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==Overview==

A '''phosphatase''' is an [[enzyme]] that removes a [[phosphate group]] from its [[substrate]] by [[Hydrolysis|hydrolysing]] [[phosphoric acid]] mono[[ester]]s into a [[phosphate]] [[ion]] and a molecule with a free [[hydroxyl]] group (see [[dephosphorylation]]). This action is directly opposite to that of [[phosphorylase]]s and [[Kinase|kinases]], which [[phosphorylation|attach phosphate groups to their substrates]] by using energetic molecules like [[adenosine triphosphate|ATP]]. A common phosphatase in many organisms is [[alkaline phosphatase]]. 

Phosphatases can be categorised into two main categories: [[Cysteine]]-dependent Phosphatases (CDPs) and metallo-phosphatases (which are dependent on metal ions in their active sites for activity). 

===Mechanism===

CDPs catalyse the hydrolysis of a phosphoester bond via a phospho-cysteine intermediate <ref>Barford, D. Molecular mechanisms of the protein serine/threonine phosphatases, (1996) ''Trends Bioch Sci'','''21''', 11, pp407</ref>.
The free [[cysteine]] [[nucleophile]] forms a bond with the [[phosphorus]] atom of the phosphate moiety, and the P-O bond linking the phosphate group to the tyrosine is protonated, either by a suitably positioned acidic [[amino acid]] residue (Asp in the diagram below) or a water molecule. The phospho-cysteine intermediate is then hydrolysed by another water molecule, thus regenerating the active site for another dephosphorylation reaction.

Metallo-phosphatases (eg PP2C) co-ordinate 2 catalytically essential metal ions within their active site. There is currently some confusion of the identity of these metal ions, as successive attempts to identify them yield different answers. There is currently evidence that these metals could be [[Magnesium]], [[Manganese]], [[Iron]], [[Zinc]], or any combination thereof. It is thought that a hydroxyl ion bridging the two metal ions takes part in [[nucleophile|nucleophilic]] attack on the [[phosphorus]] ion.

===Sub-types===
Phosphatases can be subdivided based upon their substrate specificity. 
 
{| class="wikitable"
|-
! '''Class'''
! '''Example'''
! '''Substrate'''
! '''Reference'''
|-
| [[Tyrosine]]-specific phosphatases
| PTP1B
| Phospho-Tyrosine
| <ref> Zhong-Yin Zhang, PROTEIN TYROSINE PHOSPHATASES: Structure and Function, Substrate Specificity, and Inhibitor Development (2002), ''Annual Review of Pharmacology and Toxicology'','''42''', pp209</ref>
|-
| [[Serine]]/[[Threonine]] specific phosphatases
| PP2C
| Phospho-Serine/Threonine
| <ref> Mumby, MC & Walter, G. Protein Serine/Threonine Phosphatases:
Structure, Regulation, and Functions in Cell Growth (1993) ''Physiological Reviews'','''73''',pp673</ref>
| 
|-
| Dual Specificity Phosphatases
| VHR
| Phospho-Tyrosine/Serine/Threonine
| <ref>Camps, S ''et al'', Dual specificity phosphatases: a gene family for control of MAP kinase function. (2000) ''FASEB J'','''1''',pp16 </ref>
|-
| [[Histidine]] Phosphatase
| PHP
| Phospho-Histidine
| <ref>Baumner, H ''et al'', Expression of Protein Histidine Phosphatase in Escherichia coli, Purification, and Determination of Enzyme Activity.
(2006), ''Methods Mol Biol'', '''365''', pp247</ref>
|- 
| Lipid Phosphatase
| [[PTEN (gene)|PTEN]]
| Phosphatidyl-Inositol-3,4,5-Triphosphate
| <ref>Maehama, T. ''et al'', The tumour suppressor PTEN: involvement of a tumour suppressor candidate protein in PTEN turnover (2004) ''Biochem. Soc. Trans.'' '''32''', pp343</ref>
|}

===Physiological Relevance===

Phosphatases act in opposition to [[kinases]]/phosphorylases, which add phosphate groups to proteins. The addition of a phosphate group may activate or de-activate an enzyme (e.g., Kinase signalling pathways<ref>Seger & Krebs,The MAPK Signalling cascade, ''FASEB J'','''9''',pp726</ref> ) or enable a protein-protein interaction to occur (e.g., SH3 domains <ref>Ladbury, JE, Measurement of the formation of complexes in tyrosine kinase-mediated signal transduction,(2007), ''Acta Cryst D'','''62''',pp26</ref>); therefore phosphatases are integral to many [[signal transduction]] pathways. It should be noted that phosphate addition and removal do not necessarily correspond to enzyme activation or inhibition, and that several enzymes have separate phosphorylation sites for activating or inhibiting functional regulation. CDK, for example, can be either activated or deactivated depending on the specific amino acid residue being phosphorylated. [[Phosphate]]s are important in [[signal transduction]] because they regulate the proteins to which they are attached.  To reverse the regulatory effect, the phosphate is removed. This occurs on its own by [[hydrolysis]], or is mediated by protein phosphatases.


===Protein Phosphatases===

====Serine/threonine-specific protein phosphatases====
[[Serine]] and [[threonine]] phosphates are stable under physiological conditions, so a phosphatase has to remove the phosphate to reverse the regulation. There are four known groups:
# PP1 (α, β, γ1, γ2)
# PP2A
# PP2B (AKA [[calcineurin]])
# PP2C
# PP4
# PP5
The first three have [[sequence homology]] in the [[enzyme|catalytic]] domain, but differ in substrate specifity.

Ser/Thr-specific protein phosphatases are regulated by their location within the [[cell (biology)|cell]] and by specific [[Enzyme inhibitor|inhibitor]] proteins.

===See also===
*[[Acid salt]]
*[[Endonuclease/Exonuclease/phosphatase family]]

===References===
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<references /></div>

==External links==
* {{MeshName|Phosphatases}}

{{Esterases}}

[[Category:EC 3.1.3]]
[[Category:Protein structure]]

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