Overview
| Uniprot ID | B2RYM5 |
|---|
| Protein Name | Lys-63-specific deubiquitinase BRCC36 |
|---|
| Gene Name | Brcc3 |
|---|
| Organism | Rattus norvegicus |
|---|
Kla Sites from experimental identification
| Position |
Flanking peptide |
| 280 |
LRELQREKEELMAEL |
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 (By similarity). 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 (By similarity). Deubiquitinates HDAC1 and PWWP2B leading to their stabilization (By similarity)
Protein Sequence
10
MAVPVVQAVQ
20
AVHLESDAFL
30
VCLNHALSTE
40
KEEVMGLCIG
50
ELNDDVRSES
60
KFAHAGSDVC
70
TVPEKVDSIR
80
VVHIHSVIIL
90
RRSDKRKDRV
100
EISPEQLSAA
110
STEAERLAEL
120
TGRPMRVVGW
130
YHSHPHITVW
140
PSHVDVRTQA
150
MYQMMDQGFV
160
GLIFSCFIED
170
KNTKTGRVLY
180
TCFQSVQAQK
190
SSDYERIEIP
200
VHVVPHVTIG
210
KVCLESAVEL
220
PKILCQEEQD
230
AYRRIHSLTH
240
LDSVTKIHNG
250
SVFTKNLCSQ
260
MSAVSGPLLQ
270
WLEDRLEQNQ
280
QHLRELQREK
290
EELMAELRSL
E
Gene Ontology
| Classification |
GO ID |
Description |
| Cellular Component |
GO:0070531 |
BRCA1-A complex |
| Cellular Component |
GO:0070552 |
BRISC complex |
| Cellular Component |
GO:0005737 |
cytoplasm |
| Cellular Component |
GO:0000152 |
nuclear ubiquitin ligase complex |
| Cellular Component |
GO:0005654 |
nucleoplasm |
| Cellular Component |
GO:0005634 |
nucleus |
| Cellular Component |
GO:0000922 |
spindle pole |
| Cellular Component |
GO:0000151 |
ubiquitin ligase complex |
| Molecular Function |
GO:0004843 |
cysteine-type deubiquitinase activity |
| Molecular Function |
GO:0030234 |
enzyme regulator activity |
| Molecular Function |
GO:0061578 |
K63-linked deubiquitinase activity |
| Molecular Function |
GO:0046872 |
metal ion binding |
| Molecular Function |
GO:0140492 |
metal-dependent deubiquitinase activity |
| Molecular Function |
GO:0008237 |
metallopeptidase activity |
| Molecular Function |
GO:0031593 |
polyubiquitin modification-dependent protein binding |
| Biological Process |
GO:0051301 |
cell division |
| Biological Process |
GO:0071479 |
cellular response to ionizing radiation |
| Biological Process |
GO:0006338 |
chromatin remodeling |
| Biological Process |
GO:0140861 |
DNA repair-dependent chromatin remodeling |
| Biological Process |
GO:0006302 |
double-strand break repair |
| Biological Process |
GO:0007095 |
mitotic G2 DNA damage checkpoint signaling |
| Biological Process |
GO:0045739 |
positive regulation of DNA repair |
| Biological Process |
GO:1900227 |
positive regulation of NLRP3 inflammasome complex assembly |
| Biological Process |
GO:0070536 |
protein K63-linked deubiquitination |
| Biological Process |
GO:0006508 |
proteolysis |
| Biological Process |
GO:0010212 |
response to ionizing radiation |
| Biological Process |
GO:0010165 |
response to X-ray |
Reference
[1] Sheng L, Xu H, Wang Y, Ni J, Xiang T et al.. Systematic analysis of lysine lactylation in nucleus pulposus cells.. iScience 27(11):111157. 2024 Nov 15. PMID: 39524337.