- BRCA1 (RNF53) https://www.ncbi.nlm.nih.gov/gene/672
(17q21.31) - BRCA1, BRCA1 DNA repair associated [ Homo sapiens (human) ]
- IRIS; PSCP; BRCAI; BRCC1; FANCS; PNCA4; RNF53; BROVCA1; PPP1R53
- Summary This gene encodes a nuclear phosphoprotein that plays a role in maintaining genomic stability, and it also acts as a tumor suppressor. The encoded protein combines with other tumor suppressors, DNA damage sensors, and signal transducers to form a large multi-subunit protein complex known as the BRCA1-associated genome surveillance complex (BASC). This gene product associates with RNA polymerase II, and through the C-terminal domain, also interacts with histone deacetylase (HDAC) complexes. This protein thus plays a role in transcription, DNA repair of double-stranded breaks (DSB), and recombination. Mutations in this gene are responsible for approximately 40% of inherited breast cancers and more than 80% of inherited breast and ovarian cancers. Alternative splicing plays a role in modulating the subcellular localization and physiological function of this gene. Many alternatively spliced transcript variants, some of which are disease-associated mutations, have been described for this gene, but the full-length natures of only some of these variants has been described. A related pseudogene, which is also located on chromosome 17, has been identified. [provided by RefSeq, May 2009]
- Expression Broad expression in testis (RPKM 5.2), lymph node (RPKM 3.3) and 23 other tissues See more Orthologs mouse all
- Preferred Names
- breast cancer type 1 susceptibility protein, (BRCA1)
- Names
- BRCA1/BRCA2-containing complex, subunit 1, ( BRCC1)
- Fanconi anemia, complementation group S, ( FANCS)
- RING finger protein 53, (RNF53)
- breast and ovarian cancer susceptibility protein 1, (BROVCA1)
- breast cancer 1, early onset, (BRCA1)
- early onset breast cancer 1
- protein phosphatase 1, regulatory subunit 53; (PPP1R53)
- Conserved Domains (4) summary
-
- smart00292
Location:1758 → 1842 - BRCT; breast cancer carboxy-terminal domain
- cd00027
Location:1650 → 1724 - BRCT; Breast Cancer Suppressor Protein (BRCA1), carboxy-terminal domain. The BRCT domain is found within many DNA damage repair and cell cycle checkpoint proteins. The unique diversity of this domain superfamily allows BRCT modules to interact forming homo/hetero BRCT multimers, BRCT-non-BRCT interactions, and interactions within DNA strand breaks.
- cd00162
Location:23 → 68 - RING; RING-finger (Really Interesting New Gene) domain, a specialized type of Zn-finger of 40 to 60 residues that binds two atoms of zinc; defined by the 'cross-brace' motif C-X2-C-X(9-39)-C-X(1-3)- H-X(2-3)-(N/C/H)-X2-C-X(4-48)C-X2-C; probably involved in mediating protein-protein interactions; identified in a proteins with a wide range of functions such as viral replication, signal transduction, and development; has two variants, the C3HC4-type and a C3H2C3-type (RING-H2 finger), which have different cysteine/histidine pattern; a subset of RINGs are associated with B-Boxes (C-X2-H-X7-C-X7-C-X2-C-H-X2-H). ( Kommentti. Näistä saa enemmän tietoa Zinc finger proteins in health and disease. matteo Cassandri et al. 2017, Review. Tässäkin blogissa on luetteloa. BRCA1 kuuluu näihin sinkkisormiproteiineihin ZNF , alaryhmään RNF).
- pfam12820
Location:345 → 507 - BRCT_assoc; Serine-rich domain associated with BRCT
- smart00292
Related articles in PubMed
- CRISPR/Cas9-Mediated BRCA1 Knockdown Adipose Stem Cells Promote Breast Cancer Progression. Zhao R, et al. Plast Reconstr Surg, 2019 Mar. PMID 30817646,
- Distinct Clinical Courses of Epithelial Ovarian Cancer with Mutations in BRCA1 5' and 3' Exons. Eoh KJ, et al. Anticancer Res, 2018 Dec. PMID 30504414
- Pathogenic BRCA1 mutations may be necessary but not sufficient for tissue genomic heterogeneity: Deep sequencing data from ovarian cancer patients. Kotoula V, et al. Gynecol Oncol, 2019 Feb. PMID 30446274
- Additional molecular and clinical evidence open the way to definitive IARC classification of the BRCA1 c.5332G > A (p.Asp1778Asn) variant. Minucci A, et al. Clin Biochem, 2019 Jan. PMID 30315757
- BRCA1 Promoter Methylation and Clinicopathological Characteristics in Sporadic Breast Cancer Patients in Indonesia Harahap WA, et al. Asian Pac J Cancer Prev, 2018 Sep 26. PMID 30256562, Free PMC Article
GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?
- These results suggest a modest association between BRCA1 and BRCA2 and Nonsyndromic cleft lip with or without cleft palate.
- Report on genetic variants reported in BRCA1 found in various ethnic groups, their functional implications if known; and involvement of BRCA1 in various cellular pathways/processes (review).
- DYNLL1 as an inhibitor of DNA end resection; the loss of DYNLL1 enables DNA end resection and restores homologous recombination in BRCA1-mutant cells, thereby inducing resistance to platinum drugs and inhibitors of poly(ADP-ribose) polymerase
- This study comprehensively describes the characteristics of the 1,650 unique BRCA1 and 1,731 unique BRCA2 deleterious (disease-associated) mutations identified in the CIMBA database.
- Study shows that BRCA1, PALB2 and BRCA2 can all play a significant role in both checkpoint activation and checkpoint maintenance, depending on cell type and context, and that PALB2 links BRCA1 and BRCA2 in the checkpoint response. The BRCA1-PALB2 interaction can be important for checkpoint activation, whereas PALB2-BRCA2 complex appears to be more critical for checkpoint maintenance.
- Soma-wide BRCA1 promoter hypermethylation was confirmed in blood, buccal mucosa, and hair follicles.
- Our results did not provide evidence for elevated risks of invasive breast cancer (BC) or epithelial ovarian cancer in BRCA1/BRCA2 predictive test negatives
- Be used to functionally characterize BRCA1 missense variants at scale.
- his study reveals for the first time that estrogen promotes BRCA1-deficient tumor initiation and progression by stimulation of cell proliferation and activation of EMT, which are dependent on AKT activation and independent of ER.
- BRCA1/2 mutation prevalence in unselected breast cancer patients was 1.8%.
- (Huom nämä valitut artikkelit ovat lähinä onkologian alaa, mikä heijastaakin tämän geenin ja proteiinin kliinistä ja runsaasti selviteltyä merkitystä. Soveltaminen taas kliiniseen terapiaan saattaa olla lähinnä diagnostisella ja prognostisella tasolla).
- Geenitesti BRCA1 ja BRCA2 on informoivaa luonteeltaan, mutta ne geenit eivät ole "hoidettavissa" olevia kohteita sinänsä, mutta niiden tila, olemassaolo ja niiden mutaatiot voivat vaikuttaa diagnoosin tekemiseen, hoitosuunnitelmaan ja paranemisarvioon. Ne eivät testaa syöpää itseään, vaan ihmisen perittyä genomia ja täten riskialttiutta. Nämä geenit normaaleina ovat DNA:ta korjaavasta järjestelmästä.
- Siteeraan tässä yhteydessä suomalaislähdettä:
- HUS
LAB - https://huslab.fi/ohjekirja/20532.html
"Yleistä
BRCA1- ja BRCA2-geenit ovat kasvunrajoitegeenejä, jotka osallistuvat DNA:n virheiden korjaukseen. Lisäksi niiden on osoitettu säätelevän muiden geenien ilmentymistä.BRCA1-geenivirheen kantajan riski sairastua elämänsä aikana rintasyöpään on noin 40-80 % ja munasarjasyöpään noin 25-50 %.
BRCA2-geenivirheen kantajan riski sairastua elämänsä aikana rintasyöpään on noin 40-70 % ja munasarjasyöpään noin 10-20 %.
BRCA1- ja BRCA2-geenin mutaatiot lisäävät riskiä sairastua myös eräisiin muihin syöpiin.
Tutkimus käsittää 97 Suomessa aikaisemmin tunnistettua BRCA1- ja BRCA2-geenien mutaatiota (kts. erillinen listaus Huomautuksia-kappaleessa).
Näytteestä eristetystä DNA:sta määritetään kohdealueitten emäsjärjestys PCR-amplikoneihin perustuvalla sekvensoinnilla Ion Torrent -laitteella. DNA-muutosten tunnistamiseen ja tulosten tulkintaan käytetään Torrent Serverin analyysiohjelmistoa. Lausunnossa ilmoitetaan todettu mutaatio, tutkitut mutaatiot ilmoitetaan erillisellä liitteellä. Tutkituilla alueilla sekvensoinnin kattavuus on vähintään 30-kertainen.
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