In
molecular biology
Molecular biology is the branch of biology that seeks to understand the molecular basis of biological activity in and between cells, including biomolecular synthesis, modification, mechanisms, and interactions. The study of chemical and physi ...
,
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 and ...
and
cell signaling
In biology, cell signaling (cell signalling in British English) or cell communication is the ability of a cell to receive, process, and transmit signals with its environment and with itself. Cell signaling is a fundamental property of all cellula ...
the kinome of an organism is the complete set of
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 encoded 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 ...
. Kinases are usually
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
phosphorylation
In chemistry, phosphorylation is the attachment of a phosphate group to a molecule or an ion. This process and its inverse, dephosphorylation, are common in biology and could be driven by natural selection. Text was copied from this source, wh ...
reactions (of amino acids) and fall into several groups and families, e.g., those that phosphorylate the
amino acid
Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha am ...
s
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 − form un ...
and
threonine
Threonine (symbol Thr or T) is an amino acid that is used in the biosynthesis of proteins. It contains an α-amino group (which is in the protonated −NH form under biological conditions), a carboxyl group (which is in the deprotonated −COOâ ...
, those that phosphorylate
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 non-essential amino acid with a polar side group. The word "tyrosine" is from the Gr ...
and some that can phosphorylate both, such as the MAP2K and GSK families. The term was first used in 2002 by Gerard Manning and colleagues in twin papers analyzing the 518 human protein kinases, and refers to both protein kinases and protein
pseudokinase
Pseudokinases are catalytically-deficient pseudoenzyme variants of protein kinases that are represented in all kinomes across the kingdoms of life. Pseudokinases have both physiological (signal transduction) and pathophysiological functions.
Hist ...
s
and their evolution of protein kinases throughout the eukaryotes.
Other kinomes have been determined for rice,
several fungi, nematodes, and insects,
sea urchin
Sea urchins () are spiny, globular echinoderms in the class Echinoidea. About 950 species of sea urchin live on the seabed of every ocean and inhabit every depth zone from the intertidal seashore down to . The spherical, hard shells (tests) of ...
s,
''
Dictyostelium discoideum
''Dictyostelium discoideum'' is a species of soil-dwelling amoeba belonging to the phylum Amoebozoa, infraphylum Mycetozoa. Commonly referred to as slime mold, ''D. discoideum'' is a eukaryote that transitions from a collection of unicellular ...
'',
and the process of infection by ''
Mycobacterium tuberculosis
''Mycobacterium tuberculosis'' (M. tb) is a species of pathogenic bacteria in the family Mycobacteriaceae and the causative agent of tuberculosis. First discovered in 1882 by Robert Koch, ''M. tuberculosis'' has an unusual, waxy coating on its c ...
''.
Although the primary sequence of protein kinases shows substantial divergence between unrelated eukaryotes, and amino acid differences in catalytic motifs have permitted their separation of kinomes into canonical and
pseudokinase
Pseudokinases are catalytically-deficient pseudoenzyme variants of protein kinases that are represented in all kinomes across the kingdoms of life. Pseudokinases have both physiological (signal transduction) and pathophysiological functions.
Hist ...
subtypes, the variation found in the amino acid motifs adjacent to the site of actual phosphorylation of substrates by eukaryotic kinases is much smaller.
As kinases are a major drug target and a major control point in cell behavior, the kinome has also been the target of large scale functional genomics with RNAi screens and of drug discovery efforts, especially in cancer therapeutics.
In animals, the kinome includes kinases that phosphorylate only tyrosine (tyrosine kinases), those that act on serine or threonine, and a few classes, such as
GSK3
Glycogen synthase kinase 3 (GSK-3) is a serine/threonine protein kinase that mediates the addition of phosphate molecules onto serine and threonine amino acid residues. First discovered in 1980 as a regulatory kinase for its namesake, glycogen ...
and
MAP2K
Mitogen-activated protein kinase kinase (also known as MAP2K, MEK, MAPKK) is a dual-specificity kinase enzyme which phosphorylates mitogen-activated protein kinase (MAPK).
MAP2K is classified as .
There are seven genes:
* (a.k.a. MEK1)
* (a. ...
that can act on both. Research has shown that there are specialized protein domains that bind to phosphorylated serine and threonine residues, such as BRCA and
FHA domains.
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 ...
*
Pseudokinase
Pseudokinases are catalytically-deficient pseudoenzyme variants of protein kinases that are represented in all kinomes across the kingdoms of life. Pseudokinases have both physiological (signal transduction) and pathophysiological functions.
Hist ...
*
Pseudoenzyme
Pseudoenzymes are variants of enzymes (usually proteins) that are catalytically-deficient (usually inactive), meaning that they perform little or no enzyme catalysis. They are believed to be represented in all major enzyme families in the kingdo ...
*
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 cont ...
*
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, 2
External links
KinBaseRice Kinome Database
Proteomics
Protein kinases