Kinome
Encyclopedia
In molecular biology
, the kinome of an organism is the set of protein kinases in its genome
. Kinases are enzyme
s that catalyze phosphorylation
reactions (of amino acids) and fall into several groups and families, e.g., those that phosphorylate the amino acid
s serine
and threonine
, those that phosphorylate tyrosine
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 the evolution of protein kinases throughout eukaryotes. Other kinomes have been determined for rice, several fungi, nematodes, and insects, sea urchin
s, Dictyostelium discoideum
, and the process of infection by Mycobacterium tuberculosis
. Interestingly, although the primary sequence of kinases shows substantial divergence between unrelated eukaryotes, variation in the motifs that are actually phosphorylated 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 and MAP2K that can act on both. It was long believed that serine/threonine kinases played different metabolic
roles than tyrosine kinases, the former being used mainly for inducing conformational changes versus the latter being used to create structural "handles" on proteins that to enable binding by an SH2 domain
. However, recent research has shown that there are specialized protein domains that bind to phosphorylated serine and threonine residues, such as BRCA and FHA domains
.
Molecular biology
Molecular biology is the branch of biology that deals with the molecular basis of biological activity. This field overlaps with other areas of biology and chemistry, particularly genetics and biochemistry...
, the kinome of an organism is the set of protein kinases in its genome
Genome
In modern molecular biology and genetics, the genome is the entirety of an organism's hereditary information. It is encoded either in DNA or, for many types of virus, in RNA. The genome includes both the genes and the non-coding sequences of the DNA/RNA....
. Kinases are enzyme
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
s that catalyze phosphorylation
Phosphorylation
Phosphorylation is the addition of a phosphate group to a protein or other organic molecule. Phosphorylation activates or deactivates many protein enzymes....
reactions (of amino acids) and fall into several groups and families, e.g., those that phosphorylate the amino acid
Amino acid
Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...
s serine
Serine
Serine is an amino acid with the formula HO2CCHCH2OH. It is one of the proteinogenic amino acids. By virtue of the hydroxyl group, serine is classified as a polar amino acid.-Occurrence and biosynthesis:...
and threonine
Threonine
Threonine is an α-amino acid with the chemical formula HO2CCHCHCH3. Its codons are ACU, ACA, ACC, and ACG. This essential amino acid is classified as polar...
, those that phosphorylate tyrosine
Tyrosine
Tyrosine or 4-hydroxyphenylalanine, is one of the 22 amino acids that are used by cells to synthesize proteins. Its codons are UAC and UAU. It is a non-essential amino acid with a polar side group...
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 the evolution of protein kinases throughout eukaryotes. Other kinomes have been determined for rice, several fungi, nematodes, and insects, sea urchin
Strongylocentrotus purpuratus
The purple sea urchin, Strongylocentrotus purpuratus, lives along the eastern edge of the Pacific Ocean extending from Ensenada, Mexico to British Columbia, Canada. This sea urchin species is deep purple in color and lives in lower intertidal and nearshore subtidal communities...
s, Dictyostelium discoideum
Dictyostelium discoideum
Dictyostelium discoideum is a species of soil-living amoeba belonging to the phylum Mycetozoa. D. discoideum, commonly referred to as slime mold, is a eukaryote that transitions from a collection of unicellular amoebae into a multicellular slug and then into a fruiting body within its lifetime. D...
, and the process of infection by Mycobacterium tuberculosis
Mycobacterium tuberculosis
Mycobacterium tuberculosis is a pathogenic bacterial species in the genus Mycobacterium and the causative agent of most cases of tuberculosis . First discovered in 1882 by Robert Koch, M...
. Interestingly, although the primary sequence of kinases shows substantial divergence between unrelated eukaryotes, variation in the motifs that are actually phosphorylated 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 and MAP2K that can act on both. It was long believed that serine/threonine kinases played different metabolic
Metabolism
Metabolism is the set of chemical reactions that happen in the cells of living organisms to sustain life. These processes allow organisms to grow and reproduce, maintain their structures, and respond to their environments. Metabolism is usually divided into two categories...
roles than tyrosine kinases, the former being used mainly for inducing conformational changes versus the latter being used to create structural "handles" on proteins that to enable binding by an SH2 domain
SH2 domain
The SH2 domain is a structurally conserved protein domain contained within the Src oncoprotein and in many other intracellular signal-transducing proteins...
. However, recent research has shown that there are specialized protein domains that bind to phosphorylated serine and threonine residues, such as BRCA and FHA domains
Forkhead-associated domain
In molecular biology, the forkhead-associated domain is a phosphopeptide recognition domain found in many regulatory proteins. It displays specificity for phosphothreonine-containing epitopes but will also recognise phosphotyrosine with relatively high affinity...
.