Figure 1

BRCA1 domains and interacting proteins. BRCA1 contains a RING domain at its N-terminus, two BRCT domains at the C-terminus and a coiled-coil domain upstream of BRCT domains. The interacting proteins are shown under the region of BRCA1 required for their association. BRCA1 forms an E3 ligase with BARD1 through its RING domain dimerizing with a RING domain containing protein BARD1. A ubiquitin hydrolase BAP1 also interacts with this region. The C-terminal BRCT domains form a phospho-binding module recognizing a phospho-SPxF motif. Abraxas, Bach1 and CtIP have been shown directly bind to BRCT domain through the phospho-SPxF motif. PALB2 binds to the coiled-coil domain of BRCA1 and bridges BRCA1-BRCA2 interaction. A number of other proteins have also been indicated binding to the C-terminal region of BRCA1 or the central region of BRCA1. BRCA1 contains a S/TQ cluster that is phosphorylated by ATM/ATR at multiple sites. In addition, BRCA1 is also a substrate of Chk2