BRISC complex
Definition
Target type: cellularcomponent
A protein complex that contains the FAM175B/ABRO1, BRCC3/BRCC36, BRE/BRCC45 and MERIT40/NBA1 proteins, and specifically cleaves K63-linked polyubiquitin chains. [GOC:mah, PMID:19214193]
The BRISC complex is a large multi-protein E3 ubiquitin ligase complex involved in various cellular processes, including DNA repair, signal transduction, and innate immunity. Its cellular component comprises multiple subunits, each contributing to its overall function. The BRISC complex is primarily localized to the cytoplasm, but it can also be found in the nucleus. It interacts with various cellular components, including:
* **Scaffolding subunits:** These subunits provide the structural framework for the complex, facilitating the assembly and interaction of other subunits. Key scaffolding subunits include:
* **BRCC36:** Acts as a central scaffold protein, interacting with other subunits and mediating complex assembly.
* **MERIT40:** A ubiquitin ligase that associates with BRCC36 and contributes to the overall ubiquitin ligase activity of the complex.
* **Ubiquitin ligase subunits:** These subunits possess catalytic activity, specifically responsible for attaching ubiquitin chains to target proteins. Key ubiquitin ligase subunits include:
* **RNF8:** An E3 ubiquitin ligase that plays a crucial role in DNA double-strand break repair by ubiquitinating histone H2A, a process essential for recruiting repair machinery.
* **RNF168:** Another E3 ligase that cooperates with RNF8 in DNA repair, promoting further ubiquitination of histone H2A and contributing to the formation of repair foci.
* **Adaptor subunits:** These subunits facilitate the interaction between the BRISC complex and its target proteins, ensuring substrate specificity and promoting efficient ubiquitination. Key adaptor subunits include:
* **SHPRH1:** A protein that binds to ubiquitin and recruits BRISC to ubiquitinated substrates, promoting substrate recognition and ubiquitination.
* **RAP80:** A protein that binds to ubiquitinated histone H2A, facilitating the recruitment of BRISC to sites of DNA damage and promoting the repair process.
* **Other subunits:** The BRISC complex also contains other subunits that contribute to its overall function, such as:
* **RNF169:** An E3 ubiquitin ligase that interacts with the BRISC complex and potentially regulates its activity.
* **ZNF367:** A zinc finger protein that interacts with the BRISC complex and may contribute to its stability or function.
The precise arrangement and interactions of these subunits within the BRISC complex are still under investigation. However, it is evident that this intricate complex plays a vital role in various cellular processes, and understanding its cellular component is crucial for dissecting its molecular mechanisms and potential therapeutic applications.'
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Proteins (1)
| Protein | Definition | Taxonomy |
|---|---|---|
| Serine hydroxymethyltransferase, mitochondrial | A serine hydroxymethyltransferase, mitochondrial that is encoded in the genome of human. [PRO:DNx, UniProtKB:P34897] | Homo sapiens (human) |
Compounds (9)
| Compound | Definition | Classes | Roles |
|---|---|---|---|
| oxaprozin | oxaprozin : A monocarboxylic acid that is a propionic acid derivative having a 4,5-diphenyl-1,3-oxazol-2-yl substituent at position 3. It is non-steroidal anti-inflammatory drug commonly used to relieve the pain and inflammatory responses associated with osteoarthritis and rheumatoid arthritis. Oxaprozin: An oxazole-propionic acid derivative, cyclooxygenase inhibitor, and non-steroidal anti-inflammatory drug that is used in the treatment of pain and inflammation associated with of OSTEOARTHRITIS; RHEUMATOID ARTHRITIS; and ARTHRITIS, JUVENILE. | 1,3-oxazoles; monocarboxylic acid | analgesic; non-steroidal anti-inflammatory drug |
| papaverine | papaverine : A benzylisoquinoline alkaloid that is isoquinoline substituted by methoxy groups at positions 6 and 7 and a 3,4-dimethoxybenzyl group at position 1. It has been isolated from Papaver somniferum. Papaverine: An alkaloid found in opium but not closely related to the other opium alkaloids in its structure or pharmacological actions. It is a direct-acting smooth muscle relaxant used in the treatment of impotence and as a vasodilator, especially for cerebral vasodilation. The mechanism of its pharmacological actions is not clear, but it apparently can inhibit phosphodiesterases and it may have direct actions on calcium channels. | benzylisoquinoline alkaloid; dimethoxybenzene; isoquinolines | antispasmodic drug; vasodilator agent |
| primaquine | primaquine : An N-substituted diamine that is pentane-1,4-diamine substituted by a 6-methoxyquinolin-8-yl group at the N(4) position. It is a drug used in the treatment of malaria and Pneumocystis pneumonia. Primaquine: An aminoquinoline that is given by mouth to produce a radical cure and prevent relapse of vivax and ovale malarias following treatment with a blood schizontocide. It has also been used to prevent transmission of falciparum malaria by those returning to areas where there is a potential for re-introduction of malaria. Adverse effects include anemias and GI disturbances. (From Martindale, The Extra Pharmacopeia, 30th ed, p404) | aminoquinoline; aromatic ether; N-substituted diamine | antimalarial |
| flupirtine | flupirtine: RN given refers to parent cpd without isomeric designation | aminopyridine | |
| duloxetine | duloxetine | ||
| N-[7-(2-furanyl)-5-oxo-7,8-dihydro-6H-quinazolin-2-yl]acetamide | quinazolines | ||
| pyrvinium | pyrvinium : A quinolinium ion that is 1-methylquinolinium substituted by dimethylamino group at position 6 and a (E)-2-(2,5-dimethyl-1-phenyl-1H-pyrrol-3-yl)ethenyl at position 2. It is a anthelminthic drug active against pinworms. The salts of pyrvinium can also be used as anticancer agents. pyrvinium: RN given refers to parent cpd; synonyms vanquin & vankin refer to pamoate[2:1]; structure in Merck Index, 9th ed, #7810 | quinolinium ion | anthelminthic drug; antineoplastic agent |
| 2-(2-furanylmethyl)-3-[[2-(3-pyridinyl)-3H-benzimidazol-5-yl]amino]-3H-isoindol-1-one | isoindoles | ||
| gw2974 | GW2974: quinazoline derivative, which is able to block the activation of both the EGFR and erbB2 | pyridopyrimidine |