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FANCC

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FANCC
Identifikatori
AliasiFANCC
Vanjski ID-jeviOMIM: 613899 MGI: 95480 HomoloGene: 109 GeneCards: FANCC
Lokacija gena (čovjek)
Hromosom 9 (čovjek)
Hrom.Hromosom 9 (čovjek)[1]
Hromosom 9 (čovjek)
Genomska lokacija za FANCC
Genomska lokacija za FANCC
Bend9q22.32Početak95,099,054 bp[1]
Kraj95,426,796 bp[1]
Lokacija gena (miš)
Hromosom 13 (miš)
Hrom.Hromosom 13 (miš)[2]
Hromosom 13 (miš)
Genomska lokacija za FANCC
Genomska lokacija za FANCC
Bend13 B3|13 32.8 cMPočetak63,432,857 bp[2]
Kraj63,645,092 bp[2]
Obrazac RNK ekspresije
Više referentnih podataka o ekspresiji
Ontologija gena
Molekularna funkcija GO:0001948, GO:0016582 vezivanje za proteine
Ćelijska komponenta citoplazma
citosol
Fanconi anaemia nuclear complex
jedro
nukleoplazma
Biološki proces interstrand cross-link repair
GO:0100026 Popravka DNK
cellular response to DNA damage stimulus
myeloid cell homeostasis
Popravak ekscizijom nukleotida
gamete generation
germ cell development
removal of superoxide radicals
cellular response to oxidative stress
brain morphogenesis
neuronal stem cell population maintenance
GO:0034622 protein-containing complex assembly
Izvori:Amigo / QuickGO
Ortolozi
VrsteČovjekMiš
Entrez
Ensembl
UniProt
RefSeq (mRNK)

NM_000136
NM_001243743
NM_001243744

NM_001042673
NM_001282942
NM_007985
NM_001347514
NM_001347515

RefSeq (bjelančevina)

NP_000127
NP_001230672
NP_001230673

NP_001036138
NP_001269871
NP_001334443
NP_001334444
NP_032011

Lokacija (UCSC)Chr 9: 95.1 – 95.43 MbChr 13: 63.43 – 63.65 Mb
PubMed pretraga[3][4]
Wikipodaci
Pogledaj/uredi – čovjekPogledaj/uredi – miš

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

Struktura

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Prtotein C-grupe Fanconijeve anaemije
Identifikatori
SimbolFanc-C

Aminokiselinska sekvenca

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Dužina polipeptidnog lanca je 558 aminokiselina, a molekulska težina 63 429 Da.[6]

1020304050
MAQDSVDLSCDYQFWMQKLSVWDQASTLETQQDTCLHVAQFQEFLRKMYE
ALKEMDSNTVIERFPTIGQLLAKACWNPFILAYDESQKILIWCLCCLINK
EPQNSGQSKLNSWIQGVLSHILSALRFDKEVALFTQGLGYAPIDYYPGLL
KNMVLSLASELRENHLNGFNTQRRMAPERVASLSRVCVPLITLTDVDPLV
EALLICHGREPQEILQPEFFEAVNEAILLKKISLPMSAVVCLWLRHLPSL
EKAMLHLFEKLISSERNCLRRIECFIKDSSLPQAACHPAIFRVVDEMFRC
ALLETDGALEIIATIQVFTQCFVEALEKASKQLRFALKTYFPYTSPSLAM
VLLQDPQDIPRGHWLQTLKHISELLREAVEDQTHGSCGGPFESWFLFIHF
GGWAEMVAEQLLMSAAEPPTALLWLLAFYYGPRDGRQQRAQTMVQVKAVL
GHLLAMSRSSSLSAQDLQTVAGQGTDTDLRAPAQQLIRHLLLNFLLWAPG
GHTIAWDVITLMAHTAEITHEIIGFLDQTLYRWNRLGIESPRSEKLAREL
LKELRTQV

Funkcija

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Protein koji je kodiran ovim genom odgađa početak apoptoza i podstiče popravku oštećene DNK homolognom rekombinacijom. Mutacije ovog gena rezultiraju Fanconijevom anemijom.[6]

Jedarni kompleks koji sadrži FANCC protein (kao i FANCA, FANCF i FANCG) je neophodan za aktivaciju proteina FANCD2 u monoubikvizirane izoforme.[7] U normalnim, nemutantnim ćelijama FANCD2 je monoubikviniran kao odgovor na oštećenje DNK. FANCC zajedno sa FANCE-om djeluje kao adapter supstrata za ovu reakciju [8] Aktivirani protein FANCD2 kolokalizuje se sa BRCA1 (proteinom osjetljivosti na rak dojke) u žarištima izazvanim ionizirajućim zračenjem i u sinaptonemskim kompleksima mejotskih hromosoma. Aktivirani protein FANCD2 može funkcionirati prije početka mejotske rekombinacije, možda da pripremi hromosome za sinapsu ili da reguliše naknadne događaje rekombinacije.[7]

FANCC(–/–) mutanti mužjaka i ženki miševa su ugrozili gametogenezu, dovodeći do značajnog oštećenja plodnosti, što je karakteristika pacijenata sa Fanconijevom anemijom.[9] I mužjaci i ženke FANCC mutantnih miševa imaju smanjen broj germinativnih ćelija.[10]

Interakcije

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Pokazalo se da komplementaciona grupa C Fanconijeve anemije reaguje sa:

Reference

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  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000158169 - Ensembl, maj 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000021461 - 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. ^ Strathdee CA, Duncan AM, Buchwald M (Jun 1992). "Evidence for at least four Fanconi anaemia genes including FACC on chromosome 9". Nature Genetics. 1 (3): 196–8. doi:10.1038/ng0692-196. PMID 1303234. S2CID 7341515.
  6. ^ a b c "Entrez Gene: FANCC Fanconi anemia, complementation group C".
  7. ^ a b 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.
  8. ^ van Twest, S; Murphy, VJ; Hodson, C; Tan, W; Swuec, P; O'Rourke, JJ; Heierhorst, J; Crismani, W; Deans, AJ (19. 1. 2017). "Mechanism of Ubiquitination and Deubiquitination in the Fanconi Anemia Pathway". Molecular Cell. 65 (2): 247–259. doi:10.1016/j.molcel.2016.11.005. PMID 27986371.
  9. ^ Chen M, Tomkins DJ, Auerbach W, McKerlie C, Youssoufian H, Liu L, Gan O, Carreau M, Auerbach A, Groves T, Guidos CJ, Freedman MH, Cross J, Percy DH, Dick JE, Joyner AL, Buchwald M (1996). "Inactivation of Fac in mice produces inducible chromosomal instability and reduced fertility reminiscent of Fanconi anaemia". Nat. Genet. 12 (4): 448–51. doi:10.1038/ng0496-448. PMID 8630504. S2CID 34666783.
  10. ^ Whitney MA, Royle G, Low MJ, Kelly MA, Axthelm MK, Reifsteck C, Olson S, Braun RE, Heinrich MC, Rathbun RK, Bagby GC, Grompe M (1996). "Germ cell defects and hematopoietic hypersensitivity to gamma-interferon in mice with a targeted disruption of the Fanconi anemia C gene". Blood. 88 (1): 49–58. doi:10.1182/blood.V88.1.49.49. PMID 8704201.
  11. ^ a b c d e Reuter TY, Medhurst AL, Waisfisz Q, Zhi Y, Herterich S, Hoehn H, Gross HJ, Joenje H, Hoatlin ME, Mathew CG, Huber PA (Oct 2003). "Yeast two-hybrid screens imply involvement of Fanconi anemia proteins in transcription regulation, cell signaling, oxidative metabolism, and cellular transport". Experimental Cell Research. 289 (2): 211–21. doi:10.1016/s0014-4827(03)00261-1. PMID 14499622.
  12. ^ Kupfer GM, Yamashita T, Naf D, Suliman A, Asano S, D'Andrea AD (Aug 1997). "The Fanconi anemia polypeptide, FAC, binds to the cyclin-dependent kinase, cdc2". Blood. 90 (3): 1047–54. doi:10.1182/blood.V90.3.1047. PMID 9242535.
  13. ^ a b McMahon LW, Walsh CE, Lambert MW (Nov 1999). "Human alpha spectrin II and the Fanconi anemia proteins FANCA and FANCC interact to form a nuclear complex". The Journal of Biological Chemistry. 274 (46): 32904–8. doi:10.1074/jbc.274.46.32904. PMID 10551855.
  14. ^ a b de Winter JP, van der Weel L, de Groot J, Stone S, Waisfisz Q, Arwert F, Scheper RJ, Kruyt FA, Hoatlin ME, Joenje H (Nov 2000). "The Fanconi anemia protein FANCF forms a nuclear complex with FANCA, FANCC and FANCG". Human Molecular Genetics. 9 (18): 2665–74. doi:10.1093/hmg/9.18.2665. PMID 11063725.
  15. ^ Garcia-Higuera I, Kuang Y, Näf D, Wasik J, D'Andrea AD (Jul 1999). "Fanconi anemia proteins FANCA, FANCC, and FANCG/XRCC9 interact in a functional nuclear complex". Molecular and Cellular Biology. 19 (7): 4866–73. doi:10.1128/mcb.19.7.4866. PMC 84285. PMID 10373536.
  16. ^ Reuter T, Herterich S, Bernhard O, Hoehn H, Gross HJ (Jan 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.
  17. ^ Thomashevski A, High AA, Drozd M, Shabanowitz J, Hunt DF, Grant PA, Kupfer GM (Jun 2004). "The Fanconi anemia core complex forms four complexes of different sizes in different subcellular compartments". The Journal of Biological Chemistry. 279 (25): 26201–9. doi:10.1074/jbc.M400091200. PMID 15082718.
  18. ^ 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 (Oct 2003). "A novel ubiquitin ligase is deficient in Fanconi anemia". Nature Genetics. 35 (2): 165–70. doi:10.1038/ng1241. PMID 12973351. S2CID 10149290.
  19. ^ 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.
  20. ^ 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". Journal of Cellular Biochemistry (Submitted manuscript). 86 (4): 613–23. doi:10.1002/jcb.10270. PMID 12210728. S2CID 42471384.
  21. ^ a b 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 (Sep 2004). "The Fanconi anemia gene product FANCF is a flexible adaptor protein". The Journal of Biological Chemistry. 279 (38): 39421–30. doi:10.1074/jbc.M407034200. PMID 15262960.
  22. ^ Gordon SM, Buchwald M (Jul 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. ^ Medhurst AL, Huber PA, Waisfisz Q, de Winter JP, Mathew CG (Feb 2001). "Direct interactions of the five known Fanconi anaemia proteins suggest a common functional pathway". Human Molecular Genetics. 10 (4): 423–9. doi:10.1093/hmg/10.4.423. PMID 11157805.
  24. ^ Pace P, Johnson M, Tan WM, Mosedale G, Sng C, Hoatlin M, de Winter J, Joenje H, Gergely F, Patel KJ (Jul 2002). "FANCE: the link between Fanconi anaemia complex assembly and activity". The EMBO Journal. 21 (13): 3414–23. doi:10.1093/emboj/cdf355. PMC 125396. PMID 12093742.
  25. ^ Cumming RC, Lightfoot J, Beard K, Youssoufian H, O'Brien PJ, Buchwald M (Jul 2001). "Fanconi anemia group C protein prevents apoptosis in hematopoietic cells through redox regulation of GSTP1". Nature Medicine. 7 (7): 814–20. doi:10.1038/89937. PMID 11433346. S2CID 35177844.
  26. ^ Pang Q, Christianson TA, Keeble W, Koretsky T, Bagby GC (decembar 2002). "The anti-apoptotic function of Hsp70 in the interferon-inducible double-stranded RNA-dependent protein kinase-mediated death signaling pathway requires the Fanconi anemia protein, FANCC". The Journal of Biological Chemistry. 277 (51): 49638–43. doi:10.1074/jbc.M209386200. PMID 12397061.
  27. ^ McMahon LW, Sangerman J, Goodman SR, Kumaresan K, Lambert MW (Jun 2001). "Human alpha spectrin II and the FANCA, FANCC, and FANCG proteins bind to DNA containing psoralen interstrand cross-links". Biochemistry. 40 (24): 7025–34. doi:10.1021/bi002917g. PMID 11401546.
  28. ^ Pang Q, Fagerlie S, Christianson TA, Keeble W, Faulkner G, Diaz J, Rathbun RK, Bagby GC (Jul 2000). "The Fanconi anemia protein FANCC binds to and facilitates the activation of STAT1 by gamma interferon and hematopoietic growth factors". Molecular and Cellular Biology. 20 (13): 4724–35. doi:10.1128/mcb.20.13.4724-4735.2000. PMC 85895. PMID 10848598.
  29. ^ Pang Q, Christianson TA, Keeble W, Diaz J, Faulkner GR, Reifsteck C, Olson S, Bagby GC (Sep 2001). "The Fanconi anemia complementation group C gene product: structural evidence of multifunctionality". Blood. 98 (5): 1392–401. doi:10.1182/blood.v98.5.1392. PMID 11520787. S2CID 12153966.
  30. ^ Hoatlin ME, Zhi Y, Ball H, Silvey K, Melnick A, Stone S, Arai S, Hawe N, Owen G, Zelent A, Licht JD (decembar 1999). "A novel BTB/POZ transcriptional repressor protein interacts with the Fanconi anemia group C protein and PLZF". Blood. 94 (11): 3737–47. doi:10.1182/blood.V94.11.3737. PMID 10572087.

Dopunska literatura

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Vanjski linkovi

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