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 2250232553 1538 MSMVVSGLTPEEFMLVYKFARKHHITLTNLITEETTHVVMKTDAEFVCERTLKYFLGIAGGKWVVSYFWVTQSIKERKML 1617
Cdd:cd17735      1 MSMVASGLTPEELMLVQKFARKTGSTLTSQFTEETTHVIMKTDAELVCERTLKYFLGIAGRKWVVSYQWITQSIKEGKIL 80

                           90
                   ....*....|....*..
gi 2250232553 1618 NEHDFEVRGDVVNGRNH 1634
Cdd:cd17735     81 PEHDFEVRGDVVNGRNH 97

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 2250232553    2 SLQESTRFSQLVEELLKIICAFQLDTGL 29
Cdd:cd16498     67 SLQESTRFKQLVEAVKKLIDAFELDTGL 94

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 2250232553 1538 MSMVVSGLTPEEFMLVYKFARKHHITLTNLITEETTHVVMKTDAEFVCERTLKYFLGIAGGKWVVSYFWVTQSIKERKML 1617
Cdd:cd17735      1 MSMVASGLTPEELMLVQKFARKTGSTLTSQFTEETTHVIMKTDAELVCERTLKYFLGIAGRKWVVSYQWITQSIKEGKIL 80

                           90
                   ....*....|....*..
gi 2250232553 1618 NEHDFEVRGDVVNGRNH 1634
Cdd:cd17735     81 PEHDFEVRGDVVNGRNH 97

breast cancer carboxy-terminal domain;

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2250232553  1646 RKIFRGLEICCYGPFTNMPTDQLEWMVQLCGASVVKELSSFTLgtgVHPIVVVQPDAWTEdngfHAIGQMCEAPVVTREW 1725
Cdd:smart00292    1 PKLFKGKTFYITGSFDKEERDELKELIEALGGKVTSSLSSKTT---THVIVGSPEGGKLE----LLKAIALGIPIVKEEW 73

                    ....*
gi 2250232553  1726 VLDSV 1730
Cdd:smart00292   74 LLDCL 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        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2250232553 1532 ERVNKRMSMVVSGLTPEEFMLVYKFARKHHITLTNLITEETTHVVmktdaefVCERTLKYFLGIAGGKWVVSYFWVTQSI 1611
Cdd:pfam00533    3 EKLFSGKTFVITGLDGLERDELKELIEKLGGKVTDSLSKKTTHVI-------VEARTKKYLKAKELGIPIVTEEWLLDCI 75

breast cancer carboxy-terminal domain;

                            10        20        30        40        50        60        70
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2250232553  1550 FMLVYKFARKHHITLTNLITE----ETTHVVMKTDAEFVCE----RTLKYFLGIAGGKWVVSYFWVTQSI 1611
Cdd:smart00292    9 FYITGSFDKEERDELKELIEAlggkVTSSLSSKTTTHVIVGspegGKLELLKAIALGIPIVKEEWLLDCL 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 2250232553 1538 MSMVVSGLTPEEFMLVYKFARKHHITLTNLITEETTHVVMKTDAEFVCERTLKYFLGIAGGKWVVSYFWVTQSIKERKML 1617
Cdd:cd17735      1 MSMVASGLTPEELMLVQKFARKTGSTLTSQFTEETTHVIMKTDAELVCERTLKYFLGIAGRKWVVSYQWITQSIKEGKIL 80

                           90
                   ....*....|....*..
gi 2250232553 1618 NEHDFEVRGDVVNGRNH 1634
Cdd:cd17735     81 PEHDFEVRGDVVNGRNH 97

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 2250232553 1543 SGLTPEEFMLVYKFARKHHITLTNLITEETTHVVMKTDAEFVCERTLKYFLGIAGGKWVVSYFWVTQSIKERK 1615
Cdd:cd17734      6 SGLSSEQKKLLEKLAQLLKAKVVTEFSPEVTHVVVPADERGVCPRTMKYLMGILAGKWIVSFEWVEACLKAKK 78

breast cancer carboxy-terminal domain;

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2250232553  1646 RKIFRGLEICCYGPFTNMPTDQLEWMVQLCGASVVKELSSFTLgtgVHPIVVVQPDAWTEdngfHAIGQMCEAPVVTREW 1725
Cdd:smart00292    1 PKLFKGKTFYITGSFDKEERDELKELIEALGGKVTSSLSSKTT---THVIVGSPEGGKLE----LLKAIALGIPIVKEEW 73

                    ....*
gi 2250232553  1726 VLDSV 1730
Cdd:smart00292   74 LLDCL 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        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2250232553 1646 RKIFRGLEICCYGpFTNMPTDQLEWMVQLCGASVVKELSSFTlgtgvHPIVVVqpdawtEDNGFHAIGQMCEAPVVTREW 1725
Cdd:pfam00533    3 EKLFSGKTFVITG-LDGLERDELKELIEKLGGKVTDSLSKKT-----THVIVE------ARTKKYLKAKELGIPIVTEEW 70

                   ....*
gi 2250232553 1726 VLDSV 1730
Cdd:pfam00533   71 LLDCI 75

RING finger, HC subclass, found in breast cancer type 1 susceptibility protein (BRCA1) and similar proteins; BRCA1, also known as RING finger protein 53 (RNF53), is a RING finger protein encoded by the tumor suppressor gene BRCA1 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.

                           10        20
                   ....*....|....*....|....*...
gi 2250232553    2 SLQESTRFSQLVEELLKIICAFQLDTGL 29
Cdd:cd16498     67 SLQESTRFKQLVEAVKKLIDAFELDTGL 94

breast cancer carboxy-terminal domain;

                            10        20        30        40        50        60        70
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2250232553  1550 FMLVYKFARKHHITLTNLITE----ETTHVVMKTDAEFVCE----RTLKYFLGIAGGKWVVSYFWVTQSI 1611
Cdd:smart00292    9 FYITGSFDKEERDELKELIEAlggkVTSSLSSKTTTHVIVGspegGKLELLKAIALGIPIVKEEWLLDCL 78