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 1032200096 277 RTLVMTSMPTEKQEVVFKVIRNLGGFTVVDDVCESTSHVVSGSPRRTVNILLGIARGCWILSFEWIMWCLEHQQWV 352
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 1032200096 378 GEYQQDLFHNQLPMFVSPYSQPPCGRLKELIKLCGGTVCRSVRQAGICIGGYNGKkpEGSRSLSEQWILDCVTHLIL 454
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 1032200096 277 RTLVMTSMPTEKQEVVFKVIRNLGGFTVVDDVCESTSHVVSGSPRRTVNILLGIARGCWILSFEWIMWCLEHQQWV 352
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 1032200096 378 GEYQQDLFHNQLPMFVSPYSQPPCGRLKELIKLCGGTVCRSVRQAGICIGGYNGKkpEGSRSLSEQWILDCVTHLIL 454
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 1032200096 381 QQDLFHNqLPMFVSPYSQPPCGRLKELIKLCGGTVCRSVRQAGICI-----GGYNGKKPEGSRSLSEQWILDCVTHLILL 455
Cdd:pfam16589   1 LPNLFEP-LRFYINAIPSPSRSKLKRLIEANGGTVVDNINPAVYIViapynKTDKLAENTKLGVVSPQWIFDCVKKGKLL 79

                  ....*
gi 1032200096 456 PYKNY 460
Cdd:pfam16589  80 PLENY 84

breast cancer carboxy-terminal domain;

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1032200096  294 KVIRNLGGfTVVDDVCE-STSHVVSGSP-RRTVNILLGIARGCWILSFEWI 342
Cdd:smart00292  25 ELIEALGG-KVTSSLSSkTTTHVIVGSPeGGKLELLKAIALGIPIVKEEWL 74

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 1032200096 277 RTLVMTSMPTEKQEVVFKVIRNLGGFTVVDDVCESTSHVVSGSPRRTVNILLGIARGCWILSFEWIMWCLEHQQWV 352
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 1032200096 378 GEYQQDLFHNQLPMFVSPYSQPPCGRLKELIKLCGGTVCRSVRQAGICIGGYNGKkpEGSRSLSEQWILDCVTHLIL 454
Cdd:cd17751     1 SRYRQNLFADGGPIYVSSNSVPPKDKLEELVLLCGGKVVKSSRKADICIGKTPPN--PDKPSVSEKWLLDSITNHKL 75

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 1032200096 282 TSMPTEKQEVVFKVIRNLGGfTVVDDVCESTSHVVSGSP-----RRTVNILLGIARGCWILSFEWIMWCLEHQQWV 352
Cdd:cd17734     6 SGLSSEQKKLLEKLAQLLKA-KVVTEFSPEVTHVVVPADergvcPRTMKYLMGILAGKWIVSFEWVEACLKAKKLV 80

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 1032200096 280 VMTSM--PTEKQEvvfKVIRNLGGfTVVDDVCESTsHVVSGSPRRTVNILLGIARGCWILSFEWIMWCLEHQQWV 352
Cdd:cd17744     3 VLFTGvsDKEEGE---KIIKKLGG-SVVDSVEDCT-HLVTDKVRRTVKFLCALARGIPIVSPDWLEASIKANKFL 72

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 1032200096 278 TLVMTSMPTEKQEVVFKVIRNLGGfTVVDDVCESTSHVV--SGSP---RRTVNILLGIARGCWILSFEWIMWCLEHQQWV 352
Cdd:cd17735     2 SMVASGLTPEELMLVQKFARKTGS-TLTSQFTEETTHVImkTDAElvcERTLKYFLGIAGRKWVVSYQWITQSIKEGKIL 80

                  ....*.
gi 1032200096 353 SEEPFE 358
Cdd:cd17735    81 PEHDFE 86

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 1032200096  26 SRMEDYSDPFIEQL-QDMGAQVSKTLNKQVTHVIFKH-GRPSTWKKALKIGVKIVSVHWVARC 86
Cdd:cd00027     6 SGLDDEEREELKKLiEALGGKVSESLSSKVTHLIAKSpSGEKYYLAALAWGIPIVSPEWLLDC 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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1032200096  12 FLKDVVAYVdvwsaSRMEDYSDPFIEQ-LQDMGAQVSKTLNKQVTHVIfKHGRPSTWKKALKIGVKIVSVHWVARC 86
Cdd:pfam00533   5 LFSGKTFVI-----TGLDGLERDELKElIEKLGGKVTDSLSKKTTHVI-VEARTKKYLKAKELGIPIVTEEWLLDC 74

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
                  ....*....|....*....|....*....|....*....|....*
gi 1032200096  39 LQDMGAQVSKTLNKQVTHVIFKHGRPSTWKKALKIGVKIVSVHWV 83
Cdd:cd17711    25 IEEHGGEVVDEYSPRVTHVICESQDSPEYQQALRDGKRVVTAYWL 69

breast cancer carboxy-terminal domain;

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1032200096   33 DPFIEQLQDMGAQVSKTLN-KQVTHVIFK--HGRPSTWKKALKIGVKIVSVHWVARC 86
Cdd:smart00292  21 DELKELIEALGGKVTSSLSsKTTTHVIVGspEGGKLELLKAIALGIPIVKEEWLLDC 77

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.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1032200096 280 VMTSMPTEKQEVVFKVIRNLGgFTVVDDVCESTsHVVSGSPRRTVNILLGIARGCWILSFEWIMWCLE 347
Cdd:cd17743     3 LLFTGYKLWTEKEIKKLKKLG-ISIVEDPDECT-HLVAPKIVRTEKFLCALAYAPVIVTTDWLEACLK 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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1032200096 268 KKDKCLKkNRTLVMTSMPTEKQEVVFKVIRNLGGfTVVDDVCESTSHVVSgsPRRTVNILLGIARGCWILSFEWIMWCL 346
Cdd:pfam00533   1 PKEKLFS-GKTFVITGLDGLERDELKELIEKLGG-KVTDSLSKKTTHVIV--EARTKKYLKAKELGIPIVTEEWLLDCI 75

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 1032200096 283 SMPTEKQEVVFKVIRNLGGfTVVDDVCESTSHVVSGSPRRTVNILLGIARGCWILSFEWIM 343
Cdd:cd17741     9 CLDSEEKKKLKQIIAKLGG-KVVNEWTEECTHLVMSKIKVTVKVICALISGKPIVTPEYLD 68

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
                  ....*....|....*....|....*....|....*....|....*..
gi 1032200096  42 MGAQVSKTLNKQVTHVIFKhgRPS--TWKKALKIGVKIVSVHWVARC 86
Cdd:cd17730    23 MGAKYTGYLTRSNTHLICK--RPEgeKYEKAKEWRIPVVNAQWLEDI 67