BRCTbreast cancer carboxy-terminal domain
|SMART accession number:||SM00292|
|Interpro abstract (IPR001357):|
The BRCT domain (after the C_terminal domain of a breast cancer susceptibility protein) is found predominantly in proteins involved in cell cycle checkpoint functions responsive to DNA damage [(PUBMED:9034168)], for example as found in the breast cancer DNA-repair protein BRCA1. The domain is an approximately 100 amino acid tandem repeat, which appears to act as a phospho-protein binding domain [(PUBMED:14576433)].
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 (P38398) (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 Solution structure of the dna binding brct domain from the large subunit of human replication factor c 2k7f Haddock calculated model of the complex between the brct region of rfc p140 and dsdna 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 The structure of fcp1, an essential rna polymerase ii ctd phosphatase 3ef1 The structure of fcp1, an essential rna polymerase ii ctd phosphatase 3fa2 Crystal structure of the brca1 associated ring domain (bard1) tandem brct domains 3ii6 Structure of human xrcc4 in complex with the tandem brct domains of dna ligaseiv.
- Links (links to other resources describing this domain)
PFAM BRCT INTERPRO IPR001357