fifth 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 fifth BRCT domain.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034630952  645 PLEDCVISFSQCAGAEKESLTFLANLLGASVQEYFVRKSNAKKGMFASTHLILKERGGSKYEAAKKWNLPAVTIAWLLET 724
Cdd:cd18434      1 PLNGCVISVSQFTGTERDCLTHLAELLGAKVQDYFVRKANPSKGLLASTHLVLKEPEGSKYEAAKKWNLPAVTKSWLFEC 80

                   ....*....
gi 1034630952  725 ARTGKRADE 733
Cdd:cd18434     81 ARTGKKVPE 89

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 1034630952  353 QAPEDLLDGCRIYLCGFSGRKLDKLRRLINSGGGVRFNQLNEDVTHVIVGDYDDELKQFWNKSAHRPHVVGAKWLLECFS 432
Cdd:cd17718      1 EKAGDFLDGCKIYLSGFSGAELDKLRRIINAGGGTRFNQLNESVTHVVVGESSEELLKELAKLAGRPHVVTPSWLLECFK 80

                   ..
gi 1034630952  433 KG 434
Cdd:cd17718     81 QG 82

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 1034630952  905 LHKVVVCVSKKLSKKQSELNGIAASLGADYRWSFDETVTHFIYQGRPNDTNREYKSVKERGVHIVSEHWLLDCAQ 979
Cdd:cd17727      1 LKGVVICVSKKLSKRQGELNKIAASLGAEYRWTYDESCTHFIYQGKANDTNREYKSAKEQGKFIVSPHWLYACKE 75

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 1034630952  198 PIFLGCIICVTGLCGLDRKEVQQLTVKHGGQYMGQLKMNeCTHLIVQEPKGQKYECAKRWN-VHCVTTQWFFDSIEKG 274
Cdd:cd17731      1 PPFKGLVICVTGFDSEERKEIQQLVEQNGGSYSPDLSKN-CTHLIAGSPSGQKYEFARKWNsIHIVTPEWLYDSIEAG 77

fifth 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 fifth BRCT domain.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034630952  645 PLEDCVISFSQCAGAEKESLTFLANLLGASVQEYFVRKSNAKKGMFASTHLILKERGGSKYEAAKKWNLPAVTIAWLLET 724
Cdd:cd18434      1 PLNGCVISVSQFTGTERDCLTHLAELLGAKVQDYFVRKANPSKGLLASTHLVLKEPEGSKYEAAKKWNLPAVTKSWLFEC 80

                   ....*....
gi 1034630952  725 ARTGKRADE 733
Cdd:cd18434     81 ARTGKKVPE 89

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 1034630952  353 QAPEDLLDGCRIYLCGFSGRKLDKLRRLINSGGGVRFNQLNEDVTHVIVGDYDDELKQFWNKSAHRPHVVGAKWLLECFS 432
Cdd:cd17718      1 EKAGDFLDGCKIYLSGFSGAELDKLRRIINAGGGTRFNQLNESVTHVVVGESSEELLKELAKLAGRPHVVTPSWLLECFK 80

                   ..
gi 1034630952  433 KG 434
Cdd:cd17718     81 QG 82

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 1034630952  905 LHKVVVCVSKKLSKKQSELNGIAASLGADYRWSFDETVTHFIYQGRPNDTNREYKSVKERGVHIVSEHWLLDCAQ 979
Cdd:cd17727      1 LKGVVICVSKKLSKRQGELNKIAASLGAEYRWTYDESCTHFIYQGKANDTNREYKSAKEQGKFIVSPHWLYACKE 75

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 1034630952  198 PIFLGCIICVTGLCGLDRKEVQQLTVKHGGQYMGQLKMNeCTHLIVQEPKGQKYECAKRWN-VHCVTTQWFFDSIEKG 274
Cdd:cd17731      1 PPFKGLVICVTGFDSEERKEIQQLVEQNGGSYSPDLSKN-CTHLIAGSPSGQKYEFARKWNsIHIVTPEWLYDSIEAG 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 1034630952  195 FKCPIFLGCIICVTGLCGLDRKEVQQLTVKHGGQYMGQLkMNECTHLIVqEPKGQKYECAKRWNVHCVTTQWFFDSI 271
Cdd:pfam00533    1 PKEKLFSGKTFVITGLDGLERDELKELIEKLGGKVTDSL-SKKTTHVIV-EARTKKYLKAKELGIPIVTEEWLLDCI 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 1034630952  105 VMSDVTISCTSLEKEKREEVHKYVQMMGGRVYRDLNVSVTHLIAGEvGSKKYLVAANLKKPILLPSWIKTLW 176
Cdd:pfam00533    5 LFSGKTFVITGLDGLERDELKELIEKLGGKVTDSLSKKTTHVIVEA-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        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1034630952  355 PEDLLDGCRIYLCGFSGRKLDKLRRLINSGGGVRFNQLNEDVTHVIVgdyDDELKQFWNKSAHRPHVVGAKWLLECF 431
Cdd:pfam00533    2 KEKLFSGKTFVITGLDGLERDELKELIEKLGGKVTDSLSKKTTHVIV---EARTKKYLKAKELGIPIVTEEWLLDCI 75

breast cancer carboxy-terminal domain;

                            10        20        30        40        50        60        70
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1034630952   902 PKPLHKVVVCVSKKLSKKQ-SELNGIAASLGADYRWSFDE-TVTHFIYqGRPNDTNREYKSVKERGVHIVSEHWLLDC 977
Cdd:smart00292    1 PKLFKGKTFYITGSFDKEErDELKELIEALGGKVTSSLSSkTTTHVIV-GSPEGGKLELLKAIALGIPIVKEEWLLDC 77

breast cancer carboxy-terminal domain;

                            10        20        30        40        50        60        70
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1034630952   105 VMSDVTISCTS-LEKEKREEVHKYVQMMGGRVYRDLN-VSVTHLIAG--EVGSKKYLVAANLKKPILLPSWIKTLW 176
Cdd:smart00292    3 LFKGKTFYITGsFDKEERDELKELIEALGGKVTSSLSsKTTTHVIVGspEGGKLELLKAIALGIPIVKEEWLLDCL 78

breast cancer carboxy-terminal domain;

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034630952   643 MTPLEDCVISFS-QCAGAEKESLTFLANLLGASVQEYFVRKSNakkgmfasTHLILKERGGSKYE--AAKKWNLPAVTIA 719
Cdd:smart00292    1 PKLFKGKTFYITgSFDKEERDELKELIEALGGKVTSSLSSKTT--------THVIVGSPEGGKLEllKAIALGIPIVKEE 72

                    ....
gi 1034630952   720 WLLE 723
Cdd:smart00292   73 WLLD 76

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 1034630952  550 EGLFSQKSFLVLGFSNENESNIANIIKENAGKIMSLLSRTVADYAVVPLLG--CEVEATVGEVVTNTWLVTCI 620
Cdd:pfam00533    3 EKLFSGKTFVITGLDGLERDELKELIEKLGGKVTDSLSKKTTHVIVEARTKkyLKAKELGIPIVTEEWLLDCI 75

fifth 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 fifth BRCT domain.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034630952  645 PLEDCVISFSQCAGAEKESLTFLANLLGASVQEYFVRKSNAKKGMFASTHLILKERGGSKYEAAKKWNLPAVTIAWLLET 724
Cdd:cd18434      1 PLNGCVISVSQFTGTERDCLTHLAELLGAKVQDYFVRKANPSKGLLASTHLVLKEPEGSKYEAAKKWNLPAVTKSWLFEC 80

                   ....*....
gi 1034630952  725 ARTGKRADE 733
Cdd:cd18434     81 ARTGKKVPE 89

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 1034630952  353 QAPEDLLDGCRIYLCGFSGRKLDKLRRLINSGGGVRFNQLNEDVTHVIVGDYDDELKQFWNKSAHRPHVVGAKWLLECFS 432
Cdd:cd17718      1 EKAGDFLDGCKIYLSGFSGAELDKLRRIINAGGGTRFNQLNESVTHVVVGESSEELLKELAKLAGRPHVVTPSWLLECFK 80

                   ..
gi 1034630952  433 KG 434
Cdd:cd17718     81 QG 82

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 1034630952  905 LHKVVVCVSKKLSKKQSELNGIAASLGADYRWSFDETVTHFIYQGRPNDTNREYKSVKERGVHIVSEHWLLDCAQ 979
Cdd:cd17727      1 LKGVVICVSKKLSKRQGELNKIAASLGAEYRWTYDESCTHFIYQGKANDTNREYKSAKEQGKFIVSPHWLYACKE 75

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 1034630952  198 PIFLGCIICVTGLCGLDRKEVQQLTVKHGGQYMGQLKMNeCTHLIVQEPKGQKYECAKRWN-VHCVTTQWFFDSIEKG 274
Cdd:cd17731      1 PPFKGLVICVTGFDSEERKEIQQLVEQNGGSYSPDLSKN-CTHLIAGSPSGQKYEFARKWNsIHIVTPEWLYDSIEAG 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 1034630952  195 FKCPIFLGCIICVTGLCGLDRKEVQQLTVKHGGQYMGQLkMNECTHLIVqEPKGQKYECAKRWNVHCVTTQWFFDSI 271
Cdd:pfam00533    1 PKEKLFSGKTFVITGLDGLERDELKELIEKLGGKVTDSL-SKKTTHVIV-EARTKKYLKAKELGIPIVTEEWLLDCI 75

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 1034630952  203 CIICVTGLCGLDRKEVQQLTVKHGGQYMGQLKmNECTHLIVQEPKGQKYECAKRWNVHCVTTQW 266
Cdd:pfam12738    1 LVICVTGFDGDDREGLQKLIEAMGAEYTKDLT-KSVTHLICKSGEGEKYEKAKEWGIPVVSPLW 63

breast cancer carboxy-terminal domain;

                            10        20        30        40        50        60        70
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1034630952   198 PIFLGCIICVTG-LCGLDRKEVQQLTVKHGGQYMGQLKMNECTHLIVQEPKGQKYEC--AKRWNVHCVTTQWFFDSI 271
Cdd:smart00292    2 KLFKGKTFYITGsFDKEERDELKELIEALGGKVTSSLSSKTTTHVIVGSPEGGKLELlkAIALGIPIVKEEWLLDCL 78

first 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 the 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 first one.

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1034630952  104 MVMSDVTISCTSLEKEKREEVHKYVQMMGGRVYRDLNVSVTHLIAGEVGSKKYLVAANLKK--PILLPSWIKTLWEKSQ 180
Cdd:cd17740      1 KPLSGIVLCCTSIPAEQRTEIATKASKMGAAYTADLTSDVTHLVAGQVNTTKYKFAARSRPdiKVMTVEWVEHLYESWQ 79

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 1034630952  198 PIFLGCIICVTGLCGLDRKEVQQLTVKHGGQYMGQLKmNECTHLIVQEPKGQKYECAKRWNVHCVTTQWFFDSIEKGFCQ 277
Cdd:cd17746      5 PTLFKCRVCLTNIGQPERSRIENYVLKHGGTFCPDLT-RDVTHLIAGTSSGRKYEYALKWKINVVCVEWLWQSIQRNAVL 83

                   ....*.
gi 1034630952  278 DESIYK 283
Cdd:cd17746     84 EPQYFQ 89

fifth 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 fifth BRCT domain.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034630952  202 GCIICVTGLCGLDRKEVQQLTVKHGG--QYMGQLKMNE------CTHLIVQEPKGQKYECAKRWNVHCVTTQWFFDSIEK 273
Cdd:cd18434      4 GCVISVSQFTGTERDCLTHLAELLGAkvQDYFVRKANPskgllaSTHLVLKEPEGSKYEAAKKWNLPAVTKSWLFECART 83

                   .
gi 1034630952  274 G 274
Cdd:cd18434     84 G 84

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 1034630952  106 MSDVTISCTSLEKekREEVHKYVQM---MGGRVYRDLNVSVTHLIAGEVGSKKYLVAANLKKPILLPSWIKTLWEK 178
Cdd:cd17733      1 MENLVLCFTGFRK--KEELSRLVNLvhhMGGSIRKDFSSKVTHLVANSTQGEKYRVAVSLGTPIMTEDWIYKAWEK 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
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1034630952  902 PKPLHKVVVCVSKKLSKKQSELNGIAASLGADYRWSFDETVTHFIYqgrpNDTNREYKSVKERGVHIVSEHWLLDC 977
Cdd:pfam00533    3 EKLFSGKTFVITGLDGLERDELKELIEKLGGKVTDSLSKKTTHVIV----EARTKKYLKAKELGIPIVTEEWLLDC 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        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034630952  908 VVVCVSKKLSKKQSELNGIAASLGADYRWSFDETVTHFIYqgRPNDTNREYKSVKERGVHIVSEHWLLDC 977
Cdd:cd00027      1 LVICFSGLDDEEREELKKLIEALGGKVSESLSSKVTHLIA--KSPSGEKYYLAALAWGIPIVSPEWLLDC 68

breast cancer carboxy-terminal domain;

                            10        20        30        40        50        60        70
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1034630952   902 PKPLHKVVVCVSKKLSKKQ-SELNGIAASLGADYRWSFDE-TVTHFIYqGRPNDTNREYKSVKERGVHIVSEHWLLDC 977
Cdd:smart00292    1 PKLFKGKTFYITGSFDKEErDELKELIEALGGKVTSSLSSkTTTHVIV-GSPEGGKLELLKAIALGIPIVKEEWLLDC 77

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 1034630952  650 VISFSQCAGAEKESLTFLANLLGASVQEYFVRKSnakkgmfasTHLILKERGGSKYEAAKKWNLPAVTIAWLLETARTGK 729
Cdd:cd17730      2 VISVTGFDGSEREDIKRMIELMGAKYTGYLTRSN---------THLICKRPEGEKYEKAKEWRIPVVNAQWLEDILLGGR 72

                   .
gi 1034630952  730 R 730
Cdd:cd17730     73 L 73

breast cancer carboxy-terminal domain;

                            10        20        30        40        50        60        70
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1034630952   105 VMSDVTISCTS-LEKEKREEVHKYVQMMGGRVYRDLN-VSVTHLIAG--EVGSKKYLVAANLKKPILLPSWIKTLW 176
Cdd:smart00292    3 LFKGKTFYITGsFDKEERDELKELIEALGGKVTSSLSsKTTTHVIVGspEGGKLELLKAIALGIPIVKEEWLLDCL 78

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 1034630952  649 CVISFSQCAGAEKESLTFLANLLGASVQEYFVRKsnakkgmfaSTHLILKERGGSKY-EAAKKWNLPAVTIAWLLE 723
Cdd:cd00027      1 LVICFSGLDDEEREELKKLIEALGGKVSESLSSK---------VTHLIAKSPSGEKYyLAALAWGIPIVSPEWLLD 67

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 1034630952  643 MTPLEDCVISFSQCAGAEKESLTFLANLLGASVQEYFVRKSnakkgmfasTHLILkERGGSKYEAAKKWNLPAVTIAWLL 722
Cdd:pfam00533    3 EKLFSGKTFVITGLDGLERDELKELIEKLGGKVTDSLSKKT---------THVIV-EARTKKYLKAKELGIPIVTEEWLL 72

                   .
gi 1034630952  723 E 723
Cdd:pfam00533   73 D 73

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 1034630952 1262 EELKKQYIFQLSSLNPQERIDYCHLIEKLGGLVIEkqCFDPTCTHIVVghPLRNEKYLASVAAGKWVLHRSYLEAC 1337
Cdd:pfam00533    3 EKLFSGKTFVITGLDGLERDELKELIEKLGGKVTD--SLSKKTTHVIV--EARTKKYLKAKELGIPIVTEEWLLDC 74

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 1034630952 1266 KQYIFQLSSLNPQERIDYCHLIEKLGGLVIEKQCFDpTCTHIVVGHPLRNEKYLASVAAGKWVLHRSYLEACRTAGHFVQ 1345
Cdd:cd17750      2 QKHIIQLTGFKGEEKEALVKLLLKLDCVFIKSEKYE-NCTHLIAKKPCRSEKFLAACAAGKWILTKDYIINSAKSGRWLD 80

                   .
gi 1034630952 1346 E 1346
Cdd:cd17750     81 E 81

breast cancer carboxy-terminal domain;

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034630952   643 MTPLEDCVISFS-QCAGAEKESLTFLANLLGASVQEYFVRKSNakkgmfasTHLILKERGGSKYE--AAKKWNLPAVTIA 719
Cdd:smart00292    1 PKLFKGKTFYITgSFDKEERDELKELIEALGGKVTSSLSSKTT--------THVIVGSPEGGKLEllKAIALGIPIVKEE 72

                    ....
gi 1034630952   720 WLLE 723
Cdd:smart00292   73 WLLD 76

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
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1034630952 1273 SSLNPQERIDYCHLIEKLGGLVIEKqcFDPTCTHIVV-----GHPLRNEKYLASVAAGKWVLHRSYLEACRTAGHFV 1344
Cdd:cd17734      6 SGLSSEQKKLLEKLAQLLKAKVVTE--FSPEVTHVVVpaderGVCPRTMKYLMGILAGKWIVSFEWVEACLKAKKLV 80

First (central) BRCT domain in X-ray repair cross-complementing protein 1 (XRCC1) and similar proteins; XRCC1 is a DNA repair protein that corrects defective DNA strand-break repair and sister chromatid exchange following treatment with ionizing radiation and alkylating agents. It forms homodimers and interacts with polynucleotide kinase (PNK), DNA polymerase-beta (POLB), DNA ligase III (LIG3), APTX, APLF, and APEX1. XRCC1 contains an N-terminal XRCC1-specific domain and two BRCT domains. This family corresponds to the first one.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034630952  907 KVVVCVSKKLSKKQSELNGIAASLGADYRWSFDETVTHFI--YQGRPndtnrEYKSVKERGVHIVSEHWLLDCAQECKHL 984
Cdd:cd17725      1 GVVFVLSGFQNPFRGELRDKALEMGAKYRPDWTADCTHLIcaFANTP-----KYKQVKGAGGIIVSKEWILDCYKKKKRL 75