Phosphatidylinositol-5-phosphate 4-kinase type-2 alpha 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 in humans is encoded by the ''PIP4K2A''
gene
In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...
.
Function
Phosphatidylinositol-4,5-bisphosphate, the precursor to second messengers of the
phosphoinositide
Phosphatidylinositol or inositol phospholipid is a biomolecule. It was initially called "inosite" when it was discovered by Léon Maquenne and Johann Joseph von Scherer in the late 19th century. It was discovered in bacteria but later also found ...
signal transduction pathways, is thought to be involved in the regulation of secretion,
cell proliferation
Cell proliferation is the process by which ''a cell grows and divides to produce two daughter cells''. Cell proliferation leads to an exponential increase in cell number and is therefore a rapid mechanism of tissue growth. Cell proliferation ...
, differentiation, and
motility
Motility is the ability of an organism to move independently using metabolism, metabolic energy. This biological concept encompasses movement at various levels, from whole organisms to cells and subcellular components.
Motility is observed in ...
. The protein encoded by this gene is one of a family of enzymes capable of catalyzing the
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 ...
of
phosphatidylinositol-4-phosphate on the fifth
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 ...
of the myo-inositol ring to form phosphatidylinositol-4,5-bisphosphate.
The
amino acid
Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although over 500 amino acids exist in nature, by far the most important are the 22 α-amino acids incorporated into proteins. Only these 22 a ...
sequence of this enzyme does not show
homology to other
kinases
In biochemistry, a kinase () is an enzyme that catalysis, catalyzes the transfer of phosphate groups from High-energy phosphate, high-energy, phosphate-donating molecules to specific Substrate (biochemistry), substrates. This process is known as ...
, but the
recombinant protein
Protein production is the biotechnological process of generating a specific protein. It is typically achieved by the manipulation of gene expression in an organism such that it expresses large amounts of a recombinant gene. This includes the ...
does exhibit kinase activity. This gene is a member of the
phosphatidylinositol-4-phosphate 5-kinase
Phosphatidylinositol-4-phosphate 5-kinases (PIP5Ks, or PI4P5Ks) are a class of enzymes that phosphorylate phosphatidylinositol 4-phosphate. They perform this reaction on the fifth Hydroxy group, hydroxyl of the myo-inositol ring to form phosphati ...
family.
Clinical significance
Through
genome wide association studies (GWAS), some of the
single nucleotide polymorphisms
In genetics and bioinformatics, a single-nucleotide polymorphism (SNP ; plural SNPs ) is a germline substitution of a single nucleotide at a specific position in the genome. Although certain definitions require the substitution to be present in ...
(SNPs) located in this gene have been noticed to be significantly associated with susceptibility of childhood
acute lymphoblastic leukaemia in ethnically diverse populations.
PIP4K2A Inhibitors
THZ-P1-2 (covalent inhibitor) as well as BAY-091 and BAY-297 (reversible inhibitors) have been reported as potent and selective PIP4K2A inhibitors. BAY-091 fulfills the quality criteria for a 'Donated Chemical Probe' as defined by the
Structural Genomics Consortium
The Structural Genomics Consortium (SGC) is a public-private-partnership focusing on elucidating the functions and disease relevance of all proteins encoded by the human genome, with an emphasis on those that are relatively understudied. The SGC pl ...
.
References
Further reading
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External links
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