Phosphatase Subfamily VSP

Phosphatase Classification: Superfamily CC1: Family PTEN: Subfamily VSP

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The Voltage Sensitive Phosphatase (VSP) members consist of a voltage sensor consisting of four transmembrane segments, 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.

Evolution

VSPs are holozoan-specific and lost in both nematodes and insects. There are two human genes, TPTE (PTEN2) and TPTE2 (TPIP). TPTE is a primate specific duplicate of the TPTE2 locus (found in human and Gorilla, but not in chimp) There are 7 family pseudogenes, some of which are expressed in testis, and at least one of which is conserved in orangutan.

Domain Structure

VSPs consist of an N-terminal voltage sensor with four transmembrane regions, followed by a phosphatase domain and a PTEN_C2 domain

Functions

Both human genes are testis specific (GTEx: TPTE, TPTE2). The single mouse gene is localized to the Golgi apparatus [1], while TPTE has been reported to be on the plasma membrane, while splice variants of TPTE2 are found in the ER or in the cytoplasm [2].

TPTE is predicted to be catalytically inactive, and TPTE2 has been shown to have phosphoinositide 3-phosphatase activity [2].

The Ciona homolog, Ci-VSP encodes a functional voltage-sensing domain expressed in sperm, and transduces membrane depolarization into alteration of phosphoinositide levels [3]. Ci-VSP has phosphatase activity against PI(3,4,5)P3 and PI(4,5)P2 [4]. The PI(4,5)P2 activity is not seen in PTEN, and change in levels of PI(4,5)P2 affects the activity of a family of potassium channels. CI-VSP has also been seen expressed in stomach and blood cells [5].

References

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