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Anti-BRCA1 Antibody, clone MS13 detects level of BRCA1 & has been published & validated for use in Western Blotting, IHC, ICC.
More>>Anti-BRCA1 Antibody, clone MS13 detects level of BRCA1 & has been published & validated for use in Western Blotting, IHC, ICC. Less<<
Anti-BRCA1 Antibody, clone MS13: SDB (Sicherheitsdatenblätter), Analysenzertifikate und Qualitätszertifikate, Dossiers, Broschüren und andere verfügbare Dokumente.
Breast cancer type 1 susceptibility protein (BCRA1; RING finger protein 53) functions as a tumor suppressor. BRCA1 is an important member of the DNA repair pathway. After DNA damage, BRCA1 is phosphorylated on multiple serine residues by the ATR kinase or Chk2, and is localized to lesion sites with PCNA. BRCA1 interacts with a wide range of proteins including Rad50, NBS1, and Mre11, c-Abl tyrosine kinase, and γH2A.X, involved in the detection of damaged DNA and activation of appropriate repair pathways. BRCA1 may also respond to DNA damage by promoting gene expression through association with transcriptional proteins and RNA polymerase II, and may regulate the p53 pathway by this mechanism. Previous studies have indicated that mutations in the BRCA1 gene may contribute to the development of breast and ovarian cancer.
References
Product Information
Format
Purified
Control
HeLa nuclear extract
Presentation
Purified mouse monoclonal IgG1κ in buffer containing 0.1 M Tris-Glycine (pH 7.4), 150 mM NaCl with 0.05% sodium azide.
This gene encodes a nuclear phosphoprotein that plays a role in maintaining genomic stability, and it also acts as a tumor suppressor. The encoded protein combines with other tumor suppressors, DNA damage sensors, and signal transducers to form a large multi-subunit protein complex known as the BRCA1-associated genome surveillance complex (BASC). This gene product associates with RNA polymerase II, and through the C-terminal domain, also interacts with histone deacetylase complexes. This protein thus plays a role in transcription, DNA repair of double-stranded breaks, and recombination. Mutations in this gene are responsible for approximately 40% of inherited breast cancers and more than 80% of inherited breast and ovarian cancers. Alternative splicing plays a role in modulating the subcellular localization and physiological function of this gene. Many alternatively spliced transcript variants, some of which are disease-associated mutations, have been described for this gene, but the full-length natures of only some of these variants has been described. A related pseudogene, which is also located on chromosome 17, has been identified. [provided by RefSeq, May 2009].
FUNCTION: E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage. It is unclear whether it also mediates the formation of other types of polyubiquitin chains. The E3 ubiquitin-protein ligase activity is required for its tumor suppressor function. The BRCA1-BARD1 heterodimer coordinates a diverse range of cellular pathways such as DNA damage repair, ubiquitination and transcriptional regulation to maintain genomic stability. Regulates centrosomal microtubule nucleation. Required for normal cell cycle progression from G2 to mitosis. Required for appropriate cell cycle arrests after ionizing irradiation in both the S-phase and the G2 phase of the cell cycle. Involved in transcriptional regulation of P21 in response to DNA damage. Required for FANCD2 targeting to sites of DNA damage. May function as a transcriptional regulator. Inhibits lipid synthesis by binding to inactive phosphorylated ACACA and preventing its dephosphorylation. Contributes to homologous recombination repair (HRR) via its direct interaction with PALB2, fine-tunes recombinational repair partly through its modulatory role in the PALB2-dependent loading of BRCA2-RAD51 repair machinery at DNA breaks. ENZYME REGULATION: The E3 ubiquitin-protein ligase activity is inhibited by phosphorylation by AURKA. Activity is increased by phosphatase treatment.
PATHWAY: Protein modification; protein ubiquitination.
SUBUNIT STRUCTURE: Heterodimer with BARD1. Part of the BRCA1-associated genome surveillance complex (BASC), which contains BRCA1, MSH2, MSH6, MLH1, ATM, BLM, PMS2 and the RAD50-MRE11-NBN protein complex. This association could be a dynamic process changing throughout the cell cycle and within subnuclear domains. Component of the BRCA1-A complex, at least composed of the BRCA1, BARD1, UIMC1/RAP80, FAM175A/Abraxas, BRCC3/BRCC36, BRE/BRCC45 and BABAM1/NBA1. Interacts (via BRCT domains) with FAM175A/Abraxas and RBBP8. Associates with RNA polymerase II holoenzyme. Interacts with SMC1A and COBRA1/NELFB. Interacts (via BRCT domains) with phosphorylated BRIP1. Interacts with FANCD2 (ubiquitinated). Interacts with BAP1. Interacts with DCLRE1C/Artemis and CLSPN. Interacts with H2AFX (phosphorylated on 'Ser-140'). Interacts with CHEK1 and CHEK2. Interacts with BRCC3. Interacts (via BRCT domains) with ACACA (phosphorylated); the interaction prevents dephosphorylation of ACACA. Interacts with AURKA. Interacts with UBXN1. Part of a trimeric complex containing BRCA1, BRCA2 and PALB2. Interacts with PALB2 and this interaction is essential for its function in HRR. Interacts with BRCA2 only in the presence of PALB2 which serves as the bridging protein.
SUBCELLULAR LOCATION: Nucleus. Note: Localizes at sites of DNA damage at double-strand breaks (DSBs); recruitment to DNA damage sites is mediated by the BRCA1-A complex.
Isoform 3: Cytoplasm
Isoform 5: Cytoplasm
TISSUE SPECIFICITY: Isoform 1 and isoform 3 are widely expressed. Isoform 3 is reduced or absent in several breast and ovarian cancer cell lines.
DOMAIN: The BRCT domains recognize and bind phosphorylated pSXXF motif on proteins. The interaction with the phosphorylated pSXXF motif of FAM175A/Abraxas, recruits BRCA1 at DNA damage sites. Ref.56
The RING-type zinc finger domain interacts with BAP1.
PTM: Phosphorylation at Ser-308 by AURKA is required for normal cell cycle progression from G2 to mitosis. Phosphorylated in response to IR, UV, and various stimuli that cause checkpoint activation, probably by ATM or ATR. Phosphorylation at Ser-988 by CHEK2 regulates mitotic spindle assembly. Ref.13 Ref.14 Ref.18 Ref.27 Ref.30 Ref.33 Ref.36 Ref.39 Ref.40
Autoubiquitinated, undergoes 'Lys-6'-linked polyubiquitination. 'Lys-6'-linked polyubiquitination does not promote degradation.
POLYMORPHISM: There is evidence that the presence of the rare form of Gln-356-Arg and Leu-871-Pro polymorphisms may be associated with an increased risk for developing ovarian cancer.
INVOLVEMENT IN DISEASE: Defects in BRCA1 are a cause of susceptibility to breast cancer (BC) [MIM:114480]. A common malignancy originating from breast epithelial tissue. Breast neoplasms can be distinguished by their histologic pattern. Invasive ductal carcinoma is by far the most common type. Breast cancer is etiologically and genetically heterogeneous. Important genetic factors have been indicated by familial occurrence and bilateral involvement. Mutations at more than one locus can be involved in different families or even in the same case. Note=Mutations in BRCA1 are thought to be responsible for 45% of inherited breast cancer. Moreover, BRCA1 carriers have a 4-fold increased risk of colon cancer, whereas male carriers face a 3-fold increased risk of prostate cancer. Cells lacking BRCA1 show defects in DNA repair by homologous recombination. Ref.1 Ref.15 Ref.50 Ref.52 Ref.55 Ref.58 Ref.59 Ref.60 Ref.61
Defects in BRCA1 are a cause of susceptibility to familial breast-ovarian cancer type 1 (BROVCA1) [MIM:604370]. A condition associated with familial predisposition to cancer of the breast and ovaries. Characteristic features in affected families are an early age of onset of breast cancer (often before age 50), increased chance of bilateral cancers (cancer that develop in both breasts, or both ovaries, independently), frequent occurrence of breast cancer among men, increased incidence of tumors of other specific organs, such as the prostate. Note=Mutations in BRCA1 are thought to be responsible for more than 80% of inherited breast-ovarian cancer.
Defects in BRCA1 are a cause of susceptibility to ovarian cancer (OC) [MIM:167000]. The term ovarian cancer defines malignancies originating from ovarian tissue. Although many histologic types of ovarian tumors have been described, epithelial ovarian carcinoma is the most common form. Ovarian cancers are often asymptomatic and the recognized signs and symptoms, even of late-stage disease, are vague. Consequently, most patients are diagnosed with advanced disease.
Defects in BRCA1 are a cause of susceptibility to pancreatic cancer type 4 (PNCA4) [MIM:614320]. A malignant neoplasm of the pancreas. Tumors can arise from both the exocrine and endocrine portions of the pancreas, but 95% of them develop from the exocrine portion, including the ductal epithelium, acinar cells, connective tissue, and lymphatic tissue.
SEQUENCE SIMILARITIES: Contains 2 BRCT domains.
Contains 1 RING-type zinc finger.
Molecular Weight
~220 kDa observed. The calculated molecular weight of this protein is 208 kDa, but can be observed at ~220 kDa due to high glycosylation. An uncharacterized band appears at ~65 kDa in some lysates.
Physicochemical Information
Dimensions
Materials Information
Toxicological Information
Safety Information according to GHS
Safety Information
Product Usage Statements
Quality Assurance
Evaluated by Western Blot in HeLa nuclear extract.
Western Blot Analysis: 0.5 µg/mL of this antibody detected BRCA1 on 10 µg of HeLa nuclear extract.
Usage Statement
Unless otherwise stated in our catalog or other company documentation accompanying the product(s), our products are intended for research use only and are not to be used for any other purpose, which includes but is not limited to, unauthorized commercial uses, in vitro diagnostic uses, ex vivo or in vivo therapeutic uses or any type of consumption or application to humans or animals.