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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 329666174   5 MSMVVSGLTPEEFMLVYKFARKHHITLTNLITEETTHVVMKTDAEFVCEQTLKYFLGIAGGKWVVSYFWVTQSIKERKML 84
Cdd:cd17735    1 MSMVASGLTPEELMLVQKFARKTGSTLTSQFTEETTHVIMKTDAELVCERTLKYFLGIAGRKWVVSYQWITQSIKEGKIL 80

                         90
                 ....*....|....*..
gi 329666174  85 NEHDFEVRGDVVNGRNH 101
Cdd:cd17735   81 PEHDFEVRGDVVNGRNH 97

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 329666174   5 MSMVVSGLTPEEFMLVYKFARKHHITLTNLITEETTHVVMKTDAEFVCEQTLKYFLGIAGGKWVVSYFWVTQSIKERKML 84
Cdd:cd17735    1 MSMVASGLTPEELMLVQKFARKTGSTLTSQFTEETTHVIMKTDAELVCERTLKYFLGIAGRKWVVSYQWITQSIKEGKIL 80

                         90
                 ....*....|....*..
gi 329666174  85 NEHDFEVRGDVVNGRNH 101
Cdd:cd17735   81 PEHDFEVRGDVVNGRNH 97

breast cancer carboxy-terminal domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 329666174   113 RKIFRGLEICCYGPFTNMPTDQLEWMVQLCGASVVKELSSFTLgtgVHPIVVVQPDAWTEdngfHAIGQMCEAPVVTREW 192
Cdd:smart00292   1 PKLFKGKTFYITGSFDKEERDELKELIEALGGKVTSSLSSKTT---THVIVGSPEGGKLE----LLKAIALGIPIVKEEW 73

                   ....*
gi 329666174   193 VLDSV 197
Cdd:smart00292  74 LLDCL 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 329666174    5 MSMVVSGLTPEEFMLVYKFARKHHITLTNLITEETTHVVmktdaefVCEQTLKYFLGIAGGKWVVSYFWVTQSI 78
Cdd:pfam00533   9 KTFVITGLDGLERDELKELIEKLGGKVTDSLSKKTTHVI-------VEARTKKYLKAKELGIPIVTEEWLLDCI 75

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 329666174   5 MSMVVSGLTPEEFMLVYKFARKHHITLTNLITEETTHVVMKTDAEFVCEQTLKYFLGIAGGKWVVSYFWVTQSIKERKML 84
Cdd:cd17735    1 MSMVASGLTPEELMLVQKFARKTGSTLTSQFTEETTHVIMKTDAELVCERTLKYFLGIAGRKWVVSYQWITQSIKEGKIL 80

                         90
                 ....*....|....*..
gi 329666174  85 NEHDFEVRGDVVNGRNH 101
Cdd:cd17735   81 PEHDFEVRGDVVNGRNH 97

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 329666174  10 SGLTPEEFMLVYKFARKHHITLTNLITEETTHVVMKTDAEFVCEQTLKYFLGIAGGKWVVSYFWVTQSIKERK 82
Cdd:cd17734    6 SGLSSEQKKLLEKLAQLLKAKVVTEFSPEVTHVVVPADERGVCPRTMKYLMGILAGKWIVSFEWVEACLKAKK 78

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 329666174   5 MSMVVSGLTPEEFMLVYKFARKH-HITLTNLITEETTHVVMKTDAefvceQTLKYFLGIAGGKWVVSYFWVTQSIKERKM 83
Cdd:cd17736    1 RTLVMTSVHSEEQELLESVVKKLgGFRVEDSVTEKTTHVVVGSPR-----RTLNVLLGIARGCWILSPDWVLESLEAGKW 75

                 .
gi 329666174  84 L 84
Cdd:cd17736   76 L 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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 329666174  113 RKIFRGLEICCYGpFTNMPTDQLEWMVQLCGASVVKELSSFTlgtgvHPIVVVqpdawtEDNGFHAIGQMCEAPVVTREW 192
Cdd:pfam00533   3 EKLFSGKTFVITG-LDGLERDELKELIEKLGGKVTDSLSKKT-----THVIVE------ARTKKYLKAKELGIPIVTEEW 70

                  ....*
gi 329666174  193 VLDSV 197
Cdd:pfam00533  71 LLDCI 75

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

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 329666174 121 ICCYGpFTNMPTDQLEWMVQLCGASVVKELSSFTlgTgvhpIVVVQPDAWTEdngFHAIGQMCEAPVVTREWVLDS 196
Cdd:cd00027    3 ICFSG-LDDEEREELKKLIEALGGKVSESLSSKV--T----HLIAKSPSGEK---YYLAALAWGIPIVSPEWLLDC 68