Tchem PIKFYVE 1-phosphatidylinositol 3-phosphate 5-kinase

Protein Summary

Description

The PI(3,5)P2 regulatory complex regulates both the synthesis and turnover of phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2). Catalyzes the phosphorylation of phosphatidylinositol 3-phosphate on the fifth hydroxyl of the myo-inositol ring, to form phosphatidylinositol 3,5-bisphosphate. Required for endocytic-vacuolar pathway and nuclear migration. Plays a role in the biogenesis of endosome carrier vesicles (ECV)/ multivesicular bodies (MVB) transport intermediates from early endosomes. Phosphorylated derivatives of phosphatidylinositol (PtdIns) regulate cytoskeletal functions, membrane trafficking, and receptor signaling by recruiting protein complexes to cell- and endosomal-membranes. Humans have multiple PtdIns proteins that differ by the degree and position of phosphorylation of the inositol ring. This gene encodes an enzyme (PIKfyve; also known as phosphatidylinositol-3-phosphate 5-kinase type III or PIPKIII) that phosphorylates the D-5 position in PtdIns and phosphatidylinositol-3-phosphate (PtdIns3P) to make PtdIns5P and PtdIns(3,5)biphosphate. The D-5 position also can be phosphorylated by type I PtdIns4P-5-kinases (PIP5Ks) that are encoded by distinct genes and preferentially phosphorylate D-4 phosphorylated PtdIns. In contrast, PIKfyve preferentially phosphorylates D-3 phosphorylated PtdIns. In addition to being a lipid kinase, PIKfyve also has protein kinase activity. PIKfyve regulates endomembrane homeostasis and plays a role in the biogenesis of endosome carrier vesicles from early endosomes. Mutations in this gene cause corneal fleck dystrophy (CFD); an autosomal dominant disorder characterized by numerous small white flecks present in all layers of the corneal stroma. Histologically, these flecks appear to be keratocytes distended with lipid and mucopolysaccharide filled intracytoplasmic vacuoles. Alternative splicing results in multiple transcript variants encoding distinct isoforms.[provided by RefSeq, May 2010]

Uniprot Accession IDs

• Q9Y2I7
• Q08AR7
• Q08AR8
• Q53ST3
• Q53T36
• Q8N5H0
• Q8NB67
• Phosphatidylinositol 3-phosphate 5-kinase

Gene Name

• PIKFYVE

Ensembl ID

• ENST00000264380
• ENSP00000264380
• ENSG00000115020
• ENST00000308862
• ENSP00000308715
• ENST00000392202
• ENSP00000376038
• ENST00000407449
• ENSP00000384356

Symbol

• KIAA0981
• PIP5K3
• CFD
• FAB1
• HEL37
• PIP5K
• PIP5K3
• ZFYVE29

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
protein domain	1
molecular function	0.99
transcription factor binding site profile	0.88
microRNA	0.84
cell line	0.72

Protein Classes

DTO Classes

Protein / Kinase / Non-protein Kinase / Lipid Kinase / 1-phosphatidylinositol 3-phosphate 5-kinase

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 301.98   (req: < 5)

Gene RIFs: 48   (req: <= 3)

Antibodies: 304   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 301.98   (req: >= 5)

Gene RIFs: 48   (req: > 3)

Antibodies: 304   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 12

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligand: 1

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0