BRCA1

BRCA1
Dostupne strukture PDB Pretraga ortologa: PDBe RCSB Spisak PDB ID kodova 1JM7, 1JNX, 1N5O, 1OQA, 1T15, 1T29, 1T2U, 1T2V, 1Y98, 2ING, 3COJ, 3K0H, 3K0K, 3K15, 3PXA, 3PXB, 3PXC, 3PXD, 3PXE, 4IFI, 4IGK, 4JLU, 4OFB, 4U4A, 4Y18, 4Y2G
Identifikatori
Aliasi	BRCA1
Vanjski ID-jevi	OMIM: 113705 MGI: 104537 HomoloGene: 5276 GeneCards: BRCA1
Lokacija gena (čovjek) Hrom. Hromosom 17 (čovjek)[1] Bend 17q21.31 Početak 43,044,295 bp[1] Kraj 43,170,245 bp[1]
Lokacija gena (miš) Hrom. Hromosom 11 (miš)[2] Bend 11 65.18 cM|11 D Početak 101,379,590 bp[2] Kraj 101,442,781 bp[2]
Obrazac RNK ekspresije Više referentnih podataka o ekspresiji
Ontologija gena Molekularna funkcija • vezivanje tubulina • vezivanje iona metala • vezivanje enzima • vezivanje iona cinka • oštećeno vezivanje sa DNK • GO:0001948, GO:0016582 vezivanje za proteine • GO:0001105 transcription coactivator activity • androgen receptor binding • vezivanje sa RNK • ubiquitin protein ligase binding • GO:0050372 aktivnost sa transferazom ubikvitina • vezivanje sa DNK • aktivnost sa transferazom • RNA polymerase binding • vezivanje identičnih proteina Ćelijska komponenta • kompleks BRCA1-BARD1 • kondenzovani nuklearni hromosom • kompleks BRCA1-A • kompleks ubikvitin-ligaze • ćelijska membrana • nukleoplazma • kondenzovani hromosom • citoplazma • hromosom • jedro • lateralni element • GO:0009327 makromolekulani kompleks • ribonukleoprotein Biološki proces • response to ionizing radiation • centrosome cycle • hromosomska segregacija • protein K6-linked ubiquitination • intrinsic apoptotic signaling pathway in response to DNA damage • ćelijski ciklus • double-strand break repair via nonhomologous end joining • GO:0097285 apoptoza • regulation of apoptotic process • regulation of gene expression by genetic imprinting • GO:0009373 regulation of transcription, DNA-templated • negative regulation of fatty acid biosynthetic process • transcription, DNA-templated • regulation of transcription by RNA polymerase III • fatty acid biosynthetic process • regulation of DNA methylation • negative regulation of intracellular estrogen receptor signaling pathway • protein autoubiquitination • positive regulation of histone H3-K9 methylation • DNA recombination • positive regulation of angiogenesis • response to estrogen • cellular response to indole-3-methanol • negative regulation of extrinsic apoptotic signaling pathway via death domain receptors • GO:0045996 negative regulation of transcription, DNA-templated • positive regulation of protein ubiquitination • androgen receptor signaling pathway • negative regulation of centriole replication • Postreplikacijska reparacija • lipid metabolism • cellular response to tumor necrosis factor • GO:1900404 positive regulation of DNA repair • fatty acid metabolic process • GO:1901313 positive regulation of gene expression • negative regulation of histone H3-K4 methylation • regulation of cell population proliferation • negative regulation of reactive oxygen species metabolic process • positive regulation of vascular endothelial growth factor production • DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator • GO:0003257, GO:0010735, GO:1901228, GO:1900622, GO:1904488 positive regulation of transcription by RNA polymerase II • positive regulation of histone H4-K20 methylation • DNA double-strand break processing • double-strand break repair via homologous recombination • negative regulation of histone acetylation • protein ubiquitination • positive regulation of histone H3-K4 methylation • GO:0100026 Popravka DNK • double-strand break repair • positive regulation of histone acetylation • dosage compensation by inactivation of X chromosome • negative regulation of histone H3-K9 methylation • positive regulation of histone H3-K9 acetylation • GO:0060469, GO:0009371 positive regulation of transcription, DNA-templated • chordate embryonic development • positive regulation of histone H4-K16 acetylation • cellular response to DNA damage stimulus • protein deubiquitination • Replikacija DNK • mitotic G2/M transition checkpoint • GO:0044324, GO:0003256, GO:1901213, GO:0046019, GO:0046020, GO:1900094, GO:0061216, GO:0060994, GO:1902064, GO:0003258, GO:0072212 regulation of transcription by RNA polymerase II • negative regulation of G0 to G1 transition • transcription by RNA polymerase II • mitotic G2 DNA damage checkpoint signaling • regulation of signal transduction by p53 class mediator Izvori:Amigo / QuickGO
Ortolozi
Vrste	Čovjek	Miš
Entrez	672	12189
Ensembl	ENSG00000012048	ENSMUSG00000017146
UniProt	P38398	P48754
RefSeq (mRNK)	NM_007294 NM_007295 NM_007296 NM_007297 NM_007298 NM_007299 NM_007300 NM_007301 NM_007302 NM_007303 NM_007305 NM_007306	NM_009764
RefSeq (bjelančevina)	NP_009225 NP_009228 NP_009229 NP_009230 NP_009231	NP_033894
Lokacija (UCSC)	Chr 17: 43.04 – 43.17 Mb	Chr 11: 101.38 – 101.44 Mb
PubMed pretraga	[3]	[4]
Wikipodaci
Pogledaj/uredi – čovjek Pogledaj/uredi – miš

Protein osjetljivosti na rak dojke tip 1 je protein koji je kod ljudi kodiran genom BRCA1.^[5] Ortolozi su česti kod drugih kičmenjačkih vrsta, dok genomi beskičmenjaka mogu imati srodni gen.^[6] BRCA1 je ljudski gen supresije tumora ^[7][8] (poznat i kao domarski gen) i odgovoran je za popravak DNK.^[9]

BRCA1 i BRCA2 su nepovezani proteini,^[10] ali oba se normalno eksprimiraju u ćelijama dojke i drugom tkivu, gdje pomažu u popravljanju oštećene DNK ili uništavanju ćelija, ako DNK nije moguće popraviti. Oni su uključeni u popravak hromosomskog oštećenja s važnom ulogom u nepogrešivim popravcima prekida dvolančana DNK.^[11][12] Ako su BRCA1 ili BRCA2 sami oštećeni BRCA mutacijom, oštećena DNK se ne popravlja pravilno, a to povećava rizik za rak dojke.^[13][14] BRCA1 i BRCA2 opisani su kao "geni osjetljivosti na rak dojke" i "proteini osjetljivosti na rak dojke". Prevladavajući alel ima normalnu funkciju supresije tumora, dok mutacije s visokom penetrabilnošću u ovim genima uzrokuju gubitak funkcije supresije tumora, što korelira s povećanim rizikom od raka dojke.^[15]

BRCA1 se kombinira s drugim supresorima tumora, senzorima oštećenja DNK i pretvaračima signala da bi stvorio veliki kompleks multijedinica proteina poznat kao BRCA1-asocirani kompleks za nadzor genoma (BASC).^[16] Protein BRCA1 povezuje se s RNK-polimerazom II, te putem C-terminalnog domena takođe komunicira sa kompleksima histon-deacetilaza. Dakle, ovaj protein ima ulogu u transkripciji i popravljanju prekida dvolančane DNK^[14] ubikvitinaciji, transkripcijskoj regulaciji, kao i drugim funkcijamaa.^[17]

Metodi za ispitivanje vjerovatnoće pacijenta sa mutacijama u BRCA1 i BRCA2 koje uzrokuju rak obuhvaćene su patentima u vlasništvu ili pod kontrolom Myriad Genetics. Myriadov poslovni model nuđenja dijagnostičkog testa vodio je isključivo od toga da je 1994. bio startup kompanija, koja je bila javna kompanija sa 1.200 zaposlenih i oko 500 miliona dolara godišnjeg prihoda u 2012.;^[18][19] to je također dovelo do kontroverze oko visokih cijena i nemogućnosti dobivanja drugih mišljenja od drugih dijagnostičkih laboratorija, što je zauzvrat dovelo do značajne tužbe Udruženja za molekulsku patologiju protiv Association for Molecular Pathology v. Myriad Genetics.^[20]

1. ^ ^{a b c} GRCh38: Ensembl release 89: ENSG00000012048 - Ensembl, maj 2017
2. ^ ^{a b c} GRCm38: Ensembl release 89: ENSMUSG00000017146 - 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. ^ Hamel PJ (29. 5. 2007). "BRCA1 and BRCA2: No Longer the Only Troublesome Genes Out There". HealthCentral. Pristupljeno 2. 7. 2010.
6. ^ "BRCA1 gene tree". Ensembl.
7. ^ Duncan JA, Reeves JR, Cooke TG (oktobar 1998). "BRCA1 and BRCA2 proteins: roles in health and disease". Molecular Pathology. 51 (5): 237–47. doi:10.1136/mp.51.5.237. PMC 395646. PMID 10193517.
8. ^ Yoshida K, Miki Y (novembar 2004). "Role of BRCA1 and BRCA2 as regulators of DNA repair, transcription, and cell cycle in response to DNA damage". Cancer Science. 95 (11): 866–71. doi:10.1111/j.1349-7006.2004.tb02195.x. PMID 15546503. S2CID 24297965.
9. ^ Check W (1. 9. 2006). "BRCA: What we know now". College of American Pathologists. Pristupljeno 23. 8. 2010.
10. ^ Irminger-Finger I, Ratajska M, Pilyugin M (2016). "New concepts on BARD1: Regulator of BRCA pathways and beyond". The International Journal of Biochemistry & Cell Biology. 72: 1–17. doi:10.1016/j.biocel.2015.12.008. PMID 26738429.
11. ^ Friedenson B (august 2007). "The BRCA1/2 pathway prevents hematologic cancers in addition to breast and ovarian cancers". BMC Cancer. 7: 152–162. doi:10.1186/1471-2407-7-152. PMC 1959234. PMID 17683622.
12. ^ Friedenson B (8. 6. 2008). "Breast cancer genes protect against some leukemias and lymphomas" (video). SciVee.
13. ^ "Breast and Ovarian Cancer Genetic Screening". Palo Alto Medical Foundation. Arhivirano s originala, 4. 10. 2008. Pristupljeno 11. 10. 2008.
14. ^ ^{a b} Friedenson B (2007). "The BRCA1/2 pathway prevents hematologic cancers in addition to breast and ovarian cancers". BMC Cancer. 7: 152. doi:10.1186/1471-2407-7-152. PMC 1959234. PMID 17683622.
15. ^ O'Donovan PJ, Livingston DM (april 2010). "BRCA1 and BRCA2: breast/ovarian cancer susceptibility gene products and participants in DNA double-strand break repair". Carcinogenesis. 31 (6): 961–7. doi:10.1093/carcin/bgq069. PMID 20400477.
16. ^ Greška kod citiranja: Nevaljana oznaka <ref>; nije naveden tekst za reference s imenom pmid10783165
17. ^ Starita LM, Parvin JD (2003). "The multiple nuclear functions of BRCA1: transcription, ubiquitination and DNA repair". Current Opinion in Cell Biology. 15 (3): 345–350. doi:10.1016/S0955-0674(03)00042-5. PMID 12787778.
18. ^ Myriad Investor Page—see "Myriad at a glance" Arhivirano 18. 10. 2012. na Wayback Machine.
19. ^ Webarchive|url=https://web.archive.org/web/20121018224334/http://investor.myriad.com/index.cfm |date=2012-10-18 }} accessed October 2012
20. ^ Schwartz J (12. 5. 2009). "Cancer Patients Challenge the Patenting of a Gene". The New York Times. Health.