Wikipedia

FANCG

Protein grupe G Fanconijeve anemije jest protein koji je kod ljudi kodiran genom FANCG sa hromosoma 9.[5][6][7]

FANCG
Identifikatori
AliasiFANCG
Vanjski ID-jeviOMIM: 602956 MGI: 1926471 HomoloGene: 3402 GeneCards: FANCG
Lokacija gena (čovjek)
Hromosom 9 (čovjek)
Hrom.Hromosom 9 (čovjek)[1]
Hromosom 9 (čovjek)
Genomska lokacija za FANCG
Genomska lokacija za FANCG
Bend9p13.3Početak35,073,835 bp[1]
Kraj35,080,004 bp[1]
Lokacija gena (miš)
Hromosom 4 (miš)
Hrom.Hromosom 4 (miš)[2]
Hromosom 4 (miš)
Genomska lokacija za FANCG
Genomska lokacija za FANCG
Bend4|4 A5Početak43,002,343 bp[2]
Kraj43,010,506 bp[2]
Obrazac RNK ekspresije
Više referentnih podataka o ekspresiji
Ontologija gena
Molekularna funkcija• oštećeno vezivanje sa DNK
• GO:0001948, GO:0016582 vezivanje za proteine
• signal transducer activity
Ćelijska komponenta• ćelijska membrana
• Jedarce
• Fanconi anaemia nuclear complex
• mitohondrija
• jedro
• nukleoplazma
• citoplazma
• citosol
• intracellular anatomical structure
Biološki proces• ovarian follicle development
• response to radiation
• mitochondrion organization
• interstrand cross-link repair
• GO:0100026 Popravka DNK
• spermatid development
• cellular response to DNA damage stimulus
• phosphorelay signal transduction system
Izvori:Amigo / QuickGO
Ortolozi
VrsteČovjekMiš
Entrez

2189

60534

Ensembl

ENSG00000221829

ENSMUSG00000028453

UniProt

O15287

Q9EQR6

RefSeq (mRNK)

NM_004629

NM_001163233
NM_053081

RefSeq (bjelančevina)

NP_004620

NP_001156705
NP_444311

Lokacija (UCSC)Chr 9: 35.07 – 35.08 MbChr 4: 43 – 43.01 Mb
PubMed pretraga[3][4]
Wikipodaci
Pogledaj/uredi – čovjekPogledaj/uredi – miš

Aminokiselinska sekvenca

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Dužina polipeptidnog lanca je 622 aminokiseline, a molekulska težina 68.554 Da.[7]

1020304050
MSRQTTSVGSSCLDLWREKNDRLVRQAKVAQNSGLTLRRQQLAQDALEGL
RGLLHSLQGLPAAVPVLPLELTVTCNFIILRASLAQGFTEDQAQDIQRSL
ERVLETQEQQGPRLEQGLRELWDSVLRASCLLPELLSALHRLVGLQAALW
LSADRLGDLALLLETLNGSQSGASKDLLLLLKTWSPPAEELDAPLTLQDA
QGLKDVLLTAFAYRQGLQELITGNPDKALSSLHEAASGLCPRPVLVQVYT
ALGSCHRKMGNPQRALLYLVAALKEGSAWGPPLLEASRLYQQLGDTTAEL
ESLELLVEALNVPCSSKAPQFLIEVELLLPPPDLASPLHCGTQSQTKHIL
ASRCLQTGRAGDAAEHYLDLLALLLDSSEPRFSPPPSPPGPCMPEVFLEA
AVALIQAGRAQDALTLCEELLSRTSSLLPKMSRLWEDARKGTKELPYCPL
WVSATHLLQGQAWVQLGAQKVAISEFSRCLELLFRATPEEKEQGAAFNCE
QGCKSDAALQQLRAAALISRGLEWVASGQDTKALQDFLLSVQMCPGNRDT
YFHLLQTLKRLDRRDEATALWWRLEAQTKGSHEDALWSLPLYLESYLSWI
RPSDRDAFLEEFRTSLPKSCDL

Funkcija

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Rekombinacijski popravak oštećenja dvostrukog lanca DNK – neki ključni koraci. ATM (ATM) je protein-kinaza koja se regrutuje i aktivira pomoću dvostrukih lomova DNK. Dvolančana oštećenja DNK također aktiviraju Kompleks jezgra Fanconi anemije (FANCA/FANCB/FANCC/FANCE/FANCF/FANCG/FANCL/FANCM).[8] The FA core complex monoubiquitinates the downstream targets FANCD2 and FANCI.[9] ATM aktivira (fosforilira) CHEK2 i FANCD2[10] CHEK2 fosforilizira BRCA1.[11] Ubikvitinirani kompleksi FANCD2 sa BRCA1 i RAD51.[12] The PALB2 protein acts as a hub,[13] spajajući BRCA1, BRCA2 i RAD51 na mjestu prekida dvolančanog DNK, a takođe se vezuje za RAD51C, člana RAD51 paralognog kompleksa RAD51B-RAD51C-RAD51D-XRCC2 (BCDX2). BCDX2 kompleks je odgovoran za regrutaciju RAD51 ili stabilizaciju na mjestima oštećenja.[14] RAD51 ima glavnu ulogu u homolognorekombinacijskoj popravci DNK tokom popravke dvostrukog lanca. U ovom procesu, odvija se razmjena lanaca DNK, zavisna od ATP-a, u kojoj jedan lanac napada lance uparene bazama homolognih molekula DNK. RAD51 je uključen u potragu za homologijom i fazama uparivanja lanaca u procesu.

FANCG, uključen u Fanconijevu anemiju, daje rezistenciju i na higromicin B i mitomicin C. FANCG sadrži 5' GC-bogatu neprevedenu regiju, karakterističnu za domaćinske gene. Pretpostavljeni protein od 622 aminokiseline ima motiv leucinskog zatvarača na svom N-terminalu. Fanconijeva anemija je autosomno recesivni poremećaj s različitim kliničkim simptomima, uključujući razvojne anomalije, zatajenje koštane srži i ranu pojavu maligniteta. Identificirano je najmanje 8 FA gena. FANCG gen je odgovoran za komplementacijsku grupu G.[7]

Klinički fenotip svih komplementarnih grupa Fanconijeve anemije (FA) je sličan. Ovaj fenotip karakterizira progresivno zatajenje koštane srži, sklonost kanceru i tipski urođeni defekti. Glavni ćelijski fenotip je preosjetljivost na oštećenje DNK, posebno unakrsne veze DNK među lancima. FA proteini međusobno djeluju putem multiproteinskog puta. Međulančane umrežene veze DNK su vrlo štetna oštećenja koja se popravljaju homolognom rekombinacijom, uključujući koordinaciju FA proteina i "gena za osjetljivost na rak dojke 1 (BRCA1)", ali tačne biohemijske uloge ovih proteina još su nejasne.

Jedarni kompleks koji sadrži FANCG (kao i FANCA, FANCB, FANCC, FANCE, FANCF, FANCL i FANCM) je neophodan za aktivaciju proteina FANCD2 u monoubikvitiranu izoformu.[8] U normalnim, nemutantnim ćelijama, FANCD2 je monoubikvitiniran kao odgovor na oštećenje DNK. Aktivirani protein FANCD2 kolokalizira se s BRCA1 (protein osjetljivosti na rak dojke) na žarištima izazvanim ionizujućim zračenjem i u sinaptonemskom kompleksu mejotskih hromosoma (vidi sliku: Rekombinacijski popravak dvostrukih oštećenje niti).

Mejoza

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Aktivirani protein FANCD2 može funkcionirati prije početka mejotske rekombinacije, možda da pripremi hromosome za sinapsu ili da reguliše naknadne događaje rekombinacije.[15]

Mužjaci i ženke FANCG mutantnih miševa imaju defektnu gametogenezu, hipogonadizam i poremećenu plodnost, u skladu sa fenotipom pacijenata sa FA.[16][17] Kod nemutantnog miša, FANCG protein je izražen u spermatogonijama, preleptotenskim spermatocitima i spermatocitima u fazi leptotena, zigotena i ranog pahitena mejoze.[18]

Starenje

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Gubitak FANCG uzrokuje apoptozu nervnog progenitora tokom razvoja prednjeg mozga, vjerovatno povezanu s defektnom popravkom DNK.[19] (Sii-Felice et al., 2008). Ovaj efekt traje i u odrasloj dobi, što dovodi do iscrpljivanja skupa nervnih matičnih ćelija sa starenjem. Fenotip FA se može tumačiti kao prerano starenje matičnih ćelija, a oštećenja DNK su pokretačka snaga starenja.[19]

Interakcije

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Pokazalo se da FANCG reaguje sa FANCF,[20][21][22][23]

FANCA,[22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39] FANCE[23][37][40] and BRCA2.[41]

Reference

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  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000221829 - Ensembl, maj 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000028453 - 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. ^ Liu N, Lamerdin JE, Tucker JD, Zhou ZQ, Walter CA, Albala JS, Busch DB, Thompson LH (Sep 1997). "The human XRCC9 gene corrects chromosomal instability and mutagen sensitivities in CHO UV40 cells". Proc Natl Acad Sci U S A. 94 (17): 9232–7. Bibcode:1997PNAS...94.9232L. doi:10.1073/pnas.94.17.9232. PMC 23130. PMID 9256465.
  6. ^ Joenje H, Oostra AB, Wijker M, di Summa FM, van Berkel CG, Rooimans MA, Ebell W, van Weel M, Pronk JC, Buchwald M, Arwert F (Nov 1997). "Evidence for at least eight Fanconi anemia genes". Am J Hum Genet. 61 (4): 940–4. doi:10.1086/514881. PMC 1715980. PMID 9382107.
  7. ^ a b c "Entrez Gene: FANCG Fanconi anemia, complementation group G".
  8. ^ a b D'Andrea AD (2010). "Susceptibility pathways in Fanconi's anemia and breast cancer". N. Engl. J. Med. 362 (20): 1909–19. doi:10.1056/NEJMra0809889. PMC 3069698. PMID 20484397.
  9. ^ Sobeck A, Stone S, Landais I, de Graaf B, Hoatlin ME (2009). "The Fanconi anemia protein FANCM is controlled by FANCD2 and the ATR/ATM pathways". J. Biol. Chem. 284 (38): 25560–8. doi:10.1074/jbc.M109.007690. PMC 2757957. PMID 19633289.
  10. ^ Castillo P, Bogliolo M, Surralles J (2011). "Coordinated action of the Fanconi anemia and ataxia telangiectasia pathways in response to oxidative damage". DNA Repair (Amst.). 10 (5): 518–25. doi:10.1016/j.dnarep.2011.02.007. PMID 21466974.
  11. ^ Stolz A, Ertych N, Bastians H (2011). "Tumor suppressor CHK2: regulator of DNA damage response and mediator of chromosomal stability". Clin. Cancer Res. 17 (3): 401–5. doi:10.1158/1078-0432.CCR-10-1215. PMID 21088254.
  12. ^ Taniguchi T, Garcia-Higuera I, Andreassen PR, Gregory RC, Grompe M, D'Andrea AD (2002). "S-phase-specific interaction of the Fanconi anemia protein, FANCD2, with BRCA1 and RAD51". Blood. 100 (7): 2414–20. doi:10.1182/blood-2002-01-0278. PMID 12239151.
  13. ^ Park JY, Zhang F, Andreassen PR (2014). "PALB2: the hub of a network of tumor suppressors involved in DNA damage responses". Biochim. Biophys. Acta. 1846 (1): 263–75. doi:10.1016/j.bbcan.2014.06.003. PMC 4183126. PMID 24998779.
  14. ^ Chun J, Buechelmaier ES, Powell SN (2013). "Rad51 paralog complexes BCDX2 and CX3 act at different stages in the BRCA1-BRCA2-dependent homologous recombination pathway". Mol. Cell. Biol. 33 (2): 387–95. doi:10.1128/MCB.00465-12. PMC 3554112. PMID 23149936.
  15. ^ Garcia-Higuera I, Taniguchi T, Ganesan S, Meyn MS, Timmers C, Hejna J, Grompe M, D'Andrea AD (2001). "Interaction of the Fanconi anemia proteins and BRCA1 in a common pathway". Mol. Cell. 7 (2): 249–62. doi:10.1016/s1097-2765(01)00173-3. PMID 11239454.
  16. ^ Yang Y, Kuang Y, Montes De Oca R, Hays T, Moreau L, Lu N, Seed B, D'Andrea AD (2001). "Targeted disruption of the murine Fanconi anemia gene, Fancg/Xrcc9". Blood. 98 (12): 3435–40. doi:10.1182/blood.v98.12.3435. PMID 11719385.
  17. ^ Koomen M, Cheng NC, van de Vrugt HJ, Godthelp BC, van der Valk MA, Oostra AB, Zdzienicka MZ, Joenje H, Arwert F (2002). "Reduced fertility and hypersensitivity to mitomycin C characterize Fancg/Xrcc9 null mice". Hum. Mol. Genet. 11 (3): 273–81. doi:10.1093/hmg/11.3.273. PMID 11823446.
  18. ^ Jamsai D, O'Connor AE, O'Donnell L, Lo JC, O'Bryan MK (2015). "Uncoupling of transcription and translation of Fanconi anemia (FANC) complex proteins during spermatogenesis". Spermatogenesis. 5 (1): e979061. doi:10.4161/21565562.2014.979061. PMC 4581071. PMID 26413409.
  19. ^ a b Sii-Felice K, Barroca V, Etienne O, Riou L, Hoffschir F, Fouchet P, Boussin FD, Mouthon MA (2008). "Role of Fanconi DNA repair pathway in neural stem cell homeostasis". Cell Cycle. 7 (13): 1911–5. doi:10.4161/cc.7.13.6235. PMID 18604174.
  20. ^ Léveillé F, Blom E, Medhurst AL, Bier P, Laghmani el H, Johnson M, Rooimans MA, Sobeck A, Waisfisz Q, Arwert F, Patel KJ, Hoatlin ME, Joenje H, de Winter JP (septembar 2004). "The Fanconi anemia gene product FANCF is a flexible adaptor protein" (PDF). J. Biol. Chem. 279 (38): 39421–30. doi:10.1074/jbc.M407034200. PMID 15262960. S2CID 8189071.
  21. ^ de Winter JP, van der Weel L, de Groot J, Stone S, Waisfisz Q, Arwert F, Scheper RJ, Kruyt FA, Hoatlin ME, Joenje H (novembar 2000). "The Fanconi anemia protein FANCF forms a nuclear complex with FANCA, FANCC and FANCG". Hum. Mol. Genet. 9 (18): 2665–74. doi:10.1093/hmg/9.18.2665. PMID 11063725.
  22. ^ a b Gordon SM, Buchwald M (juli 2003). "Fanconi anemia protein complex: mapping protein interactions in the yeast 2- and 3-hybrid systems". Blood. 102 (1): 136–41. doi:10.1182/blood-2002-11-3517. PMID 12649160.
  23. ^ a b c Medhurst AL, Huber PA, Waisfisz Q, de Winter JP, Mathew CG (februar 2001). "Direct interactions of the five known Fanconi anaemia proteins suggest a common functional pathway". Hum. Mol. Genet. 10 (4): 423–9. doi:10.1093/hmg/10.4.423. PMID 11157805.
  24. ^ Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE, Roth FP, Vidal M (oktobar 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173–8. Bibcode:2005Natur.437.1173R. doi:10.1038/nature04209. PMID 16189514. S2CID 4427026.
  25. ^ Garcia-Higuera I, Kuang Y, Näf D, Wasik J, D'Andrea AD (juli 1999). "Fanconi anemia proteins FANCA, FANCC, and FANCG/XRCC9 interact in a functional nuclear complex". Mol. Cell. Biol. 19 (7): 4866–73. doi:10.1128/mcb.19.7.4866. PMC 84285. PMID 10373536.
  26. ^ Park SJ, Ciccone SL, Beck BD, Hwang B, Freie B, Clapp DW, Lee SH (juli 2004). "Oxidative stress/damage induces multimerization and interaction of Fanconi anemia proteins". J. Biol. Chem. 279 (29): 30053–9. doi:10.1074/jbc.M403527200. PMID 15138265.
  27. ^ van de Vrugt HJ, Koomen M, Berns MA, de Vries Y, Rooimans MA, van der Weel L, Blom E, de Groot J, Schepers RJ, Stone S, Hoatlin ME, Cheng NC, Joenje H, Arwert F (mart 2002). "Characterization, expression and complex formation of the murine Fanconi anaemia gene product Fancg". Genes Cells. 7 (3): 333–42. doi:10.1046/j.1365-2443.2002.00518.x. PMID 11918676. S2CID 23489983.
  28. ^ Yagasaki H, Adachi D, Oda T, Garcia-Higuera I, Tetteh N, D'Andrea AD, Futaki M, Asano S, Yamashita T (decembar 2001). "A cytoplasmic serine protein kinase binds and may regulate the Fanconi anemia protein FANCA". Blood. 98 (13): 3650–7. doi:10.1182/blood.V98.13.3650. PMID 11739169.
  29. ^ Huber PA, Medhurst AL, Youssoufian H, Mathew CG (februar 2000). "Investigation of Fanconi anemia protein interactions by yeast two-hybrid analysis". Biochem. Biophys. Res. Commun. 268 (1): 73–7. doi:10.1006/bbrc.1999.2055. PMID 10652215.
  30. ^ Kruyt FA, Abou-Zahr F, Mok H, Youssoufian H (novembar 1999). "Resistance to mitomycin C requires direct interaction between the Fanconi anemia proteins FANCA and FANCG in the nucleus through an arginine-rich domain". J. Biol. Chem. 274 (48): 34212–8. doi:10.1074/jbc.274.48.34212. PMID 10567393.
  31. ^ Reuter T, Herterich S, Bernhard O, Hoehn H, Gross HJ (januar 2000). "Strong FANCA/FANCG but weak FANCA/FANCC interaction in the yeast 2-hybrid system". Blood. 95 (2): 719–20. doi:10.1182/blood.V95.2.719. PMID 10627486.
  32. ^ Blom E, van de Vrugt HJ, de Vries Y, de Winter JP, Arwert F, Joenje H (januar 2004). "Multiple TPR motifs characterize the Fanconi anemia FANCG protein". DNA Repair (Amst.). 3 (1): 77–84. doi:10.1016/j.dnarep.2003.09.007. PMID 14697762.
  33. ^ Kuang Y, Garcia-Higuera I, Moran A, Mondoux M, Digweed M, D'Andrea AD (septembar 2000). "Carboxy terminal region of the Fanconi anemia protein, FANCG/XRCC9, is required for functional activity". Blood. 96 (5): 1625–32. doi:10.1182/blood.V96.5.1625. PMID 10961856.
  34. ^ Thomashevski A, High AA, Drozd M, Shabanowitz J, Hunt DF, Grant PA, Kupfer GM (juni 2004). "The Fanconi anemia core complex forms four complexes of different sizes in different subcellular compartments". J. Biol. Chem. 279 (25): 26201–9. doi:10.1074/jbc.M400091200. PMID 15082718.
  35. ^ Waisfisz Q, de Winter JP, Kruyt FA, de Groot J, van der Weel L, Dijkmans LM, Zhi Y, Arwert F, Scheper RJ, Youssoufian H, Hoatlin ME, Joenje H (august 1999). "A physical complex of the Fanconi anemia proteins FANCG/XRCC9 and FANCA". Proc. Natl. Acad. Sci. U.S.A. 96 (18): 10320–5. Bibcode:1999PNAS...9610320W. doi:10.1073/pnas.96.18.10320. PMC 17886. PMID 10468606.
  36. ^ Meetei AR, de Winter JP, Medhurst AL, Wallisch M, Waisfisz Q, van de Vrugt HJ, Oostra AB, Yan Z, Ling C, Bishop CE, Hoatlin ME, Joenje H, Wang W (oktobar 2003). "A novel ubiquitin ligase is deficient in Fanconi anemia". Nat. Genet. 35 (2): 165–70. doi:10.1038/ng1241. PMID 12973351. S2CID 10149290.
  37. ^ a b Taniguchi T, D'Andrea AD (oktobar 2002). "The Fanconi anemia protein, FANCE, promotes the nuclear accumulation of FANCC". Blood. 100 (7): 2457–62. doi:10.1182/blood-2002-03-0860. PMID 12239156.
  38. ^ Otsuki T, Young DB, Sasaki DT, Pando MP, Li J, Manning A, Hoekstra M, Hoatlin ME, Mercurio F, Liu JM (2002). "Fanconi anemia protein complex is a novel target of the IKK signalsome". J. Cell. Biochem. 86 (4): 613–23. doi:10.1002/jcb.10270. PMID 12210728. S2CID 42471384.
  39. ^ Garcia-Higuera I, Kuang Y, Denham J, D'Andrea AD (novembar 2000). "The fanconi anemia proteins FANCA and FANCG stabilize each other and promote the nuclear accumulation of the Fanconi anemia complex". Blood. 96 (9): 3224–30. doi:10.1182/blood.V96.9.3224. PMID 11050007.
  40. ^ Pace P, Johnson M, Tan WM, Mosedale G, Sng C, Hoatlin M, de Winter J, Joenje H, Gergely F, Patel KJ (juli 2002). "FANCE: the link between Fanconi anaemia complex assembly and activity". EMBO J. 21 (13): 3414–23. doi:10.1093/emboj/cdf355. PMC 125396. PMID 12093742.
  41. ^ Hussain S, Witt E, Huber PA, Medhurst AL, Ashworth A, Mathew CG (oktobar 2003). "Direct interaction of the Fanconi anaemia protein FANCG with BRCA2/FANCD1". Hum. Mol. Genet. 12 (19): 2503–10. doi:10.1093/hmg/ddg266. PMID 12915460.

Dopunska literatura

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Vanjski linkovi

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Preuzeto iz "https://bs.wikipedia.org/w/index.php?title=FANCG&oldid=3481589"