sixth 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 sixth BRCT domain. The Trp-X-X-X-Cys/Ser signature motif of the BRCT family is not conserved in this family.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 93141033  972 LFKAKYFYITPGICPSLSTMKAIVECAGGKVLSKQPSFRKLMEhKQNSSLSEIILISCENDLHLCREYFARGIDVHNAEF 1051
Cdd:cd18440    1 LFKGKYFYITPGVKPSPSVLKEIIESAGGKVEKKRPSLKKIME-KNNQGPPSYIIITCENDLHLCRDLFRKNIDVYNAEF 79

                         90
                 ....*....|.
gi 93141033 1052 VLTGVLTQTLD 1062
Cdd:cd18440   80 ILTGVLRQKLD 90

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 93141033  709 HIISVTGFVDSDRDDLKLMAYLAGAKYTGYLCRSNTVLICKEPTGLKYEKAKEWRIPCVNAQWLGDILLGNFE 781
Cdd:cd17730    1 QVISVTGFDGSEREDIKRMIELMGAKYTGYLTRSNTHLICKRPEGEKYEKAKEWRIPVVNAQWLEDILLGGRL 73

third 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 third BRCT domain.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 93141033  608 GCVFAIADYPEQMSDkQLLATWKRIIQAHGGTVDPTFTSRCTHLLCESQVSSAYAQAIRERKRCVTAHWLNTVLKKKKMV 687
Cdd:cd17711    1 GCVFFIADYPEQMGD-QEIATWKKVIEEHGGEVVDEYSPRVTHVICESQDSPEYQQALRDGKRVVTAYWLNDVLKRGKLL 79

                 ..
gi 93141033  688 PP 689
Cdd:cd17711   80 PP 81

sixth 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 sixth BRCT domain. The Trp-X-X-X-Cys/Ser signature motif of the BRCT family is not conserved in this family.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 93141033  972 LFKAKYFYITPGICPSLSTMKAIVECAGGKVLSKQPSFRKLMEhKQNSSLSEIILISCENDLHLCREYFARGIDVHNAEF 1051
Cdd:cd18440    1 LFKGKYFYITPGVKPSPSVLKEIIESAGGKVEKKRPSLKKIME-KNNQGPPSYIIITCENDLHLCRDLFRKNIDVYNAEF 79

                         90
                 ....*....|.
gi 93141033 1052 VLTGVLTQTLD 1062
Cdd:cd18440   80 ILTGVLRQKLD 90

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 93141033  709 HIISVTGFVDSDRDDLKLMAYLAGAKYTGYLCRSNTVLICKEPTGLKYEKAKEWRIPCVNAQWLGDILLGNFE 781
Cdd:cd17730    1 QVISVTGFDGSEREDIKRMIELMGAKYTGYLTRSNTHLICKRPEGEKYEKAKEWRIPVVNAQWLEDILLGGRL 73

third 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 third BRCT domain.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 93141033  608 GCVFAIADYPEQMSDkQLLATWKRIIQAHGGTVDPTFTSRCTHLLCESQVSSAYAQAIRERKRCVTAHWLNTVLKKKKMV 687
Cdd:cd17711    1 GCVFFIADYPEQMGD-QEIATWKKVIEEHGGEVVDEYSPRVTHVICESQDSPEYQQALRDGKRVVTAYWLNDVLKRGKLL 79

                 ..
gi 93141033  688 PP 689
Cdd:cd17711   80 PP 81

Regulator of Ty1 transposition protein 107 BRCT domain; This is the fifth BRCT domain of regulator of Ty1 transposition protein 107 (RTT107). It is involved in binding phosphorylated histone H2A.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 93141033    859 KKLTPELTPFVLFTGFE--PVQVQQYIKKLYILGGEVAESAQKCTHLIASKVTRTVKFLTAISVVKHIVTPEWLEECFRC 936
Cdd:pfam16770    1 KKSLPPYDIRAVLTGCErwIDKEDLDKKKLRLLGIKIVQDPSKCNHLIAPKILRTEKFLCALAFAPYILSPDFITDCLKE 80

                           90
                   ....*....|.
gi 93141033    937 QKFIDEQNYIL 947
Cdd:pfam16770   81 GKLPDEEDYLL 91

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 93141033    102 ITACLSQVSSEDRSALWALVTFYGGDCQLTLNKKCTHLIVPEPKGEKYECALKRAsIKIVTPDW 165
Cdd:pfam12738    1 LVICVTGFDGDDREGLQKLIEAMGAEYTKDLTKSVTHLICKSGEGEKYEKAKEWG-IPVVSPLW 63

breast cancer carboxy-terminal domain;

                            10        20        30        40        50        60        70
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 93141033     704 KPCSQHIISVTG-FVDSDRDDLKLMAYLAGAKYTGYLCR-SNTVLICKEPTG--LKYEKAKEWRIPCVNAQWLGDIL 776
Cdd:smart00292    2 KLFKGKTFYITGsFDKEERDELKELIEALGGKVTSSLSSkTTTHVIVGSPEGgkLELLKAIALGIPIVKEEWLLDCL 78

breast cancer carboxy-terminal domain;

                            10        20        30        40        50        60        70
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 93141033     868 FVLFTGFEPVQVQQYIKKLYILGGEVAESAQK--CTHLIASKV-TRTVKFLTAISVVKHIVTPEWLEECF 934
Cdd:smart00292    9 FYITGSFDKEERDELKELIEALGGKVTSSLSSktTTHVIVGSPeGGKLELLKAIALGIPIVKEEWLLDCL 78

breast cancer carboxy-terminal domain;

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 93141033     970 SPLFKAKYFYITPGIC-PSLSTMKAIVECAGGKVLSKQPSFrklmehkqnsSLSEIILISCENDLHLCREYFARGIDVHN 1048
Cdd:smart00292    1 PKLFKGKTFYITGSFDkEERDELKELIEALGGKVTSSLSSK----------TTTHVIVGSPEGGKLELLKAIALGIPIVK 70

                    ....*
gi 93141033    1049 AEFVL 1053
Cdd:smart00292   71 EEWLL 75

sixth 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 sixth BRCT domain. The Trp-X-X-X-Cys/Ser signature motif of the BRCT family is not conserved in this family.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 93141033  972 LFKAKYFYITPGICPSLSTMKAIVECAGGKVLSKQPSFRKLMEhKQNSSLSEIILISCENDLHLCREYFARGIDVHNAEF 1051
Cdd:cd18440    1 LFKGKYFYITPGVKPSPSVLKEIIESAGGKVEKKRPSLKKIME-KNNQGPPSYIIITCENDLHLCRDLFRKNIDVYNAEF 79

                         90
                 ....*....|.
gi 93141033 1052 VLTGVLTQTLD 1062
Cdd:cd18440   80 ILTGVLRQKLD 90

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 93141033  709 HIISVTGFVDSDRDDLKLMAYLAGAKYTGYLCRSNTVLICKEPTGLKYEKAKEWRIPCVNAQWLGDILLGNFE 781
Cdd:cd17730    1 QVISVTGFDGSEREDIKRMIELMGAKYTGYLTRSNTHLICKRPEGEKYEKAKEWRIPVVNAQWLEDILLGGRL 73

third 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 third BRCT domain.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 93141033  608 GCVFAIADYPEQMSDkQLLATWKRIIQAHGGTVDPTFTSRCTHLLCESQVSSAYAQAIRERKRCVTAHWLNTVLKKKKMV 687
Cdd:cd17711    1 GCVFFIADYPEQMGD-QEIATWKKVIEEHGGEVVDEYSPRVTHVICESQDSPEYQQALRDGKRVVTAYWLNDVLKRGKLL 79

                 ..
gi 93141033  688 PP 689
Cdd:cd17711   80 PP 81

sixth BRCT domain of PAX-interacting protein 1 (PAXIP1), second BRCT domain of mediator of DNA damage checkpoint protein 1 (MDC1) 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. 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 sixth BRCT domain of PAXIP1 and the second BRCT domain of MDC1.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 93141033  972 LFKAKYFYITPGICPSLSTMKAIVECAGGKVLSKQPSFRklmehkQNSSLSEIILISCENDLHLCREYFARGIDVHNAEF 1051
Cdd:cd18432    1 LFEGYTFYVTPNVKPPPEELKEIIEAAGGKVLKKLPTKR------IEDDDPDTIVISCEEDRKLWKPLKKKGIPIYSVEF 74

                         90
                 ....*....|.
gi 93141033 1052 VLTGVLTQTLD 1062
Cdd:cd18432   75 ILTGILRQKLD 85

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 93141033    710 IISVTGFVDSDRDDLKLMAYLAGAKYTGYLCRSNTVLICKEPTGLKYEKAKEWRIPCVNAQW 771
Cdd:pfam12738    2 VICVTGFDGDDREGLQKLIEAMGAEYTKDLTKSVTHLICKSGEGEKYEKAKEWGIPVVSPLW 63

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 93141033  867 PFVLFTGFEPVQvqQYIKKLYILGGEVAESAQKCTHLIASKVTRTVKFLTAISVVKHIVTPEWLEECFRCQKFI 940
Cdd:cd17744    1 PRVLFTGVSDKE--EGEKIIKKLGGSVVDSVEDCTHLVTDKVRRTVKFLCALARGIPIVSPDWLEASIKANKFL 72

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 93141033    102 ITACLSQVSSEDRSALWALVTFYGGDCQLTLNKKCTHLIVPEPKGEKYECALKRAsIKIVTPDW 165
Cdd:pfam12738    1 LVICVTGFDGDDREGLQKLIEAMGAEYTKDLTKSVTHLICKSGEGEKYEKAKEWG-IPVVSPLW 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 93141033    704 KPCSQHIISVTGFVDSDRDDLKLMAYLAGAKYTGYLCRSNTVLICKEPTgLKYEKAKEWRIPCVNAQWLGDIL 776
Cdd:pfam00533    4 KLFSGKTFVITGLDGLERDELKELIEKLGGKVTDSLSKKTTHVIVEART-KKYLKAKELGIPIVTEEWLLDCI 75

second 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 contains six BRCT domains. This family corresponds to the second repeat.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 93141033   99 FFGITACLSQVSSEDRSALWALVTFYGGDCQLTLNKKCTHLIVPEPKGEKYECALKRAS--IKIVTPDWVLDCV 170
Cdd:cd18436    1 FSGVVITCSDLPSGDKEAIYGGVLALGGQYSDELTRDVTHLIALSPDGDKYKTALKRPElnIKIVLPHWFDDCF 74

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 93141033  710 IISVTGFVDSDRDDLKLMAYLAGAKYTGYLCR---------SNTVLICKEPTGLKYEKAKEWRIPCVNAQWL 772
Cdd:cd18434    6 VISVSQFTGTERDCLTHLAELLGAKVQDYFVRkanpskgllASTHLVLKEPEGSKYEAAKKWNLPAVTKSWL 77

fourth 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. Members in this family contains six BRCT domains. This family corresponds to the fourth repeat.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 93141033  710 IISVTGFVDSDRDDLKLMAYLAGAKYTGYLCRSNTVLICKEPTGLKYEKAKEWRIPCVNAQWLGD 774
Cdd:cd18438    2 KITITNYTGAARQYLEKLILALGATYTKNLKPDNTHLITASPEGEKYEAAKEWNIPIVNHLWLYD 66

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 93141033  710 IISVTGFVDSDRDDLKLMAYLAGAKYTGYLCRSNTVLICKEPTGLKY-EKAKEWRIPCVNAQWL 772
Cdd:cd00027    2 VICFSGLDDEEREELKKLIEALGGKVSESLSSKVTHLIAKSPSGEKYyLAALAWGIPIVSPEWL 65

breast cancer carboxy-terminal domain;

                            10        20        30        40        50        60        70
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 93141033      98 IFFGITACLSQV-SSEDRSALWALVTFYGGDCQLTLNKK-CTHLIVPEPKGEKYECALKRAS-IKIVTPDWVLDCV 170
Cdd:smart00292    3 LFKGKTFYITGSfDKEERDELKELIEALGGKVTSSLSSKtTTHVIVGSPEGGKLELLKAIALgIPIVKEEWLLDCL 78

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 93141033     98 IFFGITACLSQVSSEDRSALWALVTFYGGDCQLTLNKKCTHLIVpEPKGEKYECALKRaSIKIVTPDWVLDCV 170
Cdd:pfam00533    5 LFSGKTFVITGLDGLERDELKELIEKLGGKVTDSLSKKTTHVIV-EARTKKYLKAKEL-GIPIVTEEWLLDCI 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 93141033  105 CLSQVSSEDRSALWALVTFYGGDCQLTLNKK---------CTHLIVPEPKGEKYECAlKRASIKIVTPDWVLDCVSEKTK 175
Cdd:cd18434    8 SVSQFTGTERDCLTHLAELLGAKVQDYFVRKanpskgllaSTHLVLKEPEGSKYEAA-KKWNLPAVTKSWLFECARTGKK 86

                 ...
gi 93141033  176 KDE 178
Cdd:cd18434   87 VPE 89

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 93141033    869 VLFTGFEPVQVQQYIKKLYILGGEVAESA-QKCTHLIAskVTRTVKFLTAISVVKHIVTPEWLEECF 934
Cdd:pfam00533   11 FVITGLDGLERDELKELIEKLGGKVTDSLsKKTTHVIV--EARTKKYLKAKELGIPIVTEEWLLDCI 75

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 93141033  101 GITACLSQVSSEDRSALWALVTFYGGDCQLTLNKKCTHLI----VPEPKGEkYECAlKRASIKIVTPDWVLDC 169
Cdd:cd17727    3 GVVICVSKKLSKRQGELNKIAASLGAEYRWTYDESCTHFIyqgkANDTNRE-YKSA-KEQGKFIVSPHWLYAC 73

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 93141033  604 GFLLGCVFAIADYPEQmsDKQLLatwKRIIQAHGGTVDPTFTSRCTHLLCESQVSSAYAQAIRERK-RCVTAHWLNTVLK 682
Cdd:cd17731    1 PPFKGLVICVTGFDSE--ERKEI---QQLVEQNGGSYSPDLSKNCTHLIAGSPSGQKYEFARKWNSiHIVTPEWLYDSIE 75

                 ..
gi 93141033  683 KK 684
Cdd:cd17731   76 AG 77

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
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 93141033  622 DKQLLATWKRIIQAHGGTVDPTFTSRCTHLLCESQVSSAY-AQAIRERKRCVTAHWL 677
Cdd:cd00027    9 DDEEREELKKLIEALGGKVSESLSSKVTHLIAKSPSGEKYyLAALAWGIPIVSPEWL 65

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 93141033   99 FFGITACLSQVSSEDRSALWALVTFYGGDCQLTLNKKCTHLIVPEPKGEKYECALKrASIKIVTPDWVLDCVSEKTKKDE 178
Cdd:cd17746    7 LFKCRVCLTNIGQPERSRIENYVLKHGGTFCPDLTRDVTHLIAGTSSGRKYEYALK-WKINVVCVEWLWQSIQRNAVLEP 85

                 ...
gi 93141033  179 AFY 181
Cdd:cd17746   86 QYF 88

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 93141033  608 GCVFAIAdypeQMSDKQLLATWkRIIQAHGGTVDPTFTSRCTHLLCESQVSSAYAQAIRERK-RCVTAHWLNTVLKKKKM 686
Cdd:cd17710    4 GVVVCPS----QISAEDRLKLW-AMVTFHGGKCQLNLDKKCTHLVTGKASGAKYECALKHEGiKIVTPDWVTDCIKAKTL 78

                 ...
gi 93141033  687 VPP 689
Cdd:cd17710   79 LDE 81

BRCT domain of yeast chitin biosynthesis protein CHS5 and similar proteins; CHS5, also termed protein CAL3, is a component of the CHS5/6 complex which mediates export of specific cargo proteins, including chitin synthase CHS3. It is also involved in targeting FUS1 to sites of polarized growth.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 93141033  718 DSDRDDLKLMAYLAGAKYTGYLCRSNTVLICKEPTGLKYEKAKEWRIPCVNAQWL 772
Cdd:cd17742   13 PESVDELEQCLERIGAKPTDRVAIDTTHFVCTVPSGPEYEKAKEMNIPIVRPEWL 67

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 93141033  101 GITACLSQVSSEDRSALWALVTFYGGDCQLTLNKKCTHLIVPEPKGEKYECALK-RASIKIVTPDWVLDC 169
Cdd:cd17740    5 GIVLCCTSIPAEQRTEIATKASKMGAAYTADLTSDVTHLVAGQVNTTKYKFAARsRPDIKVMTVEWVEHL 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 93141033  106 LSQVSSEDRSALWALVTFYGGDCQL--TLNKKCTHLIVPEPK-GEKYECALkrAS-IKIVTPDWVLDCVSEK 173
Cdd:cd17738    6 LSGFSEDEKKELISIIEKLGGKVLDsdEFDPKCTHLICGKPSrSEKFLAAC--AAgKWILHPSYIEASAKAG 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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 93141033  872 TGFEPV---QVQQYIKKLyilGGEVAESAQK-CTHLIASKVTrTVKFLTAI--SVVkHIVTPEWLEEC 933
Cdd:cd17731   11 TGFDSEerkEIQQLVEQN---GGSYSPDLSKnCTHLIAGSPS-GQKYEFARkwNSI-HIVTPEWLYDS 73

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 93141033  105 CLSQVSSEDRSALWALVTFYGGDCQLTLNKKCTHLIVPEPKGEKYECAlKRASIKIVTPDWVLDCV 170
Cdd:cd17730    4 SVTGFDGSEREDIKRMIELMGAKYTGYLTRSNTHLICKRPEGEKYEKA-KEWRIPVVNAQWLEDIL 68

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.