ITPKA
Inozitol-trisfosfat 3-kinaza A jest enzim koji je kod ljudi kodiran genom ITPKA.[5][6][7]
Aminokiselinska sekvenca
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
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
ITPKA učestvuje u procesima učenja i pamćenja u neuronima.[13][14]
Uloge u ljudskim bolestima
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
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
- ^ 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
- 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.
Content Disclaimer
Informasi ini disarikan dari Wikipedia dan disajikan kembali untuk tujuan edukasi. Konten tersedia di bawah lisensi CC BY-SA 3.0. Kami tidak bertanggung jawab atas ketidakakuratan data yang bersumber dari kontribusi publik tersebut.
- The information displayed on this website is sourced in part or in whole from Wikipedia and has been adapted for the purpose of restating it. We strive to provide accurate and relevant information, however:
- There is no guarantee of absolute accuracy. Wikipedia is an open, collaborative project that can be edited by anyone, so information is subject to change.
- It is not intended to constitute professional advice. The content displayed is for informational and educational purposes only. For important decisions (e.g., medical, legal, or financial), please consult a professional.
- Content copyright. Wikipedia is licensed under the Creative Commons Attribution-ShareAlike License (CC BY-SA). This means that content may be reused with appropriate attribution and shared under a similar license.
- Responsible use. Any risk arising from the use of information from this website is entirely the responsibility of the user.