CPLM-022350

Genbank Nucleotide ID

BRCA1-A complex subunit BRE

Protein Synonyms/Alias

BRCA1/BRCA2-containing complex subunit 45; Brain and reproductive organ-expressed protein

Homo sapiens (Human)

Position	Peptide	Type	References
26	SSVVRNGKVGLDATN	ubiquitination	[1]
41	CLRITDLKSGCTSLT	ubiquitination	[1]
161	NMEIYAGKKNNWTGE	ubiquitination	[2]
162	MEIYAGKKNNWTGEF	ubiquitination	[1, 3]
270	YVIQGYHKRREYIAA	acetylation	[4]
360	WDGNEMAKRAKAYFK	ubiquitination	[1]
367	KRAKAYFKTFVPQFQ	ubiquitination	[3]
382	EAAFANGKL******	ubiquitination	[1, 2, 3, 5, 6, 7, 8, 9, 10, 11, 12]

[1] 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]
[2] 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]
[3] 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]
[4] Lysine acetylation targets protein complexes and co-regulates major cellular functions.
Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M.
Science. 2009 Aug 14;325(5942):834-40. [PMID: 19608861]
[5] A data set of human endogenous protein ubiquitination sites.
Shi Y, Chan DW, Jung SY, Malovannaya A, Wang Y, Qin J.
Mol Cell Proteomics. 2011 May;10(5):M110.002089. [PMID: 20972266]
[6] Mass spectrometric analysis of lysine ubiquitylation reveals promiscuity at site level.
Danielsen JM, Sylvestersen KB, Bekker-Jensen S, Szklarczyk D, Poulsen JW, Horn H, Jensen LJ, Mailand N, Nielsen ML.
Mol Cell Proteomics. 2011 Mar;10(3):M110.003590. [PMID: 21139048]
[7] 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]
[8] Ubiquitin ligase substrate identification through quantitative proteomics at both the protein and peptide levels.
Lee KA, Hammerle LP, Andrews PS, Stokes MP, Mustelin T, Silva JC, Black RA, Doedens JR.
J Biol Chem. 2011 Dec 2;286(48):41530-8. [PMID: 21987572]
[9] 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]
[10] 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]
[11] hCKSAAP_UbSite: improved prediction of human ubiquitination sites by exploiting amino acid pattern and properties.
Chen Z, Zhou Y, Song J, Zhang Z.
Biochim Biophys Acta. 2013 Aug;1834(8):1461-7. [PMID: 23603789]
[12] 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

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). The BRCA1-A complex also possesses deubiquitinase activity that specifically removes 'Lys-63'-linked ubiquitin on histones H2A and H2AX. In the BRCA1-A complex, it acts as an adapter that bridges the interaction between BABAM1/NBA1 and the rest of the complex, thereby being required for the complex integrity and modulating the E3 ubiquitin ligase activity of the BRCA1-BARD1 heterodimer. Probably also plays a role as a component of the BRISC complex, a multiprotein complex that specifically cleaves 'Lys-63'-linked ubiquitin. May play a role in homeostasis or cellular differentiation in cells of neural, epithelial and germline origins. May also act as a death receptor-associated anti- apoptotic protein, which inhibits the mitochondrial apoptotic pathway. May regulate TNF-alpha signaling through its interactions with TNFRSF1A; however these effects may be indirect.

REGION 30 147 UEV-like 1.
REGION 275 364 UEV-like 2.
MOD_RES 1 1 N-acetylmethionine.
MOD_RES 2 2 Phosphoserine.

Acetylation; Alternative splicing; Apoptosis; Chromatin regulator; Complete proteome; Cytoplasm; DNA damage; DNA repair; Nucleus; Phosphoprotein; Reference proteome; Repeat.

UniProt (SWISSPROT/TrEMBL); GenBank; EMBL

GO:0070531; C:BRCA1-A complex; IDA:UniProtKB.
GO:0070552; C:BRISC complex; IDA:UniProtKB.
GO:0005737; C:cytoplasm; IDA:UniProtKB.
GO:0000152; C:nuclear ubiquitin ligase complex; IDA:UniProtKB.
GO:0000268; F:peroxisome targeting sequence binding; TAS:UniProtKB.
GO:0031593; F:polyubiquitin binding; IDA:UniProtKB.
GO:0005164; F:tumor necrosis factor receptor binding; IDA:UniProtKB.
GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
GO:0016568; P:chromatin modification; IEA:UniProtKB-KW.
GO:0006302; P:double-strand break repair; IMP:UniProtKB.
GO:0031572; P:G2 DNA damage checkpoint; IMP:UniProtKB.
GO:0045739; P:positive regulation of DNA repair; IMP:UniProtKB.
GO:0010212; P:response to ionizing radiation; IMP:UniProtKB.
GO:0007165; P:signal transduction; TAS:ProtInc.

IPR010358; Brain/reproduct-express_prot.