Inositol-trisphosphate 3-kinase A 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 ''ITPKA''
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 ...
.
Structure
ITPKA is one of three inositol-trisphosphate 3-kinase (ITP3K) genes in humans.
ITP3K proteins regulate
inositol phosphate
Inositol phosphates are a group of mono- to hexaphosphorylated inositols. Each form of inositol phosphate is distinguished by the number and position of the phosphate group on the inositol ring.
* inositol monophosphate (IP)
* inositol bisphospha ...
metabolism by
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 the second messenger
inositol 1,4,5-trisphosphate
Inositol trisphosphate or inositol 1,4,5-trisphosphate abbreviated InsP3 or Ins3P or IP3 is an inositol phosphate signaling molecule. It is made by hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2), a phospholipid that is located in the p ...
to produce Ins(1,3,4,5)P
4, which is sometimes abbreviated as IP
4. Structurally, ITPKA belongs to the
inositol polyphosphate kinase (IPK) family. The activity of the inositol 1,4,5-trisphosphate 3-kinase is responsible for regulating the levels of a large number of inositol polyphosphates that are important in cellular signaling, most notably,
inositol trisphosphate
Inositol trisphosphate or inositol 1,4,5-trisphosphate abbreviated InsP3 or Ins3P or IP3 is an inositol phosphate signaling molecule. It is made by hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2), a phospholipid that is located in the ...
, which is the enzyme's only substrate. Both calcium/
calmodulin
Calmodulin (CaM) (an abbreviation for calcium-modulated protein) is a multifunctional intermediate calcium-binding messenger protein expressed in all Eukaryote, eukaryotic cells. It is an intracellular target of the Second messenger system, sec ...
and protein phosphorylation mechanisms control its activity. It is also a substrate for the
cyclic AMP-dependent protein kinase
In cell biology, protein kinase A (PKA) is a family of serine-threonine kinases whose activity is dependent on cellular levels of cyclic AMP (cAMP). PKA is also known as cAMP-dependent protein kinase (). PKA has several functions in the cell, i ...
,
calcium/calmodulin- dependent protein kinase II, and
protein kinase C
In cell biology, protein kinase C, commonly abbreviated to PKC (EC 2.7.11.13), is a family of protein kinase enzymes that are involved in controlling the function of other proteins through the phosphorylation of hydroxyl groups of serine and t ...
in vitro. ITPKA and ITPKB are 68% identical in the
C-terminus
The C-terminus (also known as the carboxyl-terminus, carboxy-terminus, C-terminal tail, carboxy tail, C-terminal end, or COOH-terminus) is the end of an amino acid chain (protein
Proteins are large biomolecules and macromolecules that comp ...
region The amino- terminal region of ITPKA binds filamentous
actin
Actin is a family of globular multi-functional proteins that form microfilaments in the cytoskeleton, and the thin filaments in muscle fibrils. It is found in essentially all eukaryotic cells, where it may be present at a concentration of ...
. This property localizes the ITPKA to
dendritic spine
A dendritic spine (or spine) is a small membrane protrusion from a neuron's dendrite that typically receives input from a single axon at the synapse. Dendritic spines serve as a storage site for synaptic strength and help transmit electrical sign ...
s in principal neurons.
ITPKA is expressed physiologically in neurons, but it is sometimes expressed in cancer cells and may contribute to processes of metastasis.
Physiological function
ITPKA participates in learning and memory processes in neurons.
Roles in human disease
Although ITPKA is expressed physiologically in neurons and testis, it sometimes becomes expressed in cancer cells, and the expression usually makes the cancer more aggressive.
Relationship to F-tractin
F-tractin is amino acids 9-52 of rat ITPKA. It was later determined that amino acids 9-40 were sufficient for binding filamentous actin.
When fused to a reporter, such as
green fluorescent protein
The green fluorescent protein (GFP) is a protein that exhibits green fluorescence when exposed to light in the blue to ultraviolet range. The label ''GFP'' traditionally refers to the protein first isolated from the jellyfish ''Aequorea victo ...
, It is useful for the visualization of actin dynamics in living cells.
References
Further reading
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{{PDB Gallery, geneid=3706