
In
biochemistry
Biochemistry, or biological chemistry, is the study of chemical processes within and relating to living organisms. A sub-discipline of both chemistry and biology, biochemistry may be divided into three fields: structural biology, enzymology, a ...
, a phosphatase is an
enzyme
An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different mol ...
that uses water to cleave a
phosphoric acid
Phosphoric acid (orthophosphoric acid, monophosphoric acid or phosphoric(V) acid) is a colorless, odorless phosphorus-containing solid, and inorganic compound with the chemical formula . It is commonly encountered as an 85% aqueous solution, ...
monoester
In chemistry, an ester is a compound derived from an acid (either organic or inorganic) in which the hydrogen atom (H) of at least one acidic hydroxyl group () of that acid is replaced by an organyl group (R). These compounds contain a distinct ...
into a
phosphate
Phosphates are the naturally occurring form of the element phosphorus.
In chemistry, a phosphate is an anion, salt, functional group or ester derived from a phosphoric acid. It most commonly means orthophosphate, a derivative of orthop ...
ion and an
alcohol
Alcohol may refer to:
Common uses
* Alcohol (chemistry), a class of compounds
* Ethanol, one of several alcohols, commonly known as alcohol in everyday life
** Alcohol (drug), intoxicant found in alcoholic beverages
** Alcoholic beverage, an alco ...
. Because a phosphatase enzyme
catalyzes
Catalysis () is the increase in rate of a chemical reaction due to an added substance known as a catalyst (). Catalysts are not consumed by the reaction and remain unchanged after it. If the reaction is rapid and the catalyst recycles quick ...
the
hydrolysis
Hydrolysis (; ) is any chemical reaction in which a molecule of water breaks one or more chemical bonds. The term is used broadly for substitution reaction, substitution, elimination reaction, elimination, and solvation reactions in which water ...
of its
substrate
Substrate may refer to:
Physical layers
*Substrate (biology), the natural environment in which an organism lives, or the surface or medium on which an organism grows or is attached
** Substrate (aquatic environment), the earthy material that exi ...
, it is a subcategory of
hydrolase
In biochemistry, hydrolases constitute a class of enzymes that commonly function as biochemical catalysts that use water to break a chemical bond:
:\ce \quad \xrightarrowtext\quad \ce
This typically results in dividing a larger molecule into s ...
s.
Phosphatase enzymes are essential to many biological functions, because
phosphorylation
In biochemistry, phosphorylation is described as the "transfer of a phosphate group" from a donor to an acceptor. A common phosphorylating agent (phosphate donor) is ATP and a common family of acceptor are alcohols:
:
This equation can be writ ...
(e.g. by
protein kinases
A protein kinase is a kinase which selectively modifies other proteins by covalently adding phosphates to them (phosphorylation) as opposed to kinases which modify lipids, carbohydrates, or other molecules. Phosphorylation usually results in a fun ...
) and
dephosphorylation
In biochemistry, dephosphorylation is the removal of a phosphate () group from an organic compound by hydrolysis. It is a reversible post-translational modification. Dephosphorylation and its counterpart, phosphorylation, activate and deactivate e ...
(by phosphatases) serve diverse roles in
cellular regulation and
signaling. Whereas phosphatases remove phosphate groups from molecules,
kinase
In biochemistry, a kinase () is an enzyme that catalyzes the transfer of phosphate groups from high-energy, phosphate-donating molecules to specific substrates. This process is known as phosphorylation, where the high-energy ATP molecule don ...
s catalyze the transfer of phosphate groups to molecules from
ATP. Together, kinases and phosphatases direct a form of
post-translational modification
In molecular biology, post-translational modification (PTM) is the covalent process of changing proteins following protein biosynthesis. PTMs may involve enzymes or occur spontaneously. Proteins are created by ribosomes, which translation (biolog ...
that is essential to the cell's regulatory network.
Phosphatase enzymes are not to be confused with
phosphorylase
In biochemistry, phosphorylases are enzymes that catalyze the addition of a phosphate group from an inorganic phosphate (phosphate+hydrogen) to an acceptor.
:A-B + P A + P-B
They include allosteric enzymes that catalyze the production of glu ...
enzymes, which catalyze the transfer of a phosphate group from hydrogen phosphate to an acceptor. Due to their prevalence in cellular regulation, phosphatases are an area of interest for pharmaceutical research.
Biochemistry

Phosphatases
catalyze
Catalysis () is the increase in rate of a chemical reaction due to an added substance known as a catalyst (). Catalysts are not consumed by the reaction and remain unchanged after it. If the reaction is rapid and the catalyst recycles quick ...
the
hydrolysis
Hydrolysis (; ) is any chemical reaction in which a molecule of water breaks one or more chemical bonds. The term is used broadly for substitution reaction, substitution, elimination reaction, elimination, and solvation reactions in which water ...
of a phosphomonoester, removing a
phosphate
Phosphates are the naturally occurring form of the element phosphorus.
In chemistry, a phosphate is an anion, salt, functional group or ester derived from a phosphoric acid. It most commonly means orthophosphate, a derivative of orthop ...
moiety from the substrate. Water is split in the reaction, with the -OH group attaching to the phosphate ion, and the H+ protonating the
hydroxyl
In chemistry, a hydroxy or hydroxyl group is a functional group with the chemical formula and composed of one oxygen atom covalently bonded to one hydrogen atom. In organic chemistry, alcohols and carboxylic acids contain one or more hydroxy ...
group of the other product. 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.
Phosphatases are able to dephosphorylate seemingly different sites on their substrates with great specificity. 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
The eukaryotes ( ) constitute the Domain (biology), domain of Eukaryota or Eukarya, organisms whose Cell (biology), cells have a membrane-bound cell nucleus, nucleus. All animals, plants, Fungus, fungi, seaweeds, and many unicellular organisms ...
'phosphatome'
genome
A genome is all the genetic information of an organism. It consists of nucleotide sequences of DNA (or RNA in RNA viruses). The nuclear genome includes protein-coding genes and non-coding genes, other functional regions of the genome such as ...
s is now available. Studies reveal that so called "docking interactions" play a significant role in substrate binding.
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
In biology and biochemistry, the active site is the region of an enzyme where substrate molecules bind and undergo a chemical reaction. The active site consists of amino acid residues that form temporary bonds with the substrate, the ''binding s ...
. Although each individual docking interaction is weak, many interactions occur simultaneously, conferring a cumulative effect on binding specificity. Docking interactions can also
allosterically regulate phosphatases and thus influence their catalytic activity.
Functions
In contrast to kinases, phosphatase enzymes recognize and catalyze a wider array of substrates and reactions. For example, in humans, Ser/Thr kinases outnumber Ser/Thr phosphatases by a factor of ten.
To some extent, this disparity results from incomplete knowledge of the human
phosphatome
The phosphatome of an organism is the set of phosphatase genes in its genome. Phosphatases are enzymes that catalyze the removal of phosphate from biomolecules. Over half of all cellular proteins are modified by phosphorylation which typically con ...
, that is, the complete set of phosphatases expressed in a cell, tissue, or organism.
Many phosphatases have yet to be discovered, and for numerous known phosphatases, a substrate has yet to be identified. 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.
Distinctions
Phosphatases should not be confused with
phosphorylases
In biochemistry, phosphorylases are enzymes that catalyze the addition of a phosphate group from an inorganic phosphate (phosphate+hydrogen) to an acceptor.
:A-B + P A + P-B
They include allosteric enzymes that catalyze the production of glu ...
, which add phosphate groups.
Protein phosphatases
A
protein phosphatase
A protein phosphatase is a phosphatase enzyme that removes a phosphate group from the phosphorylated amino acid residue of its Substrate (biochemistry), substrate protein. Protein phosphorylation is one of the most common forms of reversible protei ...
is an enzyme that dephosphorylates an amino acid residue of its protein substrate. 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. The tandem work of kinases and phosphatases constitute a significant element of the cell's regulatory network.
Phosphorylation (and dephosphorylation) is among the most common modes of
posttranslational modification
In molecular biology, post-translational modification (PTM) is the covalent process of changing proteins following protein biosynthesis. PTMs may involve enzymes or occur spontaneously. Proteins are created by ribosomes, which translate mRNA ...
in proteins, and it is estimated that, at any given time, up to 30% of all proteins are phosphorylated.
Two notable protein phosphatases are PP2A and PP2B. PP2A is involved in multiple regulatory processes, such as DNA replication, metabolism, transcription, and development. PP2B, also called
calcineurin
Calcineurin (CaN) is a calcium and calmodulin dependent serine/threonine protein phosphatase (also known as protein phosphatase 3, and calcium-dependent serine-threonine phosphatase). It activates the T cells of the immune system and can be block ...
, is involved in the proliferation of
T cell
T cells (also known as T lymphocytes) are an important part of the immune system and play a central role in the adaptive immune response. T cells can be distinguished from other lymphocytes by the presence of a T-cell receptor (TCR) on their cell ...
s; because of this, it is the target of some drugs that seek to suppress the immune system.
Nucleotidases
A
nucleotidase is an enzyme that catalyzes the hydrolysis of a
nucleotide
Nucleotides are Organic compound, organic molecules composed of a nitrogenous base, a pentose sugar and a phosphate. They serve as monomeric units of the nucleic acid polymers – deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), both o ...
, forming a
nucleoside
Nucleosides are glycosylamines that can be thought of as nucleotides without a phosphate group. A nucleoside consists simply of a nucleobase (also termed a nitrogenous base) and a five-carbon sugar (ribose or 2'-deoxyribose) whereas a nucleotid ...
and a phosphate ion. Nucleotidases are essential for cellular
homeostasis
In biology, homeostasis (British English, British also homoeostasis; ) is the state of steady internal physics, physical and chemistry, chemical conditions maintained by organism, living systems. This is the condition of optimal functioning fo ...
, because they are partially responsible for maintaining a balanced ratio of nucleotides to nucleosides. Some nucleotidases function outside the cell, creating nucleosides that can be transported into the cell and used to regenerate nucleotides via
salvage pathways. Inside the cell, nucleotidases may help to maintain energy levels under stress conditions. 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.
In gluconeogenesis
Phosphatases can also act on
carbohydrate
A carbohydrate () is a biomolecule composed of carbon (C), hydrogen (H), and oxygen (O) atoms. The typical hydrogen-to-oxygen atomic ratio is 2:1, analogous to that of water, and is represented by the empirical formula (where ''m'' and ''n'' ...
s, such as intermediates in
gluconeogenesis
Gluconeogenesis (GNG) is a metabolic pathway that results in the biosynthesis of glucose from certain non-carbohydrate carbon substrates. It is a ubiquitous process, present in plants, animals, fungi, bacteria, and other microorganisms. In verte ...
. Gluconeogenesis is a
biosynthetic
Biosynthesis, i.e., chemical synthesis occurring in biological contexts, is a term most often referring to multi-step, enzyme- catalyzed processes where chemical substances absorbed as nutrients (or previously converted through biosynthesis) serve ...
pathway wherein
glucose
Glucose is a sugar with the Chemical formula#Molecular formula, molecular formula , which is often abbreviated as Glc. It is overall the most abundant monosaccharide, a subcategory of carbohydrates. It is mainly made by plants and most algae d ...
is created from noncarbohydrate precursors; the pathway is essential because many tissues can only derive energy from glucose.
Two phosphatases, glucose-6-phosphatase and fructose-1,6-bisphosphatase, catalyze irreversible steps in gluconeogenesis.
Each cleaves a phosphate group from a six-carbon
sugar phosphate intermediate.
Classification
Within the larger class of phosphatase, the
Enzyme Commission recognizes 104 distinct enzyme families. Phosphatases are classified by substrate specificity and sequence homology in catalytic domains.
Despite their classification into over one hundred families, all phosphatases still catalyze the same general hydrolysis reaction.
In in-vitro experiments, phosphatase enzymes seem to recognize many different substrates, and one substrate may be recognized by many different phosphatases. However, when experiments have been carried out in-vivo, phosphatase enzymes have been shown to be incredibly specific.
In some cases, a protein phosphatase (i.e. one defined by its recognition of protein substrates) can catalyze the dephosphorylation of nonprotein substrates.
Similarly, dual-specificity
tyrosine phosphatases can dephosphorylate not only
tyrosine
-Tyrosine or tyrosine (symbol Tyr or Y) or 4-hydroxyphenylalanine is one of the 20 standard amino acids that are used by cells to synthesize proteins. It is a conditionally essential amino acid with a polar side group. The word "tyrosine" is ...
residues, but also
serine
Serine
(symbol Ser or S) is an α-amino acid that is used in the biosynthesis of proteins. It contains an α- amino group (which is in the protonated − form under biological conditions), a carboxyl group (which is in the deprotonated − ...
residues. Thus, one phosphatase can exhibit the qualities of multiple phosphatase families.
See also
*
Acid phosphatase
Acid phosphatase (EC 3.1.3.2, systematic name ''phosphate-monoester phosphohydrolase (acid optimum)'') is an enzyme that frees attached phosphoryl groups from other molecules during digestion. It can be further classified as a phosphoric monoeste ...
*
Alkaline phosphatase
The enzyme alkaline phosphatase (ALP, alkaline phenyl phosphatase, also abbreviated PhoA) is a phosphatase with the physiological role of dephosphorylating compounds. The enzyme is found across a multitude of organisms, prokaryotes and eukaryo ...
*
Endonuclease/Exonuclease/phosphatase family
*
Kinase
In biochemistry, a kinase () is an enzyme that catalyzes the transfer of phosphate groups from high-energy, phosphate-donating molecules to specific substrates. This process is known as phosphorylation, where the high-energy ATP molecule don ...
*
Phosphatome
The phosphatome of an organism is the set of phosphatase genes in its genome. Phosphatases are enzymes that catalyze the removal of phosphate from biomolecules. Over half of all cellular proteins are modified by phosphorylation which typically con ...
*
Phosphotransferase
In molecular biology, phosphotransferases are proteins in the transferase family of enzymes ( EC number 2.7) that catalyze certain chemical reactions. The general form of the phosphorylation reactions they catalyze is:
\ce
Where P is a phosphat ...
*
Protein phosphatase
A protein phosphatase is a phosphatase enzyme that removes a phosphate group from the phosphorylated amino acid residue of its Substrate (biochemistry), substrate protein. Protein phosphorylation is one of the most common forms of reversible protei ...
*
Protein phosphatase 2
Protein phosphatase 2 (PP2), also known as PP2A, is an enzyme that in humans is encoded by the ''PPP2CA'' gene. The PP2A heterotrimeric protein phosphatase is ubiquitously expressed, accounting for a large fraction of phosphatase activity in ...
(PP2A)
References
External links
*
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EC 3.1.3