ITPKA

{{Short description|Protein-coding gene in the species Homo sapiens}} {{Infobox_gene}}

'''Inositol-trisphosphate 3-kinase A''' is an enzyme that in humans is encoded by the ''ITPKA'' gene.<ref name="pmid1330886">{{cite journal | vauthors = Erneux C, Roeckel N, Takazawa K, Mailleux P, Vassart G, Mattei MG | title = 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 | journal = Genomics | volume = 14 | issue = 2 | pages = 546–7 | date = October 1992 | pmid = 1330886 | doi = 10.1016/S0888-7543(05)80265-4 }}</ref><ref name="pmid2175886">{{cite journal | vauthors = Takazawa K, Perret J, Dumont JE, Erneux C | title = Human brain inositol 1,4,5-trisphosphate 3-kinase cDNA sequence | journal = Nucleic Acids Research | volume = 18 | issue = 23 | page = 7141 | date = December 1990 | pmid = 2175886 | pmc = 332787 | doi = 10.1093/nar/18.23.7141 }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: ITPKA inositol 1,4,5-trisphosphate 3-kinase A| url = https://www.ncbi.nlm.nih.gov/gene?Db=gene&Cmd=ShowDetailView&TermToSearch=3706 }}</ref>

== 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)P<small>4</small>, which is sometimes abbreviated as IP<small>4</small>. 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.<ref name="pmid8387863">{{cite journal | vauthors = Yamada M, Kakita A, Mizuguchi M, Rhee SG, Kim SU, Ikuta F | title = Specific expression of inositol 1,4,5-trisphosphate 3-kinase in dendritic spines | journal = Brain Research | volume = 606 | issue = 2 | pages = 335–40 | date = March 1993 | pmid = 8387863 | doi = 10.1016/0006-8993(93)91004-C| s2cid = 10790958 }}</ref><ref name="pmid11468283">{{cite journal | vauthors = Schell MJ, Erneux C, Irvine RF | title = Inositol 1,4,5-trisphosphate 3-kinase A associates with F-actin and dendritic spines via its N terminus | journal = The Journal of Biological Chemistry | volume = 276 | issue = 40 | pages = 37537–46 | date = October 2001 | pmid = 11468283 | doi = 10.1074/jbc.M104101200 | doi-access = free }}</ref><ref name="pmid22120525">{{cite journal | vauthors = Windhorst S, Minge D, Bähring R, Hüser S, Schob C, Blechner C, Lin HY, Mayr GW, Kindler S | title = Inositol-1,4,5-trisphosphate 3-kinase A regulates dendritic morphology and shapes synaptic Ca2+ transients | journal = Cellular Signalling | volume = 24 | issue = 3 | pages = 750–7 | date = March 2012 | pmid = 22120525 | doi = 10.1016/j.cellsig.2011.11.010 }}</ref> ITPKA is expressed physiologically in neurons, but it is sometimes expressed in cancer cells and may contribute to processes of metastasis.<ref name="pmid20022963">{{cite journal | vauthors = 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 | title = 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 | journal = The Journal of Biological Chemistry | volume = 285 | issue = 8 | pages = 5541–54 | date = February 2010 | pmid = 20022963 | pmc = 2820782 | doi = 10.1074/jbc.M109.047050 | doi-access = free }}</ref>

== Physiological function == ITPKA participates in learning and memory processes in neurons.<ref name="pmid27053114">{{cite journal | vauthors = 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 | title = The role of inositol 1,4,5-trisphosphate 3-kinase A in regulating emotional behavior and amygdala function | journal = Scientific Reports | volume = 6 | article-number = 23757 | date = April 2016 | pmid = 27053114 | pmc = 4823716 | doi = 10.1038/srep23757 | bibcode = 2016NatSR...623757C }}</ref><ref name="pmid29617377">{{cite journal | vauthors = Choi B, Lee HW, Mo S, Kim JY, Kim HW, Rhyu IJ, Hong E, Lee YK, Choi JS, Kim CH, Kim H | title = Inositol 1,4,5-trisphosphate 3-kinase A overexpressed in mouse forebrain modulates synaptic transmission and mGluR-LTD of CA1 pyramidal neurons | journal = PLOS ONE | volume = 13 | issue = 4 | article-number = e0193859 | year = 2018 | pmid = 29617377 | pmc = 5884490 | doi = 10.1371/journal.pone.0193859 | bibcode = 2018PLoSO..1393859C | doi-access = free }}</ref>

== 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.<ref name="pmid20022963"/><ref name="pmid28377279">{{cite journal | vauthors = Windhorst S, Song K, Gazdar AF | title = Inositol-1,4,5-trisphosphate 3-kinase-A (ITPKA) is frequently over-expressed and functions as an oncogene in several tumor types | journal = Biochemical Pharmacology | volume = 137 | pages = 1–9 | date = August 2017 | pmid = 28377279 | pmc = 5555585 | doi = 10.1016/j.bcp.2017.03.023 }}</ref>

== 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.<ref name="pmid19846664">{{cite journal | vauthors = Johnson HW, Schell MJ | title = Neuronal IP3 3-kinase is an F-actin-bundling protein: role in dendritic targeting and regulation of spine morphology | journal = Molecular Biology of the Cell | volume = 20 | issue = 24 | pages = 5166–80 | date = December 2009 | pmid = 19846664 | pmc = 2793293 | doi = 10.1091/mbc.E09-01-0083 }}</ref><ref name="pmid22219382">{{cite journal | vauthors = Yi J, Wu XS, Crites T, Hammer JA | title = Actin retrograde flow and actomyosin II arc contraction drive receptor cluster dynamics at the immunological synapse in Jurkat T cells | journal = Molecular Biology of the Cell | volume = 23 | issue = 5 | pages = 834–52 | date = March 2012 | pmid = 22219382 | pmc = 3290643 | doi = 10.1091/mbc.E11-08-0731 }}</ref> When fused to a reporter, such as green fluorescent protein, It is useful for the visualization of actin dynamics in living cells.<ref name="pmid26317264">{{cite journal | vauthors = Belin BJ, Goins LM, Mullins RD | title = Comparative analysis of tools for live cell imaging of actin network architecture | journal = Bioarchitecture | volume = 4 | issue = 6 | pages = 189–202 | year = 2014 | pmid = 26317264 | pmc = 4914014 | doi = 10.1080/19490992.2014.1047714 }}</ref><ref name="pmid28082420">{{cite journal | vauthors = Melak M, Plessner M, Grosse R | title = Actin visualization at a glance | journal = Journal of Cell Science | volume = 130 | issue = 3 | pages = 525–530 | date = February 2017 | pmid = 28082420 | doi = 10.1242/jcs.189068 | doi-access = free }}</ref>

== References == {{Reflist}}

== Further reading == {{refbegin | 2}} * {{cite journal | vauthors = Takazawa K, Perret J, Dumont JE, Erneux C | title = Molecular cloning and expression of a new putative inositol 1,4,5-trisphosphate 3-kinase isoenzyme | journal = The Biochemical Journal | volume = 278 | issue = Pt 3 | pages = 883–6 | date = September 1991 | pmid = 1654894 | pmc = 1151429 | doi = 10.1042/bj2780883}} * {{cite journal | vauthors = Takazawa K, Erneux C | title = Identification of residues essential for catalysis and binding of calmodulin in rat brain inositol 1,4,5-trisphosphate 3-kinase | journal = The Biochemical Journal | volume = 280 | issue = Pt 1 | pages = 125–9 | date = November 1991 | pmid = 1660262 | pmc = 1130609 | doi = 10.1042/bj2800125}} * {{cite journal | vauthors = Takazawa K, Perret J, Dumont JE, Erneux C | title = Molecular cloning and expression of a human brain inositol 1,4,5-trisphosphate 3-kinase | journal = Biochemical and Biophysical Research Communications | volume = 174 | issue = 2 | pages = 529–35 | date = January 1991 | pmid = 1847047 | doi = 10.1016/0006-291X(91)91449-M | bibcode = 1991BBRC..174..529T }} * {{cite journal | vauthors = Lin AN, Barnes S, Wallace RW | title = Phosphorylation by protein kinase C inactivates an inositol 1,4,5-trisphosphate 3-kinase purified from human platelets | journal = Biochemical and Biophysical Research Communications | volume = 170 | issue = 3 | pages = 1371–6 | date = August 1990 | pmid = 2167676 | doi = 10.1016/0006-291X(90)90546-Y | bibcode = 1990BBRC..170.1371L }} * {{cite journal | vauthors = Takazawa K, Vandekerckhove J, Dumont JE, Erneux C | title = Cloning and expression in Escherichia coli of a rat brain cDNA encoding a Ca2+/calmodulin-sensitive inositol 1,4,5-trisphosphate 3-kinase | journal = The Biochemical Journal | volume = 272 | issue = 1 | pages = 107–12 | date = November 1990 | pmid = 2176078 | pmc = 1149663 | doi = 10.1042/bj2720107}} * {{cite journal | vauthors = Ryu SH, Lee SY, Lee KY, Rhee SG | title = Catalytic properties of inositol trisphosphate kinase: activation by Ca2+ and calmodulin | journal = FASEB Journal | volume = 1 | issue = 5 | pages = 388–93 | date = November 1987 | pmid = 2824270 | doi = 10.1096/fasebj.1.5.2824270| doi-access = free | s2cid = 26541634 }} * {{cite journal | vauthors = Communi D, Vanweyenberg V, Erneux C | title = 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 | journal = The EMBO Journal | volume = 16 | issue = 8 | pages = 1943–52 | date = April 1997 | pmid = 9155020 | pmc = 1169797 | doi = 10.1093/emboj/16.8.1943 }} * {{cite journal | vauthors = Woodring PJ, Garrison JC | title = Expression, purification, and regulation of two isoforms of the inositol 1,4,5-trisphosphate 3-kinase | journal = The Journal of Biological Chemistry | volume = 272 | issue = 48 | pages = 30447–54 | date = November 1997 | pmid = 9374536 | doi = 10.1074/jbc.272.48.30447 | doi-access = free }} * {{cite journal | vauthors = Schell MJ, Erneux C, Irvine RF | title = Inositol 1,4,5-trisphosphate 3-kinase A associates with F-actin and dendritic spines via its N terminus | journal = The Journal of Biological Chemistry | volume = 276 | issue = 40 | pages = 37537–46 | date = October 2001 | pmid = 11468283 | doi = 10.1074/jbc.M104101200 | doi-access = free }} * {{cite journal | vauthors = Mishra J, Bhalla US | title = Simulations of inositol phosphate metabolism and its interaction with InsP(3)-mediated calcium release | journal = Biophysical Journal | volume = 83 | issue = 3 | pages = 1298–316 | date = September 2002 | pmid = 12202356 | pmc = 1302229 | doi = 10.1016/S0006-3495(02)73901-5 | bibcode = 2002BpJ....83.1298M }} * {{cite journal | vauthors = Dewaste V, Moreau C, De Smedt F, Bex F, De Smedt H, Wuytack F, Missiaen L, Erneux C | title = 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 | journal = The Biochemical Journal | volume = 374 | issue = Pt 1 | pages = 41–9 | date = August 2003 | pmid = 12747803 | pmc = 1223573 | doi = 10.1042/BJ20021963 }} * {{cite journal | vauthors = González B, Schell MJ, Letcher AJ, Veprintsev DB, Irvine RF, Williams RL | title = Structure of a human inositol 1,4,5-trisphosphate 3-kinase: substrate binding reveals why it is not a phosphoinositide 3-kinase | journal = Molecular Cell | volume = 15 | issue = 5 | pages = 689–701 | date = September 2004 | pmid = 15350214 | doi = 10.1016/j.molcel.2004.08.004 | doi-access = free }} * {{cite journal | vauthors = Kato H, Uzawa K, Onda T, Kato Y, Saito K, Nakashima D, Ogawara K, Bukawa H, Yokoe H, Tanzawa H | title = Down-regulation of 1D-myo-inositol 1,4,5-trisphosphate 3-kinase A protein expression in oral squamous cell carcinoma | journal = International Journal of Oncology | volume = 28 | issue = 4 | pages = 873–81 | date = April 2006 | pmid = 16525636 | doi = 10.3892/ijo.28.4.873 | doi-access = free }} {{refend}}

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