Search Results

Overview

Uniprot ID	P46736
Protein Name	Lys-63-specific deubiquitinase BRCC36
Gene Name	BRCC3
Organism	Homo sapiens

Kla Sites from experimental identification

Position	Flanking peptide
51	DDTRSDSKFAYTGTE

Function

Metalloprotease that specifically cleaves 'Lys-63'-linked polyubiquitin chains (PubMed:19214193, PubMed:20656690, PubMed:24075985, PubMed:26344097). 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)

Protein Sequence

10 MAVQVVQAVQ 20 AVHLESDAFL 30 VCLNHALSTE 40 KEEVMGLCIG 50 ELNDDTRSDS 60 KFAYTGTEMR 70 TVAEKVDAVR 80 IVHIHSVIIL 90 RRSDKRKDRV 100 EISPEQLSAA 110 STEAERLAEL 120 TGRPMRVVGW 130 YHSHPHITVW 140 PSHVDVRTQA 150 MYQMMDQGFV 160 GLIFSCFIED 170 KNTKTGRVLY 180 TCFQSIQAQK 190 SSESLHGPRD 200 FWSSSQHISI 210 EGQKEEERYE 220 RIEIPIHIVP 230 HVTIGKVCLE 240 SAVELPKILC 250 QEEQDAYRRI 260 HSLTHLDSVT 270 KIHNGSVFTK 280 NLCSQMSAVS 290 GPLLQWLEDR 300 LEQNQQHLQE 310 LQQEKEELMQ ELSSLE

Gene Ontology

Classification	GO ID	Description
Cellular Component	GO:0070531	BRCA1-A complex
Biological Process	GO:0006282	regulation of DNA repair
Biological Process	GO:0010212	response to ionizing radiation
Biological Process	GO:0034516	response to vitamin B6
Biological Process	GO:0010165	response to X-ray
Cellular Component	GO:0070552	BRISC complex
Cellular Component	GO:0005737	cytoplasm
Cellular Component	GO:0005829	cytosol
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: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:0044818	mitotic G2/M transition checkpoint
Biological Process	GO:0045739	positive regulation of DNA repair
Biological Process	GO:1900227	positive regulation of NLRP3 inflammasome complex assembly
Biological Process	GO:0016579	protein deubiquitination
Biological Process	GO:0070536	protein K63-linked deubiquitination
Biological Process	GO:0006508	proteolysis
Biological Process	GO:2000001	regulation of DNA damage checkpoint

Reference

[1] Yang Z, Yan C, Ma J, Peng P, Ren X et al.. Lactylome analysis suggests lactylation-dependent mechanisms of metabolic adaptation in hepatocellular carcinoma.. Nat Metab 5(1):61-79. 2023 Jan. PMID: 36593272.

[2] He J, Lai T, Zhou Z, Yang H, Lei Z et al.. Multiomics profiling reveals the involvement of protein lactylation in nonhomologous end joining pathway conferring radioresistance in lung adenocarcinoma cell.. Sci Rep 15(1):24651. 2025 Jul 9. PMID: 40634431.