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 2220285774  64 VIVLSaGCCLPIRHHLSKKLIEMGAEIQKTIDNRTTHIVVDRYADEKLVGEAMSRKPEppmMVDVKWIQEC 134
Cdd:cd00027     2 VICFS-GLDDEEREELKKLIEALGGKVSESLSSKVTHLIAKSPSGEKYYLAALAWGIP---IVSPEWLLDC 68

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 2220285774 539 IFANfHLRMWIAPECTPDSADLAWMIEKCGGKVTRHLHRADLVIAPenweIPAENDVefELATPLFVIDSIS 610
Cdd:cd17751     7 LFAD-GGPIYVSSNSVPPKDKLEELVLLCGGKVVKSSRKADICIGK----TPPNPDK--PSVSEKWLLDSIT 71

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 2220285774  64 VIVLSaGCCLPIRHHLSKKLIEMGAEIQKTIDNRTTHIVVDRYADEKLVGEAMSRKPEppmMVDVKWIQEC 134
Cdd:cd00027     2 VICFS-GLDDEEREELKKLIEALGGKVSESLSSKVTHLIAKSPSGEKYYLAALAWGIP---IVSPEWLLDC 68

breast cancer carboxy-terminal domain;

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 2220285774  446 VIFTGFSKDSPIeKKLKTIVRRFKMTISTEIDE-ERTLCVVSRHGKRTLLVLRAICCDVPIVRPQWLEESF 515
Cdd:smart00292   9 FYITGSFDKEER-DELKELIEALGGKVTSSLSSkTTTHVIVGSPEGGKLELLKAIALGIPIVKEEWLLDCL 78

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 2220285774 539 IFANfHLRMWIAPECTPDSADLAWMIEKCGGKVTRHLHRADLVIAPenweIPAENDVefELATPLFVIDSIS 610
Cdd:cd17751     7 LFAD-GGPIYVSSNSVPPKDKLEELVLLCGGKVVKSSRKADICIGK----TPPNPDK--PSVSEKWLLDSIT 71

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 2220285774 447 IFTGFS-----KDSPIEKKLKTIVRRFKMTISTEIDEERTLCVVSRHGKRTLLVLRaiccDVPIVRPQWLEESFEDSQLL 521
Cdd:pfam16589   4 LFEPLRfyinaIPSPSRSKLKRLIEANGGTVVDNINPAVYIVIAPYNKTDKLAENT----KLGVVSPQWIFDCVKKGKLL 79

                  ....*
gi 2220285774 522 PSSDY 526
Cdd:pfam16589  80 PLENY 84

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 2220285774  64 VIVLSaGCCLPIRHHLSKKLIEMGAEIQKTIDNRTTHIVVDRYADEKLVGEAMSRKPEppmMVDVKWIQEC 134
Cdd:cd00027     2 VICFS-GLDDEEREELKKLIEALGGKVSESLSSKVTHLIAKSPSGEKYYLAALAWGIP---IVSPEWLLDC 68

breast cancer carboxy-terminal domain;

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 2220285774  446 VIFTGFSKDSPIeKKLKTIVRRFKMTISTEIDE-ERTLCVVSRHGKRTLLVLRAICCDVPIVRPQWLEESF 515
Cdd:smart00292   9 FYITGSFDKEER-DELKELIEALGGKVTSSLSSkTTTHVIVGSPEGGKLELLKAIALGIPIVKEEWLLDCL 78

BRCT domain of RNA polymerase II subunit A C-terminal domain phosphatase (CTDP1) and similar proteins; CTDP1 (EC 3.1.3.16), also termed TFIIF-associating CTD phosphatase, or TFIIF- associating RNA polymerase C-terminal domain phosphatase (FCP1), promotes the activity of RNA polymerase II through processively dephosphorylating 'Ser-2' and 'Ser-5' of the heptad repeats YSPTSPS in the C-terminal domain of the largest RNA polymerase II subunit. It plays a role in the exit from mitosis by dephosphorylating crucial mitotic substrates (USP44, CDC20 and WEE1) that are required for M-phase-promoting factor (MPF)/CDK1 inactivation.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2220285774  60 LAGTVIVLSAGccLPI-----RHHLSKKLIEMGAEIQKTIDNRTTHIVVDRYADEKlVGEAMSRKPEPpmMVDVKWIQEC 134
Cdd:cd17729    14 LKGCVIVFSGV--IPTgidpeRSRLWKLAESLGAKVVTDLSPRTTHLVAAKLGTEK-VKQALKMPGIH--VVHPDWLWAC 88

                  ....*....
gi 2220285774 135 LDNRQKCKE 143
Cdd:cd17729    89 AERWERVDE 97

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 2220285774 446 VIFTGFSKDSPIEKKLKTIvrrfkmtiSTEIDEERTLC--VVSRHGKRTLLVLRAICCDVPIVRPQWLEES 514
Cdd:cd17744     3 VLFTGVSDKEEGEKIIKKL--------GGSVVDSVEDCthLVTDKVRRTVKFLCALARGIPIVSPDWLEAS 65

first (N-terminal) 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 first repeat.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 2220285774  79 LSKKLIEMGAEIQKTIDNRTTHiVVDRYADEKLVGEAMSRKPEppmMVDVKWIQECLDNRQ 139
Cdd:cd17716    20 FRSILEELGAKVVKRLTKTVTH-VVFKDGSQSTLEKAKKRNVK---LVSPLWVEACKETGK 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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 2220285774  59 YLAGTVIVLSAGCCLPiRHHLSKKLIEMGAEIQKTIDNRTTHIVVDRYADEKLvgEAMSRKPEppmMVDVKWIQECL 135
Cdd:pfam00533   5 LFSGKTFVITGLDGLE-RDELKELIEKLGGKVTDSLSKKTTHVIVEARTKKYL--KAKELGIP---IVTEEWLLDCI 75

BRCT domain of RNA polymerase II subunit A C-terminal domain phosphatase (CTDP1) and similar proteins; CTDP1 (EC 3.1.3.16), also termed TFIIF-associating CTD phosphatase, or TFIIF- associating RNA polymerase C-terminal domain phosphatase (FCP1), promotes the activity of RNA polymerase II through processively dephosphorylating 'Ser-2' and 'Ser-5' of the heptad repeats YSPTSPS in the C-terminal domain of the largest RNA polymerase II subunit. It plays a role in the exit from mitosis by dephosphorylating crucial mitotic substrates (USP44, CDC20 and WEE1) that are required for M-phase-promoting factor (MPF)/CDK1 inactivation.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 2220285774 446 VIFTG-FSKDSPIEK-KLKTIVRRFKMTISTEIDEERTLCVVSRhgKRTLLVLRAICC-DVPIVRPQWLEESFE 516
Cdd:cd17729    19 IVFSGvIPTGIDPERsRLWKLAESLGAKVVTDLSPRTTHLVAAK--LGTEKVKQALKMpGIHVVHPDWLWACAE 90

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 2220285774  74 PIRHHLSKKLIEMGAEIQKTIDNRTTHIVVDRYADEKLVGEAMSRkpeppmMVDVKWIQECLDNRQKCKENDF 146
Cdd:pfam16589  18 PSRSKLKRLIEANGGTVVDNINPAVYIVIAPYNKTDKLAENTKLG------VVSPQWIFDCVKKGKLLPLENY 84