The domain within your query sequence starts at position 690 and ends at position 766; the E-value for the BRCT domain shown below is 1.67e-15.

GKPCSQHIISVTGFVDNDRDDLKLMAYLAGAKYTGYLCRSNTVLICKEPSGLKYEKAKEW
RIPCVNAQWLGDILLGN

BRCT

breast cancer carboxy-terminal domain

• SMART accession number: SM00292
• Description: -
• Interpro abstract (IPR001357):

  The breast cancer susceptibility gene contains at its C terminus two copies of a conserved domain that was named BRCT for BRCA1 C terminus. This domain of about 95 amino acids is found in a large variety of proteins involved in DNA repair, recombination and cell cycle control [ (PUBMED:8673121) (PUBMED:9034168) (PUBMED:9000507) ]. The BRCT domain is not limited to the C-terminal of protein sequences and can be found in multiple copies or in a single copy as in RAP1 and TdT. BRCT domains are often found as tandem-repeat pairs [ (PUBMED:15501676) ]. Some data [ (PUBMED:9799248) ] indicate that the BRCT domain functions as a protein-protein interaction module.

  The structure of the first of the two C-terminal BRCT domains of the human DNA repair protein XRCC1 has recently been determined by X-ray crystallography [ (PUBMED:9799248) ].

  Structures of the BRCA1 BRCT domains revealed a basis for a widely utilised head-to-tail BRCT-BRCT oligomerisation mode [ (PUBMED:11573086) ]. This conserved tandem BRCT architecture facilitates formation of the canonical BRCT phospho-peptide interaction cleft at a groove between the BRCT domains. BRCT domains disrupt peptide binding by directly occluding this peptide binding groove, or by disrupting key conserved BRCT core folding determinants [ (PUBMED:15133503) ].

There are 72534 BRCT domains in 52588 proteins in SMART's nrdb database.

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

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)

% 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	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.
3jct	3JCT
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
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
4jlu	4JLU
4n40	4N40
4ofb	4OFB
4q66	4Q66
4u4a	4U4A
4xpz	4XPZ
4xq0	4XQ0
4y18	4Y18
4y2g	4Y2G
4yg8	4YG8
5ecg	5ECG

Links (links to other resources describing this domain)

• PFAM: BRCT
• INTERPRO: IPR001357