P46736 · BRCC3_HUMAN
- ProteinLys-63-specific deubiquitinase BRCC36
- GeneBRCC3
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids316 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Does not have activity toward 'Lys-48'-linked polyubiquitin chains (PubMed:19214193, PubMed:20656690, PubMed:24075985, PubMed:26344097).
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) (PubMed:14636569, PubMed:16707425, PubMed:17525341, PubMed:19202061, PubMed:19261746, PubMed:19261748, PubMed:19261749).
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) (PubMed:20656690).
Catalytic subunit of the BRISC complex, a multiprotein complex that specifically cleaves 'Lys-63'-linked ubiquitin in various substrates (PubMed:20656690, PubMed:24075985, PubMed:26195665, PubMed:26344097).
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 (PubMed:19214193).
The BRISC complex is required for normal mitotic spindle assembly and microtubule attachment to kinetochores via its role in deubiquitinating NUMA1 (PubMed:26195665).
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 (PubMed:24075985, PubMed:26344097).
Acts as a regulator of the NLRP3 inflammasome by mediating deubiquitination of NLRP3, leading to NLRP3 inflammasome assembly (By similarity).
Down-regulates the response to bacterial lipopolysaccharide (LPS) via its role in IFNAR1 deubiquitination (PubMed:24075985).
Deubiquitinates HDAC1 and PWWP2B leading to their stabilization (By similarity).
Cofactor
Features
Showing features for binding site.
GO annotations
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Protein family/group databases
Names & Taxonomy
Protein names
- Recommended nameLys-63-specific deubiquitinase BRCC36
- EC number
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionP46736
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
Disease & Variants
Involvement in disease
Features
Showing features for mutagenesis, natural variant.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 23 | Abolishes localization to sites of DNA damage and interaction with ABRAXAS2; UIMC1; SHMT2; BARAM2 and BABAM1; when associated with R-27. | ||||
Sequence: L → R | ||||||
Mutagenesis | 27 | Abolishes localization to sites of DNA damage and interaction with ABRAXAS2; UIMC1; SHMT2; BABAM2 and BABAM1; when associated with R-23. | ||||
Sequence: L → R | ||||||
Natural variant | VAR_050097 | 74 | in dbSNP:rs28997578 | |||
Sequence: I → V | ||||||
Mutagenesis | 122 | Loss of deubiquitinase activity. | ||||
Sequence: H → Q | ||||||
Mutagenesis | 122-124 | Abolishes metalloprotease activity and function in DNA repair. | ||||
Sequence: HSH → QSQ | ||||||
Mutagenesis | 278 | Abolishes interaction with UIMC1 and SHMT2. | ||||
Sequence: A → R |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 187 variants from UniProt as well as other sources including ClinVar and dbSNP.
Keywords
- Disease
Organism-specific databases
Miscellaneous
Chemistry
Genetic variation databases
PTM/Processing
Features
Showing features for initiator methionine, modified residue, chain, modified residue (large scale data).
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Initiator methionine | 1 | UniProt | Removed | ||||
Sequence: M | |||||||
Modified residue | 2 | UniProt | N-acetylalanine | ||||
Sequence: A | |||||||
Chain | PRO_0000213967 | 2-316 | UniProt | Lys-63-specific deubiquitinase BRCC36 | |||
Sequence: AVQVVQAVQAVHLESDAFLVCLNHALSTEKEEVMGLCIGELNDDTRSDSKFAYTGTEMRTVAEKVDAVRIVHIHSVIILRRSDKRKDRVEISPEQLSAASTEAERLAELTGRPMRVVGWYHSHPHITVWPSHVDVRTQAMYQMMDQGFVGLIFSCFIEDKNTKTGRVLYTCFQSIQAQKSSESLHGPRDFWSSSQHISIEGQKEEERYERIEIPIHIVPHVTIGKVCLESAVELPKILCQEEQDAYRRIHSLTHLDSVTKIHNGSVFTKNLCSQMSAVSGPLLQWLEDRLEQNQQHLQELQQEKEELMQELSSLE | |||||||
Modified residue (large scale data) | 54 | PRIDE | Phosphotyrosine | ||||
Sequence: Y | |||||||
Modified residue (large scale data) | 252 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 258 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 258 | PRIDE | Phosphoserine | ||||
Sequence: S |
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Gene expression databases
Organism-specific databases
Interaction
Subunit
Component of the BRCA1-A complex, at least composed of BRCA1, BARD1, UIMC1/RAP80, ABRAXAS1, BRCC3/BRCC36, babam2 and BABAM1/NBA1. In the BRCA1-A complex, interacts directly with ABRAXAS1 and babam2 (PubMed:18077395, PubMed:19261748).
Component of the BRISC complex, at least composed of ABRAXAS2, BRCC3/BRCC36, BABAM2 and BABAM1/NBA1 (PubMed:24075985, PubMed:25283148, PubMed:26344097).
Identified in a complex with SHMT2 and the other subunits of the BRISC complex (PubMed:24075985).
In the BRISC complex, interacts directly with ABRAXAS2 (PubMed:20656690, PubMed:26344097).
Identified in a complex with ABRAXAS2 and NUMA1 (PubMed:26195665).
The BRISC complex interacts with the CSN complex. Component of the BRCA1/BRCA2 containing complex (BRCC), which also contains BRCA1, BRCA2, BARD1, BABAM2 and RAD51. BRCC is a ubiquitin E3 ligase complex that enhances cellular survival following DNA damage. Interacts with BRCA1. Binds polyubiquitin. Interacts with PWWP2B (By similarity).
Interacts with HDAC1; this interaction is enhanced in the presence of PWWP2B (By similarity).
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | P46736 | ABRAXAS1 Q6UWZ7 | 4 | EBI-750352, EBI-1263451 | |
BINARY | P46736 | ABRAXAS2 Q15018 | 8 | EBI-750352, EBI-1056583 | |
BINARY | P46736 | ANKRD11 X5D778 | 3 | EBI-750352, EBI-17183751 | |
BINARY | P46736 | SHMT2 P34897 | 4 | EBI-750352, EBI-352908 | |
BINARY | P46736 | UIMC1 Q96RL1-1 | 4 | EBI-750352, EBI-9640371 |
Protein-protein interaction databases
Chemistry
Miscellaneous
Structure
Family & Domains
Features
Showing features for domain, motif.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Domain | 12-179 | MPN | ||||
Sequence: VHLESDAFLVCLNHALSTEKEEVMGLCIGELNDDTRSDSKFAYTGTEMRTVAEKVDAVRIVHIHSVIILRRSDKRKDRVEISPEQLSAASTEAERLAELTGRPMRVVGWYHSHPHITVWPSHVDVRTQAMYQMMDQGFVGLIFSCFIEDKNTKTGRVLYTCFQSIQAQ | ||||||
Motif | 122-135 | JAMM motif | ||||
Sequence: HSHPHITVWPSHVD |
Sequence similarities
Phylogenomic databases
Family and domain databases
Sequence & Isoforms
- Sequence statusComplete
This entry describes 5 isoforms produced by Alternative splicing.
P46736-1
This isoform has been chosen as the canonical sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
- Name2
- Length316
- Mass (Da)36,072
- Last updated2002-05-10 v2
- Checksum5720358C1A2F7421
P46736-2
- Name1
- Differences from canonical
- 184-208: Missing
P46736-3
- Name3
P46736-4
- Name4
- Differences from canonical
- 1-114: Missing
P46736-5
- Name5
- Differences from canonical
- 183-252: ESLHGPRDFWSSSQHISIEGQKEEERYERIEIPIHIVPHVTIGKVCLESAVELPKILCQEEQDAYRRIHS → D
Computationally mapped potential isoform sequences
There are 3 potential isoforms mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
A0A0A0MS96 | A0A0A0MS96_HUMAN | BRCC3 | 90 | ||
H7C413 | H7C413_HUMAN | BRCC3 | 85 | ||
X6RJS7 | X6RJS7_HUMAN | BRCC3 | 226 |
Sequence caution
Features
Showing features for alternative sequence, sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Alternative sequence | VSP_037257 | 1-114 | in isoform 4 | |||
Sequence: Missing | ||||||
Alternative sequence | VSP_037258 | 46 | in isoform 3 | |||
Sequence: T → TS | ||||||
Alternative sequence | VSP_037259 | 183-252 | in isoform 5 | |||
Sequence: ESLHGPRDFWSSSQHISIEGQKEEERYERIEIPIHIVPHVTIGKVCLESAVELPKILCQEEQDAYRRIHS → D | ||||||
Alternative sequence | VSP_003261 | 184-208 | in isoform 1 and isoform 3 | |||
Sequence: Missing | ||||||
Sequence conflict | 225 | in Ref. 2; AAB29005 | ||||
Sequence: G → W |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
X64643 EMBL· GenBank· DDBJ | CAA45917.1 EMBL· GenBank· DDBJ | mRNA | ||
S68015 EMBL· GenBank· DDBJ | AAB29005.2 EMBL· GenBank· DDBJ | mRNA | Different initiation | |
AY438030 EMBL· GenBank· DDBJ | AAR30498.1 EMBL· GenBank· DDBJ | mRNA | ||
AK298886 EMBL· GenBank· DDBJ | BAG60999.1 EMBL· GenBank· DDBJ | mRNA | ||
AK299194 EMBL· GenBank· DDBJ | BAG61237.1 EMBL· GenBank· DDBJ | mRNA | ||
AK313544 EMBL· GenBank· DDBJ | BAG36320.1 EMBL· GenBank· DDBJ | mRNA | ||
BX293995 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
BX470111 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
BC002999 EMBL· GenBank· DDBJ | AAH02999.1 EMBL· GenBank· DDBJ | mRNA | ||
BC006540 EMBL· GenBank· DDBJ | AAH06540.1 EMBL· GenBank· DDBJ | mRNA |