FANCI

FANCI
Identifikatori
Aliasi	FANCI
Vanjski ID-jevi	OMIM: 611360 MGI: 2384790 HomoloGene: 49530 GeneCards: FANCI
Lokacija gena (čovjek) Hrom. Hromosom 15 (čovjek)[1] Bend 15q26.1 Početak 89,243,945 bp[1] Kraj 89,317,261 bp[1]
Lokacija gena (miš) Hrom. Hromosom 7 (miš)[2] Bend 7|7 D2 Početak 79,041,677 bp[2] Kraj 79,100,012 bp[2]
Obrazac RNK ekspresije Više referentnih podataka o ekspresiji
Ontologija gena Molekularna funkcija • vezivanje sa DNK • GO:0001948, GO:0016582 vezivanje za proteine • DNA polymerase binding Ćelijska komponenta • membrana • jedro • nukleoplazma • citosol Biološki proces • ćelijski ciklus • mitotic G2 DNA damage checkpoint signaling • positive regulation of protein ubiquitination • interstrand cross-link repair • cellular response to DNA damage stimulus • GO:0100026 Popravka DNK Izvori:Amigo / QuickGO
Ortolozi
Vrste	Čovjek	Miš
Entrez	55215	208836
Ensembl	ENSG00000140525	ENSMUSG00000039187
UniProt	Q9NVI1	Q8K368
RefSeq (mRNK)	NM_001113378 NM_018193 NM_001376910 NM_001376911	NM_145946
RefSeq (bjelančevina)	NP_001106849 NP_060663 NP_001363839 NP_001363840	NP_666058
Lokacija (UCSC)	Chr 15: 89.24 – 89.32 Mb	Chr 7: 79.04 – 79.1 Mb
PubMed pretraga	[3]	[4]
Wikipodaci
Pogledaj/uredi – čovjek Pogledaj/uredi – miš

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

Dužina polipeptidnog lanca je 1.328 aminokiselina, a molekulska težina 149.324 Da.^[5]

• 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

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

Komplementarna 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]

Mejoza

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

1. GRCh38: Ensembl release 89: ENSG00000140525 - Ensembl, maj 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000039187 - Ensembl, maj 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. "Entrez Gene: FANCI".
6. 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.
7. 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.
8. 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.
9. 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.
10. 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.
11. 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.
12. 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.
13. 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.
14. 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.
15. 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
16. 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

• 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

Ovaj članak uključuje tekst iz Nacionalne medicinske biblioteke Sjedinjenih Država, koji je u javnom vlasništvu.