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 BABAM1/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 AURKA. Interacts with UBXN1. Part of a trimeric complex containing BRCA1, BRCA2 and PALB2. Interacts with PALB2 and this interaction is essential for its function in HRR. Interacts with BRCA2 only in the presence of PALB2 which serves as the bridging protein (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.
COPYRIGHT: Protein annotation is derived from the UniProt Consortium (http://www.uniprot.org/). Distributed under the Creative Commons Attribution-NoDerivs License.