ITPKA
Inozitol-trisfosfat 3-kinaza A jest enzim koji je kod ljudi kodiran genom ITPKA.[5][6][7]
Aminokiselinska sekvenca
[uredi | uredi izvor]Dužina polipeptidnog lanca je 461 aminokiselina, a molekulska težina 51.009 Da.[8].
| 10 | 20 | 30 | 40 | 50 | ||||
|---|---|---|---|---|---|---|---|---|
| MTLPGGPTGM | ARPGGARPCS | PGLERAPRRS | VGELRLLFEA | RCAAVAAAAA | ||||
| AGEPRARGAK | RRGGQVPNGL | PRAPPAPVIP | QLTVTAEEPD | VPPTSPGPPE | ||||
| RERDCLPAAG | SSHLQQPRRL | STSSVSSTGS | SSLLEDSEDD | LLSDSESRSR | ||||
| GNVQLEAGED | VGQKNHWQKI | RTMVNLPVIS | PFKKRYAWVQ | LAGHTGSFKA | ||||
| AGTSGLILKR | CSEPERYCLA | RLMADALRGC | VPAFHGVVER | DGESYLQLQD | ||||
| LLDGFDGPCV | LDCKMGVRTY | LEEELTKARE | RPKLRKDMYK | KMLAVDPEAP | ||||
| TEEEHAQRAV | TKPRYMQWRE | GISSSTTLGF | RIEGIKKADG | SCSTDFKTTR | ||||
| SREQVLRVFE | EFVQGDEEVL | RRYLNRLQQI | RDTLEVSEFF | RRHEVIGSSL | ||||
| LFVHDHCHRA | GVWLIDFGKT | TPLPDGQILD | HRRPWEEGNR | EDGYLLGLDN | ||||
| LIGILASLAE | R |
- Simboli
C: Cistein
D: Asparaginska kiselina
E: Glutaminska kiselina
F: Fenilalanin
G: Glicin
H: Histidin
I: Izoleucin
K: Lizin
L: Leucin
M: Metionin
N: Asparagin
P: Prolin
Q: Glutamin
R: Arginin
S: Serin
T: Treonin
V: Valin
W: Triptofan
Y: Tirozin
Struktura
[uredi | uredi izvor]ITPKA je jedan od tri gena inozitol-trisfosfat 3-kinaze (ITP3K) kod ljudi. ITP3K proteini reguliraju metabolizam inozitol-fosfata, fosforilacijom drugog prenosnika inozitol 1,4,5-trisfosfata, dajući Ins (1,3 , 4,5) P4, što se ponekad skraćuje kao IP4. Strukturno, ITPKA pripada porodici inozitol-polifosfat kinaza (IPK). Aktivnost inozitol 1,4,5-trisfosfat 3-kinaze odgovorna je za regulaciju nivoa velikog broja inozitol-polifosfata, koji su važni u ćelijskoj signalizaciji, ponajviše inozitol-trifosfat, koji je jedini enzimska podloga. I mehanizmi fosforilacije kalcija/ kalmodulina i proteina kontroliraju njegovu aktivnost. Takođe je supstrat za cikličnu protein-kinazu koja zavisi od AMP, Ca2 + / protein-kinaza ovisna od kalcija kalmodulina i protein-kinaza C in vitro. ITPKA i ITPKB su 68% identični u C-terminalnoj regiji. Amino-terminalni region ITPKA veže filamentni aktin. Ovo svojstvo lokalizira ITPKA na dendritsku kičmu u glavnim neuronima.[9][10][11] ITPKA se fiziološki eksprimira u neuronima, ali ponekad i u ćelijama karcinoma i može doprinijeti procesima metastaziranja.[12]
Fiziološka funkcija
[uredi | uredi izvor]ITPKA učestvuje u procesima učenja i pamćenja u neuronima.[13][14]
Uloge u ljudskim bolestima
[uredi | uredi izvor]Iako se ITPKA fiziološki eksprimira u neuronima i sjemenicima, ponekad se izražava i u ćelijama karcinoma, a ekspresija čini karcinom agresivnijim.[12][15]
Odnos sa F-traktinom
[uredi | uredi izvor]F-traktin obuhvata pacovske ITPKA aminokiseline 9-52. Kasnije je utvrđeno da su aminokiseline 9-40 dovoljne za vezivanje nitastih aktina.[16][17] Kada se stopi sa reporterom, kao što je zeleni fluorescentni protein, koristan je za vizualizaciju dinamike aktina u živim ćelijama.[18][19]
Reference
[uredi | uredi izvor]- ^ a b c GRCh38: Ensembl release 89: ENSG00000137825 - Ensembl, maj 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000027296 - Ensembl, maj 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ Erneux C, Roeckel N, Takazawa K, Mailleux P, Vassart G, Mattei MG (oktobar 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.
- ^ Takazawa K, Perret J, Dumont JE, Erneux C (decembar 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.
- ^ name="entrez""Entrez Gene: ITPKA inositol 1,4,5-trisphosphate 3-kinase A".
- ^ "UniProt, P23677". Pristupljeno 15. 7. 2021.
- ^ Yamada M, Kakita A, Mizuguchi M, Rhee SG, Kim SU, Ikuta F (mart 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.
- ^ Schell MJ, Erneux C, Irvine RF (oktobar 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.
- ^ Windhorst S, Minge D, Bähring R, Hüser S, Schob C, Blechner C, Lin HY, Mayr GW, Kindler S (mart 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 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 (februar 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.
- ^ 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.
- ^ 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.
- ^ 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.
- ^ Johnson HW, Schell MJ (decembar 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.
- ^ Yi J, Wu XS, Crites T, Hammer JA (mart 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.
- ^ 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.
- ^ Melak M, Plessner M, Grosse R (februar 2017). "Actin visualization at a glance". Journal of Cell Science. 130 (3): 525–530. doi:10.1242/jcs.189068. PMID 28082420.
Dopunska literatura
[uredi | uredi izvor]- Takazawa K, Perret J, Dumont JE, Erneux C (septembar 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 (novembar 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 (januar 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 (novembar 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 (novembar 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 (novembar 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 (oktobar 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 (septembar 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 (septembar 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.