| IED ID | IndEnz0002006165 |
| Enzyme Type ID | protease006165 |
| Protein Name |
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 |
| Gene Name | Brcc3 Brcc36 C6.1a |
| Organism | Mus musculus (Mouse) |
| Taxonomic Lineage | cellular organisms Eukaryota Opisthokonta Metazoa Eumetazoa Bilateria Deuterostomia Chordata Craniata Vertebrata Gnathostomata (jawed vertebrates) Teleostomi Euteleostomi Sarcopterygii Dipnotetrapodomorpha Tetrapoda Amniota Mammalia Theria Eutheria Boreoeutheria Euarchontoglires Glires (Rodents and rabbits) Rodentia Myomorpha (mice and others) Muroidea Muridae Murinae Mus Mus Mus musculus (Mouse) |
| Enzyme Sequence | MAVQVVQAVQAVHLESDAFLVCLNHALSTEKEEVMGLCIGELNDDIRSDSKFTYTGTEMRTVQEKMDTIRIVHIHSVIILRRSDKRKDRVEISPEQLSAASTEAERLAELTGRPMRVVGWYHSHPHITVWPSHVDVRTQAMYQMMDQGFVGLIFSCFIEDKNTKTGRVLYTCFQSIQAQKSSEYERIEIPIHIVPHITIGKVCLESAVELPKILCQEEQDAYRRIHSLTHLDSVTKIHNGSVFTKNLCSQMSAVSGPLLQWLEDRLEQNQQHLQELQQEKEELMEELSSLE |
| Enzyme Length | 291 |
| Uniprot Accession Number | P46737 |
| Absorption | |
| Active Site | |
| Activity Regulation | |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | |
| DNA Binding | |
| EC Number | 3.4.19.- |
| Enzyme Function | FUNCTION: Metalloprotease that specifically cleaves 'Lys-63'-linked polyubiquitin chains. Does not have activity toward 'Lys-48'-linked polyubiquitin chains. 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). 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). Catalytic subunit of the BRISC complex, a multiprotein complex that specifically cleaves 'Lys-63'-linked ubiquitin in various substrates. 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. The BRISC complex is required for normal mitotic spindle assembly and microtubule attachment to kinetochores via its role in deubiquitinating NUMA1. 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. Down-regulates the response to bacterial lipopolysaccharide (LPS) via its role in IFNAR1 deubiquitination (By similarity). Deubiquitinates HDAC1 and PWWP2B leading to their stabilization (PubMed:34180153). {ECO:0000250|UniProtKB:P46736, ECO:0000269|PubMed:34180153}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Alternative sequence (1); Chain (1); Domain (1); Initiator methionine (1); Metal binding (3); Modified residue (2); Motif (1); Sequence conflict (3) |
| Keywords | 3D-structure;Acetylation;Alternative splicing;Cell cycle;Cell division;Chromatin regulator;Cytoplasm;Cytoskeleton;DNA damage;DNA repair;Hydrolase;Metal-binding;Metalloprotease;Mitosis;Nucleus;Phosphoprotein;Protease;Reference proteome;Ubl conjugation pathway;Zinc |
| Interact With | |
| Induction | |
| Subcellular Location | 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}. |
| Modified Residue | MOD_RES 2; /note=N-acetylalanine; /evidence=ECO:0000250|UniProtKB:P46736; MOD_RES 233; /note=Phosphoserine; /evidence=ECO:0000250|UniProtKB:P46736 |
| Post Translational Modification | |
| Signal Peptide | |
| Structure 3D | X-ray crystallography (1) |
| Cross Reference PDB | 6GVW; |
| Mapped Pubmed ID | 11217851; 12466851; 14610273; 15618518; 16615898; 18323671; 21267068; 21274006; 21677750; 22974638; 23246432; 23451117; 26045162; 30755420; 31253574; 31485755; 31787240; 31866999; |
| Motif | MOTIF 122..135; /note=JAMM motif; /evidence=ECO:0000255|PROSITE-ProRule:PRU01182 |
| Gene Encoded By | |
| Mass | 33,340 |
| Kinetics | |
| Metal Binding | METAL 122; /note=Zinc; catalytic; /evidence=ECO:0000255|PROSITE-ProRule:PRU01182; METAL 124; /note=Zinc; catalytic; /evidence=ECO:0000255|PROSITE-ProRule:PRU01182; METAL 135; /note=Zinc; catalytic; /evidence=ECO:0000255|PROSITE-ProRule:PRU01182 |
| Rhea ID | |
| Cross Reference Brenda |