Protein: Lys-63-specific deubiquitinase BRCC36 (EC 3.4.19.-) (BRCA1-A complex subunit BRCC36) (BRCA1/BRCA2-containing complex subunit 3) (BRCA1/BRCA2-containing complex subunit 36) (BRISC complex subunit BRCC36) (P46737)
Organism: Mus musculus (Mouse)
Function: Metalloprotease that specifically cleaves 'Lys-63'-linked polyubiquitin chains. Does not have activity toward 'Lys-48'-linked polyubiquitin chains (By similarity). 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) (By similarity). In the BRCA1-A complex, it specifically removes 'Lys-63'-linked ubiquitin on histones H2A and H2AX, antagonizing the RNF8-dependent ubiquitination at double-strand breaks (DSBs) (By similarity). Catalytic subunit of the BRISC complex, a multiprotein complex that specifically cleaves 'Lys-63'-linked ubiquitin in various substrates (By similarity). Mediates the specific 'Lys-63'-specific deubiquitination associated with the COP9 signalosome complex (CSN), via the interaction of the BRISC complex with the CSN complex (By similarity). The BRISC complex is required for normal mitotic spindle assembly and microtubule attachment to kinetochores via its role in deubiquitinating NUMA1 (By similarity). Plays a role in interferon signaling via its role in the deubiquitination of the interferon receptor IFNAR1; deubiquitination increases IFNAR1 activity by enhancing its stability and cell surface expression (By similarity). Acts as a regulator of the NLRP3 inflammasome by mediating deubiquitination of NLRP3, leading to NLRP3 inflammasome assembly. Down-regulates the response to bacterial lipopolysaccharide (LPS) via its role in IFNAR1 deubiquitination (By similarity). Deubiquitinates HDAC1 and PWWP2B leading to their stabilization.
Subcellular location: Nucleus {ECO:0000250|UniProtKB:P46736}. Cytoplasm {ECO:0000250|UniProtKB:P46736}. Cytoplasm, cytoskeleton, spindle pole {ECO:0000250|UniProtKB:P46736}. Note=Localizes at sites of DNA damage at double-strand breaks (DSBs). Interaction with ABRAXAS2 retains BRCC3 in the cytoplasm. {ECO:0000250|UniProtKB:P46736}.
Sequence: MAVQVVQAVQAVHLESDAFLVCLNHALSTEKEEVMGLCIGELNDDIRSDSKFTYTGTEMRTVQEKMDTIRIVHIHSVIILRRSDKRKDRVEISPEQLSAASTEAERLAELTGRPMRVVGWYHSHPHITVWPSHVDVRTQAMYQMMDQGFVGLIFSCFIEDKNTKTGRVLYTCFQSIQAQKSSEYERIEIPIHIVPHITIGKVCLESAVELPKILCQEEQDAYRRIHSLTHLDSVTKIHNGSVFTKNLCSQMSAVSGPLLQWLEDRLEQNQQHLQELQQEKEELMEELSSLE
InterPro domains: - IPR033860: Brcc36 isopeptidase (family) [13-267]
- IPR037518: MPN domain (domain) [12-179]
- IPR000555: JAB1/MPN/MOV34 metalloenzyme domain (domain) [8-178]
- IPR050242: JAMM/MPN+ metalloenzymes, peptidase M67A (family) [7-286]
- IPR040749: BRCC36, C-terminal helical domain (domain) [203-283]
Interaction partners: - BRISC complex subunit Abraxas 2
- BRISC and BRCA1-A complex member 2
- BRISC and BRCA1-A complex member 1
- BRCA1-A complex subunit RAP80
- BRCA1-A complex subunit Abraxas 1
- Breast cancer type 1 susceptibility protein homolog
- BRCA1-associated RING domain protein 1
- NACHT, LRR and PYD domains-containing protein 3
- Serine hydroxymethyltransferase, mitochondrial
- Breast cancer type 2 susceptibility protein homolog
Gene Ontology annotations:
Molecular Function (MF): GO:0003674 (molecular function), GO:0098772 (molecular function regulator activity), GO:0005488 (binding), GO:0003824 (catalytic activity), GO:0030234 (enzyme regulator activity), GO:0140677 (molecular function activator activity), GO:0016787 (hydrolase activity), GO:0140096 (catalytic activity, acting on a protein), GO:0005515 (protein binding), GO:0008233 (peptidase activity), GO:0140030 (modification-dependent protein binding), GO:0031593 (polyubiquitin modification-dependent protein binding), GO:0008237 (metallopeptidase activity), GO:0019783 (ubiquitin-like protein peptidase activity), GO:0101005 (deubiquitinase activity), GO:0140492 (metal-dependent deubiquitinase activity), GO:0061578 (K63-linked deubiquitinase activity)
Biological Process (BP): GO:0008150 (biological process), GO:0008152 (metabolic process), GO:0065007 (biological regulation), GO:0050896 (response to stimulus), GO:0050789 (regulation of biological process), GO:0009987 (cellular process), GO:0048519 (negative regulation of biological process), GO:0044237 (cellular metabolic process), GO:0006807 (nitrogen compound metabolic process), GO:0050794 (regulation of cellular process), GO:0051716 (cellular response to stimulus), GO:0006950 (response to stress), GO:0071704 (organic substance metabolic process), GO:0048523 (negative regulation of cellular process), GO:0044238 (primary metabolic process), GO:1901360 (organic cyclic compound metabolic process), GO:0060548 (negative regulation of cell death), GO:0010941 (regulation of cell death), GO:0006139 (nucleobase-containing compound metabolic process), GO:0046483 (heterocycle metabolic process), GO:0033554 (cellular response to stress), GO:0006725 (cellular aromatic compound metabolic process), GO:0034641 (cellular nitrogen compound metabolic process), GO:0044260 (cellular macromolecule metabolic process), GO:0043170 (macromolecule metabolic process), GO:0090304 (nucleic acid metabolic process), GO:0006974 (cellular response to DNA damage stimulus), GO:0043069 (negative regulation of programmed cell death), GO:0043067 (regulation of programmed cell death), GO:0006259 (DNA metabolic process), GO:0042981 (regulation of apoptotic process), GO:0043066 (negative regulation of apoptotic process), GO:0006281 (DNA repair)
Cellular Component (CC): GO:0005575 (cellular component), GO:0110165 (cellular anatomical entity), GO:0005622 (intracellular anatomical structure), GO:0043226 (organelle), GO:0043229 (intracellular organelle), GO:0043227 (membrane-bounded organelle), GO:0043231 (intracellular membrane-bounded organelle), GO:0005634 (nucleus)