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A phosphatase is an enzyme that uses water to cleave a phosphoric acid monoester into a phosphate ion and an alcohol. Phosphatase_sentence_0

Because a phosphatase enzyme catalyzes the hydrolysis of its substrate, it is a subcategory of hydrolases. Phosphatase_sentence_1

Phosphatase enzymes are essential to many biological functions, because phosphorylation (e.g. by protein kinases) and dephosphorylation (by phosphatases) serve diverse roles in cellular regulation and signaling. Phosphatase_sentence_2

Whereas phosphatases remove phosphate groups from molecules, kinases catalyze the transfer of phosphate groups to molecules from ATP. Phosphatase_sentence_3

Together, kinases and phosphatases direct a form of post-translational modification that is essential to the cell's regulatory network. Phosphatase_sentence_4

Phosphatase enzymes are not to be confused with phosphorylase enzymes, which catalyze the transfer of a phosphate group from hydrogen phosphate to an acceptor. Phosphatase_sentence_5

Due to their prevalence in cellular regulation, phosphatases are an area of interest for pharmaceutical research. Phosphatase_sentence_6

Biochemistry Phosphatase_section_0

Phosphatases catalyze the hydrolysis of a phosphomonoester, removing a phosphate moiety from the substrate. Phosphatase_sentence_7

Water is split in the reaction, with the -OH group attaching to the phosphate ion, and the H+ protonating the hydroxyl group of the other product. Phosphatase_sentence_8

The net result of the reaction is the destruction of a phosphomonoester and the creation of both a phosphate ion and a molecule with a free hydroxyl group. Phosphatase_sentence_9

Phosphatases are able to dephosphorylate seemingly different sites on their substrates with great specificity. Phosphatase_sentence_10

Identifying the "phosphatase code," that is, the mechanisms and rules that govern substrate recognition for phosphatases, is still a work in progress, but the first comparative analysis of all the protein phosphatases encoded across nine eukaryotic 'phosphatome' genomes is now available. Phosphatase_sentence_11

Studies reveal that so called "docking interactions" play a significant role in substrate binding. Phosphatase_sentence_12

A phosphatase recognizes and interacts with various motifs (elements of secondary structure) on its substrate; these motifs bind with low affinity to docking sites on the phosphatase, which are not contained within its active site. Phosphatase_sentence_13

Although each individual docking interaction is weak, many interactions occur simultaneously, conferring a cumulative effect on binding specificity. Phosphatase_sentence_14

Docking interactions can also allosterically regulate phosphatases and thus influence their catalytic activity. Phosphatase_sentence_15

Functions Phosphatase_section_1

In contrast to kinases, phosphatase enzymes recognize and catalyze a wider array of substrates and reactions. Phosphatase_sentence_16

For example, in humans, Ser/Thr kinases outnumber Ser/Thr phosphatases by a factor of ten. Phosphatase_sentence_17

To some extent, this disparity results from incomplete knowledge of the human phosphatome, that is, the complete set of phosphatases expressed in a cell, tissue, or organism. Phosphatase_sentence_18

Many phosphatases have yet to be discovered, and for numerous known phosphatases, a substrate has yet to be identified. Phosphatase_sentence_19

However, among well-studied phosphatase/kinase pairs, phosphatases exhibit greater variety than their kinase counterparts in both form and function; this may result from the lesser degree of conservation among phosphatases. Phosphatase_sentence_20

Protein phosphatases Phosphatase_section_2

Main article: Protein phosphatase Phosphatase_sentence_21

A protein phosphatase is an enzyme that dephosphorylates an amino acid residue of its protein substrate. Phosphatase_sentence_22

Whereas protein kinases act as signaling molecules by phosphorylating proteins, phosphatases remove the phosphate group, which is essential if the system of intracellular signaling is to be able to reset for future use. Phosphatase_sentence_23

The tandem work of kinases and phosphatases constitute a significant element of the cell's regulatory network. Phosphatase_sentence_24

Phosphorylation (and dephosphorylation) is among the most common modes of posttranslational modification in proteins, and it is estimated that, at any given time, up to 30% of all proteins are phosphorylated. Phosphatase_sentence_25

Two notable protein phosphatases are PP2A and PP2B. Phosphatase_sentence_26

PP2A is involved in multiple regulatory processes, such as DNA replication, metabolism, transcription, and development. Phosphatase_sentence_27

PP2B, also called calcineurin, is involved in the proliferation of T cells; because of this, it is the target of some drugs that seek to suppress the immune system. Phosphatase_sentence_28

Nucleotidases Phosphatase_section_3

Main article: Nucleotidase Phosphatase_sentence_29

A nucleotidase is an enzyme that catalyzes the hydrolysis of a nucleotide, forming a nucleoside and a phosphate ion. Phosphatase_sentence_30

Nucleotidases are essential for cellular homeostasis, because they are partially responsible for maintaining a balanced ratio of nucleotides to nucleosides. Phosphatase_sentence_31

Some nucleotidases function outside the cell, creating nucleosides that can be transported into the cell and used to regenerate nucleotides via salvage pathways. Phosphatase_sentence_32

Inside the cell, nucleotidases may help to maintain energy levels under stress conditions. Phosphatase_sentence_33

A cell deprived of oxygen and nutrients may catabolize more nucleotides to boost levels of nucleoside triphosphates such as ATP, the primary energy currency of the cell. Phosphatase_sentence_34

In gluconeogenesis Phosphatase_section_4

Phosphatases can also act on carbohydrates, such as intermediates in gluconeogenesis. Phosphatase_sentence_35

Gluconeogenesis is a biosynthetic pathway wherein glucose is created from noncarbohydrate precursors; the pathway is essential because many tissues can only derive energy from glucose. Phosphatase_sentence_36

Two phosphatases, glucose-6-phosphatase and fructose-1,6-bisphosphatase, catalyze irreversible steps in gluconeogenesis. Phosphatase_sentence_37

Each cleaves a phosphate group from a six-carbon sugar phosphate intermediate. Phosphatase_sentence_38

Classification Phosphatase_section_5

Within the larger class of phosphatase, the Enzyme Commission recognizes 104 distinct enzyme families. Phosphatase_sentence_39

Phosphatases are classified by substrate specificity and sequence homology in catalytic domains. Phosphatase_sentence_40

Despite their classification into over one hundred families, all phosphatases still catalyze the same general hydrolysis reaction. Phosphatase_sentence_41

In in-vitro experiments, phosphatase enzymes seem to recognize many different substrates, and one substrate may be recognized by many different phosphatases. Phosphatase_sentence_42

However, when experiments have been carried out in-vivo, phosphatase enzymes have been shown to be incredibly specific. Phosphatase_sentence_43

In some cases, a protein phosphatase (i.e. one defined by its recognition of protein substrates) can catalyze the dephosphorylation of nonprotein substrates. Phosphatase_sentence_44

Similarly, dual-specificity tyrosine phosphatases can dephosphorylate not only tyrosine residues, but also serine residues. Phosphatase_sentence_45

Thus, one phosphatase can exhibit the qualities of multiple phosphatase families. Phosphatase_sentence_46

See also Phosphatase_section_6


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