Phosphatase Family PTEN

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Phosphatase Classification: Superfamily CC1: Family PTEN

PTEN is a family of lipid phosphatases and lipid-binding proteins that is closely related to the DSP family. PTEN itself is found in all eukaryotes and is a negative regulator of PI3K signaling. Other defined subfamilies are largely holozoan-specific and frequently appear to be catalytically inactive and to function as lipid-binding domains of larger proteins. All subfamilies have a specialized C2 domain (C2_PTEN) immediately following the phosphatase domain.

PTEN subfamily

PTEN subfamily is named after its single member in human, PTEN, which acts as a phosphatase to dephosphorylate phosphatidylinositol (3,4,5)-trisphosphate (PtdIns (3,4,5)P3 or PIP3). PTEN is one of the most commonly lost tumor suppressors in human cancer. It is found throughout eukaryotes (unpublished data from gOrtholog).

VSP subfamily

The Voltage Sensitive Phosphatase (VSP) members consist of a voltage sensor consisting of four transmembrane segments [1], in addition to phosphatase domain and C2 domain. It has two members in human, TPTE and TPTE2 (TPIP), but TPTE is a pseudophosphatase. The subfamily is conserved in holozoa but absent from nematodes and most arthropods. It usually has a single copy in each species, and the two human copies appear to be a primate duplication.

Tensin subfamily

Tensin are adaptor proteins that link integrins to the actin cytoskeleton and are involved in a variety of signal transduction cascades.

Auxilin subfamily

Inactive phosphatases that bind phospholipids during clathrin-coated vesicle formation and uncoating. Most also have a kinase domain.


  1. Iwasaki H, Murata Y, Kim Y, Hossain MI, Worby CA, Dixon JE, McCormack T, Sasaki T, and Okamura Y. A voltage-sensing phosphatase, Ci-VSP, which shares sequence identity with PTEN, dephosphorylates phosphatidylinositol 4,5-bisphosphate. Proc Natl Acad Sci U S A. 2008 Jun 10;105(23):7970-5. DOI:10.1073/pnas.0803936105 | PubMed ID:18524949 | HubMed [Iwasaki08]