FUNCTION: SwissProt: P38398 # Plays a central role in DNA repair by facilitating cellular response to DNA repair. 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. Mediates E2-dependent ubiquitination. Inhibits lipid synthesis by binding to inactive phosphorylated ACACA and preventing its dephosphorylation.
SIZE: 1863 amino acids; 207721 Da
SUBUNIT: 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. CTIP interacts specifically with the BRCT domains. Interacts with RNA polymerase II holoenzyme. Interacts with SMC1A and COBRA1/NELFB. Binds BRIP1 through the BRCT domains. Interacts with ubiquitinated FANCD2. Interacts with BAP1. Interacts with DCLRE1C/Artemis and CLSPN. Interacts with histone H2AFX and this requires phosphorylation of H2AFX on 'Ser-139'. Interacts with CHEK1/CHK1. Interacts with BRCC3. Interacts through its BRCT domains with phosphorylated ACACA and prevents its dephosphorylation.
SUBCELLULAR LOCATION: Nucleus.
DOMAIN: SwissProt: P38398 The RING-type zinc finger domain interacts with BAP1.
PTM: Phosphorylated in response to IR, UV, and various stimuli that cause checkpoint activation, probably by ATM or ATR.
DISEASE: "SwissProt: P38398 # Defects in BRCA1 are a cause of genetic susceptibility to breast cancer (BC) [MIM:113705, 114480]. BC is an extremely common malignancy, affecting one in eight women during their lifetime. A positive family history has been identified as major contributor to risk of development of the disease, and this link is striking for early-onset breast cancer. Mutations in BRCA1 are thought to be responsible for 45% of inherited breast cancer. Moreover, BRCA1 carriers have a 4-fold increased risk of colon cancer, whereas male carriers face a 3-fold increased risk of prostate cancer. Cells lacking BRCA1 show defects in DNA repair by homologous recombination. & Defects in BRCA1 are a cause of genetic susceptibility to breast-ovarian cancer (BOC) [MIM:113705]. Mutations in BRCA1 are thought to be responsible for more than 80% of inherited breast- ovarian cancer. & Defects in BRCA1 are a cause of genetic susceptibility to ovarian cancer [MIM:113705]."
SIMILARITY: Contains 2 BRCT domains. & Contains 1 RING-type zinc finger.