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 2078134802  15 GVVAFVDVWSSNRtENYSKMFSQQLLNLGAKVSKTFNKQVTHLVFKDGSQSTWDKAVKSKVKLVSVLWVEKCREMDLHV 93
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 2078134802  15 GVVAFVDVWSSNRtENYSKMFSQQLLNLGAKVSKTFNKQVTHLVFKDGSQSTWDKAVKSKVKLVSVLWVEKCREMDLHV 93
Cdd:cd17716     1 GVVAYVDVRSGDG-ADRSSAFRSILEELGAKVVKRLTKTVTHVVFKDGSQSTLEKAKKRNVKLVSPLWVEACKETGKRV 78

breast cancer carboxy-terminal domain;

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2078134802  639 SMSTEKQSMIIQVVKKFGGFLFSDEVCETTTHVIAGSP-RRTLNIILGIARGCWILSYDWVL 699
Cdd:smart00292  14 SFDKEERDELKELIEALGGKVTSSLSSKTTTHVIVGSPeGGKLELLKAIALGIPIVKEEWLL 75

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 2078134802 638 TSMSTEKQSMIIQVVKKFGGfLFSDEVCETTTHVIAgsPRRTLNIILGIARGCWILSYDWVL 699
Cdd:pfam00533  14 TGLDGLERDELKELIEKLGG-KVTDSLSKKTTHVIV--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 2078134802  15 GVVAFVDVWSSNRtENYSKMFSQQLLNLGAKVSKTFNKQVTHLVFKDGSQSTWDKAVKSKVKLVSVLWVEKCREMDLHV 93
Cdd:cd17716     1 GVVAYVDVRSGDG-ADRSSAFRSILEELGAKVVKRLTKTVTHVVFKDGSQSTLEKAKKRNVKLVSPLWVEACKETGKRV 78

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 2078134802 634 SLVMTSMSTEKQSMIIQVVKKFGGfLFSDEVCETTTHVIAGSP-----RRTLNIILGIARGCWILSYDWVLWSLERGHWI 708
Cdd:cd17735     2 SMVASGLTPEELMLVQKFARKTGS-TLTSQFTEETTHVIMKTDaelvcERTLKYFLGIAGRKWVVSYQWITQSIKEGKIL 80

                  ....*.
gi 2078134802 709 PEEPYE 714
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 2078134802 638 TSMSTEKQSMIIQVVKKFGGFLfSDEVCETTTHVIAGSP-----RRTLNIILGIARGCWILSYDWVLWSLERGHWI 708
Cdd:cd17734     6 SGLSSEQKKLLEKLAQLLKAKV-VTEFSPEVTHVVVPADergvcPRTMKYLMGILAGKWIVSFEWVEACLKAKKLV 80

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
                  ....*....|....*....|....*....|....*....|....*.
gi 2078134802  42 LGAKVSKTFNKQVTHLVFK-DGSQSTWDKAVKSKVKLVSVLWVEKC 86
Cdd:cd00027    23 LGGKVSESLSSKVTHLIAKsPSGEKYYLAALAWGIPIVSPEWLLDC 68

breast cancer carboxy-terminal domain;

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2078134802  639 SMSTEKQSMIIQVVKKFGGFLFSDEVCETTTHVIAGSP-RRTLNIILGIARGCWILSYDWVL 699
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        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2078134802  10 SRILTGVV-AFVDVWSSN---RTENYSKMFSQqllnLGAKVSKTFNKQVTHLVF-KDGSQSTwDKAVKSK-VKLVSVLWV 83
Cdd:cd17729    11 SKVLKGCViVFSGVIPTGidpERSRLWKLAES----LGAKVVTDLSPRTTHLVAaKLGTEKV-KQALKMPgIHVVHPDWL 85

                          90
                  ....*....|..
gi 2078134802  84 EKCREMDLHVDE 95
Cdd:cd17729    86 WACAERWERVDE 97

breast cancer carboxy-terminal domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2078134802   10 SRILTGVVAFVdvwSSNRTENYSKMFSQQLLNLGAKVSKTFN-KQVTHLVFKDGSQST--WDKAVKSKVKLVSVLWVEKC 86
Cdd:smart00292   1 PKLFKGKTFYI---TGSFDKEERDELKELIEALGGKVTSSLSsKTTTHVIVGSPEGGKleLLKAIALGIPIVKEEWLLDC 77

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 2078134802 638 TSMSTEKQSMIIQVVKKFGGfLFSDEVCETTTHVIAgsPRRTLNIILGIARGCWILSYDWVL 699
Cdd:pfam00533  14 TGLDGLERDELKELIEKLGG-KVTDSLSKKTTHVIV--EARTKKYLKAKELGIPIVTEEWLL 72

BRCT domain of yeast chitin biosynthesis protein CHS5 and similar proteins; CHS5, also termed protein CAL3, is a component of the CHS5/6 complex which mediates export of specific cargo proteins, including chitin synthase CHS3. It is also involved in targeting FUS1 to sites of polarized growth.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 2078134802  36 SQQLLNLGAKVSKTFNKQVTHLVFKDGSQSTWDKAVKSKVKLVSVLWVEKC 86
Cdd:cd17742    20 EQCLERIGAKPTDRVAIDTTHFVCTVPSGPEYEKAKEMNIPIVRPEWLRAC 70

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        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 2078134802 636 VM-TSMSTEKQSMIIQVVKKFGGFLFSDEV-CettTHVIAGSPRRTLNIILGIARGCWILSYDWVLWSLERGHWI 708
Cdd:cd17712     4 VLfTGFDPVQVRKLTKKVTILGGEVVESPQeC---THLVAPKVSRTVKFLTAISVCKHIVTPEWLEESFKQGKFL 75