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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 290560274 114 RKIFRGLEICCYGPFTNMPTDQLEWMVQLCGASVVKELSSFTLGTGVHPIVVVQPDAWTEDNGFHAIGQMCEAPVVTREW 193
Cdd:cd17721    1 KLLFRGFEICCYGPFTNMTKDQLEWLLELCGATVVKEPSLFTAKPGKKRLIVVQPDAWTEDNDYNAIYRRYKALVVTREW 80

                         90
                 ....*....|....*...
gi 290560274 194 VLTSVALYQCQELDTYLI 211
Cdd:cd17721   81 VLDSVALYKVQPLDAYLL 98

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 290560274 114 RKIFRGLEICCYGPFTNMPTDQLEWMVQLCGASVVKELSSFTLGTGVHPIVVVQPDAWTEDNGFHAIGQMCEAPVVTREW 193
Cdd:cd17721    1 KLLFRGFEICCYGPFTNMTKDQLEWLLELCGATVVKEPSLFTAKPGKKRLIVVQPDAWTEDNDYNAIYRRYKALVVTREW 80

                         90
                 ....*....|....*...
gi 290560274 194 VLTSVALYQCQELDTYLI 211
Cdd:cd17721   81 VLDSVALYKVQPLDAYLL 98

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 290560274    6 MSMVVSGLTPEEFMLVYKFARKHHITLTNLITEETTHVVmktdaefVCERTLKYFLGIAGGKWVVSYFWVTQSI 79
Cdd:pfam00533   9 KTFVITGLDGLERDELKELIEKLGGKVTDSLSKKTTHVI-------VEARTKKYLKAKELGIPIVTEEWLLDCI 75

breast cancer carboxy-terminal domain;

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 290560274    18 FMLVYKFARKHHITLTNLITE----ETTHVVMKTDAEFVCE----RTLKYFLGIAGGKWVVSYFWVTQSI 79
Cdd:smart00292   9 FYITGSFDKEERDELKELIEAlggkVTSSLSSKTTTHVIVGspegGKLELLKAIALGIPIVKEEWLLDCL 78

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 290560274 114 RKIFRGLEICCYGPFTNMPTDQLEWMVQLCGASVVKELSSFTLGTGVHPIVVVQPDAWTEDNGFHAIGQMCEAPVVTREW 193
Cdd:cd17721    1 KLLFRGFEICCYGPFTNMTKDQLEWLLELCGATVVKEPSLFTAKPGKKRLIVVQPDAWTEDNDYNAIYRRYKALVVTREW 80

                         90
                 ....*....|....*...
gi 290560274 194 VLTSVALYQCQELDTYLI 211
Cdd:cd17721   81 VLDSVALYKVQPLDAYLL 98

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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 290560274   6 MSMVVSGLTPEEFMLVYKFARKH-HITLTNLITEETTHVVMKTDAefvceRTLKYFLGIAGGKWVVSYFWVTQSIKERKM 84
Cdd:cd17736    1 RTLVMTSVHSEEQELLESVVKKLgGFRVEDSVTEKTTHVVVGSPR-----RTLNVLLGIARGCWILSPDWVLESLEAGKW 75

                 .
gi 290560274  85 L 85
Cdd:cd17736   76 L 76

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 290560274   6 MSMVVSGLTPEEFMLVYKFARKHHITLTNLITEETTHVVMKTDaefvcERTLKYFLGIAGGKWVVSYFWVTQS 78
Cdd:cd00027    1 LVICFSGLDDEEREELKKLIEALGGKVSESLSSKVTHLIAKSP-----SGEKYYLAALAWGIPIVSPEWLLDC 68

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 290560274  114 RKIFRGLEICCYGpFTNMPTDQLEWMVQLCGASVVKELSSFTlgtgvHPIVVVqpdawtEDNGFHAIGQMCEAPVVTREW 193
Cdd:pfam00533   3 EKLFSGKTFVITG-LDGLERDELKELIEKLGGKVTDSLSKKT-----THVIVE------ARTKKYLKAKELGIPIVTEEW 70

                  ....*
gi 290560274  194 VLTSV 198
Cdd:pfam00533  71 LLDCI 75

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
                 ....*....|....*....|....*....|....*....|....*...
gi 290560274  38 EETTHVVMKTDaefvcERTLKYFLGIAGGKWVVSYFWVTQSIKERKML 85
Cdd:cd17744   30 EDCTHLVTDKV-----RRTVKFLCALARGIPIVSPDWLEASIKANKFL 72