ITPKA

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

ITPKA
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1W2C, 1W2D, 1W2F, 4UPU
Identifiers
Aliases	ITPKA, IP3-3KA, IP3KA, inositol-trisphosphate 3-kinase A
External IDs	OMIM: 147521 MGI: 1333822 HomoloGene: 1671 GeneCards: ITPKA
Gene location (Human) Chr. Chromosome 15 (human)[1] Band 15q15.1 Start 41,493,393 bp[1] End 41,503,551 bp[1]
Gene location (Mouse) Chr. Chromosome 2 (mouse)[2] Band 2|2 E5 Start 119,742,337 bp[2] End 119,751,263 bp[2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • calmodulin-dependent protein kinase activity • transferase activity • nucleotide binding • Rac GTPase binding • inositol-1,4,5-trisphosphate 3-kinase activity • ATP binding • calmodulin binding • kinase activity Cellular component • cytosol • dendritic spine Biological process • dendritic spine maintenance • protein phosphorylation • inositol phosphate metabolic process • positive regulation of dendritic spine morphogenesis • actin cytoskeleton organization • inositol metabolic process • phosphorylation • signal transduction • regulation of synaptic plasticity • inositol phosphate biosynthetic process Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
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: 119.74 – 119.75 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

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. GRCh38: Ensembl release 89: ENSG00000137825 - Ensembl, May 2017
2. 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. name="entrez""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.
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. 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. 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. 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

• Takazawa K, Perret J, Dumont JE, Erneux C (September 1991). "Molecular cloning and expression of a new putative inositol 1,4,5-trisphosphate 3-kinase isoenzyme". The Biochemical Journal. 278 (Pt 3): 883–6. doi:10.1042/bj2780883. PMC 1151429. PMID 1654894.
• Takazawa K, Erneux C (November 1991). "Identification of residues essential for catalysis and binding of calmodulin in rat brain inositol 1,4,5-trisphosphate 3-kinase". The Biochemical Journal. 280 (Pt 1): 125–9. doi:10.1042/bj2800125. PMC 1130609. PMID 1660262.
• Takazawa K, Perret J, Dumont JE, Erneux C (January 1991). "Molecular cloning and expression of a human brain inositol 1,4,5-trisphosphate 3-kinase". Biochemical and Biophysical Research Communications. 174 (2): 529–35. doi:10.1016/0006-291X(91)91449-M. PMID 1847047.
• Lin AN, Barnes S, Wallace RW (August 1990). "Phosphorylation by protein kinase C inactivates an inositol 1,4,5-trisphosphate 3-kinase purified from human platelets". Biochemical and Biophysical Research Communications. 170 (3): 1371–6. doi:10.1016/0006-291X(90)90546-Y. PMID 2167676.
• Takazawa K, Vandekerckhove J, Dumont JE, Erneux C (November 1990). "Cloning and expression in Escherichia coli of a rat brain cDNA encoding a Ca2+/calmodulin-sensitive inositol 1,4,5-trisphosphate 3-kinase". The Biochemical Journal. 272 (1): 107–12. doi:10.1042/bj2720107. PMC 1149663. PMID 2176078.
• Ryu SH, Lee SY, Lee KY, Rhee SG (November 1987). "Catalytic properties of inositol trisphosphate kinase: activation by Ca2+ and calmodulin". FASEB Journal. 1 (5): 388–93. doi:10.1096/fasebj.1.5.2824270. PMID 2824270.
• Communi D, Vanweyenberg V, Erneux C (April 1997). "D-myo-inositol 1,4,5-trisphosphate 3-kinase A is activated by receptor activation through a calcium:calmodulin-dependent protein kinase II phosphorylation mechanism". The EMBO Journal. 16 (8): 1943–52. doi:10.1093/emboj/16.8.1943. PMC 1169797. PMID 9155020.
• Woodring PJ, Garrison JC (November 1997). "Expression, purification, and regulation of two isoforms of the inositol 1,4,5-trisphosphate 3-kinase". The Journal of Biological Chemistry. 272 (48): 30447–54. doi:10.1074/jbc.272.48.30447. PMID 9374536.
• 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.
• Mishra J, Bhalla US (September 2002). "Simulations of inositol phosphate metabolism and its interaction with InsP(3)-mediated calcium release". Biophysical Journal. 83 (3): 1298–316. doi:10.1016/S0006-3495(02)73901-5. PMC 1302229. PMID 12202356.
• Dewaste V, Moreau C, De Smedt F, Bex F, De Smedt H, Wuytack F, Missiaen L, Erneux C (August 2003). "The three isoenzymes of human inositol-1,4,5-trisphosphate 3-kinase show specific intracellular localization but comparable Ca2+ responses on transfection in COS-7 cells". The Biochemical Journal. 374 (Pt 1): 41–9. doi:10.1042/BJ20021963. PMC 1223573. PMID 12747803.
• González B, Schell MJ, Letcher AJ, Veprintsev DB, Irvine RF, Williams RL (September 2004). "Structure of a human inositol 1,4,5-trisphosphate 3-kinase: substrate binding reveals why it is not a phosphoinositide 3-kinase". Molecular Cell. 15 (5): 689–701. doi:10.1016/j.molcel.2004.08.004. PMID 15350214.
• Kato H, Uzawa K, Onda T, Kato Y, Saito K, Nakashima D, Ogawara K, Bukawa H, Yokoe H, Tanzawa H (April 2006). "Down-regulation of 1D-myo-inositol 1,4,5-trisphosphate 3-kinase A protein expression in oral squamous cell carcinoma". International Journal of Oncology. 28 (4): 873–81. doi:10.3892/ijo.28.4.873. PMID 16525636.