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 2255447825 379 MSMVVSGLTPEEFMLVYKFARKHHITLTNLITEETTHVVMKTDAEFVCERTLKYFLGIAGGKWVVSYFWVTQSIKERKML 458
Cdd:cd17735     1 MSMVASGLTPEELMLVQKFARKTGSTLTSQFTEETTHVIMKTDAELVCERTLKYFLGIAGRKWVVSYQWITQSIKEGKIL 80

                          90
                  ....*....|....*..
gi 2255447825 459 NEHDFEVRGDVVNGRNH 475
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 2255447825 379 MSMVVSGLTPEEFMLVYKFARKHHITLTNLITEETTHVVMKTDAEFVCERTLKYFLGIAGGKWVVSYFWVTQSIKERKML 458
Cdd:cd17735     1 MSMVASGLTPEELMLVQKFARKTGSTLTSQFTEETTHVIMKTDAELVCERTLKYFLGIAGRKWVVSYQWITQSIKEGKIL 80

                          90
                  ....*....|....*..
gi 2255447825 459 NEHDFEVRGDVVNGRNH 475
Cdd:cd17735    81 PEHDFEVRGDVVNGRNH 97

breast cancer carboxy-terminal domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2255447825  487 RKIFRGLEICCYGPFTNMPTDQLEWMVQLCGASVVKELSSFTLgtgVHPIVVVQPDAWTEdngfHAIGQMCEAPVVTREW 566
Cdd:smart00292   1 PKLFKGKTFYITGSFDKEERDELKELIEALGGKVTSSLSSKTT---THVIVGSPEGGKLE----LLKAIALGIPIVKEEW 73

                   ....*
gi 2255447825  567 VLDSV 571
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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2255447825 373 ERVNKRMSMVVSGLTPEEFMLVYKFARKHHITLTNLITEETTHVVmktdaefVCERTLKYFLGIAGGKWVVSYFWVTQSI 452
Cdd:pfam00533   3 EKLFSGKTFVITGLDGLERDELKELIEKLGGKVTDSLSKKTTHVI-------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 2255447825 379 MSMVVSGLTPEEFMLVYKFARKHHITLTNLITEETTHVVMKTDAEFVCERTLKYFLGIAGGKWVVSYFWVTQSIKERKML 458
Cdd:cd17735     1 MSMVASGLTPEELMLVQKFARKTGSTLTSQFTEETTHVIMKTDAELVCERTLKYFLGIAGRKWVVSYQWITQSIKEGKIL 80

                          90
                  ....*....|....*..
gi 2255447825 459 NEHDFEVRGDVVNGRNH 475
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 2255447825 384 SGLTPEEFMLVYKFARKHHITLTNLITEETTHVVMKTDAEFVCERTLKYFLGIAGGKWVVSYFWVTQSIKERK 456
Cdd:cd17734     6 SGLSSEQKKLLEKLAQLLKAKVVTEFSPEVTHVVVPADERGVCPRTMKYLMGILAGKWIVSFEWVEACLKAKK 78

breast cancer carboxy-terminal domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2255447825  487 RKIFRGLEICCYGPFTNMPTDQLEWMVQLCGASVVKELSSFTLgtgVHPIVVVQPDAWTEdngfHAIGQMCEAPVVTREW 566
Cdd:smart00292   1 PKLFKGKTFYITGSFDKEERDELKELIEALGGKVTSSLSSKTT---THVIVGSPEGGKLE----LLKAIALGIPIVKEEW 73

                   ....*
gi 2255447825  567 VLDSV 571
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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2255447825 487 RKIFRGLEICCYGpFTNMPTDQLEWMVQLCGASVVKELSSFTlgtgvHPIVVVqpdawtEDNGFHAIGQMCEAPVVTREW 566
Cdd:pfam00533   3 EKLFSGKTFVITG-LDGLERDELKELIEKLGGKVTDSLSKKT-----THVIVE------ARTKKYLKAKELGIPIVTEEW 70

                  ....*
gi 2255447825 567 VLDSV 571
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 2255447825 495 ICCYGpFTNMPTDQLEWMVQLCGASVVKELSSFTlgTgvhpIVVVQPDAWTEdngFHAIGQMCEAPVVTREWVLDS 570
Cdd:cd00027     3 ICFSG-LDDEEREELKKLIEALGGKVSESLSSKV--T----HLIAKSPSGEK---YYLAALAWGIPIVSPEWLLDC 68

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 2255447825 411 EETTHVVmkTDAEfvcERTLKYFLGIAGGKWVVSYFWVTQSIKERKML 458
Cdd:cd17744    30 EDCTHLV--TDKV---RRTVKFLCALARGIPIVSPDWLEASIKANKFL 72