ZCCHC6
Terminalna uridililtransferaza 7 (TUT7), znana I kao cinkov prst sa domenom CCHC 6, je enzim koji je kod ljudi kodiran genom ZCCHC6 sa hromosoma 9.[5][6] ZCCHC6 protein posreduje terminalnu uridilaciju RNK transkripta s kratkim poli-A repovima i uključen je u razgradnju iRNK i mikroRNK.
Aminokiselinska sekvenca
urediDužina polipeptidnog lanca je 1.495 aminokiselina, a molekulska težina 171.229 Da.[7]
| 10 | 20 | 30 | 40 | 50 | ||||
|---|---|---|---|---|---|---|---|---|
| MGDTAKPYFV | KRTKDRGTMD | DDDFRRGHPQ | QDYLIIDDHA | KGHGSKMEKG | ||||
| LQKKKITPGN | YGNTPRKGPC | AVSSNPYAFK | NPIYSQPAWM | NDSHKDQSKR | ||||
| WLSDEHTGNS | DNWREFKPGP | RIPVINRQRK | DSFQENEDGY | RWQDTRGCRT | ||||
| VRRLFHKDLT | SLETTSEMEA | GSPENKKQRS | RPRKPRKTRN | EENEQDGDLE | ||||
| GPVIDESVLS | TKELLGLQQA | EERLKRDCID | RLKRRPRNYP | TAKYTCRLCD | ||||
| VLIESIAFAH | KHIKEKRHKK | NIKEKQEEEL | LTTLPPPTPS | QINAVGIAID | ||||
| KVVQEFGLHN | ENLEQRLEIK | RIMENVFQHK | LPDCSLRLYG | SSCSRLGFKN | ||||
| SDVNIDIQFP | AIMSQPDVLL | LVQECLKNSD | SFIDVDADFH | ARVPVVVCRE | ||||
| KQSGLLCKVS | AGNENACLTT | KHLTALGKLE | PKLVPLVIAF | RYWAKLCSID | ||||
| RPEEGGLPPY | VFALMAIFFL | QQRKEPLLPV | YLGSWIEGFS | LSKLGNFNLQ | ||||
| DIEKDVVIWE | HTDSAAGDTG | ITKEEAPRET | PIKRGQVSLI | LDVKHQPSVP | ||||
| VGQLWVELLR | FYALEFNLAD | LVISIRVKEL | VSRELKDWPK | KRIAIEDPYS | ||||
| VKRNVARTLN | SQPVFEYILH | CLRTTYKYFA | LPHKITKSSL | LKPLNAITCI | ||||
| SEHSKEVINH | HPDVQTKDDK | LKNSVLAQGP | GATSSAANTC | KVQPLTLKET | ||||
| AESFGSPPKE | EMGNEHISVH | PENSDCIQAD | VNSDDYKGDK | VYHPETGRKN | ||||
| EKEKVGRKGK | HLLTVDQKRG | EHVVCGSTRN | NESESTLDLE | GFQNPTAKEC | ||||
| EGLATLDNKA | DLDGESTEGT | EELEDSLNHF | THSVQGQTSE | MIPSDEEEED | ||||
| DEEEEEEEEP | RLTINQREDE | DGMANEDELD | NTYTGSGDED | ALSEEDDELG | ||||
| EAAKYEDVKE | CGKHVERALL | VELNKISLKE | ENVCEEKNSP | VDQSDFFYEF | ||||
| SKLIFTKGKS | PTVVCSLCKR | EGHLKKDCPE | DFKRIQLEPL | PPLTPKFLNI | ||||
| LDQVCIQCYK | DFSPTIIEDQ | AREHIRQNLE | SFIRQDFPGT | KLSLFGSSKN | ||||
| GFGFKQSDLD | VCMTINGLET | AEGLDCVRTI | EELARVLRKH | SGLRNILPIT | ||||
| TAKVPIVKFF | HLRSGLEVDI | SLYNTLALHN | TRLLSAYSAI | DPRVKYLCYT | ||||
| MKVFTKMCDI | GDASRGSLSS | YAYTLMVLYF | LQQRNPPVIP | VLQEIYKGEK | ||||
| KPEIFVDGWN | IYFFDQIDEL | PTYWSECGKN | TESVGQLWLG | LLRFYTEEFD | ||||
| FKEHVISIRR | KSLLTTFKKQ | WTSKYIVIED | PFDLNHNLGA | GLSRKMTNFI | ||||
| MKAFINGRRV | FGIPVKGFPK | DYPSKMEYFF | DPDVLTEGEL | APNDRCCRIC | ||||
| GKIGHFMKDC | PMRRKVRRRR | DQEDALNQRY | PENKEKRSKE | DKEIHNKYTE | ||||
| REVSTKEDKP | IQCTPQKAKP | MRAAADLGRE | KILRPPVEKW | KRQDDKDLRE | ||||
| KRCFICGREG | HIKKECPQFK | GSSGSLSSKY | MTQGKASAKR | TQQES |
Struktura
urediGen ZCCHC6 sadrži 33 egzona s najmanje šest poznatih izoformi zbog alternativne prerade. ZCCHC6 gen kodira protein sa molekulskom težinom od 171 kDa i lokaliziran je u citoplazmi.
Funkcija
urediOn katalizira sljedeću reakciju, zahtijevajući Mg2 + i Mn2+ kao kofaktore.
Uridilaciju koju katalizira ZCCHC6 odvija se lahko na mrtdenilovanoj iRNK unutar ćelija.[9] Prečišćeni ZZHC6 selektivno "in vitro" prepoznaje i uridilira molekule RNK koje posjeduju kratke poli (A) repove (manje od 25 nukleotida). U ćelijama koje su osiromašene ZCCHC6-om, većina iRNK gubi svojstveni oligo (U) rep, koji je karakterističan za reaktivnost ZCCHC6, pa se poluživot molekula iRNK u skladu s tim produžuje.[9]
Osim razgradnje iRNK, smatra se da uridilacija funkcionira i prije sazrijevanja mikroRNK, pri čemu neka pre-mikroRNK grupe II zahtijeva 3'mono-uridilaciju za obradu Dicer-om.[10] Smatra se da ZCCHC6 djeluje redundantno sa ZCCHC11, kako bi posredovao biogenezu let-7 mikroRNK putem uridilacije.[11]
Reference
uredi- ^ a b c GRCh38: Ensembl release 89: ENSG00000083223 - Ensembl, maj 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000035248 - 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.
- ^ Nagase T, Kikuno R, Hattori A, Kondo Y, Okumura K, Ohara O (Dec 2000). "Prediction of the coding sequences of unidentified human genes. XIX. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro". DNA Research. 7 (6): 347–55. doi:10.1093/dnares/7.6.347. PMID 11214970.
- ^ "Entrez Gene: ZCCHC6 zinc finger, CCHC domain containing 6".
- ^ "UniProt, Q5VYS8". Pristupljeno 10. 9. 2021.
- ^ Rissland OS, Mikulasova A, Norbury CJ (2007). "Efficient RNA polyuridylation by noncanonical poly(A) polymerases". Mol. Cell. Biol. 27 (10): 3612–24. doi:10.1128/MCB.02209-06. PMC 1899984. PMID 17353264.
- ^ a b Lim J, Ha M, Chang H, Kwon SC, Simanshu DK, Patel DJ, Kim VN (2014). "Uridylation by TUT4 and TUT7 marks mRNA for degradation". Cell. 159 (6): 1365–76. doi:10.1016/j.cell.2014.10.055. PMC 4720960. PMID 25480299.
- ^ Heo I, Ha M, Lim J, Yoon MJ, Park JE, Kwon SC, Chang H, Kim VN (2012). "Mono-uridylation of pre-microRNA as a key step in the biogenesis of group II let-7 microRNAs". Cell. 151 (3): 521–32. doi:10.1016/j.cell.2012.09.022. PMID 23063654.
- ^ Thornton JE, Chang HM, Piskounova E, Gregory RI (2012). "Lin28-mediated control of let-7 microRNA expression by alternative TUTases Zcchc11 (TUT4) and Zcchc6 (TUT7)". RNA. 18 (10): 1875–85. doi:10.1261/rna.034538.112. PMC 3446710. PMID 22898984.
Dopunska literatura
uredi- Hartley JL, Temple GF, Brasch MA (Nov 2000). "DNA cloning using in vitro site-specific recombination". Genome Research. 10 (11): 1788–95. doi:10.1101/gr.143000. PMC 310948. PMID 11076863.
- Wiemann S, Weil B, Wellenreuther R, Gassenhuber J, Glassl S, Ansorge W, Böcher M, Blöcker H, Bauersachs S, Blum H, Lauber J, Düsterhöft A, Beyer A, Köhrer K, Strack N, Mewes HW, Ottenwälder B, Obermaier B, Tampe J, Heubner D, Wambutt R, Korn B, Klein M, Poustka A (Mar 2001). "Toward a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs". Genome Research. 11 (3): 422–35. doi:10.1101/gr.GR1547R. PMC 311072. PMID 11230166.
- Wiemann S, Arlt D, Huber W, Wellenreuther R, Schleeger S, Mehrle A, Bechtel S, Sauermann M, Korf U, Pepperkok R, Sültmann H, Poustka A (Oct 2004). "From ORFeome to biology: a functional genomics pipeline". Genome Research. 14 (10B): 2136–44. doi:10.1101/gr.2576704. PMC 528930. PMID 15489336.
- Mehrle A, Rosenfelder H, Schupp I, del Val C, Arlt D, Hahne F, Bechtel S, Simpson J, Hofmann O, Hide W, Glatting KH, Huber W, Pepperkok R, Poustka A, Wiemann S (Jan 2006). "The LIFEdb database in 2006". Nucleic Acids Research. 34 (Database issue): D415–8. doi:10.1093/nar/gkj139. PMC 1347501. PMID 16381901.