The phosphatome of an organism is the set of
phosphatase
In biochemistry, a phosphatase is an enzyme that uses water to cleave a phosphoric acid Ester, monoester into a phosphate ion and an Alcohol (chemistry), alcohol. Because a phosphatase enzyme catalysis, catalyzes the hydrolysis of its Substrate ...
genes in its
genome
In the fields of molecular biology and genetics, 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 ge ...
. Phosphatases are
enzyme
Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products. A ...
s that catalyze the removal of
phosphate
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 orthophosphoric acid .
The phosphate or orthophosphate ion is derived from phospho ...
from
biomolecules
A biomolecule or biological molecule is a loosely used term for molecules present in organisms that are essential to one or more typically biological processes, such as cell division, morphogenesis, or development. Biomolecules include large ...
. Over half of all cellular proteins are modified by phosphorylation which typically controls their functions. Protein phosphorylation is controlled by the opposing actions of
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 ...
s and
protein kinase
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 fu ...
s.
Most phosphorylation sites are not linked to a specific phosphatase, so the phosphatome approach allows a global analysis of dephosphorylation, screening to find the phosphatase responsible for a given reaction, and comparative studies between different phosphatases, similar to how protein kinase research has been impacted by the
kinome
In molecular biology, biochemistry and cell signaling the kinome of an organism is the complete set of protein kinases encoded in its genome. Kinases are usually enzymes that catalyze phosphorylation reactions (of amino acids) and fall into severa ...
approach.
The Protein Phosphatome
Protein phosphatases remove phosphates from proteins, usually on Serine, Threonine, and Tyrosine residues, reversing the action of protein kinases. The PTP family of protein phosphatases is tyrosine-specific, and several other families (PPPL, PPM, HAD) appear to be serine/threonine specific, while other families are unknown or have a variety of substrates (DSPs dephosphorylate any amino acid, while some protein phosphatases also have non-protein substrates). In the human genome, 20 different folds of protein are known to be phosphatases, of which 10 include protein phosphatases.
Protein phosphatomes have been cataloged for human and 8 other key eukaryotes,
for Plasmodium and Trypanosomes
and phosphatomes have been used for functional analysis, by experimentally investing all known protein phosphatases, in the yeast Fusarium, in Plasmodium and in human cancer
Large scale databases exist for human and animal phosphatome
Phosphatome.net parasitic protozoan
ProtozPhosDBand for the substrates of human phosphatase
DEPOD
Non-Protein Phosphatases
Non-protein phosphorylation has three general forms
* As a regulatory mechanism to control the function of the substrate, similar to the role of protein phosphorylation.
Phosphoinositide
Phosphatidylinositol (or Inositol Phospholipid) consists of a family of lipids as illustrated on the right, where red is x, blue is y, and black is z, in the context of independent variation, a class of the phosphatidylglycerides. In such molecul ...
lipids are important signaling molecules that have a variety of dedicated kinases and phosphatases.
* As an energetic intermediate. The phosphate bond is high-energy, so adding a phosphate increases the energy of a molecule, and removal of the phosphate can provide energy for an otherwise unfavorable reaction. For instance
Glucose 6-phosphatase
The enzyme glucose 6-phosphatase (EC 3.1.3.9, G6Pase; systematic name D-glucose-6-phosphate phosphohydrolase) catalyzes the hydrolysis of glucose 6-phosphate, resulting in the creation of a phosphate group and free glucose:
: D-glucose 6-phos ...
removes a phosphate group from glucose to complete gluconeogenesis.
* In biosynthesis, where the phosphate is a functional part of the mature molecule, and dephosphorylation degrades it or changes function.
Nucleotidase
A nucleotidase is a hydrolytic enzyme that catalyzes the hydrolysis of a nucleotide into a nucleoside and a phosphate.
: A nucleotide + H2O = a nucleoside + phosphate
For example, it converts adenosine monophosphate to adenosine, and guanosine mon ...
s are phosphatases used in nucleotide biosynthesis and breakdown.
The human non-protein phosphatome has been cataloged,
but most phosphatome analyses are restricted to protein and lipid phosphatases that have regulatory functions.
Pseudophosphatases
The phosphatome includes proteins that are structurally closely related to phosphatases but lack catalytic activity. These retain biological function, and may regulate pathways that involve active phosphatases, or bind to phosphorylated substrates without cleaving them.
Examples includ
STYX where the phosphatase domain has become a phospho-tyrosine binding domain, an
GAK whose inactive phosphatase domain instead binds phospholipids.
See also
*
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 ...
*
Kinome
In molecular biology, biochemistry and cell signaling the kinome of an organism is the complete set of protein kinases encoded in its genome. Kinases are usually enzymes that catalyze phosphorylation reactions (of amino acids) and fall into severa ...
*
Phosphatase
In biochemistry, a phosphatase is an enzyme that uses water to cleave a phosphoric acid Ester, monoester into a phosphate ion and an Alcohol (chemistry), alcohol. Because a phosphatase enzyme catalysis, catalyzes the hydrolysis of its Substrate ...
*
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 ...
References
{{Reflist
External links
phosphatome.net A database of protein phosphatases in 8 eukaryotic genomes.
Phosphatome WikiWiki focused on protein phosphatase classification and evolution.
DEPODDatabase of protein phosphatase substrates, pathways, and interactions
Genomics
Enzymes
Post-translational modification
Signal transduction