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Search results 1 to 13 out of 13 for Brca2

Category restricted to ProteinDomain (x)

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Categories

Category: ProteinDomain
Type Details Score
Protein Domain
Type: Family
Description: The breast cancer type 2 susceptibility protein (BRCA2) is a breast tumour suppressor involved in double-strand break repair and/or homologous recombination []. BRCA2 gene expression is regulated in a cell-cycle dependent manner and peak expression of BRCA2 mRNA occurring in S phase, suggesting BRCA2 may participate in regulating cell proliferation. BRCA2, and related protein BRCA1, have transcriptional activation potential and the two proteins are associated with the activation of double-strand break repair and/or homologous recombination. The two proteins have been shown to coexist and colocalize in a biochemical complex. BRCA2 has a number of 39 amino acid repeats []that are critical for binding to RAD51 (a key protein in DNA recombinational repair) and resistance to methyl methanesulphonate treatment [, , ]. There are eight repeats in BRCA2 designated as BRC1 to BRC8. BRC1, BRC2, BRC3, BRC4, BRC7, and BRC8 have high sequence identity and bind to Rad51, whereas BRC5 and BRC6 are less well conserved and are unable to bind Rad51 []. It has been suggested that BRCA2 plays a role in positioning Rad51 at the site of DNA repair or in removing Rad51 from DNA once repair has been completed.Mutations in BRCA1 and BRCA2 have been linked to an elevated risk of young onset breast cancer and confer a high risk of the disease through a dominantly inherited fashion []. BRCA2 mutations are typically microdeletions.Homologues exist in plants: the BRCA2A and BRCA2B proteins from Arabidopsis thalianaare required for repair of breaks in double-stranded DNA and homologous recombination and in the prophase stage of meiosis are required for formation of RAD51 and DMC1 foci in males [].
Protein Domain
Type: Repeat
Description: The breast cancer type 2 susceptibility protein has a number of 39 amino acid repeats []that are critical for binding to RAD51 (a key protein in DNA recombinational repair) and resistance to methyl methanesulphonate treatment [, , ]. BRCA2 is a breast tumour suppressor with a potential function in the cellular response to DNA damage. At the cellular level, expressionis regulated in a cell-cycle dependent manner and peak expression of BRCA2 mRNA is found in S phase, suggesting BRCA2 may participate in regulating cell proliferation. There are eight repeats in BRCA2 designated as BRC1 to BRC8. BRC1, BRC2, BRC3, BRC4, BRC7, and BRC8 are highly conserved and bind to Rad51, whereas BRC5 and BRC6 are less well conserved and do not bind to Rad51 []. It has been suggested that BRCA2 plays a role in positioning Rad51 at the site of DNA repair or in removing Rad51 from DNA once repair has been completed.
Protein Domain
Type: Homologous_superfamily
Description: This entry represents a domain found in BRCA2 proteins. This domain adopts a helical structure, consisting of a four-helix cluster core (alpha 1, alpha 8, alpha 9, alpha 10) and two successive β-hairpins (beta 1 to beta 4). An approximately 50-amino acid segment that contains four short helices (alpha 2 to alpha 4), meanders around the surface of the core structure. In BRCA2, thealpha 9 and alpha 10 helices pack with BRCA-2_OB1 () through van der Waals contacts involving hydrophobic and aromatic residues, and also through side-chain and backbone hydrogen bonds. This domain binds the 70-amino acid DSS1 (deleted in split-hand/split foot syndrome) protein, which was originally identified as one of three genes that map to a 1.5-Mb locus deleted in an inherited developmental malformation syndrome [].
Protein Domain
Type: Family
Description: PALB2 (partner and Localizer of BRCA2) binds to the N-terminal region of BRCA2, and is vital for its function by facilitating its subnuclear localization []. It binds BRCA1 and BRCA2 and serves as the molecular scaffold in the formation of the BRCA1-PALB2-BRCA2 complex, which is required for homologous recombination repair []. It has also been shown to bind DNA and physically interacts with RAD51 []. Biallelic mutations in PALB2 cause Fanconi anemia (FA) subtype FA-N, whereas monoallelic mutations predispose to breast, and pancreatic familial cancers[].
Protein Domain
Type: Domain
Description: This domain is found at the C terminus of partner and localiser of BRCA2 (PALB2). It is a seven-bladed WD40-type β-propeller. It binds to the N terminus of BRCA2 [].
Protein Domain
Type: Family
Description: This family of proteins includes BRCA2 and CDKN1A-interacting protein (BCCIP) and Bcp1. In fungi, Bcp1 is involved in nuclear export, actin cytoskeleton organisation and vesicular transport []. Its homologue in human and mouse, BCCIP, may promote cell cycle arrest by enhancing the inhibition of CDK2 activity by CDKN1A/p21 and may be required for repair of DNA damage by homologous recombination in conjunction with BRCA2 [, , , ].
Protein Domain
Type: Family
Description: DNA repair protein XRCC2 is a RAD51 paralogue. In humans, it is part of the protein complex BCDX2 (contains RAD51B, RAD51C, RAD51D, and XRCC2), which acts in the BRCA1-BRCA2-dependent homologous recombination pathway [, ]. Upon DNA damage, BCDX2 acts downstream of BRCA2 recruitment and upstream of RAD51 recruitment. BCDX2 bind single-stranded DNA, single-stranded gaps in duplex DNA and specifically to nicks in duplex DNA []. Interestingly, XRCC2 and other homologous recombination proteins are associated with centrosomes and are required for mitotic stability [].
Protein Domain
Type: Domain
Description: This domain adopts a secondary structure consisting of a pair of long, antiparallel α-helices (thestem) that support a three-helix bundle (3HB) at their end. The 3HB contains a helix-turn-helix motif and is similar to the DNA binding domains of the bacterial site-specific recombinases, and of eukaryotic Myb and homeodomain transcription factors. The Tower domain has an important role in the tumour suppressor function of BRCA2, and is essential for appropriate binding of BRCA2 to DNA [].
Protein Domain
Type: Family
Description: EMSY was originally reported as a transcriptional repressor and breast cancer-associated protein that interacts with the BRCA2 protein []. It contains an N-terminal ENT domain which can bind BRCA2. It is involved in DNA damage repair, genomic instability, and chromatin remodeling []. EMSY can function as an integral component of an NIF-1 complex and play an important role in the regulation of nuclear receptor-mediated transcription []. It is also part of the EMSY/KDM5A/SIN3B complex that may function as a transcriptional repressor [].
Protein Domain
Type: Domain
Description: BRCA2 participates in homologous recombination-mediated repair of double-strand DNA breaks [, ]. It stimulates the displacement of Replication protein A (RPA), the most abundant eukaryotic ssDNA binding protein []. Mutations that map throughout the BRCA2 protein are associated with breast cancer susceptibility []. BRCA2 is a large nuclear protein and its most conserved region is the C-terminal BRCA2DBD. BRCA2DBD binds ssDNA in vitro, and is composed of five structural domains, three of which are OB folds (OB1, OB2, and OB3). BRCA2DBD OB2 and OB3 are arranged in tandem, and their mode of binding can be considered qualitatively similar to two OB folds of RPA1, DBD-A and DBD-B (the major DBDs of RPA) []. This entry represents OB1, which consists of a highly curved five-stranded β-sheet that closes on itself to form a β-barrel. OB1 has a shallow groove formed by one face of the curved sheet and is demarcated by two loops, one between beta 1 and beta 2 and another between beta 4 and beta 5, which allows for weak single strand DNA binding. The domain also binds the 70-amino acid DSS1 (deleted in split-hand/split foot syndrome) protein, which was originally identified as one of three genes that map to a 1.5-Mb locus deleted in an inherited developmental malformation syndrome [].
Protein Domain
Type: Domain
Description: BRCA2 participates in homologous recombination-mediated repair of double-strand DNA breaks [, ]. It stimulates the displacement of Replication protein A (RPA), the most abundant eukaryotic ssDNA binding protein []. Mutations that map throughout the BRCA2 protein are associated with breast cancer susceptibility []. BRCA2 is a large nuclear protein and its most conserved region is the C-terminal BRCA2DBD. BRCA2DBD binds ssDNA in vitro, and is composed of five structural domains, three of which are OB folds (OB1, OB2, and OB3). BRCA2DBD OB2 and OB3 are arranged in tandem, and their mode of binding can be considered qualitatively similar to two OB folds of RPA1, DBD-A and DBD-B (the major DBDs of RPA) []. This entry represents OB3, which consists of a highly curved five-stranded β-sheet that closes on itself to form a β-barrel. OB3 has a pronounced groove formed by one face of the curved sheet and is demarcated by two loops, one between beta 1 and beta 2 and another between beta 4 and beta 5, which allows for strong ssDNA binding [].
Protein Domain
Type: Domain
Description: This entry represents a domain found in BRCA2 proteins. This domain adopts a helical structure, consisting of a four-helix cluster core (alpha 1, alpha 8, alpha 9, alpha 10) and two successive β-hairpins (beta 1 to beta 4). An approximately 50-amino acid segment that contains four short helices (alpha 2 to alpha 4), meanders around the surface of the core structure. In BRCA2, the alpha 9 and alpha 10 helices pack with BRCA-2_OB1 () through van der Waals contacts involving hydrophobic and aromatic residues, and also through side-chain and backbone hydrogen bonds. This domain binds the 70-amino acid DSS1 (deleted in split-hand/split foot syndrome) protein, which was originally identified as one of three genes that map to a 1.5-Mb locus deleted in an inherited developmental malformation syndrome [].
Protein Domain
Type: Family
Description: This entry represents MRG protein family, whose members include MORF4L1/2 (MRG15/MRGX) and MSL3L1/2 from humans, ESA1-associated factor 3 (Eaf3) from yeasts and male-specific lethal 3 (MSL3) from flies. They contain an N-terminal chromodomain that binds H3K36me3, a histone mark associated with transcription elongation []. Saccharomyces cerevisiae Eaf3 is a component of both NuA4 histone acetyltransferase and Rpd3S histone deacetylase complexes [, ]. It was found that Eaf3 mediates preferential deacetylation of coding regions through an interaction between the Eaf3 chromodomain and methylated H3-K36 that presumably results in preferential association of the Rpd3 complex []. The Drosophila MSL proteins (MSL1, MSL2, MSL3, MLE, and MOF) are essential for elevating transcription of the single X chromosome in the male (X chromosome dosage compensation) []. Together with two partlyredundant non-coding RNAs, roX1 and roX2, they form the MSL complex, also known as dosage compensation complex or DCC. MSL complex upregulates transcription by spreading the histone H4 Lys16 (H4K16) acetyl mark []and allows compensation for the loss of one X-chromosomal allele by increasing the transcription from the retained allele []. The MSL3 chromodomain has been shown to bind DNA and methylated H4K20 in vitro []. Human MORF4L1, also known as MRG15, is a component of the NuA4 histone acetyltransferase complex that transcriptional activates genes by acetylation of nucleosomal histones H4 and H2A. This modification may both alter nucleosome - DNA interactions and promote interaction of the modified histones with other proteins which positively regulate transcription. NuA4 complex may also play a direct role in DNA repair when directly recruited to sites of DNA damage. MRG15 is also a component of the mSin3A/Pf1/HDAC complex which acts to repress transcription by deacetylation of nucleosomal histones. MRG15 was found to interact with PALB2, a tumour suppressor protein that plays a crucial role in DNA damage repair by homologous recombination []. Furthermore, MRG15 play a role in the response to double strand breaks (DSBs) by recruiting the BRCA complex (BRCA1, PALB2, BRCA2 and RAD51) to sites of damaged DNA [, ].