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 1063695903  60 SKLMEGVVFVLSGFVNPERSTLRSQALTMGATYQPDWNAGSTLLICAfPNTPKFRQVETNGGTIISKEWITECY 133
Cdd:pfam00533   3 EKLFSGKTFVITGLDGLERDELKELIEKLGGKVTDSLSKKTTHVIVE-ARTKKYLKAKELGIPIVTEEWLLDCI 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 1063695903  66 VVFVLSGFVNPERSTLRSQALTMGATYQPDWNAGSTLLICAFPNTPKFRQVETNGGT-IISKEWITEC 132
Cdd:cd00027     1 LVICFSGLDDEEREELKKLIEALGGKVSESLSSKVTHLIAKSPSGEKYYLAALAWGIpIVSPEWLLDC 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 1063695903  60 SKLMEGVVFVLSGFVNPERSTLRSQALTMGATYQPDWNAGSTLLICAfPNTPKFRQVETNGGTIISKEWITECY 133
Cdd:pfam00533   3 EKLFSGKTFVITGLDGLERDELKELIEKLGGKVTDSLSKKTTHVIVE-ARTKKYLKAKELGIPIVTEEWLLDCI 75

breast cancer carboxy-terminal domain;

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1063695903   60 SKLMEGVVFVLSG-FVNPERSTLRSQALTMGATYQPDWNAGS-TLLICAFPNTPK--FRQVETNGGTIISKEWITECY 133
Cdd:smart00292   1 PKLFKGKTFYITGsFDKEERDELKELIEALGGKVTSSLSSKTtTHVIVGSPEGGKleLLKAIALGIPIVKEEWLLDCL 78

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        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063695903  65 GVVFVLSGFVN----PERSTLRSQALTMGATYQPDWNAGSTLLICAFPNTPKFRQVETNGGTIISKEWITECYAQKKLVD 140
Cdd:cd17711     1 GCVFFIADYPEqmgdQEIATWKKVIEEHGGEVVDEYSPRVTHVICESQDSPEYQQALRDGKRVVTAYWLNDVLKRGKLLP 80

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 1063695903  60 SKLMEGVVFVLSGFV----NPERSTLRSQALTMGATYQPDWNAGSTLLICAFPNTPKFRQVETNGGT-IISKEWITECY 133
Cdd:cd17729    11 SKVLKGCVIVFSGVIptgiDPERSRLWKLAESLGAKVVTDLSPRTTHLVAAKLGTEKVKQALKMPGIhVVHPDWLWACA 89

second 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 second BRCT domain.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063695903  62 LMEGVVFVLSGFVNPERSTLRSQALTMGATYQPDWNAGSTLLICAFPNTPKFRQVETNGG-TIISKEWITECYAQKKLVD 140
Cdd:cd17710     1 LFSGVVVCPSQISAEDRLKLWAMVTFHGGKCQLNLDKKCTHLVTGKASGAKYECALKHEGiKIVTPDWVTDCIKAKTLLD 80

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        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1063695903  75 NPERSTLRSQALTMGATYQPDWNAGSTLLICAFPNTPKFRQVETNGGTIISKEWITECYAQKKLV 139
Cdd:cd17742    13 PESVDELEQCLERIGAKPTDRVAIDTTHFVCTVPSGPEYEKAKEMNIPIVRPEWLRACEVEKKIV 77