ITPKA

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; OMA:ITPKA - orthologs
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 119,572,818 bp [2] End 119,581,744 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in mucosa of transverse colon right frontal lobe Brodmann area 9 prefrontal cortex middle temporal gyrus caudate nucleus putamen cingulate gyrus anterior cingulate cortex nucleus accumbens Top expressed in Region I of hippocampus proper hippocampus proper primary visual cortex prefrontal cortex superior frontal gyrus dentate gyrus of hippocampal formation granule cell dorsal striatum temporal lobe nucleus accumbens amygdala More reference expression data BioGPS More reference expression data
Gene ontology Molecular function calmodulin-dependent protein kinase activity transferase activity nucleotide 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: 119.57 – 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]}

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. "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. 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

• 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. Bibcode:1991BBRC..174..529T. 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. Bibcode:1990BBRC..170.1371L. 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. S2CID   26541634.
• 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. Bibcode:2002BpJ....83.1298M. 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.