first 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 first BRCT domain.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 315075308  109 DVTVSCTNLDKEARSEVMDLIQLMGGRVYRDLNVSVTHLVAGEVGSKKYLVAASLGKPILLPSWVKACWEKS 180
Cdd:cd17737     1 DVTISCTSLEKEEREEVHKYVQLMGGRVSRDLTVSVTHLIAGEVGSKKYLVAASLKKPIMLPSWVKTLWEKS 72

sixth 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 sixth BRCT domain.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 315075308  910 LSGVVVCVSKKLSKKQSELNAVAASLGAEFRWSCDDSVTHYIYQGKVGDNSKEYRAVKERGLYIVSQHWLQACAD 984
Cdd:cd17727     1 LKGVVICVSKKLSKRQGELNKIAASLGAEYRWTYDESCTHFIYQGKANDTNREYKSAKEQGKFIVSPHWLYACKE 75

third 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 third BRCT domain.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315075308  357 CRVDDLLDGCKLYLCGLSGKKLEKLRRMVNTAGGLRFNQPTQELTHIVMGEADQGIKAFLDNATHRPHIVTVQWLLESFS 436
Cdd:cd17718     1 EKAGDFLDGCKIYLSGFSGAELDKLRRIINAGGGTRFNQLNESVTHVVVGESSEELLKELAKLAGRPHVVTPSWLLECFK 80

                  ...
gi 315075308  437 RGS 439
Cdd:cd17718    81 QGK 83

eighth (C-terminal) 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 eighth BRCT domain. The Trp-X-X-X-Cys/Ser signature motif of the BRCT family is not conserved in this group.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315075308 1402 GWIVMLNIDQAREAGFRRLLQSGGAKVLPD--PSPSLFKETTHLFVDFSRLKPGDvrvDISEASAHGVKCLKPEYIADYL 1479
Cdd:cd17728     1 GWKVLLVVDIAKEDGFKRLLEAGGAKVIPSspPYSLKLKDATHAFVDLTKDTSVD---LISLLAKAGVPCLKPEYIAEYL 77

                  ...
gi 315075308 1480 MQE 1482
Cdd:cd17728    78 MKD 80

first 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 first BRCT domain.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 315075308  109 DVTVSCTNLDKEARSEVMDLIQLMGGRVYRDLNVSVTHLVAGEVGSKKYLVAASLGKPILLPSWVKACWEKS 180
Cdd:cd17737     1 DVTISCTSLEKEEREEVHKYVQLMGGRVSRDLTVSVTHLIAGEVGSKKYLVAASLKKPIMLPSWVKTLWEKS 72

sixth 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 sixth BRCT domain.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 315075308  910 LSGVVVCVSKKLSKKQSELNAVAASLGAEFRWSCDDSVTHYIYQGKVGDNSKEYRAVKERGLYIVSQHWLQACAD 984
Cdd:cd17727     1 LKGVVICVSKKLSKRQGELNKIAASLGAEYRWTYDESCTHFIYQGKANDTNREYKSAKEQGKFIVSPHWLYACKE 75

third 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 third BRCT domain.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315075308  357 CRVDDLLDGCKLYLCGLSGKKLEKLRRMVNTAGGLRFNQPTQELTHIVMGEADQGIKAFLDNATHRPHIVTVQWLLESFS 436
Cdd:cd17718     1 EKAGDFLDGCKIYLSGFSGAELDKLRRIINAGGGTRFNQLNESVTHVVVGESSEELLKELAKLAGRPHVVTPSWLLECFK 80

                  ...
gi 315075308  437 RGS 439
Cdd:cd17718    81 QGK 83

eighth (C-terminal) 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 eighth BRCT domain. The Trp-X-X-X-Cys/Ser signature motif of the BRCT family is not conserved in this group.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315075308 1402 GWIVMLNIDQAREAGFRRLLQSGGAKVLPD--PSPSLFKETTHLFVDFSRLKPGDvrvDISEASAHGVKCLKPEYIADYL 1479
Cdd:cd17728     1 GWKVLLVVDIAKEDGFKRLLEAGGAKVIPSspPYSLKLKDATHAFVDLTKDTSVD---LISLLAKAGVPCLKPEYIAEYL 77

                  ...
gi 315075308 1480 MQE 1482
Cdd:cd17728    78 MKD 80

twin BRCT domain; This is a BRCT domain that appears in duplicate in most member sequences. BRCT domains are peptide- and phosphopeptide-binding modules. BRCT domains are present in a number of proteins involved in DNA checkpoint controls and DNA repair.

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 315075308   636 CVLSVSQFTGAERDSLIQLAKHLGASVQDYFVRTAnqrkgmlasTHLVLQTPEGTKYQAAQKWGLPAVTIRW 707
Cdd:pfam12738    1 LVICVTGFDGDDREGLQKLIEAMGAEYTKDLTKSV---------THLICKSGEGEKYEKAKEWGIPVVSPLW 63

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 315075308   107 MADVTVSCTNLDKEARSEVMDLIQLMGGRVYRDLNVSVTHLVAGEvGSKKYLVAASLGKPILLPSWVKACW 177
Cdd:pfam00533    6 FSGKTFVITGLDGLERDELKELIEKLGGKVTDSLSKKTTHVIVEA-RTKKYLKAKELGIPIVTEEWLLDCI 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
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 315075308  1272 FLLSSLNPQERIDYSHLIEELGGVVLEkqSFDPSCTHVIVghPLRNEKYLAAMAAGKWILHRSYLEAC 1339
Cdd:pfam00533   11 FVITGLDGLERDELKELIEKLGGKVTD--SLSKKTTHVIV--EARTKKYLKAKELGIPIVTEEWLLDC 74

breast cancer carboxy-terminal domain;

                            10        20        30        40        50        60
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 315075308   1272 FLLSSLNPQERIDYSHLIEELGGVVLEKQSfDPSCTHVIVG-HPLRNEKYLAAMAAGKWILHRSYLEAC 1339
Cdd:smart00292   10 YITGSFDKEERDELKELIEALGGKVTSSLS-SKTTTHVIVGsPEGGKLELLKAIALGIPIVKEEWLLDC 77

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 315075308   909 PLSGVVVCVSKKLSKKQSELNAVAASLGAEFRWSCDDSVTHYIyqgkVGDNSKEYRAVKERGLYIVSQHWLQAC 982
Cdd:pfam00533    5 LFSGKTFVITGLDGLERDELKELIEKLGGKVTDSLSKKTTHVI----VEARTKKYLKAKELGIPIVTEEWLLDC 74

breast cancer carboxy-terminal domain;

                            10        20        30        40        50        60        70
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 315075308    361 DLLDGCKLYLCG-LSGKKLEKLRRMVNTAGGLRFNQPTQ-ELTHIVMGEADQGIKAFLDNATHRPHIVTVQWLLESF 435
Cdd:smart00292    2 KLFKGKTFYITGsFDKEERDELKELIEALGGKVTSSLSSkTTTHVIVGSPEGGKLELLKAIALGIPIVKEEWLLDCL 78

first 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 first BRCT domain.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 315075308  109 DVTVSCTNLDKEARSEVMDLIQLMGGRVYRDLNVSVTHLVAGEVGSKKYLVAASLGKPILLPSWVKACWEKS 180
Cdd:cd17737     1 DVTISCTSLEKEEREEVHKYVQLMGGRVSRDLTVSVTHLIAGEVGSKKYLVAASLKKPIMLPSWVKTLWEKS 72

sixth 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 sixth BRCT domain.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 315075308  910 LSGVVVCVSKKLSKKQSELNAVAASLGAEFRWSCDDSVTHYIYQGKVGDNSKEYRAVKERGLYIVSQHWLQACAD 984
Cdd:cd17727     1 LKGVVICVSKKLSKRQGELNKIAASLGAEYRWTYDESCTHFIYQGKANDTNREYKSAKEQGKFIVSPHWLYACKE 75

third 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 third BRCT domain.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315075308  357 CRVDDLLDGCKLYLCGLSGKKLEKLRRMVNTAGGLRFNQPTQELTHIVMGEADQGIKAFLDNATHRPHIVTVQWLLESFS 436
Cdd:cd17718     1 EKAGDFLDGCKIYLSGFSGAELDKLRRIINAGGGTRFNQLNESVTHVVVGESSEELLKELAKLAGRPHVVTPSWLLECFK 80

                  ...
gi 315075308  437 RGS 439
Cdd:cd17718    81 QGK 83

eighth (C-terminal) 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 eighth BRCT domain. The Trp-X-X-X-Cys/Ser signature motif of the BRCT family is not conserved in this group.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315075308 1402 GWIVMLNIDQAREAGFRRLLQSGGAKVLPD--PSPSLFKETTHLFVDFSRLKPGDvrvDISEASAHGVKCLKPEYIADYL 1479
Cdd:cd17728     1 GWKVLLVVDIAKEDGFKRLLEAGGAKVIPSspPYSLKLKDATHAFVDLTKDTSVD---LISLLAKAGVPCLKPEYIAEYL 77

                  ...
gi 315075308 1480 MQE 1482
Cdd:cd17728    78 MKD 80

first BRCT domain of epithelial cell-transforming sequence 2 protein (ECT2) and similar proteins; ECT2 is a guanine nucleotide exchange factor (GEF) for Rho GTPases, phosphorylated in G2/M phases, and is involved in the regulation of cytokinesis. It contains two tandem BRCT domains. The family corresponds to the first BRCT domain.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 315075308  107 MADVTVSCTNL-DKEARSEVMDLIQLMGGRVYRDLNVSVTHLVAGEVGSKKYLVAASLGKPILLPSWVKACWEK 179
Cdd:cd17733     1 MENLVLCFTGFrKKEELSRLVNLVHHMGGSIRKDFSSKVTHLVANSTQGEKYRVAVSLGTPIMTEDWIYKAWEK 74

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 315075308  110 VTVSCTNLDKEARSEVMDLIQLMGGRVYRDLNVSVTHLVAGEV-GSKKYLVAASLGKPILLPSWVKAC 176
Cdd:cd00027     1 LVICFSGLDDEEREELKKLIEALGGKVSESLSSKVTHLIAKSPsGEKYYLAALAWGIPIVSPEWLLDC 68

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 315075308 1270 PRFLLSSLNPQERIDYSHLIEELGGVVLEkqSFDPSCTHVIVGHPLRNEKYLAAMAAGKWILHRSYLEAC 1339
Cdd:cd00027     1 LVICFSGLDDEEREELKKLIEALGGKVSE--SLSSKVTHLIAKSPSGEKYYLAALAWGIPIVSPEWLLDC 68

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 315075308  110 VTVSCTNLDKEARSEVMDLIQLMGGRVYRDLNVSVTHLVAGEVGSKKYLVAASLGK-PILLPSWVKACWEKS 180
Cdd:cd17731     6 LVICVTGFDSEERKEIQQLVEQNGGSYSPDLSKNCTHLIAGSPSGQKYEFARKWNSiHIVTPEWLYDSIEAG 77

second BRCT domain of Schizosaccharomyces pombe S-M checkpoint control protein Rad4 and similar proteins; Rad4, also termed P74, or protein cut5, is an essential component for DNA replication and the checkpoint control system which couples S and M phases. It may directly or indirectly interact with chromatin proteins to form the complex required for the initiation and/or progression of DNA synthesis. Rad4 contains four BRCT repeats. The family corresponds to the second one.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315075308  198 PVLKGCTVCVTGLSTVERKEVQRLCDQNGATYTGQLKmNECTHLIVNEPTGQKYEFARKWNVYCVSLHWLFDSIEKGFCQ 277
Cdd:cd17746     5 PTLFKCRVCLTNIGQPERSRIENYVLKHGGTFCPDLT-RDVTHLIAGTSSGRKYEYALKWKINVVCVEWLWQSIQRNAVL 83

                  ....*...
gi 315075308  278 DESRYAVE 285
Cdd:cd17746    84 EPQYFQLD 91

breast cancer carboxy-terminal domain;

                            10        20        30        40        50        60        70
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 315075308    198 PVLKGCTVCVTG-LSTVERKEVQRLCDQNGATYTGQLKMNECTHLIVNEPTGQKYEF--ARKWNVYCVSLHWLFDSI 271
Cdd:smart00292    2 KLFKGKTFYITGsFDKEERDELKELIEALGGKVTSSLSSKTTTHVIVGSPEGGKLELlkAIALGIPIVKEEWLLDCL 78

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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315075308  632 PLKDCVLSVSQFTGAERDSLIQLAKHLGASVQDYFVRTanqrkgmlaSTHLVLQTPEGTKYQAAQKWG-LPAVTIRWVLE 710
Cdd:cd17731     2 PFKGLVICVTGFDSEERKEIQQLVEQNGGSYSPDLSKN---------CTHLIAGSPSGQKYEFARKWNsIHIVTPEWLYD 72

                  ....*
gi 315075308  711 SARTG 715
Cdd:cd17731    73 SIEAG 77

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 315075308   198 PVLKGCTVCVTGLSTVERKEVQRLCDQNGATYTGQLkMNECTHLIVNEPTgQKYEFARKWNVYCVSLHWLFDSI 271
Cdd:pfam00533    4 KLFSGKTFVITGLDGLERDELKELIEKLGGKVTDSL-SKKTTHVIVEART-KKYLKAKELGIPIVTEEWLLDCI 75

fourth BRCT domain of PAX-interacting protein 1 (PAXIP1) and similar proteins; PAXIP1, also termed PAX transactivation activation domain-interacting protein (PTIP), is involved in DNA damage response and in transcriptional regulation through histone methyltransferase (HMT) complexes. It also facilitates ATM-mediated activation of p53 and promotes cellular resistance to ionizing radiation. PAXIP1 contains six BRCT repeats. This family corresponds to the fourth BRCT domain.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315075308  637 VLSVSQFTGAERDSLIQLAKHLGASVQDYFVRtanqrkgmlASTHLVLQTPEGTKYQAAQKWGLPAVTIRWVLESARTGK 716
Cdd:cd17730     2 VISVTGFDGSEREDIKRMIELMGAKYTGYLTR---------SNTHLICKRPEGEKYEKAKEWRIPVVNAQWLEDILLGGR 72

                  .
gi 315075308  717 R 717
Cdd:cd17730    73 L 73

second BRCT domain of PAX-interacting protein 1 (PAXIP1) and similar proteins; PAXIP1, also termed PAX transactivation activation domain-interacting protein (PTIP), is involved in DNA damage response and in transcriptional regulation through histone methyltransferase (HMT) complexes. It also facilitates ATM-mediated activation of p53 and promotes cellular resistance to ionizing radiation. PAXIP1 contains six BRCT repeats. This family corresponds to the second BRCT domain.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315075308  199 VLKGCTVCVTGLSTVERKEVQRLCDQNGATYTGQLKmNECTHLIVNEPTGQKYEFA-RKWNVYCVSLHWLFDSIEKGFCQ 277
Cdd:cd17710     1 LFSGVVVCPSQISAEDRLKLWAMVTFHGGKCQLNLD-KKCTHLVTGKASGAKYECAlKHEGIKIVTPDWVTDCIKAKTLL 79

                  ..
gi 315075308  278 DE 279
Cdd:cd17710    80 DE 81

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
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 315075308  1272 FLLSSLNPQERIDYSHLIEELGGVVLEkqSFDPSCTHVIVghPLRNEKYLAAMAAGKWILHRSYLEAC 1339
Cdd:pfam00533   11 FVITGLDGLERDELKELIEKLGGKVTD--SLSKKTTHVIV--EARTKKYLKAKELGIPIVTEEWLLDC 74

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        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315075308   630 FSPLKDCVLSVSQFTGAERDSLIQLAKHLGASVQDYFVRTAnqrkgmlasTHLVLqTPEGTKYQAAQKWGLPAVTIRWVL 709
Cdd:pfam00533    3 EKLFSGKTFVITGLDGLERDELKELIEKLGGKVTDSLSKKT---------THVIV-EARTKKYLKAKELGIPIVTEEWLL 72

                   ..
gi 315075308   710 ES 711
Cdd:pfam00533   73 DC 74

first BRCT domain of BRCA1-associated RING domain protein 1 (Bard1) and similar proteins; Bard1, also termed BARD-1, or RING-type E3 ubiquitin transferase BARD1, is a critical factor in BRCA1-mediated tumor suppression and may also serve as a target for tumorigenic lesions in some human cancers. It associates with BRCA1 (breast cancer-1) to form a heterodimeric BRCA1/BARD1 complex that is responsible for maintaining genomic stability through nuclear functions involving DNA damage signaling and repair, transcriptional regulation, and cell cycle control. The BRCA1/BARD1 complex catalyzes autoubiquitination of BRCA1 and trans ubiquitination of other protein substrates. Its E3 ligase activity is dramatically reduced in the presence of UBX domain protein 1 (UBXN1). BARD-1 contains an N-terminal C3HC4-type RING-HC finger that binds BRCA1, and a C-terminal region with three ankyrin repeats and tandem BRCT domains that bind CstF-50 (cleavage stimulation factor) to modulate mRNA processing and RNAP II stability in response to DNA damage. The family corresponds to the first BRCT domain.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 315075308 1272 FLLSSLNPQERIDYSHLIEELGGVVLekQSFDPSCTHVIV-----GHPLRNEKYLAAMAAGKWILHRSYLEACRAEGHFI 1346
Cdd:cd17734     3 LLGSGLSSEQKKLLEKLAQLLKAKVV--TEFSPEVTHVVVpaderGVCPRTMKYLMGILAGKWIVSFEWVEACLKAKKLV 80

second BRCT domain of microcephalin and similar proteins; Microcephalin is a DNA damage response protein involved in regulation of CHK1 and BRCA1. It has been implicated in chromosome condensation and DNA damage induced cellular responses. It may play a role in neurogenesis and regulation of the size of the cerebral cortex. Microcephalin contains three BRCT repeats. This family corresponds to the second repeat.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 315075308 1270 PRFLLSSLNPQERIDYSHLIEELGGVVLEKqSFDPSCTHVIVGHPLRNEKYLAAMAAGKWILHRSYLEACRAEGHFI 1346
Cdd:cd17736     1 RTLVMTSVHSEEQELLESVVKKLGGFRVED-SVTEKTTHVVVGSPRRTLNVLLGIARGCWILSPDWVLESLEAGKWL 76

breast cancer carboxy-terminal domain;

                            10        20        30        40        50        60
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 315075308   1272 FLLSSLNPQERIDYSHLIEELGGVVLEKQSfDPSCTHVIVG-HPLRNEKYLAAMAAGKWILHRSYLEAC 1339
Cdd:smart00292   10 YITGSFDKEERDELKELIEALGGKVTSSLS-SKTTTHVIVGsPEGGKLELLKAIALGIPIVKEEWLLDC 77

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 315075308 1270 PRFLLSSLNPQERidYSHLIEELGGVVLEKQSfdpSCTHVIVGHPLRNEKYLAAMAAGKWILHRSYLEACRAEGHFI 1346
Cdd:cd17744     1 PRVLFTGVSDKEE--GEKIIKKLGGSVVDSVE---DCTHLVTDKVRRTVKFLCALARGIPIVSPDWLEASIKANKFL 72

second BRCT domain of epithelial cell-transforming sequence 2 protein (ECT2) and similar proteins; ECT2 is a guanine nucleotide exchange factor (GEF) for Rho GTPases, phosphorylated in G2/M phases, and is involved in the regulation of cytokinesis. It contains two tandem BRCT domains. The family corresponds to the second BRCT domain.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 315075308  202 GCTVCVTGLSTVERKEVQRLCDQNGATYTgQLKMNECTHLIVNEPTGQKYEFARKWNVYCVSLHWLFDSIEKGFCQDE 279
Cdd:cd17732     4 GCTLSFLGFSDEEKTHMEELTEENGGKVT-PLGDPSCTHLVVDESTVKELPFEPSSKLHVVKQEWFWASIQMDACADE 80

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 315075308 1288 LIEELGGVVLEKQSFDpSCTHVIVGHPLRNEKYLAAMAAGKWILHRSYLEACRAEGHFIQE 1348
Cdd:cd17750    22 LLLKLDCVFIKSEKYE-NCTHLIAKKPCRSEKFLAACAAGKWILTKDYIINSAKSGRWLDE 81

twin BRCT domain; This is a BRCT domain that appears in duplicate in most member sequences. BRCT domains are peptide- and phosphopeptide-binding modules. BRCT domains are present in a number of proteins involved in DNA checkpoint controls and DNA repair.

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 315075308   110 VTVSCTNLDKEARSEVMDLIQLMGGRVYRDLNVSVTHLVAGEVGSKKYLVAASLGKPILLPSW 172
Cdd:pfam12738    1 LVICVTGFDGDDREGLQKLIEAMGAEYTKDLTKSVTHLICKSGEGEKYEKAKEWGIPVVSPLW 63