Phosphatase Subfamily VSP
Phosphatase Classification: Superfamily CC1: Family PTEN: Subfamily VSP
VSP is a transmembrane protein with a lipid phosphatase that is activated by a voltage sensor and controls activity of ion channels.
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 subfamily 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), though some expression in brain and stomach has been reported. 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].
