INPP5E explained

72 kDa inositol polyphosphate 5-phosphatase, also known as phosphatidylinositol-4,5-bisphosphate 5-phosphatase or Pharbin, is an enzyme that in humans is encoded by the INPP5E gene.^{[1] [2]}

Function

INPP5E is a phosphatidylinositol (3,4,5)-trisphosphate (PtdInsP3) and phosphatidylinositol 4,5-bisphosphate 5-phosphatase. Its intracellular localization is the primary cilium, a small organelle involved in signal transduction. INPP5E plays a role in hydrolyzing PtdInsP3 produced in response to various growth factors such as PDGF. Inactivation of the mouse INPP5E gene decreases primary cilia stability, leading to a multiorgan disorder, including absence of eyes, polydactyly, exencephaly and renal cysts.

Clinical significance

Mutations in the INPP5E are associated with MORM syndrome^[3] and Joubert syndrome.^[4]

Further reading

• Jin J, Smith FD, Stark C, Wells CD, Fawcett JP, Kulkarni S, Metalnikov P, O'Donnell P, Taylor P, Taylor L, Zougman A, Woodgett JR, Langeberg LK, Scott JD, Pawson T . Proteomic, functional, and domain-based analysis of in vivo 14-3-3 binding proteins involved in cytoskeletal regulation and cellular organization . Current Biology . 14 . 16 . 1436–50 . August 2004 . 15324660 . 10.1016/j.cub.2004.07.051 . 2371325 . free . 2004CBio...14.1436J .
• Kong AM, Speed CJ, O'Malley CJ, Layton MJ, Meehan T, Loveland KL, Cheema S, Ooms LM, Mitchell CA . Cloning and characterization of a 72-kDa inositol-polyphosphate 5-phosphatase localized to the Golgi network . The Journal of Biological Chemistry . 275 . 31 . 24052–64 . August 2000 . 10806194 . 10.1074/jbc.M000874200 . free .
• Jacoby M, Cox JJ, Gayral S, Hampshire DJ, Ayub M, Blockmans M, Pernot E, Kisseleva MV, Compère P, Schiffmann SN, Gergely F, Riley JH, Pérez-Morga D, Woods CG, Schurmans S . INPP5E mutations cause primary cilium signaling defects, ciliary instability and ciliopathies in human and mouse . Nature Genetics . 41 . 9 . 1027–31 . September 2009 . 19668215 . 10.1038/ng.427 . 5249668 .
• Ono A, Ablan SD, Lockett SJ, Nagashima K, Freed EO . Phosphatidylinositol (4,5) bisphosphate regulates HIV-1 Gag targeting to the plasma membrane . Proceedings of the National Academy of Sciences of the United States of America . 101 . 41 . 14889–94 . October 2004 . 15465916 . 522033 . 10.1073/pnas.0405596101 . 2004PNAS..10114889O . free .

Notes and References

1. Web site: Entrez Gene: inositol polyphosphate-5-phosphatase.
2. Kisseleva MV, Wilson MP, Majerus PW . The isolation and characterization of a cDNA encoding phospholipid-specific inositol polyphosphate 5-phosphatase . The Journal of Biological Chemistry . 275 . 26 . 20110–6 . June 2000 . 10764818 . 10.1074/jbc.M910119199 . free .
3. Hampshire DJ, Ayub M, Springell K, Roberts E, Jafri H, Rashid Y, Bond J, Riley JH, Woods CG . MORM syndrome (mental retardation, truncal obesity, retinal dystrophy and micropenis), a new autosomal recessive disorder, links to 9q34 . European Journal of Human Genetics . 14 . 5 . 543–8 . May 2006 . 16493448 . 10.1038/sj.ejhg.5201577 . 20931689 .
4. Bielas SL, Silhavy JL, Brancati F, Kisseleva MV, Al-Gazali L, Sztriha L, Bayoumi RA, Zaki MS, Abdel-Aleem A, Rosti RO, Kayserili H, Swistun D, Scott LC, Bertini E, Boltshauser E, Fazzi E, Travaglini L, Field SJ, Gayral S, Jacoby M, Schurmans S, Dallapiccola B, Majerus PW, Valente EM, Gleeson JG . Mutations in INPP5E, encoding inositol polyphosphate-5-phosphatase E, link phosphatidyl inositol signaling to the ciliopathies . Nature Genetics . 41 . 9 . 1032–6 . September 2009 . 19668216 . 2746682 . 10.1038/ng.423 .