ITPKA

Protein-coding gene in the species Homo sapiens
ITPKA
Available structures
PDBOrtholog search: PDBe RCSB
List of PDB id codes

1W2C, 1W2D, 1W2F, 4UPU

Identifiers
AliasesITPKA, IP3-3KA, IP3KA, inositol-trisphosphate 3-kinase A
External IDsOMIM: 147521; MGI: 1333822; HomoloGene: 1671; GeneCards: ITPKA; OMA:ITPKA - orthologs
Gene location (Human)
Chromosome 15 (human)
Chr.Chromosome 15 (human)[1]
Chromosome 15 (human)
Genomic location for ITPKA
Genomic location for ITPKA
Band15q15.1Start41,493,393 bp[1]
End41,503,551 bp[1]
Gene location (Mouse)
Chromosome 2 (mouse)
Chr.Chromosome 2 (mouse)[2]
Chromosome 2 (mouse)
Genomic location for ITPKA
Genomic location for ITPKA
Band2|2 E5Start119,572,818 bp[2]
End119,581,744 bp[2]
RNA expression pattern
Bgee
HumanMouse (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
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. ^ a b c GRCh38: Ensembl release 89: ENSG00000137825 – Ensembl, May 2017
  2. ^ a b c 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. ^ a b 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. 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. 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.
  • v
  • t
  • e
  • 1tzd: CRYSTAL STRUCTURE OF THE CATALYTIC CORE OF INOSITOL 1,4,5-TRISPHOSPHATE 3-KINASE
    1tzd: CRYSTAL STRUCTURE OF THE CATALYTIC CORE OF INOSITOL 1,4,5-TRISPHOSPHATE 3-KINASE
  • 1w2c: HUMAN INOSITOL (1,4,5) TRISPHOSPHATE 3-KINASE COMPLEXED WITH MN2+/AMPPNP/INS(1,4,5)P3
    1w2c: HUMAN INOSITOL (1,4,5) TRISPHOSPHATE 3-KINASE COMPLEXED WITH MN2+/AMPPNP/INS(1,4,5)P3
  • 1w2d: HUMAN INOSITOL (1,4,5)-TRISPHOSPHATE 3-KINASE COMPLEXED WITH MN2+/ADP/INS(1,3,4,5)P4
    1w2d: HUMAN INOSITOL (1,4,5)-TRISPHOSPHATE 3-KINASE COMPLEXED WITH MN2+/ADP/INS(1,3,4,5)P4
  • 1w2f: HUMAN INOSITOL (1,4,5)-TRISPHOSPHATE 3-KINASE SUBSTITUTED WITH SELENOMETHIONINE
    1w2f: HUMAN INOSITOL (1,4,5)-TRISPHOSPHATE 3-KINASE SUBSTITUTED WITH SELENOMETHIONINE