CPLM-007827

Genbank Nucleotide ID

Lys-63-specific deubiquitinase BRCC36

Protein Synonyms/Alias

BRCA1-A complex subunit BRCC36; BRCA1/BRCA2-containing complex subunit 3; BRCA1/BRCA2-containing complex subunit 36; BRISC complex subunit BRCC36

BRCC36; C6.1A; CXorf53

Homo sapiens (Human)

Position	Peptide	Type	References
51	DDTRSDSKFAYTGTE	ubiquitination	[1]
65	EMRTVAEKVDAVRIV	ubiquitination	[1]
180	FQSIQAQKSSEYERI	ubiquitination	[1, 2, 3, 4, 5, 6, 7, 8]

[1] Landscape of the PARKIN-dependent ubiquitylome in response to mitochondrial depolarization.
Sarraf SA, Raman M, Guarani-Pereira V, Sowa ME, Huttlin EL, Gygi SP, Harper JW.
Nature. 2013 Apr 18;496(7445):372-6. [PMID: 23503661]
[2] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473]
[3] Systematic and quantitative assessment of the ubiquitin-modified proteome.
Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983]
[4] Global identification of modular cullin-RING ligase substrates.
Emanuele MJ, Elia AE, Xu Q, Thoma CR, Izhar L, Leng Y, Guo A, Chen YN, Rush J, Hsu PW, Yen HC, Elledge SJ.
Cell. 2011 Oct 14;147(2):459-74. [PMID: 21963094]
[5] Proteome-wide identification of ubiquitylation sites by conjugation of engineered lysine-less ubiquitin.
Oshikawa K, Matsumoto M, Oyamada K, Nakayama KI.
J Proteome Res. 2012 Feb 3;11(2):796-807. [PMID: 22053931]
[6] Methods for quantification of in vivo changes in protein ubiquitination following proteasome and deubiquitinase inhibition.
Udeshi ND, Mani DR, Eisenhaure T, Mertins P, Jaffe JD, Clauser KR, Hacohen N, Carr SA.
Mol Cell Proteomics. 2012 May;11(5):148-59. [PMID: 22505724]
[7] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
[8] Integrated proteomic analysis of post-translational modifications by serial enrichment.
Mertins P, Qiao JW, Patel J, Udeshi ND, Clauser KR, Mani DR, Burgess MW, Gillette MA, Jaffe JD, Carr SA.
Nat Methods. 2013 Jul;10(7):634-7. [PMID: 23749302]

Functional Description

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.

DOMAIN 7 148 MPN.
MOTIF 122 135 JAMM motif.
METAL 122 122 Zinc; catalytic (Probable).
METAL 124 124 Zinc; catalytic (Probable).
METAL 135 135 Zinc; catalytic (By similarity).
MOD_RES 2 2 N-acetylalanine.

Acetylation; Alternative splicing; Chromatin regulator; Chromosomal rearrangement; Complete proteome; Direct protein sequencing; DNA damage; DNA repair; Hydrolase; Metal-binding; Metalloprotease; Nucleus; Polymorphism; Protease; Proto-oncogene; Reference proteome; Ubl conjugation pathway; Zinc.

UniProt (SWISSPROT/TrEMBL); GenBank; EMBL

GO:0070531; C:BRCA1-A complex; IDA:UniProtKB.
GO:0070552; C:BRISC complex; IDA:UniProtKB.
GO:0000152; C:nuclear ubiquitin ligase complex; IDA:UniProtKB.
GO:0030234; F:enzyme regulator activity; IDA:MGI.
GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
GO:0008237; F:metallopeptidase activity; IMP:UniProtKB.
GO:0031593; F:polyubiquitin binding; IDA:UniProtKB.
GO:0004221; F:ubiquitin thiolesterase activity; IMP:UniProtKB.
GO:0004843; F:ubiquitin-specific protease activity; IMP:UniProtKB.
GO:0006302; P:double-strand break repair; IMP:UniProtKB.
GO:0031572; P:G2 DNA damage checkpoint; IMP:UniProtKB.
GO:0070537; P:histone H2A K63-linked deubiquitination; IDA:UniProtKB.
GO:0045739; P:positive regulation of DNA repair; IMP:UniProtKB.
GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
GO:0010165; P:response to X-ray; IDA:MGI.

IPR000555; JAB1_Mov34_MPN_PAD1.