonzalez B, Feldman ME, Zunder ER, Goldenberg DD, Williams O, Loewith R, Stokoe D, Balla A, Toth B et al.. (2006) A pharmacological map of the PI3-K family defines a role for p110alpha in insulin signaling. Cell, 125 (4): 733-47. [PMID:16647110]

7. Liu Q, Wang J, Kang SA, Thoreen CC, Hur W, Ahmed T, Sabatini DM, Gray NS. (2011) Discovery of 9-(6-aminopyridin-3-yl)-1-(3-(trifluoromethyl)phenyl)benzo[h][1,6]naphthyridin-2(1H)-one (Torin2) as a potent, selective, and orally available mammalian target of rapamycin (mTOR) inhibitor for treatment of cancer. J Med Chem, 54 (5): 1473-80. [PMID:21322566]

8. 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]

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