Voltage sensitive phosphatase

Identifiers
Symbol	VSP
OPM superfamily	8
OPM protein	4g80

Voltage sensitive phosphatases or voltage sensor-containing phosphatases, commonly abbreviated VSPs, are a protein family found in many species, including humans, mice, zebrafish, frogs, and sea squirt.

The first voltage sensitive phosphatase was discovered as a result of a genome-wide search in the sea squirt Ciona intestinalis. The search was designed to identify proteins which contained a sequence of amino acids called a voltage sensor, because this sequence of amino acids confers voltage sensitivity to voltage-gated ion channels. Although the initial genomic analysis was primarily concerned with the evolution of voltage-gated ion channels, one of the results of the work was the discovery of the VSP protein in sea squirt, termed Ci-VSP.

The homologues to Ci-VSP in mammals are called Transmembrane phosphatases with tensin homology, or TPTEs. TPTE (now also called hVSP2) and the closely related TPIP (also called TPTE2 or hVSP1) were identified before the discovery of Ci-VSP, however no voltage-dependent activity was described in the initial reports of these proteins. Subsequently, computational methods were used to suggest that these proteins may be voltage sensitive, however Ci-VSP is still widely regarded as the first-identified VSP.

VSPs are found across animals and choanoflagellates, though lost from nematodes and insects. Humans contain two members, TPTE and TPTE2, which result from a primate-specific duplication [1]. Most reports indicate that VSPs are found primarily in reproductive tissue, especially the testis. Other VSPs discovered include: Dr-VSP (zebrafish Danio rerio, 2008), Gg-VSP (chicken Gallus gallus domesticus, 2014), Xl-VSP1, Xl-VSP2, and Xt-VSP (frogs: X. laevis and X. tropicalis, 2011), TPTE (mouse), etc.

VSPs are made up of two protein domains: a voltage sensor domain, and a phosphatase domain coupled to a lipid-binding C2 domain.

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