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breast cancer type 1 susceptibility protein (BRCA1)

Function: - role in DNA repair - elevated levels at G1/S transition, peak in S phase, remain elevated into G2. - phosphorylated at S phase - role in response to DNA damage - hyperphosphorylated in response to DNA damage induced by IR, UV, & various stimuli that cause checkpoint activation, probably by ATM or ATR - involved in transcriptional regulation of P21 in response to DNA damage - required for FANCD2 targeting to sites of DNA damage - may function as a transcriptional regulator - mediates E2-dependent ubiquitination - inhibits lipid synthesis by binding to inactive phosphorylated ACACA & preventing its dephosphorylation - part of the BRCA1-associated genome surveillance complex - BRCA1 forms various molecular complexes: a) BASC (BRCA1 associated genome surveillance complex) b) BRCA1/BARD1/BRCC45/BRCC36 c) BRCA1/BARD1 heterodimer - an E3 ubiquitin ligase d) BRCC holoenzyme complex Structure: - RING-type Zn+2 finger domain interacts with BAP1 - contains 2 BRCT domains - contains 1 RING-type Zn+2 finger Compartment: nucleus Pathology: 1) defects in BRCA1 are a cause of genetic susceptibility a) breast cancer b) breast-ovarian cancer c) ovarian cancer 2) 10-15% of non-familial breast cancers show hypermethylation of the BRCA1 gene. [3] 3) rare form of Gln-356-Arg & Leu-871-Pro polymorphisms may be associated with an increased risk for developing ovarian cancer 4) pathogenic variants in BRCA1 & BRCA2 are associated with increased risk of - gastric cancer - biliary tract cancer - prostate cancer [7] Laboratory: - BRCA1 gene mutation - BRCA1 Ag in tissue

Interactions

molecular events

Related

breast cancer susceptibility gene-1 [BRCA-1]

General

anti-oncoprotein (tumor suppressor protein) DNA-binding protein phosphoprotein transcription factor (TF)

Properties

SIZE: MW = 208 kD entity length = 1863 aa COMPARTMENT: cell nucleus MOTIF: Zn finger C4-type SITE: 24-64 EFFECTOR-BOUND: Zn+2 phosphorylation site BRCA1 C-terminal (BRCT) motif

References

  1. UniProt :accession P38398
  2. Zhang H, Tombline G, Weber BL. BRCA1, BRCA2, and DNA damage response: collision or collusion? Cell. 1998 Feb 20;92(4):433-6. Review. PMID: 9491884
  3. Jones PA, Baylin SB. The fundamental role of epigenetic events in cancer. Nat Rev Genet. 2002 Jun;3(6):415-28. Review. PMID: 12042769
  4. Dong Y, Hakimi MA, Chen X, Kumaraswamy E, Cooch NS, Godwin AK, Shiekhattar R. Regulation of BRCC, a holoenzyme complex containing BRCA1 and BRCA2, by a signalosome-like subunit and its role in DNA repair. Mol Cell. 2003 Nov;12(5):1087-99. PMID: 14636569
  5. Entrez Gene :accession 672
  6. GeneReviews https://www.genecards.org/cgi-bin/carddisp.pl?gene=BRCA1 SHMPD; The Singapore human mutation and polymorphism database http://shmpd.bii.a-star.edu.sg/gene.php?genestart=A&genename=BRCA1 Wikipedia; BRCA1 entry http://en.wikipedia.org/wiki/BRCA1
  7. Momozawa Y et al. Expansion of cancer risk profile for BRCA1 and BRCA2 pathogenic variants. JAMA Oncol 2022 Apr 14; [e-pub] PMID: 35420638 PMCID: PMC9011177 Free PMC article https://jamanetwork.com/journals/jamaoncology/fullarticle/2791277

Component-of

molecular complex

Databases & Figures

OMIM 113705 MORBIDMAP 113705 UniProt P38398 Entrez Gene 672 Figures/diagrams/slides/tables related to BRCA1 protein