second (C-terminal) 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 second BRCT domain.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 543583739 201 LFDGCYFYLWGTFKHH-PKDNLIKLVTAGGGQILSRKPKPDSDVTQTINTVAYhARPDSDQRFCTQYIIYEDLCNYHPER 279
Cdd:cd17720    1 LFDGCHFYFHGTFKPPtTKDDLEQLVKAGGGTVLSREPKPDSDVTQTINTVAY-ARPDSDLANCTHYIIYDKLNDKKPAK 79

                         90       100
                 ....*....|....*....|..
gi 543583739 280 VRQGKVWKAPSSWFIDCVMSFE 301
Cdd:cd17720   80 VRQGKVRVVPVSWLLDCISQFK 101

RING finger (Really Interesting New Gene) domain and U-box domain superfamily; The RING finger is a specialized type of Zn-finger of 40 to 60 residues that binds two atoms of zinc. It is defined by the "cross-brace" motif that chelates zinc atoms by eight amino acid residues, typically Cys or His, arranged in a characteristic spacing. Canonical RING motifs have been categorized into two major subclasses, RING-HC (C3HC4-type) and RING-H2 (C3H2C3-type), according to their Cys/His content. There are also many variants of RING fingers: some have different Cys/His patterns while some lack a single Cys or His residue at typical Zn ligand positions (the fourth or eighth zinc ligand is prevalently exchanged for an Asp, which can indeed chelate Zn in a RING finger as well). C4C4-, C3HC3D-, C2H2C4-, and C3HC5-type RING fingers are closely related to RING-HC fingers. In contrast, C4HC3- (RING-CH alias RINGv), C3H3C2-, C3H2C2D-, C3DHC3-, and C4HC2H-type RING fingers are more closely related to RING-H2 fingers. However, not all RING finger-containing proteins display regular RING finger features, and the RING finger family has turned out to be multifarious. The degenerate RING fingers of the Siz/PIAS RING (SP-RING) family proteins and sporulation protein RMD5, are characterized by lacking the second, fifth, and sixth Zn2+ ion-coordinating residues. They bind only one Zn2+ ion. On the other hand, the RING fingers of the human APC11 and RBX1 proteins can bind a third Zn atom since they harbor four additional Zn ligands. U-box is a modified form of the RING finger domain that lacks metal chelating Cys and His residues. It resembles the cross-brace RING structure consisting of three beta-sheets and a single alpha-helix, which would be stabilized by salt bridges instead of chelated metal ions. U-box proteins are widely distributed among eukaryotic organisms and show a higher prevalence in plants than in other organisms. RING finger/U-box-containing proteins are a group of diverse proteins with a variety of cellular functions, including oncogenesis, development, viral replication, signal transduction, the cell cycle and apoptosis. Many of them are ubiquitin-protein ligases (E3s) that serve as scaffolds for binding to ubiquitin-conjugating enzymes (E2s, also referred to as ubiquitin carrier proteins or UBCs) in close proximity to substrate proteins, which enable efficient transfer of ubiquitin from E2 to the substrates.

                         10        20
                 ....*....|....*....|.
gi 543583739  33 AWAHSRAALDRLEKLLRCSRC 53
Cdd:cd16496    1 KWARTRAALDELENLLRCSRC 21

second (C-terminal) 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 second BRCT domain.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 543583739 201 LFDGCYFYLWGTFKHH-PKDNLIKLVTAGGGQILSRKPKPDSDVTQTINTVAYhARPDSDQRFCTQYIIYEDLCNYHPER 279
Cdd:cd17720    1 LFDGCHFYFHGTFKPPtTKDDLEQLVKAGGGTVLSREPKPDSDVTQTINTVAY-ARPDSDLANCTHYIIYDKLNDKKPAK 79

                         90       100
                 ....*....|....*....|..
gi 543583739 280 VRQGKVWKAPSSWFIDCVMSFE 301
Cdd:cd17720   80 VRQGKVRVVPVSWLLDCISQFK 101

breast cancer carboxy-terminal domain;

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 543583739   101 VLIGSGLSSEQQKMLSELAVILKAKKYTEFDS-TVTHVVVpGDAVQSTLKCMLGILNGCWILKFEWVKACL 170
Cdd:smart00292   9 FYITGSFDKEERDELKELIEALGGKVTSSLSSkTTTHVIV-GSPEGGKLELLKAIALGIPIVKEEWLLDCL 78

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 543583739  105 SGLSSEQQKMLSELAVILKAKKYTEFDSTVTHVVVPGDavqsTLKCMLGILNGCWILKFEWVKACL 170
Cdd:pfam00533  14 TGLDGLERDELKELIEKLGGKVTDSLSKKTTHVIVEAR----TKKYLKAKELGIPIVTEEWLLDCI 75

RING finger, HC subclass, found in BRCA1-associated RING domain protein 1 (BARD-1) and similar proteins; BARD-1 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 C3HC4-type RING-HC finger that binds BRCA1 at its N-terminus and three tandem ankyrin repeats and tandem BRCT repeat domains at its C-terminus. The BRCT repeats bind CstF-50 (cleavage stimulation factor) to modulate mRNA processing and RNAP II stability in response to DNA damage.

                         10        20
                 ....*....|....*....|.
gi 543583739  33 AWAHSRAALDRLEKLLRCSRC 53
Cdd:cd16496    1 KWARTRAALDELENLLRCSRC 21

second (C-terminal) 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 second BRCT domain.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 543583739 201 LFDGCYFYLWGTFKHH-PKDNLIKLVTAGGGQILSRKPKPDSDVTQTINTVAYhARPDSDQRFCTQYIIYEDLCNYHPER 279
Cdd:cd17720    1 LFDGCHFYFHGTFKPPtTKDDLEQLVKAGGGTVLSREPKPDSDVTQTINTVAY-ARPDSDLANCTHYIIYDKLNDKKPAK 79

                         90       100
                 ....*....|....*....|..
gi 543583739 280 VRQGKVWKAPSSWFIDCVMSFE 301
Cdd:cd17720   80 VRQGKVRVVPVSWLLDCISQFK 101

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 543583739 100 LVLIGSGLSSEQQKMLSELAVILKAKKYTEFDSTVTHVVVPGDAvqSTLKCMLGILNGCWILKFEWVKAC 169
Cdd:cd00027    1 LVICFSGLDDEEREELKKLIEALGGKVSESLSSKVTHLIAKSPS--GEKYYLAALAWGIPIVSPEWLLDC 68

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 543583739 101 VLIGSGLSSEQQKMLSElaVILKAKKY---TEFDSTVTHVVVPGDAvqSTLKCMLGILNGCWILKFEWVKACLR 171
Cdd:cd17736    2 TLVMTSVHSEEQELLES--VVKKLGGFrveDSVTEKTTHVVVGSPR--RTLNVLLGIARGCWILSPDWVLESLE 71

breast cancer carboxy-terminal domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 543583739   199 PKLFDGCYFYLWGTFKHHPKDNLIKLVTAGGGQILSRKPKPDsdvtqtintvayharpdsdqrfcTQYIIYEDL--CNYH 276
Cdd:smart00292   1 PKLFKGKTFYITGSFDKEERDELKELIEALGGKVTSSLSSKT-----------------------TTHVIVGSPegGKLE 57

                           90       100
                   ....*....|....*....|.
gi 543583739   277 PERVRQGKVWKAPSSWFIDCV 297
Cdd:smart00292  58 LLKAIALGIPIVKEEWLLDCL 78

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 543583739  198 LPKLFDGCYFYLwGTFKHHPKDNLIKLVTAGGGQIlsrkpkpdsdvTQTINTvayharpdsdqrfCTQYIIYEDLCNYHP 277
Cdd:pfam16589   1 LPNLFEPLRFYI-NAIPSPSRSKLKRLIEANGGTV-----------VDNINP-------------AVYIVIAPYNKTDKL 55

                          90       100
                  ....*....|....*....|....*....
gi 543583739  278 ERVRQGKVWKApsSWFIDCVMSFELLPLD 306
Cdd:pfam16589  56 AENTKLGVVSP--QWIFDCVKKGKLLPLE 82

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 543583739 105 SGLSSEQQKMLSELAVILKAK--KYTEFDSTVTHVVVpGDAVQSTlKCMLGILNGCWILKFEWVKACLR 171
Cdd:cd17738    7 SGFSEDEKKELISIIEKLGGKvlDSDEFDPKCTHLIC-GKPSRSE-KFLAACAAGKWILHPSYIEASAK 73

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 543583739 115 LSELAVILKAKKYTEFDSTVTHVVVpgdAVQSTLKCMLGI-LNGCWILKFEWVKACLRR--KVCE 176
Cdd:cd17729   36 LWKLAESLGAKVVTDLSPRTTHLVA---AKLGTEKVKQALkMPGIHVVHPDWLWACAERweRVDE 97