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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 676821278 322 RTLVMTSMSPEKQNTVIQVVNKLGHFLFSDDVCETTSHVVTGSPRRTLNVMLGIARGCWIVSYEWVLWSLELGHWI 397
Cdd:cd17736    1 RTLVMTSVHSEEQELLESVVKKLGGFRVEDSVTEKTTHVVVGSPRRTLNVLLGIARGCWILSPDWVLESLEAGKWL 76

third 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 third repeat.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 676821278 423 GKYRQNLFSNQPAMFVSPTSQPPCKKLIELIQLSGGKICKALRQAKICIGKNPGKkyQEIKSLSEKWVLDSITQHRI 499
Cdd:cd17751    1 SRYRQNLFADGGPIYVSSNSVPPKDKLEELVLLCGGKVVKSSRKADICIGKTPPN--PDKPSVSEKWLLDSITNHKL 75

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 676821278 322 RTLVMTSMSPEKQNTVIQVVNKLGHFLFSDDVCETTSHVVTGSPRRTLNVMLGIARGCWIVSYEWVLWSLELGHWI 397
Cdd:cd17736    1 RTLVMTSVHSEEQELLESVVKKLGGFRVEDSVTEKTTHVVVGSPRRTLNVLLGIARGCWILSPDWVLESLEAGKWL 76

third 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 third repeat.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 676821278 423 GKYRQNLFSNQPAMFVSPTSQPPCKKLIELIQLSGGKICKALRQAKICIGKNPGKkyQEIKSLSEKWVLDSITQHRI 499
Cdd:cd17751    1 SRYRQNLFADGGPIYVSSNSVPPKDKLEELVLLCGGKVVKSSRKADICIGKTPPN--PDKPSVSEKWLLDSITNHKL 75

BRCT domain, a BRCA1 C-terminus domain; This BRCT domain, a BRCA1 C-terminus region, is found on many RAP1 proteins, usually at the very N-terminus. The function in human at least of a BRCT is to contribute to the heterogeneity of the telomere DNA length, but that may not be its general function, which remains unknown.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 676821278  427 QNLFSNqpaM--FVSPTSQPPCKKLIELIQLSGGKICKALRQAKICIGKNPGKKYQEIK-----SLSEKWVLDSITQHRI 499
Cdd:pfam16589   2 PNLFEP---LrfYINAIPSPSRSKLKRLIEANGGTVVDNINPAVYIVIAPYNKTDKLAEntklgVVSPQWIFDCVKKGKL 78

                  ....*.
gi 676821278  500 CPMENY 505
Cdd:pfam16589  79 LPLENY 84

breast cancer carboxy-terminal domain;

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 676821278    18 KTFEQQLLDMGAKVSKTLNKH-VTHVVFKD--GRLATWRKAQKMGVKIVSVLWVERC 71
Cdd:smart00292  21 DELKELIEALGGKVTSSLSSKtTTHVIVGSpeGGKLELLKAIALGIPIVKEEWLLDC 77

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 676821278 322 RTLVMTSMSPEKQNTVIQVVNKLGHFLFSDDVCETTSHVVTGSPRRTLNVMLGIARGCWIVSYEWVLWSLELGHWI 397
Cdd:cd17736    1 RTLVMTSVHSEEQELLESVVKKLGGFRVEDSVTEKTTHVVVGSPRRTLNVLLGIARGCWILSPDWVLESLEAGKWL 76

third 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 third repeat.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 676821278 423 GKYRQNLFSNQPAMFVSPTSQPPCKKLIELIQLSGGKICKALRQAKICIGKNPGKkyQEIKSLSEKWVLDSITQHRI 499
Cdd:cd17751    1 SRYRQNLFADGGPIYVSSNSVPPKDKLEELVLLCGGKVVKSSRKADICIGKTPPN--PDKPSVSEKWLLDSITNHKL 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 676821278 323 TLVMTSMSPEKQNTVIQVVNKLGHfLFSDDVCETTSHVV--TGSP---RRTLNVMLGIARGCWIVSYEWVLWSLELGHWI 397
Cdd:cd17735    2 SMVASGLTPEELMLVQKFARKTGS-TLTSQFTEETTHVImkTDAElvcERTLKYFLGIAGRKWVVSYQWITQSIKEGKIL 80

                 ....*.
gi 676821278 398 SEEPYE 403
Cdd:cd17735   81 PEHDFE 86

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 676821278 327 TSMSPEKQNTVIQVVNKLGhFLFSDDVCETTSHVVTGSP-----RRTLNVMLGIARGCWIVSYEWVLWSLELGHWI 397
Cdd:cd17734    6 SGLSSEQKKLLEKLAQLLK-AKVVTEFSPEVTHVVVPADergvcPRTMKYLMGILAGKWIVSFEWVEACLKAKKLV 80

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 676821278 326 MTSMSPEKQNTVIQVVNKLG-HFLFSDDVCETTSHVVTGSPRRTLNVMLGIARGCWIVSYEWVLWSLELG 394
Cdd:cd17738    6 LSGFSEDEKKELISIIEKLGgKVLDSDEFDPKCTHLICGKPSRSEKFLAACAAGKWILHPSYIEASAKAG 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
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 676821278  10 SNRTEDYSKTFEQQLLDMGAKVSKTLNKHVTHVVFK-DGRLATWRKAQKMGVKIVSVLWVERC 71
Cdd:cd00027    6 SGLDDEEREELKKLIEALGGKVSESLSSKVTHLIAKsPSGEKYYLAALAWGIPIVSPEWLLDC 68

BRCT domain of nibrin and similar proteins; Nibrin (NBN), also termed Nijmegen breakage syndrome protein 1 (NBS1), or cell cycle regulatory protein p95, is a novel DNA double-strand break repair protein that is mutated in Nijmegen breakage syndrome. It is a component of the MRE11-RAD50-NBN (MRN complex) which plays a critical role in the cellular response to DNA damage and the maintenance of chromosome integrity. The BRCT (Breast Cancer Suppressor Protein BRCA1, carboxy-terminal) domain is found within many DNA damage repair and cell cycle checkpoint proteins. The unique diversity of this domain superfamily allows BRCT modules to interact forming homo/hetero BRCT multimers, BRCT-non-BRCT interactions, and interactions within DNA strand breaks. The Trp-X-X-X-Cys/Ser signature motif of the BRCT family is absent in this group.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 676821278 328 SMSPEKQNTVIQVVNKLG-HFLfsDDVCETTSHVVTGSPRRTLNVMLGIARGCWIVSYEW 386
Cdd:cd17741    9 CLDSEEKKKLKQIIAKLGgKVV--NEWTEECTHLVMSKIKVTVKVICALISGKPIVTPEY 66

breast cancer carboxy-terminal domain;

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 676821278    18 KTFEQQLLDMGAKVSKTLNKH-VTHVVFKD--GRLATWRKAQKMGVKIVSVLWVERC 71
Cdd:smart00292  21 DELKELIEALGGKVTSSLSSKtTTHVIVGSpeGGKLELLKAIALGIPIVKEEWLLDC 77

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
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 676821278  18 KTFEQQLLDMGAKVSKTLNKHVTHVVFKDGRLATWRKAQKMG-VKIVSVLWVERCRETG 75
Cdd:cd17731   19 KEIQQLVEQNGGSYSPDLSKNCTHLIAGSPSGQKYEFARKWNsIHIVTPEWLYDSIEAG 77

BRCT domain of DNA repair protein Rev1 and similar proteins; REV1, also termed alpha integrin-binding protein 80, or AIBP80, or Rev1-like terminal deoxycytidyl transferase, is a DNA template-dependent dCMP transferase required for mutagenesis induced by UV light.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 676821278 435 AMFVSPTSQPPCKKLIELIQLSGGK-------------ICKALRQAKIcigKNPgKKYQEIKSLSEKWVLDSITQHRICP 501
Cdd:cd17719    6 VIYVNGYTDPSADELKRLILLHGGQyehyysrsrvthiIATNLPGSKI---KKL-KKARNYKVVRPEWIVDSIKAGRLLP 81

                 ....
gi 676821278 502 MENY 505
Cdd:cd17719   82 EAPY 85

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 676821278  426 RQNLFSNQpAMFVSPTSQPPCKKLIELIQLSGGKICKAL-RQAKICIGKNPGKKYQEIKS-----LSEKWVLDSI 494
Cdd:pfam00533   2 KEKLFSGK-TFVITGLDGLERDELKELIEKLGGKVTDSLsKKTTHVIVEARTKKYLKAKElgipiVTEEWLLDCI 75