Schultz et al. (1998) Proc. Natl. Acad. Sci. USA 95, 5857-5864
Letunic et al. (2008) Nucleic Acids Res , doi:10.1093/nar/gkn808

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BRCT breast cancer carboxy-terminal domain

There are 3173 BRCT domains in 2185 proteins in SMART's nrdb database.

Click on the following links for more information.

• Evolution (species in which this domain is found)

• Click on to expand nodes. To display all proteins with a BRCT domain in a specific node, click on it.

  This tree shows only several representative species. The complete taxonomic breakdown of all proteins with BRCT domain is also avaliable.

  Useful shortcuts: Expand all nodes or Collapse tree
  Go to specific node: Anopheles gambiae, Arabidopsis thaliana, Caenorhabditis elegans, Drosophila melanogaster, Homo sapiens, Mus musculus, Rattus norvegicus, Saccharomyces cerevisiae, Takifugu rubripes

• Literature (relevant references for this domain)

• Primary literature is listed below; Automatically-derived, secondary literature is also avaliable.

  • Chai YL, Cui J, Shao N, Shyam E, Reddy P, Rao VN
  • The second BRCT domain of BRCA1 proteins interacts with p53 and stimulates transcription from the p21WAF1/CIP1 promoter.
  • Oncogene. 1999; 18: 263-8
  • Display abstract

  • Inherited mutations in the breast and ovarian cancer susceptibility gene BRCA1 are associated with high risk for developing breast and ovarian cancers. Several studies link BRCA1 to transcriptional regulation, DNA repair, apoptosis and growth/tumor suppression. BRCA1 associates with p53 and stimulates transcription in both p53 dependent and p53-independent manners. BRCA1 splice variants BRCA1a (p110) and BRCA1b (p100) associates with CBP/p300 co-activators. Here we show that BRCA1a and BRCA1b proteins stimulate p53-dependent transcription from the p21WAF1/CIP1 promoter. In addition, the C-terminal second BRCA1 (BRCT) domain is sufficient for p53 mediated transactivation of the p21 promoter. Previous studies emphasized the importance of the BRCT domain, which shows homology with p53 binding protein (53BP1), in transcriptional activation, growth inhibition and tumor suppression. Our findings demonstrate an additional function for this domain in protein-protein interaction and co-activation of p53. We also found that BRCA1a and BRCA1b proteins interact with p53 in vitro and in vivo. The p53 interaction domain of BRCA1a/1b maps, in vitro, to the second BRCT domain (aa 1760-1863). The BRCT domain binds to the central domain of p53 which is required for sequence specific DNA binding. These results demonstrate for the first time the presence of a second p53 interaction domain in BRCA1 proteins and suggests that BRCA1a and BRCA1b proteins, like BRCA1, function as p53 co-activators. This BRCT domain also binds in vitro to CBP. These results suggest that one of the mechanisms by which BRCA1 proteins function is through recruitment of CBP/p300 associated HAT/FAT activity for acetylation of p53 to specific promoters resulting in transcriptional activation.

• Disease (disease genes where sequence variants are found in this domain)

• SwissProt sequences and OMIM curated human diseases associated with missense mutations within the BRCT domain.

  Protein	Disease
  Breast cancer type 1 susceptibility protein (SRS)(SMART)	OMIM:113705: Breast cancer-1 ; Ovarian cancer ; Breast-ovarian cancer ; Papillary serous carcinoma of the peritoneum

• Metabolism (metabolic pathways involving proteins which contain this domain)

• Click the image to view the interactive version of the map in iPath

  % proteins involved KEGG pathway ID Description 94.78 map03030 DNA replication 1.67 map04640 Hematopoietic cell lineage 0.84 map04110 Cell cycle 0.63 map00471 D-Glutamine and D-glutamate metabolism 0.63 map04111 Cell cycle - yeast 0.63 map00550 Peptidoglycan biosynthesis 0.42 map00730 Thiamine metabolism 0.42 map00230 Purine metabolism This information is based on mapping of SMART genomic protein database to KEGG orthologous groups. Percentage points are related to the number of proteins with BRCT domain which could be assigned to a KEGG orthologous group, and not all proteins containing BRCT domain. Please note that proteins can be included in multiple pathways, ie. the numbers above will not always add up to 100%.

• Structure (3D structures containing this domain)

• 3D Structures of BRCT domains in PDB

  PDB code	Main view	Title
  1cdz		Brct domain from dna-repair protein xrcc1
  1dgs		Crystal structure of nad+-dependent dna ligase from t. filiformis
  1gzh		Crystal structure of the brct domains of human 53bp1 bound to the p53 tumor supressor
  1imo		Nmr structure of human dna ligase iiialpha brct domain
  1in1		Nmr structure of human dna ligase iiialpha brct domain
  1jnx		Crystal structure of the brct repeat region from the breast cancer associated protein, brca1
  1kzy		Crystal structure of the 53bp1 brct region complexed to tumor suppressor p53
  1l0b		Crystal structure of rat brca1 tandem-brct region
  1l7b		Solution nmr structure of brct domain of t. thermophilus: northeast structural genomics consortium target wr64tt
  1n5o		Structural consequences of a cancer-causing brca1-brct missense mutation
  1oqa		Solution structure of the brct-c domain from human brca1
  1t15		Crystal structure of the brca1 brct domains in complex with the phosphorylated interacting region from bach1 helicase
  1t29		Crystal structure of the brca1 brct repeats bound to a phosphorylated bach1 peptide
  1t2u		Structural basis of phosphopeptide recognition by the brct domain of brca1: structure of brca1 missense variant v1809f
  1t2v		Structural basis of phospho-peptide recognition by the brct domain of brca1, structure with phosphopeptide
  1wf6		The third brca1 c-terminus (brct) domain of similar to s.pombe rad4+/cut5+ product
  1y98		Structure of the brct repeats of brca1 bound to a ctip phosphopeptide.
  1z56		Co-crystal structure of lif1p-lig4p
  2ado		Crystal structure of the brct repeat region from the mediator of dna damage checkpoint protein 1, mdc1
  2azm		Crystal structure of the mdc1 brct repeat in complex with the histone tail of gamma-h2ax
  2coe		Solution structure of brct domain of terminal deoxynucleotidyltransferase
  2cok		Solution structure of brct domain of poly(adp-ribose) polymerase-1
  2cou		Solution structure of the second brct domain of epithelial cell transforming 2
  2d8m		Solution structure of the first brct domain of dna-repair protein xrcc1
  2dun		Solution structure of brct domain of dna polymerase mu
  2e2w		Solution structure of the first brct domain of human dna ligase iv
  2ebu		Solution structure of the brct domain from human replication factor c large subunit 1
  2ebw		Solution structure of the brct domain from human dna repair protein rev1
  2ep8		Solution structure of the brct domain from human pescadillo homolog 1
  2etx		Crystal structure of mdc1 tandem brct domains
  2htf		The solution structure of the brct domain from human polymerase reveals homology with the tdt brct domain
  2ing		X-ray structure of the brca1 brct mutant m1775k
  2k6g
  2k7f
  2nte		Crystal structure of the bard1 brct domains
  2owo		Last stop on the road to repair: structure of e.coli dna ligase bound to nicked dna-adenylate
  2r1z		Crystal structure of the bard1 brct repeat
  2vxb		Structure of the crb2-brct2 domain
  2vxc		Structure of the crb2-brct2 domain complex with phosphopeptide.
  3coj		Crystal structure of the brct domains of human brca1 in complex with a phosphorylated peptide from human acetyl- coa carboxylase 1
  3ef0
  3ef1
  3fa2
  3ii6

• Links (links to other resources describing this domain)

• PFAM	BRCT
  INTERPRO	IPR001357