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        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 2038210914  18 DVTAYVEVWSSSRrENYSKTFSQQLLNLGAKVSKTFNKHVTHVIFKDGHQGTWDKAVKAGVKLVSVLWVEKCREAAAHI 96
Cdd:cd17716     1 GVVAYVDVRSGDG-ADRSSAFRSILEELGAKVVKRLTKTVTHVVFKDGSQSTLEKAKKRNVKLVSPLWVEACKETGKRV 78

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        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 2038210914  18 DVTAYVEVWSSSRrENYSKTFSQQLLNLGAKVSKTFNKHVTHVIFKDGHQGTWDKAVKAGVKLVSVLWVEKCREAAAHI 96
Cdd:cd17716     1 GVVAYVDVRSGDG-ADRSSAFRSILEELGAKVVKRLTKTVTHVVFKDGSQSTLEKAKKRNVKLVSPLWVEACKETGKRV 78

twin BRCT domain; This is a BRCT domain that appears in duplicate in most member sequences. BRCT domains are peptide- and phosphopeptide-binding modules. BRCT domains are present in a number of proteins involved in DNA checkpoint controls and DNA repair.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 2038210914  23 VEVWSSSRRENYSKTFSQQLLNLGAKVSKTFNKHVTHVIFKDGHQGTWDKAVKAGVKLVSVLW 85
Cdd:pfam12738   1 LVICVTGFDGDDREGLQKLIEAMGAEYTKDLTKSVTHLICKSGEGEKYEKAKEWGIPVVSPLW 63

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 2038210914 747 FISPSSQPPCDKLSEVVQLCGGKVCKALRQAKICIGKFNGKRAPDVQN-----VSEKWLLDSITQHRLHPLENY 815
Cdd:pfam16589  11 YINAIPSPSRSKLKRLIEANGGTVVDNINPAVYIVIAPYNKTDKLAENtklgvVSPQWIFDCVKKGKLLPLENY 84

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2038210914 637 TSMCSEKQNTVIQVVKKFGGFVFSDhVCETTTHVIAgsPRRTLNIILGIARGCWIISYDWVL 698
Cdd:pfam00533  14 TGLDGLERDELKELIEKLGGKVTDS-LSKKTTHVIV--EARTKKYLKAKELGIPIVTEEWLL 72

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        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 2038210914  18 DVTAYVEVWSSSRrENYSKTFSQQLLNLGAKVSKTFNKHVTHVIFKDGHQGTWDKAVKAGVKLVSVLWVEKCREAAAHI 96
Cdd:cd17716     1 GVVAYVDVRSGDG-ADRSSAFRSILEELGAKVVKRLTKTVTHVVFKDGSQSTLEKAKKRNVKLVSPLWVEACKETGKRV 78

twin BRCT domain; This is a BRCT domain that appears in duplicate in most member sequences. BRCT domains are peptide- and phosphopeptide-binding modules. BRCT domains are present in a number of proteins involved in DNA checkpoint controls and DNA repair.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 2038210914  23 VEVWSSSRRENYSKTFSQQLLNLGAKVSKTFNKHVTHVIFKDGHQGTWDKAVKAGVKLVSVLW 85
Cdd:pfam12738   1 LVICVTGFDGDDREGLQKLIEAMGAEYTKDLTKSVTHLICKSGEGEKYEKAKEWGIPVVSPLW 63

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 2038210914 634 LVMTSMCSEKQNTVIQVVKKFGGfVFSDHVCETTTHVIAGSPRRTLNIILGIARGCWIISYDWVLWS 700
Cdd:cd00027     3 ICFSGLDDEEREELKKLIEALGG-KVSESLSSKVTHLIAKSPSGEKYYLAALAWGIPIVSPEWLLDC 68

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 2038210914 636 MTSMCSEKQNTVIQVVKKFGGFVF-SDHVCETTTHVIAGSPRRTLNIILGIARGCWIISYDWVLWSLECG 704
Cdd:cd17738     6 LSGFSEDEKKELISIIEKLGGKVLdSDEFDPKCTHLICGKPSRSEKFLAACAAGKWILHPSYIEASAKAG 75

breast cancer carboxy-terminal domain;

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2038210914  638 SMCSEKQNTVIQVVKKFGGFVFSDHVCETTTHVIAGSP-RRTLNIILGIARGCWIISYDWVL 698
Cdd:smart00292  14 SFDKEERDELKELIEALGGKVTSSLSSKTTTHVIVGSPeGGKLELLKAIALGIPIVKEEWLL 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
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 2038210914  45 LGAKVSKTFNKHVTHVIFKDghQGTwDKAVKA----GVKLVSVLWVEKCREAAAHIDE 98
Cdd:cd17729    43 LGAKVVTDLSPRTTHLVAAK--LGT-EKVKQAlkmpGIHVVHPDWLWACAERWERVDE 97

sixth 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 sixth BRCT domain.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2038210914  16 LADVTAYVEVWSSSRRENYSKTFSQqllnLGAKVSKTFNKHVTHVIfkdgHQGT-------WDKAVKAGVKLVSVLWVEK 88
Cdd:cd17727     1 LKGVVICVSKKLSKRQGELNKIAAS----LGAEYRWTYDESCTHFI----YQGKandtnreYKSAKEQGKFIVSPHWLYA 72

                  ...
gi 2038210914  89 CRE 91
Cdd:cd17727    73 CKE 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 2038210914 634 LVMTSMC--SEKQNTVIQVVKKFGGFVFSDHvCETTTHVIAGSPRRTLNIILGIARGCWIISYDW 696
Cdd:cd17741     3 LVVCSSCldSEEKKKLKQIIAKLGGKVVNEW-TEECTHLVMSKIKVTVKVICALISGKPIVTPEY 66

fifth 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 fifth BRCT domain.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 2038210914 648 IQVVKKFGGFVFSDHV-CettTHVIAGSPRRTLNIILGIARGCWIISYDWVLWSLECGHWI 707
Cdd:cd17712    18 TKKVTILGGEVVESPQeC---THLVAPKVSRTVKFLTAISVCKHIVTPEWLEESFKQGKFL 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
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 2038210914  40 QQLLN-----LGAKVSKTFNKHVTHVIFKDGHQG----TWD--KAVKAGVKLVSVLWVEKC 89
Cdd:cd17734    13 KKLLEklaqlLKAKVVTEFSPEVTHVVVPADERGvcprTMKylMGILAGKWIVSFEWVEAC 73

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2038210914 637 TSMCSEKQNTVIQVVKKFGGFVFSDhVCETTTHVIAgsPRRTLNIILGIARGCWIISYDWVL 698
Cdd:pfam00533  14 TGLDGLERDELKELIEKLGGKVTDS-LSKKTTHVIV--EARTKKYLKAKELGIPIVTEEWLL 72