Phosphatase Subfamily INPP5F

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Phosphatase Classification: Fold CC1: Superfamily CC1: Family Sac: Subfamily INPP5F (SAC2)

INPP5F (SAC2) is a phosphoinositide phosphatase in the endocytic pathway. It is conserved in metazoa and fungi and is also found in a few plants and basal eukaryotes.


The INPP5F (SAC2) subfamily is found in most metazoa and fungi. It is also found in a few plants and basal eukaryotes (see gOrtholog database (internal)).


The INPP5F (SAC2) subfamily has at least one structural domain, SAC phosphatase domain. It also has a C-terminal proline-rich region.


Human INPP5F (SAC2) is expressed in most tissues and particularly abundant in brain (see GTEx). It has 5-phosphatase activity specific for phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) and phosphatidylinositol 3,4,5-trisphosphate (PI(3,4,5)P3)[1]. It also has 4-phosphatase activity toward PI(4,5)P2) in the endocytic pathway [2, 3]. It cooperates with OCRL, a 5-phosphatase, in the sequential dephosphorylation of PI(4,5)P2 at the 4 and 5 position of inositol in a partnership that mimics that of the two phosphatase modules of synaptojanin [2].


  1. Minagawa T, Ijuin T, Mochizuki Y, and Takenawa T. Identification and characterization of a sac domain-containing phosphoinositide 5-phosphatase. J Biol Chem. 2001 Jun 22;276(25):22011-5. DOI:10.1074/jbc.M101579200 | PubMed ID:11274189 | HubMed [Minagawa01]
  2. Nakatsu F, Messa M, Nández R, Czapla H, Zou Y, Strittmatter SM, and De Camilli P. Sac2/INPP5F is an inositol 4-phosphatase that functions in the endocytic pathway. J Cell Biol. 2015 Apr 13;209(1):85-95. DOI:10.1083/jcb.201409064 | PubMed ID:25869668 | HubMed [Nakatsu15]
  3. Hsu F, Hu F, and Mao Y. Spatiotemporal control of phosphatidylinositol 4-phosphate by Sac2 regulates endocytic recycling. J Cell Biol. 2015 Apr 13;209(1):97-110. DOI:10.1083/jcb.201408027 | PubMed ID:25869669 | HubMed [Hsu15]
  4. Hughes WE, Cooke FT, and Parker PJ. Sac phosphatase domain proteins. Biochem J. 2000 Sep 1;350 Pt 2:337-52. PubMed ID:10947947 | HubMed [Hughes00]
All Medline abstracts: PubMed | HubMed