FANCI
Komplementacijska grupa I Fanconijeve anemije (FANCI), znana i kao KIAA1794, jest protein koji je kod ljudi kodiran genom FANCI sa hromosoma 15.[5][6][7][8][9] Poznato je da mutacije u genu FANCI uzrokuju Fanconijevu anemiju.[10]
Aminokiselinska sekvenca
urediDužina polipeptidnog lanca je 1.328 aminokiselina, a molekulska težina 149.324 Da.[5]
| 10 | 20 | 30 | 40 | 50 | ||||
|---|---|---|---|---|---|---|---|---|
| MDQKILSLAA | EKTADKLQEF | LQTLREGDLT | NLLQNQAVKG | KVAGALLRAI | ||||
| FKGSPCSEEA | GTLRRRKIYT | CCIQLVESGD | LQKEIASEII | GLLMLEAHHF | ||||
| PGPLLVELAN | EFISAVREGS | LVNGKSLELL | PIILTALATK | KENLAYGKGV | ||||
| LSGEECKKQL | INTLCSGRWD | QQYVIQLTSM | FKDVPLTAEE | VEFVVEKALS | ||||
| MFSKMNLQEI | PPLVYQLLVL | SSKGSRKSVL | EGIIAFFSAL | DKQHNEEQSG | ||||
| DELLDVVTVP | SGELRHVEGT | IILHIVFAIK | LDYELGRELV | KHLKVGQQGD | ||||
| SNNNLSPFSI | ALLLSVTRIQ | RFQDQVLDLL | KTSVVKSFKD | LQLLQGSKFL | ||||
| QNLVPHRSYV | STMILEVVKN | SVHSWDHVTQ | GLVELGFILM | DSYGPKKVLD | ||||
| GKTIETSPSL | SRMPNQHACK | LGANILLETF | KIHEMIRQEI | LEQVLNRVVT | ||||
| RASSPISHFL | DLLSNIVMYA | PLVLQSCSSK | VTEAFDYLSF | LPLQTVQRLL | ||||
| KAVQPLLKVS | MSMRDCLILV | LRKAMFANQL | DARKSAVAGF | LLLLKNFKVL | ||||
| GSLSSSQCSQ | SLSVSQVHVD | VHSHYNSVAN | ETFCLEIMDS | LRRCLSQQAD | ||||
| VRLMLYEGFY | DVLRRNSQLA | NSVMQTLLSQ | LKQFYEPKPD | LLPPLKLEAC | ||||
| ILTQGDKISL | QEPLDYLLCC | IQHCLAWYKN | TVIPLQQGEE | EEEEEEAFYE | ||||
| DLDDILESIT | NRMIKSELED | FELDKSADFS | QSTSIGIKNN | ICAFLVMGVC | ||||
| EVLIEYNFSI | SSFSKNRFED | ILSLFMCYKK | LSDILNEKAG | KAKTKMANKT | ||||
| SDSLLSMKFV | SSLLTALFRD | SIQSHQESLS | VLRSSNEFMR | YAVNVALQKV | ||||
| QQLKETGHVS | GPDGQNPEKI | FQNLCDITRV | LLWRYTSIPT | SVEESGKKEK | ||||
| GKSISLLCLE | GLQKIFSAVQ | QFYQPKIQQF | LRALDVTDKE | GEEREDADVS | ||||
| VTQRTAFQIR | QFQRSLLNLL | SSQEEDFNSK | EALLLVTVLT | SLSKLLEPSS | ||||
| PQFVQMLSWT | SKICKENSRE | DALFCKSLMN | LLFSLHVSYK | SPVILLRDLS | ||||
| QDIHGHLGDI | DQDVEVEKTN | HFAIVNLRTA | APTVCLLVLS | QAEKVLEEVD | ||||
| WLITKLKGQV | SQETLSEEAS | SQATLPNQPV | EKAIIMQLGT | LLTFFHELVQ | ||||
| TALPSGSCVD | TLLKDLCKMY | TTLTALVRYY | LQVCQSSGGI | PKNMEKLVKL | ||||
| SGSHLTPLCY | SFISYVQNKS | KSLNYTGEKK | EKPAAVATAM | ARVLRETKPI | ||||
| PNLIFAIEQY | EKFLIHLSKK | SKVNLMQHMK | LSTSRDFKIK | GNILDMVLRE | ||||
| DGEDENEEGT | ASEHGGQNKE | PAKKKRKK |
Funkcija
urediKomplementarna grupa za Fanconijevu anemiju (FANC) uključuje FANCA, FANCB, FANCC, FANCD1 (također zvana BRCA2), FANCD2, FANCE , FANCF, FANCG, FANCI, FANCJ (također zvana i BRIP1), FANCL, FANCM i FANCN (također PALB2). Prethodno definirana grupa FANCH je ista kao i FANCA. Fanconijeva anemija je genetički heterogeni recesivni poremećaj karakteriziran citogenetičkom nestabilnošću, preosjetljivošću na agense za umrežavanje DNK, povećanim lomovima hromosoma i defektnom popravkom DNK. Članovi komplementacijske grupe za Fanconijevu anemiju ne dijele sličnost sekvenci; oni su povezani svojim sklapanjem u zajednički jedarni proteinski kompleks. Ovaj gen kodira protein za komplementacionu grupu I. Alternativna prerada RNK rezultira dvije varijante transkripta koje kodiraju različite izoforme.[5]
FANCI formira heterodimer sa proteinom FANCD2. I FANCD2 i FANCI su monoubikvitinirani podjedinicom kompleksa Fanconijeve anemije FANCL. Monoubikvitinacija FANCI je neophodna za popravku međulančanih umrežavanja DNK i spaja protein na DNK zajedno sa njegovim partnerskim proteinom FANCD2. Monoubikvitinirani kompleks FANCD2:FANCI prekriva DNK u sekvenci nalik na filamente, potencijalno kao način zaštite DNK povezane sa zastojem u replikaciji.[11]
Pored proteina koji su uključeni u popravku DNK, FANCI stupa u interakciju s proteinima lokaliziranim na jedarcetu,[12][13] jedarnom tijelu, gdje započinje biogeneza ribosoma. FANCI funkcionira u obradi preribosomske RNK (pre-rRNK) za veliku ribosomsku podjedinicu, transkribirajuči pre-rRNK pomoću RNKPI, održavajući nivoe zrele 28S ribozomske RNK (rRNK), i globalne ćelijske translacije proteina pomoću ribosoma.[12] U jedarcetu, FANCI je pretežno u deubikvitiniranom obliku i stupa u interakciju sa velikom podjedinicom RNAPI i članovima kompleksa PeBoW (PES1 i BOP1).[12] Možda postoji još jedna uloga FA proteina izvan jedarceta u biogenezama ribosoma ili translacija proteina kao FANCI i FANCD2 su jedini FA proteini povezani sa polisomima.[14]
Kod miševa, FANCI protein učestvuje u mejotskoj rekombinaciji zametnih ćelija, a deleciju gena Fanci uzrokujuči jak mejotski fenotip i teški hipogonadizam.[15] Fanci–/– mužjaci miševa imaju potpuno poremećenu spermatogenezu,[15][16] a ženke takvih miševa ne proizvode jajničke folikule.[15]
Reference
uredi- ^ a b c GRCh38: Ensembl release 89: ENSG00000140525 - Ensembl, maj 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000039187 - 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.
- ^ a b c "Entrez Gene: FANCI".
- ^ Nagase T, Nakayama M, Nakajima D, Kikuno R, Ohara O (april 2001). "Prediction of the coding sequences of unidentified human genes. XX. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro". DNA Research. 8 (2): 85–95. doi:10.1093/dnares/8.2.85. PMID 11347906.
- ^ Dorsman JC, Levitus M, Rockx D, Rooimans MA, Oostra AB, Haitjema A, et al. (2007). "Identification of the Fanconi anemia complementation group I gene, FANCI". Cellular Oncology. 29 (3): 211–218. doi:10.1155/2007/151968. PMC 4618213. PMID 17452773.
- ^ Sims AE, Spiteri E, Sims RJ, Arita AG, Lach FP, Landers T, et al. (juni 2007). "FANCI is a second monoubiquitinated member of the Fanconi anemia pathway". Nature Structural & Molecular Biology. 14 (6): 564–567. doi:10.1038/nsmb1252. PMID 17460694. S2CID 40947913.
- ^ Smogorzewska A, Matsuoka S, Vinciguerra P, McDonald ER, Hurov KE, Luo J, et al. (april 2007). "Identification of the FANCI protein, a monoubiquitinated FANCD2 paralog required for DNA repair". Cell. 129 (2): 289–301. doi:10.1016/j.cell.2007.03.009. PMC 2175179. PMID 17412408.
- ^ Levitus M, Rooimans MA, Steltenpool J, Cool NF, Oostra AB, Mathew CG, et al. (april 2004). "Heterogeneity in Fanconi anemia: evidence for 2 new genetic subtypes". Blood. 103 (7): 2498–2503. doi:10.1182/blood-2003-08-2915. PMID 14630800. S2CID 7033645.
- ^ Tan W, van Twest S, Leis A, Bythell-Douglas R, Murphy VJ, Sharp M, et al. (mart 2020). "Monoubiquitination by the human Fanconi anemia core complex clamps FANCI:FANCD2 on DNA in filamentous arrays". eLife. 9. doi:10.7554/eLife.54128. PMC 7156235. PMID 32167469.
- ^ a b c Sondalle SB, Longerich S, Ogawa LM, Sung P, Baserga SJ (februar 2019). "Fanconi anemia protein FANCI functions in ribosome biogenesis". Proceedings of the National Academy of Sciences of the United States of America. 116 (7): 2561–2570. Bibcode:2019PNAS..116.2561S. doi:10.1073/pnas.1811557116. PMC 6377447. PMID 30692263.
- ^ Moriel-Carretero M, Ovejero S, Gérus-Durand M, Vryzas D, Constantinou A (decembar 2017). "Fanconi anemia FANCD2 and FANCI proteins regulate the nuclear dynamics of splicing factors". The Journal of Cell Biology. 216 (12): 4007–4026. doi:10.1083/jcb.201702136. PMC 5716273. PMID 29030393.
- ^ Gueiderikh A, Maczkowiak-Chartois F, Rouvet G, Souquère-Besse S, Apcher S, Diaz JJ, Rosselli F (januar 2021). "Fanconi anemia A protein participates in nucleolar homeostasis maintenance and ribosome biogenesis". Science Advances. 7 (1): eabb5414. Bibcode:2021SciA....7.5414G. doi:10.1126/sciadv.abb5414. PMC 7775781. PMID 33523834.
- ^ a b c Dubois EL, Guitton-Sert L, Béliveau M, Parmar K, Chagraoui J, Vignard J, Pauty J, Caron MC, Coulombe Y, Buisson R, Jacquet K, Gamblin C, Gao Y, Laprise P, Lebel M, Sauvageau G, D d'Andrea A, Masson JY. A Fanci knockout mouse model reveals common and distinct functions for FANCI and FANCD2. Nucleic Acids Res. 2019 Aug 22;47(14):7532-7547. doi: 10.1093/nar/gkz514. PMID 31219578; PMCID: PMC6698648
- ^ Xu L, Xu W, Li D, Yu X, Gao F, Qin Y, Yang Y, Zhao S. FANCI plays an essential role in spermatogenesis and regulates meiotic histone methylation. Cell Death Dis. 2021 Aug 9;12(8):780. doi: 10.1038/s41419-021-04034-7. Erratum in: Cell Death Dis. 2021 Aug 26;12(9):808. PMID 34373449; PMCID: PMC8353022
Dopunska literatura
uredi- Nagase T, Nakayama M, Nakajima D, Kikuno R, Ohara O (april 2001). "Prediction of the coding sequences of unidentified human genes. XX. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro". DNA Research. 8 (2): 85–95. doi:10.1093/dnares/8.2.85. PMID 11347906.
- Levitus M, Rooimans MA, Steltenpool J, Cool NF, Oostra AB, Mathew CG, et al. (april 2004). "Heterogeneity in Fanconi anemia: evidence for 2 new genetic subtypes". Blood. 103 (7): 2498–2503. doi:10.1182/blood-2003-08-2915. PMID 14630800. S2CID 7033645.
- Bouwmeester T, Bauch A, Ruffner H, Angrand PO, Bergamini G, Croughton K, et al. (februar 2004). "A physical and functional map of the human TNF-alpha/NF-kappa B signal transduction pathway". Nature Cell Biology. 6 (2): 97–105. doi:10.1038/ncb1086. PMID 14743216. S2CID 11683986.
- Brandenberger R, Wei H, Zhang S, Lei S, Murage J, Fisk GJ, et al. (juni 2004). "Transcriptome characterization elucidates signaling networks that control human ES cell growth and differentiation". Nature Biotechnology. 22 (6): 707–716. doi:10.1038/nbt971. PMID 15146197. S2CID 27764390.
- Beausoleil SA, Villén J, Gerber SA, Rush J, Gygi SP (oktobar 2006). "A probability-based approach for high-throughput protein phosphorylation analysis and site localization". Nature Biotechnology. 24 (10): 1285–1292. doi:10.1038/nbt1240. PMID 16964243. S2CID 14294292.
- Ewing RM, Chu P, Elisma F, Li H, Taylor P, Climie S, et al. (2007). "Large-scale mapping of human protein-protein interactions by mass spectrometry". Molecular Systems Biology. 3 (1): 89. doi:10.1038/msb4100134. PMC 1847948. PMID 17353931.
- Smogorzewska A, Matsuoka S, Vinciguerra P, McDonald ER, Hurov KE, Luo J, et al. (april 2007). "Identification of the FANCI protein, a monoubiquitinated FANCD2 paralog required for DNA repair". Cell. 129 (2): 289–301. doi:10.1016/j.cell.2007.03.009. PMC 2175179. PMID 17412408.
- Dorsman JC, Levitus M, Rockx D, Rooimans MA, Oostra AB, Haitjema A, et al. (2007). "Identification of the Fanconi anemia complementation group I gene, FANCI". Cellular Oncology. 29 (3): 211–218. doi:10.1155/2007/151968. PMC 4618213. PMID 17452773.
- Sims AE, Spiteri E, Sims RJ, Arita AG, Lach FP, Landers T, et al. (juni 2007). "FANCI is a second monoubiquitinated member of the Fanconi anemia pathway". Nature Structural & Molecular Biology. 14 (6): 564–567. doi:10.1038/nsmb1252. PMID 17460694. S2CID 40947913.
Vanjski linkovi
urediOvaj članak uključuje tekst iz Nacionalne medicinske biblioteke Sjedinjenih Država, koji je u javnom vlasništvu.