PROSITE documentation PDOC00115

Serine/threonine specific protein phosphatases signature

Serine/threonine specific protein phosphatases (EC 3.1.3.16) (PP) [1,2,3] are enzymes that catalyze the removal of a phosphate group attached to a serine or a threonine residue. They are very important in controlling intracellular events in eukaryotic cells. In mammalian tissues four different types of PP have been identified and are known as PP1, PP2A, PP2B and PP2C. Except for PP2C, these enzymes are evolutionary related.

• Protein phosphatase-1 (PP1) is an enzyme of broad specificity. It is inhibited by two thermostable proteins, inhibitor-1 and -2. In mammals, there are two closely related isoforms of PP-1: PP-1α and PP-1β, produced by alternative splicing of the same gene. In Emericella nidulans, PP-1 (gene bimG) plays an important role in mitosis control by reversing the action of the nimA kinase. In yeast, PP-1 (gene SIT4) is involved in dephosphorylating the large subunit of RNA polymerase II.
• Protein phosphatase-2A (PP2A) is also an enzyme of broad specificity. PP2A is a trimeric enzyme that consist of a core composed of a catalytic subunit associated with a 65 Kd regulatory subunit and a third variable subunit. In mammals, there are two closely related isoforms of the catalytic subunit of PP2A: PP2A-α and PP2A-β, encoded by separate genes.
• Protein phosphatase-2B (PP2B or calcineurin), a calcium-dependent enzyme whose activity is stimulated by calmodulin. It is composed of two subunits: the catalytic A-subunit and the calcium-binding B-subunit. The specificity of PP2B is restricted.

In addition to the above-mentioned enzymes, some additional serine/threonine specific protein phosphatases have been characterized and are listed below.

• Mammalian phosphatase-X (PP-X), and Drosophila phosphatase-V (PP-V) which are closely related but yet distinct from PP2A.
• Yeast phosphatase PPH3, which is similar to PP2A, but with different enzymatic properties.
• Drosophila phosphatase-Y (PP-Y), and yeast phosphatases Z1 and Z2 (genes PPZ1 and PPZ2) which are closely related but yet distinct from PP1.
• Drosophila retinal degeneration protein C (gene rdgC), a calcium-binding phosphatase required to prevent light-induced retinal degeneration.
• Phages Lambda and Phi-80 ORF-221 which have been shown to have phosphatase activity and are related to mammalian PP's.

The best conserved regions in these proteins is a highly conserved pentapeptide that can be used as a signature pattern.