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ITPKA
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<h2 id="structure">Structure</h2> <p>ITPKA is one of three inositol-trisphosphate 3-kinase (ITP3K) genes in humans. <a href="/facts/Inositol-trisphosphate_3-kinase/fFLHqcsv">ITP3K</a> proteins regulate <a href="/facts/Inositol_phosphate/HkY9GQYb">inositol phosphate</a> metabolism by <a href="/facts/Phosphorylation/LXUEEeIL">phosphorylation</a> of the second messenger <a href="/facts/Inositol_1%2c4%2c5-trisphosphate/TDLGCWuG">inositol 1,4,5-trisphosphate</a> to produce Ins(1,3,4,5)P4, which is sometimes abbreviated as IP4. Structurally, ITPKA belongs to the <a href="/facts/Inositol_polyphosphate_kinase/mDcLwhEG">inositol polyphosphate kinase</a> (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, <a href="/facts/Inositol_trisphosphate/TDLGCWuG">inositol trisphosphate</a>, which is the enzyme's only substrate. Both calcium/<a href="/facts/Calmodulin/CbEnEYHE">calmodulin</a> and protein phosphorylation mechanisms control its activity. It is also a substrate for the <a href="/facts/Protein_kinase_A/kaKoYfbp">cyclic AMP-dependent protein kinase</a>, <a href="/facts/Ca2%252B%2fcalmodulin-dependent_protein_kinase_II/hklT8LuH">calcium/calmodulin- dependent protein kinase II</a>, and <a href="/facts/Protein_kinase_C/6WSQgAWv">protein kinase C</a> in vitro. ITPKA and ITPKB are 68% identical in the <a href="/facts/C-terminus/ws4scHgT">C-terminus</a> region The amino- terminal region of ITPKA binds filamentous <a href="/facts/Actin/Hu3qIUL9">actin</a>. This property localizes the ITPKA to <a href="/facts/Dendritic_spine/wg54o3YT">dendritic spines</a> in principal neurons.<a class="footnote-ref" id="fnref:4" href="#fn:4"><sup>4</sup></a><a class="footnote-ref" id="fnref:5" href="#fn:5"><sup>5</sup></a><a class="footnote-ref" id="fnref:6" href="#fn:6"><sup>6</sup></a> ITPKA is expressed physiologically in neurons, but it is sometimes expressed in cancer cells and may contribute to processes of metastasis.<a class="footnote-ref" id="fnref:7" href="#fn:7"><sup>7</sup></a> </p> <h2 id="physiological-function">Physiological function</h2> <p>ITPKA participates in learning and memory processes in neurons.<a class="footnote-ref" id="fnref:8" href="#fn:8"><sup>8</sup></a><a class="footnote-ref" id="fnref:9" href="#fn:9"><sup>9</sup></a> </p> <h2 id="roles-in-human-disease">Roles in human disease</h2> <p>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.<a class="footnote-ref" id="fnref:10" href="#fn:10"><sup>10</sup></a><a class="footnote-ref" id="fnref:11" href="#fn:11"><sup>11</sup></a> </p> <h2 id="relationship-to-f-tractin">Relationship to F-tractin</h2> <p><a href="/facts/F-tractin/0LgXlhpM">F-tractin</a> is amino acids 9-52 of rat ITPKA. It was later determined that amino acids 9-40 were sufficient for binding filamentous actin.<a class="footnote-ref" id="fnref:12" href="#fn:12"><sup>12</sup></a><a class="footnote-ref" id="fnref:13" href="#fn:13"><sup>13</sup></a> When fused to a reporter, such as <a href="/facts/Green_fluorescent_protein/6nWDMhSC">green fluorescent protein</a>, It is useful for the visualization of actin dynamics in living cells.<a class="footnote-ref" id="fnref:14" href="#fn:14"><sup>14</sup></a><a class="footnote-ref" id="fnref:15" href="#fn:15"><sup>15</sup></a> </p> <h2 id="further-reading">Further reading</h2> <ul><li>Takazawa K, Perret J, Dumont JE, Erneux C (September 1991). <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1151429">"Molecular cloning and expression of a new putative inositol 1,4,5-trisphosphate 3-kinase isoenzyme"</a>. <i>The Biochemical Journal</i>. 278 (Pt 3): 883–6. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1042%2Fbj2780883">10.1042/bj2780883</a>. <a href="/facts/PMC_(identifier)/dX1zMt71">PMC</a> <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1151429">1151429</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/1654894">1654894</a>.</li> <li>Takazawa K, Erneux C (November 1991). <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1130609">"Identification of residues essential for catalysis and binding of calmodulin in rat brain inositol 1,4,5-trisphosphate 3-kinase"</a>. <i>The Biochemical Journal</i>. 280 (Pt 1): 125–9. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1042%2Fbj2800125">10.1042/bj2800125</a>. <a href="/facts/PMC_(identifier)/dX1zMt71">PMC</a> <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1130609">1130609</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/1660262">1660262</a>.</li> <li>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". <i>Biochemical and Biophysical Research Communications</i>. 174 (2): 529–35. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1016%2F0006-291X%2891%2991449-M">10.1016/0006-291X(91)91449-M</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/1847047">1847047</a>.</li> <li>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". <i>Biochemical and Biophysical Research Communications</i>. 170 (3): 1371–6. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1016%2F0006-291X%2890%2990546-Y">10.1016/0006-291X(90)90546-Y</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/2167676">2167676</a>.</li> <li>Takazawa K, Vandekerckhove J, Dumont JE, Erneux C (November 1990). <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1149663">"Cloning and expression in Escherichia coli of a rat brain cDNA encoding a Ca2+/calmodulin-sensitive inositol 1,4,5-trisphosphate 3-kinase"</a>. <i>The Biochemical Journal</i>. 272 (1): 107–12. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1042%2Fbj2720107">10.1042/bj2720107</a>. <a href="/facts/PMC_(identifier)/dX1zMt71">PMC</a> <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1149663">1149663</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/2176078">2176078</a>.</li> <li>Ryu SH, Lee SY, Lee KY, Rhee SG (November 1987). <a href="https://doi.org/10.1096%2Ffasebj.1.5.2824270">"Catalytic properties of inositol trisphosphate kinase: activation by Ca2+ and calmodulin"</a>. <i>FASEB Journal</i>. 1 (5): 388–93. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1096%2Ffasebj.1.5.2824270">10.1096/fasebj.1.5.2824270</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/2824270">2824270</a>. <a href="/facts/S2CID_(identifier)/ldJsHa2Y">S2CID</a> <a href="https://api.semanticscholar.org/CorpusID:26541634">26541634</a>.</li> <li>Communi D, Vanweyenberg V, Erneux C (April 1997). <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1169797">"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"</a>. <i>The EMBO Journal</i>. 16 (8): 1943–52. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1093%2Femboj%2F16.8.1943">10.1093/emboj/16.8.1943</a>. <a href="/facts/PMC_(identifier)/dX1zMt71">PMC</a> <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1169797">1169797</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/9155020">9155020</a>.</li> <li>Woodring PJ, Garrison JC (November 1997). <a href="https://doi.org/10.1074%2Fjbc.272.48.30447">"Expression, purification, and regulation of two isoforms of the inositol 1,4,5-trisphosphate 3-kinase"</a>. <i>The Journal of Biological Chemistry</i>. 272 (48): 30447–54. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1074%2Fjbc.272.48.30447">10.1074/jbc.272.48.30447</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/9374536">9374536</a>.</li> <li>Schell MJ, Erneux C, Irvine RF (October 2001). <a href="https://doi.org/10.1074%2Fjbc.M104101200">"Inositol 1,4,5-trisphosphate 3-kinase A associates with F-actin and dendritic spines via its N terminus"</a>. <i>The Journal of Biological Chemistry</i>. 276 (40): 37537–46. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1074%2Fjbc.M104101200">10.1074/jbc.M104101200</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/11468283">11468283</a>.</li> <li>Mishra J, Bhalla US (September 2002). <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1302229">"Simulations of inositol phosphate metabolism and its interaction with InsP(3)-mediated calcium release"</a>. <i>Biophysical Journal</i>. 83 (3): 1298–316. <a href="/facts/Bibcode_(identifier)/9HtdQSGB">Bibcode</a>:<a href="https://ui.adsabs.harvard.edu/abs/2002BpJ....83.1298M">2002BpJ....83.1298M</a>. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1016%2FS0006-3495%2802%2973901-5">10.1016/S0006-3495(02)73901-5</a>. <a href="/facts/PMC_(identifier)/dX1zMt71">PMC</a> <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1302229">1302229</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/12202356">12202356</a>.</li> <li>Dewaste V, Moreau C, De Smedt F, Bex F, De Smedt H, Wuytack F, Missiaen L, Erneux C (August 2003). <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1223573">"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"</a>. <i>The Biochemical Journal</i>. 374 (Pt 1): 41–9. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1042%2FBJ20021963">10.1042/BJ20021963</a>. <a href="/facts/PMC_(identifier)/dX1zMt71">PMC</a> <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1223573">1223573</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/12747803">12747803</a>.</li> <li>González B, Schell MJ, Letcher AJ, Veprintsev DB, Irvine RF, Williams RL (September 2004). <a href="https://doi.org/10.1016%2Fj.molcel.2004.08.004">"Structure of a human inositol 1,4,5-trisphosphate 3-kinase: substrate binding reveals why it is not a phosphoinositide 3-kinase"</a>. <i>Molecular Cell</i>. 15 (5): 689–701. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1016%2Fj.molcel.2004.08.004">10.1016/j.molcel.2004.08.004</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/15350214">15350214</a>.</li> <li>Kato H, Uzawa K, Onda T, Kato Y, Saito K, Nakashima D, Ogawara K, Bukawa H, Yokoe H, Tanzawa H (April 2006). <a href="https://doi.org/10.3892%2Fijo.28.4.873">"Down-regulation of 1D-myo-inositol 1,4,5-trisphosphate 3-kinase A protein expression in oral squamous cell carcinoma"</a>. <i>International Journal of Oncology</i>. 28 (4): 873–81. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.3892%2Fijo.28.4.873">10.3892/ijo.28.4.873</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/16525636">16525636</a>.</li></ul> <h2 id="references">References</h2> <ol> <li id="fn:1"><p>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. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:1" class="footnote-back-ref">↩</a></p></li> <li id="fn:2"><p>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. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC332787" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC332787</a> <a href="#fnref:2" class="footnote-back-ref">↩</a></p></li> <li id="fn:3"><p>"Entrez Gene: ITPKA inositol 1,4,5-trisphosphate 3-kinase A". <a href="https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=3706" target="_blank">https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=3706</a> <a href="#fnref:3" class="footnote-back-ref">↩</a></p></li> <li id="fn:4"><p>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. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:4" class="footnote-back-ref">↩</a></p></li> <li id="fn:5"><p>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. <a href="https://doi.org/10.1074%2Fjbc.M104101200" target="_blank">https://doi.org/10.1074%2Fjbc.M104101200</a> <a href="#fnref:5" class="footnote-back-ref">↩</a></p></li> <li id="fn:6"><p>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. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:6" class="footnote-back-ref">↩</a></p></li> <li id="fn:7"><p>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. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2820782" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2820782</a> <a href="#fnref:7" class="footnote-back-ref">↩</a></p></li> <li id="fn:8"><p>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. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4823716" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4823716</a> <a href="#fnref:8" class="footnote-back-ref">↩</a></p></li> <li id="fn:9"><p>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. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5884490" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5884490</a> <a href="#fnref:9" class="footnote-back-ref">↩</a></p></li> <li id="fn:10"><p>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. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2820782" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2820782</a> <a href="#fnref:10" class="footnote-back-ref">↩</a></p></li> <li id="fn:11"><p>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. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5555585" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5555585</a> <a href="#fnref:11" class="footnote-back-ref">↩</a></p></li> <li id="fn:12"><p>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. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2793293" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2793293</a> <a href="#fnref:12" class="footnote-back-ref">↩</a></p></li> <li id="fn:13"><p>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. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3290643" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3290643</a> <a href="#fnref:13" class="footnote-back-ref">↩</a></p></li> <li id="fn:14"><p>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. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4914014" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4914014</a> <a href="#fnref:14" class="footnote-back-ref">↩</a></p></li> <li id="fn:15"><p>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. <a href="https://doi.org/10.1242%2Fjcs.189068" target="_blank">https://doi.org/10.1242%2Fjcs.189068</a> <a href="#fnref:15" class="footnote-back-ref">↩</a></p></li> </ol>