InterPro domain: IPR036457

Protein phosphatases remove phosphate groups from various proteins that are the key components of a number of signalling pathways in eukaryotes and prokaryotes. Protein phosphatases that dephosphorylate Ser and Thr residues are classified into the phosphoprotein (PPP) and the protein phosphatase Mg2- or Mn2-dependent (PPM) families. The core structure of PPMs is the 300-residue PPM-type phosphatase domain that catalyses the dephosphorylation of phosphoserine- and phosphothreonine-containing protein. The PPM-type phosphatase domain is found as a module in diverse structural contexts and is modulated by targeting and regulatory subunits [ 1 , 2 , 3 , 4 ].

Some proteins known to contain a PPM-type phosphatase domain are listed below:

• Bacillus subtilis stage II sporulation protein E (SpoIIE), controls the sporulation by dephosphorylating an anti-transcription factor SpoIIAA, reversing the actions of the SpoIIAB protein kinase in a process that is governed by the ADP/ATP ratio [levdikov].
• Mycobacterium tuberculosis PP2C-family Ser/Thr phosphatase (PstP).
• Eucaryotic PP2C, a negative regulator of protein kinase cascades that are activated as a result of stress.
• Yeast adenyl cyclase, plays essential roles in regulation of cellular metabolism by catalysing the synthesis of a second messenger, cAMP.
• Mammalian mitochondrial pyruvate dehydrogenase phosphatase 1 (PDP1).
• Plant kinase-associated protein phosphatase (KAPP), regulates receptor-like kinase (RLK) signalling pathways.
• Plant absissic acid-insenstive 1 and 2 (ABI1 and ABI2), play a key absissic acid (ABA) signal transduction.

The PP2C-type phosphatase domain consists of 10 segments of beta-strands and 5 segments of alpha-helix and comprises a pair of detached subdomains. The first is a small beta-sandwich with strand beta1 packed against strands beta2 and beta3; the second is a larger beta-sandwich in which a four-stranded beta-sheet packs against a three-stranded beta-sheet with flanking alpha-helices [ 5 , 5 ].

1. Crystal structure of the protein serine/threonine phosphatase 2C at 2.0 A resolution. EMBO J. 15, 6798-809
2. Protein phosphatase 2C (PP2C) function in higher plants. Plant Mol. Biol. 152, 269-74
3. Structure of the Phosphatase Domain of the Cell Fate Determinant SpoIIE from Bacillus subtilis. J. Mol. Biol. 38, 919-27
4. Function analysis of conserved amino acid residues in a Mn(2+)-dependent protein phosphatase, Pph3, from Myxococcus xanthus. J. Biochem.