seventh BRCT domain of DNA topoisomerase 2-binding protein 1; TopBP1, also termed DNA topoisomerase II-beta-binding protein 1, or DNA topoisomerase II-binding protein 1, functions in DNA replication and damage response. It binds double-stranded DNA breaks and nicks as well as single-stranded DNA. TopBP1 contains six copies of BRCT domain. The family corresponds to the seventh BRCT domain. The Trp-X-X-X-Cys/Ser signature motif of the BRCT family is missing in this group.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 313103562   9 QYIFQLSSLNPQERIDYCHLIEKLGGLVIEKQCFDPTCTHIVVGHPLRNEKYLASVAAGKWVLHRSYLEACRTAG 83
Cdd:cd17738    1 KPVFLLSGFSEDEKKELISIIEKLGGKVLDSDEFDPKCTHLICGKPSRSEKFLAACAAGKWILHPSYIEASAKAG 75

seventh BRCT domain of DNA topoisomerase 2-binding protein 1; TopBP1, also termed DNA topoisomerase II-beta-binding protein 1, or DNA topoisomerase II-binding protein 1, functions in DNA replication and damage response. It binds double-stranded DNA breaks and nicks as well as single-stranded DNA. TopBP1 contains six copies of BRCT domain. The family corresponds to the seventh BRCT domain. The Trp-X-X-X-Cys/Ser signature motif of the BRCT family is missing in this group.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 313103562   9 QYIFQLSSLNPQERIDYCHLIEKLGGLVIEKQCFDPTCTHIVVGHPLRNEKYLASVAAGKWVLHRSYLEACRTAG 83
Cdd:cd17738    1 KPVFLLSGFSEDEKKELISIIEKLGGKVLDSDEFDPKCTHLICGKPSRSEKFLAACAAGKWILHPSYIEASAKAG 75

BRCA1 C Terminus (BRCT) domain; The BRCT domain is found predominantly in proteins involved in cell cycle checkpoint functions responsive to DNA damage. The BRCT domain of XRCC1 forms a homodimer in the crystal structure. This suggests that pairs of BRCT domains associate as homo- or heterodimers. BRCT domains are often found as tandem-repeat pairs. Structures of the BRCA1 BRCT domains revealed a basis for a widely utilized head-to-tail BRCT-BRCT oligomerization mode. This conserved tandem BRCT architecture facilitates formation of the canonical BRCT phospho-peptide interaction cleft at a groove between the BRCT domains. Disease associated missense and nonsense mutations in the BRCA1 BRCT domains disrupt peptide binding by directly occluding this peptide binding groove, or by disrupting key conserved BRCT core folding determinants.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 313103562    2 PLGSLKKQYIFQLSSLNPQERIDYCHLIEKLGGLVIEkqCFDPTCTHIVVghPLRNEKYLASVAAGKWVLHRSYLEAC 79
Cdd:pfam00533   1 PKEKLFSGKTFVITGLDGLERDELKELIEKLGGKVTD--SLSKKTTHVIV--EARTKKYLKAKELGIPIVTEEWLLDC 74

seventh BRCT domain of DNA topoisomerase 2-binding protein 1; TopBP1, also termed DNA topoisomerase II-beta-binding protein 1, or DNA topoisomerase II-binding protein 1, functions in DNA replication and damage response. It binds double-stranded DNA breaks and nicks as well as single-stranded DNA. TopBP1 contains six copies of BRCT domain. The family corresponds to the seventh BRCT domain. The Trp-X-X-X-Cys/Ser signature motif of the BRCT family is missing in this group.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 313103562   9 QYIFQLSSLNPQERIDYCHLIEKLGGLVIEKQCFDPTCTHIVVGHPLRNEKYLASVAAGKWVLHRSYLEACRTAG 83
Cdd:cd17738    1 KPVFLLSGFSEDEKKELISIIEKLGGKVLDSDEFDPKCTHLICGKPSRSEKFLAACAAGKWILHPSYIEASAKAG 75

C-terminal domain of the breast cancer suppressor protein (BRCA1) and related domains; The BRCT (BRCA1 C-terminus) domain is found within many DNA damage repair and cell cycle checkpoint proteins. BRCT domains interact with each other forming homo/hetero BRCT multimers, but are also involved in BRCT-non-BRCT interactions and interactions within DNA strand breaks. BRCT tandem repeats bind to phosphopeptides; it has been shown that the repeats in human BRCA1 bind specifically to pS-X-X-F motifs, mediating the interaction between BRCA1 and the DNA helicase BACH1, or BRCA1 and CtIP, a transcriptional corepressor. It is assumed that BRCT repeats play similar roles in many signaling pathways associated with the response to DNA damage.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 313103562  10 YIFQLSSLNPQERIDYCHLIEKLGGLVIEKqcFDPTCTHIVVGHPLRNEKYLASVAAGKWVLHRSYLEAC 79
Cdd:cd00027    1 LVICFSGLDDEEREELKKLIEALGGKVSES--LSSKVTHLIAKSPSGEKYYLAALAWGIPIVSPEWLLDC 68

BRCT domain of SMC5-SMC6 complex localization factor protein 1 (SLF1) and similar proteins; SLF1, also termed Smc5/6 localization factor 1, or ankyrin repeat domain-containing protein 32 (ANKRD32), or BRCT domain-containing protein 1 (BRCTD1), plays a role in the DNA damage response (DDR) pathway by regulating post replication repair of UV-damaged DNA and genomic stability maintenance. It is a component of the SLF1-SLF2 complex that acts to link RAD18 with the SMC5-SMC6 complex at replication-coupled interstrand cross-links (ICL) and DNA double-strand break (DSB) sites on chromatin during DNA repair in response to stalled replication forks. The Trp-X-X-X-Cys/Ser signature motif of the BRCT family is missing in this group.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 313103562   8 KQYIFQLSSLNPQERIDYCHLIEKLGGLVIEKQCFDpTCTHIVVGHPLRNEKYLASVAAGKWVLHRSYLEACRTAGHFVQ 87
Cdd:cd17750    2 QKHIIQLTGFKGEEKEALVKLLLKLDCVFIKSEKYE-NCTHLIAKKPCRSEKFLAACAAGKWILTKDYIINSAKSGRWLD 80

                 .
gi 313103562  88 E 88
Cdd:cd17750   81 E 81

first BRCT domain of mediator of DNA damage checkpoint protein 1 (MDC1) and similar proteins; MDC1, also termed nuclear factor with BRCT domains 1 (NFBD1), is a nuclear chromatin-associated protein that is required for checkpoint mediated cell cycle arrest in response to DNA damage within both the S phase and G2/M phases of the cell cycle. It directly binds phosphorylated histone H2AX to regulate cellular responses to DNA double-strand breaks. MDC1 contains a forkhead-associated (FHA) domain and two BRCT domains, as well as an internal 41-amino acid repeat sequence. The family corresponds to the first BRCT domain.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 313103562  14 LSSLNPQERIdychlIEKLGGLVIEKQCfdpTCTHIVVGHPLRNEKYLASVAAGKWVLHRSYLEACRTAGHFV 86
Cdd:cd17744    8 VSDKEEGEKI-----IKKLGGSVVDSVE---DCTHLVTDKVRRTVKFLCALARGIPIVSPDWLEASIKANKFL 72

breast cancer carboxy-terminal domain;

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 313103562     6 LKKQYIFQLSS-LNPQERIDYCHLIEKLGGLVIEKQCfDPTCTHIVVG-HPLRNEKYLASVAAGKWVLHRSYLEAC 79
Cdd:smart00292   3 LFKGKTFYITGsFDKEERDELKELIEALGGKVTSSLS-SKTTTHVIVGsPEGGKLELLKAIALGIPIVKEEWLLDC 77

first BRCT domain of breast cancer type 1 susceptibility protein (BRCA1) and similar proteins; BRCA1, also termed RING finger protein 53 (RNF53), is a RING finger protein encoded by BRCA1, a tumor suppressor gene that regulates all DNA double-strand break (DSB) repair pathways. BRCA1 is frequently mutated in patients with hereditary breast and ovarian cancer (HBOC). Its mutation is also associated with an increased risk of pancreatic, stomach, laryngeal, fallopian tube, and prostate cancer. It plays an important role in the DNA damage response signaling, and has been implicated in various cellular processes such as cell cycle regulation, transcriptional regulation, chromatin remodeling, DNA DSBs, and apoptosis. BRCA1 contains an N-terminal C3HC4-type RING-HC finger, and two BRCT (BRCA1 C-terminus domain) repeats at the C-terminus. The family corresponds to the first BRCT domain.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 313103562  15 SSLNPQERIDYCHLIEKLGGLVieKQCFDPTCTHIVV--GHPL---RNEKYLASVAAGKWVLHRSYLEACRTAGHFVQEE 89
Cdd:cd17735    6 SGLTPEELMLVQKFARKTGSTL--TSQFTEETTHVIMktDAELvceRTLKYFLGIAGRKWVVSYQWITQSIKEGKILPEH 83

                         90
                 ....*....|....*..
gi 313103562  90 DYEWGSssilDVLTGIN 106
Cdd:cd17735   84 DFEVRG----DVVNGRN 96

fifth BRCT domain of Schizosaccharomyces pombe BRCT-containing protein 1 (BRC1) and similar proteins; Schizosaccharomyces pombe BRC1 is required for mitotic fidelity, specifically in the G2 phase of the cell cycle. It plays a role in chromatin organization. The family also includes Cryptococcus neoformans DNA ligase 4 (LIG4, also known as DNA ligase IV or polydeoxyribonucleotide synthase [ATP] 4), which is involved in dsDNA break repair, and plays a role in non-homologous integration (NHI) pathways where it is required in the final step of non-homologus end-joining. Members in this family contain six BRCT domains. This family corresponds to the fifth one.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 313103562  29 IEKLGGLVIEKqcfDPTCTHIVVGHPLRNEKYLASVAAGKWVLHRSYLEAC 79
Cdd:cd17743   19 LKKLGISIVED---PDECTHLVAPKIVRTEKFLCALAYAPVIVTTDWLEAC 66

second BRCT domain of DNA topoisomerase 2-binding protein 1 (TopBP1) and similar proteins; TopBP1, also termed DNA topoisomerase II-beta-binding protein 1, or DNA topoisomerase II-binding protein 1, functions in DNA replication and damage response. It binds double-stranded DNA breaks and nicks as well as single-stranded DNA. TopBP1 contains six copies of BRCT domain. The family corresponds to the second BRCT domain.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 313103562  14 LSSLNPQERIDYCHLIEKLGGlVIEKQcFDPTCTHIVVGHPlRNEKYLasvAAGKW----VLHRSYLEACRTAG 83
Cdd:cd17731   10 VTGFDSEERKEIQQLVEQNGG-SYSPD-LSKNCTHLIAGSP-SGQKYE---FARKWnsihIVTPEWLYDSIEAG 77