ANK3
| ANK3 ankirin 3, iz Ranvijerovih čvorova (ankirin G) | |
|---|---|
| Identifikatori | |
| Simbol | ANK3 |
| Alt. simboli | ankirin-G |
| Entrez | 288 |
| HUGO | 494 |
| OMIM | 600465 |
| RefSeq | NM_020987 |
| UniProt | Q12955 |
| Drugi podaci | |
| Lokus | Hromozom 10 q21 |
Ankirin 3 (ANK3), isto poznat kao ankirin-G, je protein iz ankirin familije koji je kod čoveka kodiran ANK3 genom.[1][2]
Funkcija[uredi | uredi kod]
Protein kodiran ovim genom je imunološki različit genski proizvod od ankirina ANK1 i ANK2. On je originalno otkriven u aksonskom inicijalnom segmentu i Ranvijerovim čvorovima neurona u centralnom i perifernom nervnom sistemu. Alternativno spojene varijante mogu biti izražene u drugim tkivima. Mada su višestruke transkripcione varijante koje kodiraju nekoliko različitih izoformi nađene za ovaj gen, some su dve bile potpuno karakterisane.[1]
U okviru nervnog sistema, ankirin G ja specifično lociran u neuromišićnom spoju i Ranvijerovim čvorovima.[3] U Ranvijerovim čvorovima gde su akcioni potencijali aktivno prenošeni, za ankirin G se dugo mislilo da je posredni vezujući partner neurofaskinu i naponski-kontrolisanim natrijumskim kanalima.[4] Genetičko brisanje ankirina G sa više neuronskih tipova ja pokazalo da je ankirin G neophodan za normalnu raspodelu naponski-kontrolisanih natrijumskih kanala na aksonskim humkama i za oslobađanje akcionih potencijala.[5][6]
Povezanost bolesti[uredi | uredi kod]
ANK3 protein se združuje sa srčanim natrijumskim kanalom Nav1.5 (SCN5A). Oba proteina su visoko izražena na ventrikularnom umetnutom disku i membrani T-cevčice u kardiomiocitima. Mutacija na Nav1.5 proteinu blokira vezujuću interakciju sa ANK3 i na taj način poremećava površinsko izražavanje Nav1.5 na kardiomiocitima, što dovodi do Brugada sindroma, tipa srčane aritmije.[7]
Pojedine mutacije na ANK3 genu su vezane za bipolarne poremećaje.[8][9]
Ankirin familija[uredi | uredi kod]
Protein koji kodira ANK3 gen je član ankirin familije of proteina koja povezuje integralne membrane proteina sa potpornim spektrin-aktin citoskeletonom. Ankirini igraju ključnu ulog u aktivnostima kao što su ćelijska pokretljivost, aktiviranje, proliferacija, kontakt i održavanje specijalizovanih membranskih domena. Većina ankirina se tipično sastoji of tri strukturna domena: amino-terminalni domen koji sadrži višestruka ankirin ponavljanja; centralin region sa visoko konzervisanim spektrin vezivajućim domenom; i karboksi-terminal regulatorni domen koji je najmanje konzerviran i koji je subjekat varijacije.[1]
Reference[uredi | uredi kod]
- ↑ 1,0 1,1 1,2 „Entrez Gene: ANK2 ankyrin 3, node of Ranvier”.
- ↑ Kapfhamer D, Miller DE, Lambert S, Bennett V, Glover TW, Burmeister M (May 1995). „Chromosomal localization of the ankyrin-G gene (ANK3/Ank3) to human 10q21 and mouse 10”. Genomics 27 (1): 189–91. DOI:10.1006/geno.1995.1023. PMID 7665168.
- ↑ Lambert S, Davis JQ, Bennett V (September 1997). „Morphogenesis of the node of Ranvier: co-clusters of ankyrin and ankyrin-binding integral proteins define early developmental intermediates.”. J Neurosci. 17 (18): 7025–36. PMID 9278538.
- ↑ Srinivasan Y, Lewallen M, Angelides KJ (April 1992). „Mapping the binding site on ankyrin for the voltage-dependent sodium channel from brain.”. J Biol Chem. 267 (11): 7483–9. PMID 1313804.
- ↑ Zhou D, Lambert S, Malen PL, Carpenter S, Boland LM, Bennett V (November 1998). „Ankyrin-G is required for clustering of voltage-gated Na channels at the axon hillock and normal action potential firing.”. J Cell Biol. 143 (5): 1295–1304. PMID 9832557.
- ↑ Hedstrom KL, Xu X, Ogawa Y, Frischknecht R, Seidenbecher CI, Shrager P, Rasband MN (August 2007). „Neurofascin assembles a specialized extracellular matrix at the axon initial segment.”. J Cell Biol. 178 (5): 875–886. PMID 17709431.
- ↑ Mohler PJ, Rivolta I, Napolitano C, LeMaillet G, Lambert S, Priori SG, Bennett V (December 2004). „Nav1.5 E1053K mutation causing Brugada syndrome blocks binding to ankyrin-G and expression of Nav1.5 on the surface of cardiomyocytes”. Proc. Natl. Acad. Sci. U.S.A. 101 (50): 17533–8. DOI:10.1073/pnas.0403711101. PMC 536011. PMID 15579534.
- ↑ Ferreira MA, O'Donovan MC, Meng YA, et al. (August 2008). „Collaborative genome-wide association analysis supports a role for ANK3 and CACNA1C in bipolar disorder”. Nat. Genet. 40: 1056. DOI:10.1038/ng.209. PMID 18711365.
- ↑ „Channeling Mental Illness: GWAS Links Ion Channels, Bipolar Disorder”. Schizophrenia Research Forum: News. schizophreniaforum.org. 19. 08. 2008.. Arhivirano iz originala na datum 2010-12-18. Pristupljeno 21. 08. 2008.
Literatura[uredi | uredi kod]
- Lopez C, Métral S, Eladari D i dr.. (2005). „The ammonium transporter RhBG: requirement of a tyrosine-based signal and ankyrin-G for basolateral targeting and membrane anchorage in polarized kidney epithelial cells”. J. Biol. Chem. 280 (9): 8221–8. DOI:10.1074/jbc.M413351200. PMID 15611082.
- Kizhatil K, Yoon W, Mohler PJ i dr.. (2007). „Ankyrin-G and beta2-spectrin collaborate in biogenesis of lateral membrane of human bronchial epithelial cells”. J. Biol. Chem. 282 (3): 2029–37. DOI:10.1074/jbc.M608921200. PMID 17074766.
- Weimer JM, Chattopadhyay S, Custer AW, Pearce DA (2005). „Elevation of Hook1 in a disease model of Batten disease does not affect a novel interaction between Ankyrin G and Hook1”. Biochem. Biophys. Res. Commun. 330 (4): 1176–81. DOI:10.1016/j.bbrc.2005.03.103. PMID 15823567.
- Shirahata E, Iwasaki H, Takagi M i dr.. (2006). „Ankyrin-G regulates inactivation gating of the neuronal sodium channel, Nav1.6”. J. Neurophysiol. 96 (3): 1347–57. DOI:10.1152/jn.01264.2005. PMID 16775201.
- Schulze TG, Detera-Wadleigh SD, Akula N i dr.. (2009). „Two variants in Ankyrin 3 (ANK3) are independent genetic risk factors for bipolar disorder”. Mol. Psychiatry 14 (5): 487–91. DOI:10.1038/mp.2008.134. PMC 2793269. PMID 19088739.
- Morgan AR, Turic D, Jehu L i dr.. (2007). „Association studies of 23 positional/functional candidate genes on chromosome 10 in late-onset Alzheimer's disease”. Am. J. Med. Genet. B Neuropsychiatr. Genet. 144B (6): 762–70. DOI:10.1002/ajmg.b.30509. PMID 17373700.
- Morgan AR, Hamilton G, Turic D i dr.. (2008). „Association analysis of 528 intra-genic SNPs in a region of chromosome 10 linked to late onset Alzheimer's disease”. Am. J. Med. Genet. B Neuropsychiatr. Genet. 147B (6): 727–31. DOI:10.1002/ajmg.b.30670. PMID 18163421.
- Grupe A, Li Y, Rowland C i dr.. (2006). „A Scan of Chromosome 10 Identifies a Novel Locus Showing Strong Association with Late-Onset Alzheimer Disease”. Am. J. Hum. Genet. 78 (1): 78–88. DOI:10.1086/498851. PMC 1380225. PMID 16385451.
- Stabach PR, Devarajan P, Stankewich MC i dr.. (2008). „Ankyrin facilitates intracellular trafficking of α1-Na+-K+-ATPase in polarized cells”. Am. J. Physiol., Cell Physiol. 295 (5): C1202–14. DOI:10.1152/ajpcell.00273.2008. PMC 2584975. PMID 18768923.
- Sohet F, Colin Y, Genetet S i dr.. (2008). „Phosphorylation and ankyrin-G binding of the C-terminal domain regulate targeting and function of the ammonium transporter RhBG”. J. Biol. Chem. 283 (39): 26557–67. DOI:10.1074/jbc.M803120200. PMID 18635543.
- Ignatiuk A, Quickfall JP, Hawrysh AD i dr.. (2006). „The smaller isoforms of ankyrin 3 bind to the p85 subunit of phosphatidylinositol 3'-kinase and enhance platelet-derived growth factor receptor down-regulation”. J. Biol. Chem. 281 (9): 5956–64. DOI:10.1074/jbc.M510032200. PMID 16377635.
- Colland F, Jacq X, Trouplin V i dr.. (2004). „Functional Proteomics Mapping of a Human Signaling Pathway”. Genome Res. 14 (7): 1324–32. DOI:10.1101/gr.2334104. PMC 442148. PMID 15231748.
- Glinsky GV, Berezovska O, Glinskii AB (2005). „Microarray analysis identifies a death-from-cancer signature predicting therapy failure in patients with multiple types of cancer”. J. Clin. Invest. 115 (6): 1503–21. DOI:10.1172/JCI23412. PMC 1136989. PMID 15931389.
- McEwen DP, Meadows LS, Chen C i dr.. (2004). „Sodium channel beta1 subunit-mediated modulation of Nav1.2 currents and cell surface density is dependent on interactions with contactin and ankyrin”. J. Biol. Chem. 279 (16): 16044–9. DOI:10.1074/jbc.M400856200. PMID 14761957.
- Ota T, Suzuki Y, Nishikawa T i dr.. (2004). „Complete sequencing and characterization of 21,243 full-length human cDNAs”. Nat. Genet. 36 (1): 40–5. DOI:10.1038/ng1285. PMID 14702039.
- Wang J, Robinson JF, O'Neil CH i dr.. (2006). „Ankyrin G overexpression in Hutchinson-Gilford progeria syndrome fibroblasts identified through biological filtering of expression profiles”. J. Hum. Genet. 51 (11): 934–42. DOI:10.1007/s10038-006-0042-0. PMID 17033732.
- Kizhatil K, Davis JQ, Davis L i dr.. (2007). „Ankyrin-G is a molecular partner of E-cadherin in epithelial cells and early embryos”. J. Biol. Chem. 282 (36): 26552–61. DOI:10.1074/jbc.M703158200. PMID 17620337.
- Kizhatil K, Bennett V (2004). „Lateral membrane biogenesis in human bronchial epithelial cells requires 190-kDa ankyrin-G”. J. Biol. Chem. 279 (16): 16706–14. DOI:10.1074/jbc.M314296200. PMID 14757759.