phosphoinositide kinase, FYVE-type zinc finger containing | 1-phosphatidylinositol-3-phosphate 5-kinase family | IUPHAR/BPS Guide to PHARMACOLOGY

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phosphoinositide kinase, FYVE-type zinc finger containing

target has curated data in GtoImmuPdb

Target id: 2857

Nomenclature: phosphoinositide kinase, FYVE-type zinc finger containing

Family: 1-phosphatidylinositol-3-phosphate 5-kinase family

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 2098 2q34 PIKFYVE phosphoinositide kinase, FYVE-type zinc finger containing 6
Mouse - 2052 1 C2 Pikfyve phosphoinositide kinase, FYVE type zinc finger containing
Rat - - 9q32 Pikfyve phosphoinositide kinase, FYVE-type zinc finger containing
Previous and Unofficial Names
FAB1 | phosphatidylinositol-3-phosphate/phosphatidylinositol 5-kinase, type III | PIP5K3 | zinc finger, FYVE domain containing 29 | phosphoinositide kinase, FYVE finger containing | phosphoinositide kinase | phosphoinositide kinase, FYVE type zinc finger containing
Database Links
BRENDA
CATH/Gene3D
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Enzyme
KEGG Gene
OMIM
Pharos
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Enzyme Reaction
EC Number: 2.7.1.150 ATP + 1-phosphatidyl-1D-myo-inositol 3-phosphate = ADP + 1-phosphatidyl-1D-myo-inositol 3,5-bisphosphate

Download all structure-activity data for this target as a CSV file

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
apilimod Hs Inhibition 7.2 pKd 1
pKd 7.2 (Kd 6.5x10-8 M) [1]
Description: Binding constant for Cy5-apilimod to PIKfyve kinase domain.
apilimod Hs Inhibition 7.8 pIC50 1
pIC50 7.8 (IC50 1.4x10-8 M) [1]
Description: Effect of apilimod on hPIKfyve kinase activity in vitro measuringPI(3)P conversion to PI(3,5)P2.
Immunopharmacology Comments
PIKfyve is a class III PI kinase. Evidence is revealing a crucial role for PIKfyve in Toll-like receptor (TLR) signaling via production of the cytokines IL-12 and IL-23 [1]. Pharmacological (using apilimod) or genetic inactivation of PIKfyve suppresses expression of the p40 (IL-12B) subunit shared by IL-12 and IL-23, and this has a regulatory role on TLR signaling.
Clinically-Relevant Mutations and Pathophysiology
Disease:  Corneal dystrophy, Fleck
Description: A rare, autosomal dominant disease which causes the formation of numerous tiny, dot-like white flecks scattered in all layers of the corneal stroma. A few patients present with photophobia, but the majority are asymptomatic.
Synonyms: CFD
corneal dystrophy, Francois-Neetens speckled ro flecked
OMIM: 121850
Role: 
References:  3-5
Click column headers to sort
Type Species Amino acid change Nucleotide change Description Reference
Frameshift: Deletion Human 4166_4169delAAGT or 4167_4170delAGTA This mutation deletes 4 nucleotides in exon 24 of the gene, leading to a truncated protein product. 3
Missense Human K1103R 3466A>G 4
General Comments
Pharmacological inhibition of PIKfyve by apilimod (STA-5326) has potent cytotoxic activity against B-cell non-Hodgkin lymphoma cells [2]. This effect is selective for the lymphoma cells compared to normal cells.

References

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1. Cai X, Xu Y, Cheung AK, Tomlinson RC, Alcázar-Román A, Murphy L, Billich A, Zhang B, Feng Y, Klumpp M et al.. (2013) PIKfyve, a class III PI kinase, is the target of the small molecular IL-12/IL-23 inhibitor apilimod and a player in Toll-like receptor signaling. Chem. Biol., 20 (7): 912-21. [PMID:23890009]

2. Gayle S, Landrette S, Beeharry N, Conrad C, Hernandez M, Beckett P, Ferguson SM, Mandelkern T, Zheng M, Xu T et al.. (2017) Identification of apilimod as a first-in-class PIKfyve kinase inhibitor for treatment of B-cell non-Hodgkin lymphoma. Blood, 129 (13): 1768-1778. [PMID:28104689]

3. Kawasaki S, Yamasaki K, Nakagawa H, Shinomiya K, Nakatsukasa M, Nakai Y, Kinoshita S. (2012) A novel mutation (p.Glu1389AspfsX16) of the phosphoinositide kinase, FYVE finger containing gene found in a Japanese patient with fleck corneal dystrophy. Mol. Vis., 18: 2954-60. [PMID:23288988]

4. Li S, Tiab L, Jiao X, Munier FL, Zografos L, Frueh BE, Sergeev Y, Smith J, Rubin B, Meallet MA et al.. (2005) Mutations in PIP5K3 are associated with François-Neetens mouchetée fleck corneal dystrophy. Am. J. Hum. Genet., 77 (1): 54-63. [PMID:15902656]

5. Nicholson DH, Green WR, Cross HE, Kenyon KR, Massof D. (1977) A clinical and histopathological study of François-Neetens speckled corneal dystrophy. Am. J. Ophthalmol., 83 (4): 554-60. [PMID:141212]

6. Shisheva A, Sbrissa D, Ikonomov O. (1999) Cloning, characterization, and expression of a novel Zn2+-binding FYVE finger-containing phosphoinositide kinase in insulin-sensitive cells. Mol. Cell. Biol., 19 (1): 623-34. [PMID:9858586]

How to cite this page

1-phosphatidylinositol-3-phosphate 5-kinase family: phosphoinositide kinase, FYVE-type zinc finger containing. Last modified on 11/12/2018. Accessed on 18/09/2020. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2857.