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Protein FULL name:
breast cancer type 1 susceptibility protein homolog [Mus musculus].
Brca1 (Mus musculus) is product of expression of Brca1 gene.
FUNCTION: E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage. It is unclear whether it also mediates the formation of other types of polyubiquitin chains. The E3 ubiquitin-protein ligase activity is required for its tumor suppressor function. The BRCA1-BARD1 heterodimer coordinates a diverse range of cellular pathways such as DNA damage repair, ubiquitination and transcriptional regulation to maintain genomic stability. Regulates centrosomal microtubule nucleation. Required for normal cell cycle progression from G2 to mitosis. Required for appropriate cell cycle arrests after ionizing irradiation in both the S-phase and the G2 phase of the cell cycle. 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. Inhibits lipid synthesis by binding to inactive phosphorylated ACACA and preventing its dephosphorylation (By similarity).
PATHWAY: Protein modification; protein ubiquitination.
SUBUNIT: Heterodimer with BARD1. Part of the BRCA1-associated genome surveillance complex (BASC), which contains BRCA1, MSH2, MSH6, MLH1, ATM, BLM, PMS2 and the RAD50-MRE11-NBN protein complex. This association could be a dynamic process changing throughout the cell cycle and within subnuclear domains. Component of the BRCA1-A complex, at least composed of the BRCA1, BARD1, UIMC1/RAP80, FAM175A/Abraxas, BRCC3/BRCC36, BRE/BRCC45 and MERIT40/NBA1. Interacts (via BRCT domains) with FAM175A/Abraxas and RBBP8. Associates with RNA polymerase II holoenzyme. Interacts with SMC1A and COBRA1/NELFB. Interacts (via BRCT domains) with phosphorylated BRIP1. Interacts with FANCD2 (ubiquitinated). Interacts with BAP1. Interacts with DCLRE1C/Artemis and CLSPN. Interacts with H2AFX (phosphorylated on 'Ser-140'). Interacts with CHEK1/CHK1. Interacts with BRCC3. Interacts (via BRCT domains) with ACACA (phosphorylated); the interaction prevents dephosphorylation of ACACA. Interacts with STK6/AURKA. Interacts with UBXN1 (By similarity).
SUBCELLULAR LOCATION: Nucleus (By similarity). Note=Localizes at sites of DNA damage at double-strand breaks (DSBs); recruitment to DNA damage sites is mediated by the BRCA1-A complex (By similarity).
TISSUE SPECIFICITY: In the embryo, expressed in otic vesicles at day 9.5. At day 10.5, this expression decreases and high levels are found in the neuroectoderm. At days 11-12.5, high levels in differentiating keratinocytes and whisker pad primordia. At days 14-17, expression also observed in kidney epithelial cells. In the adult, highest levels found in spleen, thymus, lymph nodes, epithelial organs, and alveolar and ductal epithelial cells of the mammary gland. Very low levels in brain, kidney, and skin. No expression in heart, liver or lung.
DEVELOPMENTAL STAGE: In the mammary gland, expression increases dramatically during pregnancy. Levels fall during lactation and increase again during post-lactational regression of the mammary gland.
DOMAIN: The BRCT domains recognize and bind phosphorylated pSXXF motif on proteins. The interaction with the phosphorylated pSXXF motif of FAM175A/Abraxas, recruits BRCA1 at DNA damage sites (By similarity).
DOMAIN: The RING-type zinc finger domain interacts with BAP1 (By similarity).
PTM: Phosphorylated in response to IR, UV, and various stimuli that cause checkpoint activation, probably by ATM or ATR.
PTM: Autoubiquitinated, undergoes 'Lys-6'-linked polyubiquitination. 'Lys-6'-linked polyubiquitination does not promote degradation (By similarity).
SIMILARITY: Contains 2 BRCT domains.
SIMILARITY: Contains 1 RING-type zinc finger.
Links to other databases:
Brca1 (Mus musculus) belongs to following protein families:
Last modification of this entry: Oct. 6, 2010.
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