background:
BRCC45 was initially suggested to be a housekeeping protein that is highly expressed in brain and reproductive organs. Later experiments indicated BRCC45 forms a complex with the breast and ovarian predisposition proteins BRCA1 and BRCA2 as well as RAD51 and BRCC36. This complex has a ubiquitin E3 ligase activity and is thought to enhance cellular survival following DNA damage. BRCC45 has also been suggested to function as a death receptor associated anti apoptotic protein by inhibiting the BID induced activation of the mitochondrial apoptotic pathway. Higher levels of BRCC45 were detected in the majority of hepatocellular carcinomas, suggesting that BRCC45 may promote tumorigenesis when overexpressed. At least three isoforms of BRCC45 are known to exist.
Function:
Component of the BRCA1-A complex, a complex that specifically recognizes 'Lys-63'-linked ubiquitinated histones H2A and H2AX at DNA lesions sites, leading to target the BRCA1-BARD1 heterodimer to sites of DNA damage at double-strand breaks (DSBs). The BRCA1-A complex also possesses deubiquitinase activity that specifically removes 'Lys-63'-linked ubiquitin on histones H2A and H2AX. In the BRCA1-A complex, it acts as an adapter that bridges the interaction between BABAM1/NBA1 and the rest of the complex, thereby being required for the complex integrity and modulating the E3 ubiquitin ligase activity of the BRCA1-BARD1 heterodimer. Probably also plays a role as a component of the BRISC complex, a multiprotein complex that specifically cleaves 'Lys-63'-linked ubiquitin. May play a role in homeostasis or cellular differentiation in cells of neural, epithelial and germline origins. May also act as a death receptor-associated anti-apoptotic protein, which inhibits the mitochondrial apoptotic pathway. May regulate TNF-alpha signaling through its interactions with TNFRSF1A; however these effects may be indirect.
Subunit:
Component of the BRCA1-A complex, at least composed of the BRCA1, BARD1, UIMC1/RAP80, FAM175A/Abraxas, BRCC3/BRCC36, BRE/BRCC45 and BABAM1/NBA1. In the BRCA1-A complex, interacts directly with FAM175A/Abraxas, BRCC3/BRCC36 and BABAM1/NBA1. Binds polyubiquitin. Component of the BRISC complex, at least composed of the FAM175B/ABRO1, BRCC3/BRCC36, BRE/BRCC45 and BABAM1/NBA1. Component of the BRCA1/BRCA2 containing complex (BRCC), which also contains BRCA1, BRCA2, BARD1, BRCC3/BRCC36 and RAD51. BRCC is a ubiquitin E3 ligase complex that enhances cellular survival following DNA damage. May interact with FAS and TNFRSF1A.
Subcellular Location:
Cytoplasm. Nucleus. Note=Localizes at sites of DNA damage at double-strand breaks (DSBs).
Tissue Specificity:
Expressed in all cell lines examined. Highly expressed in placenta.
Similarity:
Belongs to the BRE family.
Database links:
Entrez Gene: 9577 Human
Entrez Gene: 107976 Mouse
Entrez Gene: 362704 Rat
Omim: 610497 Human
SwissProt: A6QQW8 Cow
SwissProt: Q9NXR7 Human
SwissProt: Q8K3W0 Mouse
SwissProt: Q6P7Q1 Rat
Unigene: 258314 Human
Unigene: 482126 Mouse
Unigene: 224501 Rat
Important Note:
This product as supplied is intended for research use only, not for use in human, therapeutic or diagnostic applications.
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