ITPKA
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesITPKA, IP3-3KA, IP3KA, inositol-trisphosphate 3-kinase A
External IDsOMIM: 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 MbChr 2: 119.57 – 119.58 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

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

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]

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.

Further reading

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