ITPKA

Last updated
ITPKA
Protein ITPKA PDB 1tzd.png
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases ITPKA , IP3-3KA, IP3KA, inositol-trisphosphate 3-kinase A
External IDs OMIM: 147521 MGI: 1333822 HomoloGene: 1671 GeneCards: ITPKA
Orthologs
SpeciesHumanMouse
Entrez

3706

228550

Ensembl

ENSG00000137825

ENSMUSG00000027296

UniProt

P23677

Q8R071

RefSeq (mRNA)

NM_002220

NM_146125

RefSeq (protein)

NP_002211

NP_666237

Location (UCSC) Chr 15: 41.49 – 41.5 Mb Chr 2: 119.57 – 119.58 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Inositol-trisphosphate 3-kinase A is an enzyme that in humans is encoded by the ITPKA gene. [5] [6] [7]

Contents

Structure

ITPKA is one of three inositol-trisphosphate 3-kinase (ITP3K) genes in humans. ITP3K proteins regulate inositol phosphate metabolism by phosphorylation of the second messenger inositol 1,4,5-trisphosphate to produce Ins(1,3,4,5)P4, which is sometimes abbreviated as IP4. 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, which is the enzyme's only substrate. Both calcium/calmodulin and protein phosphorylation mechanisms control its activity. It is also a substrate for the cyclic AMP-dependent protein kinase, calcium/calmodulin- dependent protein kinase II, and protein kinase C in vitro. ITPKA and ITPKB are 68% identical in the C-terminus region The amino- terminal region of ITPKA binds filamentous actin. This property localizes the ITPKA to dendritic spines in principal neurons. [8] [9] [10] ITPKA is expressed physiologically in neurons, but it is sometimes expressed in cancer cells and may contribute to processes of metastasis. [11]

Physiological function

ITPKA participates in learning and memory processes in neurons. [12] [13]

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. [11] [14]

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. [15] [16] When fused to a reporter, such as green fluorescent protein, It is useful for the visualization of actin dynamics in living cells. [17] [18]

Related Research Articles

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 plasma membrane, by phospholipase C (PLC). Together with diacylglycerol (DAG), IP3 is a second messenger molecule used in signal transduction in biological cells. While DAG stays inside the membrane, IP3 is soluble and diffuses through the cell, where it binds to its receptor, which is a calcium channel located in the endoplasmic reticulum. When IP3 binds its receptor, calcium is released into the cytosol, thereby activating various calcium regulated intracellular signals.

<span class="mw-page-title-main">Dendritic spine</span> Small protrusion on a dendrite that receives input from a single axon

A dendritic spine is a small membranous 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 signals to the neuron's cell body. Most spines have a bulbous head, and a thin neck that connects the head of the spine to the shaft of the dendrite. The dendrites of a single neuron can contain hundreds to thousands of spines. In addition to spines providing an anatomical substrate for memory storage and synaptic transmission, they may also serve to increase the number of possible contacts between neurons. It has also been suggested that changes in the activity of neurons have a positive effect on spine morphology.

<span class="mw-page-title-main">Inositol trisphosphate receptor</span> Class of transport proteins

Inositol trisphosphate receptor (InsP3R) is a membrane glycoprotein complex acting as a Ca2+ channel activated by inositol trisphosphate (InsP3). InsP3R is very diverse among organisms, and is necessary for the control of cellular and physiological processes including cell division, cell proliferation, apoptosis, fertilization, development, behavior, learning and memory. Inositol triphosphate receptor represents a dominant second messenger leading to the release of Ca2+ from intracellular store sites. There is strong evidence suggesting that the InsP3R plays an important role in the conversion of external stimuli to intracellular Ca2+ signals characterized by complex patterns relative to both space and time, such as Ca2+ waves and oscillations.

<span class="mw-page-title-main">Phosphoinositide 3-kinase</span> Class of enzymes

Phosphoinositide 3-kinases (PI3Ks), also called phosphatidylinositol 3-kinases, are a family of enzymes involved in cellular functions such as cell growth, proliferation, differentiation, motility, survival and intracellular trafficking, which in turn are involved in cancer.

<span class="mw-page-title-main">Phosphatidylinositol 4,5-bisphosphate</span> Chemical compound

Phosphatidylinositol 4,5-bisphosphate or PtdIns(4,5)P2, also known simply as PIP2 or PI(4,5)P2, is a minor phospholipid component of cell membranes. PtdIns(4,5)P2 is enriched at the plasma membrane where it is a substrate for a number of important signaling proteins. PIP2 also forms lipid clusters that sort proteins.

<span class="mw-page-title-main">ITPKB</span> Protein-coding gene in the species Homo sapiens

Inositol-trisphosphate 3-kinase B is an enzyme that in humans is encoded by the ITPKB gene.

<span class="mw-page-title-main">ITPR1</span> Protein-coding gene in the species Homo sapiens

Inositol 1,4,5-trisphosphate receptor type 1 is a protein that in humans is encoded by the ITPR1 gene.

<span class="mw-page-title-main">CAMK2B</span> Protein-coding gene in the species Homo sapiens

Calcium/calmodulin-dependent protein kinase type II beta chain is an enzyme that in humans is encoded by the CAMK2B gene.

<span class="mw-page-title-main">INPPL1</span> Protein-coding gene in the species Homo sapiens

SH2-domain containing Phosphatidylinositol-3,4,5-trisphosphate 5-phosphatase 2 is an enzyme that in humans is encoded by the INPPL1 gene.

<span class="mw-page-title-main">Inositol-trisphosphate 3-kinase</span> Class of enzymes

Inositol (1,4,5) trisphosphate 3-kinase (EC 2.7.1.127), abbreviated here as ITP3K, is an enzyme that facilitates a phospho-group transfer from adenosine triphosphate to 1D-myo-inositol 1,4,5-trisphosphate. This enzyme belongs to the family of transferases, specifically those transferring phosphorus-containing groups (phosphotransferases) with an alcohol group as acceptor. The systematic name of this enzyme class is ATP:1D-myo-inositol-1,4,5-trisphosphate 3-phosphotransferase. ITP3K catalyzes the transfer of the gamma-phosphate from ATP to the 3-position of inositol 1,4,5-trisphosphate to form inositol 1,3,4,5-tetrakisphosphate. ITP3K is highly specific for the 1,4,5-isomer of IP3, and it exclusively phosphorylates the 3-OH position, producing Ins(1,3,4,5)P4, also known as inositol tetrakisphosphate or IP4.

<span class="mw-page-title-main">PLCB2</span> Protein-coding gene in the species Homo sapiens

1-Phosphatidylinositol-4,5-bisphosphate phosphodiesterase beta-2 is an enzyme that in humans is encoded by the PLCB2 gene.

<span class="mw-page-title-main">CAMK1</span> Protein-coding gene in the species Homo sapiens

Calcium/calmodulin-dependent protein kinase type 1 is an enzyme that in humans is encoded by the CAMK1 gene.

<span class="mw-page-title-main">PLCB3</span> Protein-coding gene in the species Homo sapiens

1-Phosphatidylinositol-4,5-bisphosphate phosphodiesterase beta-3 is an enzyme that in humans is encoded by the PLCB3 gene.

<span class="mw-page-title-main">EPB41L1</span> Protein-coding gene in the species Homo sapiens

Band 4.1-like protein 1 is a protein that in humans is encoded by the EPB41L1 gene.

<span class="mw-page-title-main">PLCD3</span> Protein-coding gene in the species Homo sapiens

1-Phosphatidylinositol-4,5-bisphosphate phosphodiesterase delta-3 is an enzyme that in humans is encoded by the PLCD3 gene.

<span class="mw-page-title-main">Calcium-binding protein 1</span> Protein-coding gene in the species Homo sapiens

Calcium binding protein 1 is a protein that in humans is encoded by the CABP1 gene. Calcium-binding protein 1 is a calcium-binding protein discovered in 1999. It has two EF hand motifs and is expressed in neuronal cells in such areas as hippocampus, habenular nucleus of the epithalamus, Purkinje cell layer of the cerebellum, and the amacrine cells and cone bipolar cells of the retina.

<span class="mw-page-title-main">CAMKK2</span> Protein-coding gene in humans

Calcium/calmodulin-dependent protein kinase kinase 2 is an enzyme that in humans is encoded by the CAMKK2 gene.

<span class="mw-page-title-main">ITPR2</span> Protein-coding gene in humans

Inositol 1,4,5-trisphosphate receptor, type 2, also known as ITPR2, is a protein which in humans is encoded by the ITPR2 gene. The protein encoded by this gene is both a receptor for inositol triphosphate and a calcium channel.

The spine apparatus (SA) is a specialized form of endoplasmic reticulum (ER) that is found in a subpopulation of dendritic spines in central neurons. It was discovered by Edward George Gray in 1959 when he applied electron microscopy to fixed cortical tissue. The SA consists of a series of stacked discs that are connected to each other and to the dendritic system of ER-tubules. The actin binding protein synaptopodin is an essential component of the SA. Mice that lack the gene for synaptopodin do not form a spine apparatus. The SA is believed to play a role in synaptic plasticity, learning and memory, but the exact function of the spine apparatus is still enigmatic.

<span class="mw-page-title-main">Inositol polyphosphate kinase</span> Enzyme family

Inositol polyphosphate kinase (IPK) is a family of enzymes that have a similar 3-dimensional structure. All members of the family catalyze the transfer of phosphate groups from ATP to various inositol phosphates. Members of the family include inositol-polyphosphate multikinases, inositol-hexakisphosphate kinases, inositol-trisphosphate 3-kinases, and inositol-pentakisphosphate 2-kinase, which is more distantly related to the others

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000137825 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000027296 - Ensembl, May 2017
  3. ↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ↑ Erneux C, Roeckel N, Takazawa K, Mailleux P, Vassart G, Mattei MG (October 1992). "Localization of the genes for human inositol 1,4,5-trisphosphate 3-kinase A (ITPKA) and B (ITPKB) to chromosome regions 15q14-q21 and 1q41-q43, respectively, by in situ hybridization". Genomics. 14 (2): 546–7. doi:10.1016/S0888-7543(05)80265-4. PMID   1330886.
  6. ↑ Takazawa K, Perret J, Dumont JE, Erneux C (December 1990). "Human brain inositol 1,4,5-trisphosphate 3-kinase cDNA sequence". Nucleic Acids Research. 18 (23): 7141. doi:10.1093/nar/18.23.7141. PMC   332787 . PMID   2175886.
  7. ↑ "Entrez Gene: ITPKA inositol 1,4,5-trisphosphate 3-kinase A".
  8. ↑ Yamada M, Kakita A, Mizuguchi M, Rhee SG, Kim SU, Ikuta F (March 1993). "Specific expression of inositol 1,4,5-trisphosphate 3-kinase in dendritic spines". Brain Research. 606 (2): 335–40. doi:10.1016/0006-8993(93)91004-C. PMID   8387863. S2CID   10790958.
  9. ↑ Schell MJ, Erneux C, Irvine RF (October 2001). "Inositol 1,4,5-trisphosphate 3-kinase A associates with F-actin and dendritic spines via its N terminus". The Journal of Biological Chemistry. 276 (40): 37537–46. doi: 10.1074/jbc.M104101200 . PMID   11468283.
  10. ↑ Windhorst S, Minge D, Bähring R, Hüser S, Schob C, Blechner C, Lin HY, Mayr GW, Kindler S (March 2012). "Inositol-1,4,5-trisphosphate 3-kinase A regulates dendritic morphology and shapes synaptic Ca2+ transients". Cellular Signalling. 24 (3): 750–7. doi:10.1016/j.cellsig.2011.11.010. PMID   22120525.
  11. 1 2 Windhorst S, Fliegert R, Blechner C, Möllmann K, Hosseini Z, Günther T, Eiben M, Chang L, Lin HY, Fanick W, Schumacher U, Brandt B, Mayr GW (February 2010). "Inositol 1,4,5-trisphosphate 3-kinase-A is a new cell motility-promoting protein that increases the metastatic potential of tumor cells by two functional activities". The Journal of Biological Chemistry. 285 (8): 5541–54. doi: 10.1074/jbc.M109.047050 . PMC   2820782 . PMID   20022963.
  12. ↑ Chung S, Kim IH, Lee D, Park K, Kim JY, Lee YK, Kim EJ, Lee HW, Choi JS, Son GH, Sun W, Shin KS, Kim H (April 2016). "The role of inositol 1,4,5-trisphosphate 3-kinase A in regulating emotional behavior and amygdala function". Scientific Reports. 6: 23757. Bibcode:2016NatSR...623757C. doi:10.1038/srep23757. PMC   4823716 . PMID   27053114.
  13. ↑ Choi B, Lee HW, Mo S, Kim JY, Kim HW, Rhyu IJ, Hong E, Lee YK, Choi JS, Kim CH, Kim H (2018). "Inositol 1,4,5-trisphosphate 3-kinase A overexpressed in mouse forebrain modulates synaptic transmission and mGluR-LTD of CA1 pyramidal neurons". PLOS ONE. 13 (4): e0193859. Bibcode:2018PLoSO..1393859C. doi: 10.1371/journal.pone.0193859 . PMC   5884490 . PMID   29617377.
  14. ↑ Windhorst S, Song K, Gazdar AF (August 2017). "Inositol-1,4,5-trisphosphate 3-kinase-A (ITPKA) is frequently over-expressed and functions as an oncogene in several tumor types". Biochemical Pharmacology. 137: 1–9. doi:10.1016/j.bcp.2017.03.023. PMC   5555585 . PMID   28377279.
  15. ↑ Johnson HW, Schell MJ (December 2009). "Neuronal IP3 3-kinase is an F-actin-bundling protein: role in dendritic targeting and regulation of spine morphology". Molecular Biology of the Cell. 20 (24): 5166–80. doi:10.1091/mbc.E09-01-0083. PMC   2793293 . PMID   19846664.
  16. ↑ Yi J, Wu XS, Crites T, Hammer JA (March 2012). "Actin retrograde flow and actomyosin II arc contraction drive receptor cluster dynamics at the immunological synapse in Jurkat T cells". Molecular Biology of the Cell. 23 (5): 834–52. doi:10.1091/mbc.E11-08-0731. PMC   3290643 . PMID   22219382.
  17. ↑ Belin BJ, Goins LM, Mullins RD (2014). "Comparative analysis of tools for live cell imaging of actin network architecture". Bioarchitecture. 4 (6): 189–202. doi:10.1080/19490992.2014.1047714. PMC   4914014 . PMID   26317264.
  18. ↑ Melak M, Plessner M, Grosse R (February 2017). "Actin visualization at a glance". Journal of Cell Science. 130 (3): 525–530. doi: 10.1242/jcs.189068 . PMID   28082420.

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