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)].
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- Evolution (species in which this domain is found)
Taxonomic distribution of proteins containing BRCT domain.
This tree includes only several representative species. The complete taxonomic breakdown of all proteins with BRCT domain is also avaliable.
Click on the protein counts, or double click on taxonomic names to display all proteins containing BRCT domain in the selected taxonomic class.
- 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)
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% 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 2l42 The solution structure of Rap1 BRCT domain from Saccharomyces cerevisiae 2le0 PARP BRCT Domain 2m2i NMR solution structure of BRCT domain of yeast REV1 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. 2wt8 Structure of the N-terminal BRCT domain of human microcephalin (Mcph1) 2xnh Structure and function of the Rad9-binding region of the DNA damage checkpoint adaptor TopBP1 2xnk Structure and function of the Rad9-binding region of the DNA damage checkpoint adaptor TopBP1 3al2 Crystal Structure of TopBP1 BRCT7/8 3al3 Crystal Structure of TopBP1 BRCT7/8-BACH1 peptide complex 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. 3jve Crystal Structure of the Sixth BRCT Domain of TopBP1 3k05 The crystal structure of MDC1 BRCT T2067D in complex with a minimal recognition tetrapeptide with an amidated C-terminus 3k0h The crystal structure of BRCA1 BRCT in complex with a minimal recognition tetrapeptide with an amidated C-terminus 3k0k Crystal Structure of BRCA1 BRCT in complex with a minimal recognition tetrapeptide with a free carboxy C-terminus. 3k15 Crystal Structure of BRCA1 BRCT D1840T in complex with a minimal recognition tetrapeptide with an amidated C-terminus 3k16 Crystal Structure of BRCA1 BRCT D1840T in complex with a minimal recognition tetrapeptide with a free carboxy C-terminus 3ktf Structure of the N-terminal BRCT domain of human microcephalin (MCPH1). 3l40 Crystal Structure of S. pombe Brc1 BRCT5-BRCT6 domains 3l41 Crystal Structure of S. pombe Brc1 BRCT5-BRCT6 domains in complex with phosphorylated H2A 3l46 Crystal structure of the second BRCT domain of epithelial cell transforming 2 (ECT2) 3olc Crystal structure of the N-terminal region of TopBP1 3pa6 Structure of the N-terminal BRCT domain of human microcephalin (MCPH1) 3pc6 X-ray crystal structure of the second XRCC1 BRCT domain. 3pc7 X-ray crystal structure of the DNA ligase III-alpha BRCT domain. 3pc8 X-ray crystal structure of the heterodimeric complex of XRCC1 and DNA ligase III-alpha BRCT domains. 3pd7 Crystal Structure of the Sixth BRCT Domain of Human TopBP1 3pxa Impact of BRCA1 BRCT domain missense substitutions on phospho-peptide recognition: G1656D 3pxb Impact of BRCA1 BRCT domain missense substitutions on phospho-peptide recognition: T1700A 3pxc Impact of BRCA1 BRCT domain missense substitutions on phospho-peptide recognition: R1699Q 3pxd Impact of BRCA1 BRCT domain missense substitutions on phospho-peptide recognition: R1835P 3pxe Impact of BRCA1 BRCT domain missense substitutions on phospho-peptide recognition: E1836K 3qvg XRCC1 bound to DNA ligase 3sht Crystal structure of human MCPH1 tandem BRCT domains 3shv Crystal structure of human MCPH1 tandem BRCT domains-gamma H2AX complex 3sqd Crystal structure of human PTIP BRCT5/6-gamma H2AX complex 3szm STRUCTURE OF HUMAN MICROCEPHALIN (MCPH1) TANDEM BRCT DOMAINS IN COMPLEX WITH A GAMMA-H2AX PHOSPHOPEPTIDE 3t1n Structure of human MICROCEPHALIN (MCPH1) TANDEM BRCT domains in complex with a CDC27 phosphopeptide 3u3z Structure of human microcephalin (MCPH1) tandem BRCT domains in complex with an H2A.X peptide phosphorylated at Ser139 and Tyr142 3uen Crystal structure of TopBP1 BRCT4/5 domains 3ueo Crystal structure of TopBP1 BRCT4/5 domains in complex with a phospho-peptide 4bmc Crystal structure of s.pombe Rad4 BRCT1,2 4bmd Crystal structure of S.pombe Rad4 BRCT3,4 4bu0 Crystal structure of Rad4 BRCT1,2 in complex with a Crb2 phosphopeptide 4bu1 Crystal structure of Rad4 BRCT1,2 in complex with a Crb2 phosphopeptide 4gns Crystal Structure of the Chs5-Chs6 Exomer Cargo Adaptor Complex 4id3 Crystal Structure of the BRCT domain of S. Cerevisiae Rev1 4ifi Structure of human BRCA1 BRCT in complex with BAAT peptide 4igk Structure of human BRCA1 BRCT in complex with ATRIP peptide
- Links (links to other resources describing this domain)
PFAM BRCT INTERPRO IPR001357