CPLM-008842

Genbank Nucleotide ID

Protein Synonyms/Alias

Machado-Joseph disease protein 1; Spinocerebellar ataxia type 3 protein

ATX3; MJD; MJD1; SCA3

Homo sapiens (Human)

Position	Peptide	Type	References
117	RSFICNYKEHWFTVR	ubiquitination	[1, 2, 3, 4, 5, 6]
190	VQQMHRPKLIGEELA	ubiquitination	[2, 4, 5]
200	GEELAQLKEQRVHKT	ubiquitination	[1, 2, 3, 4, 5]
206	LKEQRVHKTDLERVL	ubiquitination	[2, 3, 4, 5, 7]
291	RREAYFEKQQQKQQQ	ubiquitination	[2, 4, 5]

[1] Global analysis of lysine ubiquitination by ubiquitin remnant immunoaffinity profiling.
Xu G, Paige JS, Jaffrey SR.
Nat Biotechnol. 2010 Aug;28(8):868-73. [PMID: 20639865]
[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] 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]
[4] 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]
[5] 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]
[6] 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]
[7] 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]

Functional Description

Deubiquitinating enzyme involved in protein homeostasis maintenance, transcription, cytoskeleton regulation, myogenesis and degradation of misfolded chaperone substrates. Binds long polyubiquitin chains and trims them, while it has weak or no activity against chains of 4 or less ubiquitins. Involved in degradation of misfolded chaperone substrates via its interaction with STUB1/CHIP: recruited to monoubiquitinated STUB1/CHIP, and restricts the length of ubiquitin chain attached to STUB1/CHIP substrates and preventing further chain extension. In response to misfolded substrate ubiquitination, mediates deubiquitination of monoubiquitinated STUB1/CHIP. Interacts with key regulators of transcription and represses transcription: acts as a histone- binding protein that regulates transcription.

DOMAIN 1 180 Josephin.
REPEAT 224 243 UIM 1.
REPEAT 244 263 UIM 2.
REPEAT 331 348 UIM 3.
ACT_SITE 14 14 Nucleophile.
ACT_SITE 119 119 Proton acceptor (Probable).
ACT_SITE 134 134 Probable.
MOD_RES 219 219 Phosphoserine (By similarity).

3D-structure; Alternative splicing; Complete proteome; Hydrolase; Neurodegeneration; Nucleus; Phosphoprotein; Polymorphism; Protease; Reference proteome; Repeat; Spinocerebellar ataxia; Thiol protease; Transcription; Transcription regulation; Triplet repeat expansion; Ubl conjugation; Ubl conjugation pathway.

UniProt (SWISSPROT/TrEMBL); GenBank; EMBL

GO:0005737; C:cytoplasm; TAS:ProtInc.
GO:0005759; C:mitochondrial matrix; IEA:Compara.
GO:0031966; C:mitochondrial membrane; IEA:Compara.
GO:0042405; C:nuclear inclusion body; IEA:Compara.
GO:0016363; C:nuclear matrix; IEA:UniProtKB-SubCell.
GO:0005654; C:nucleoplasm; TAS:ProtInc.
GO:0008242; F:omega peptidase activity; IEA:InterPro.
GO:0001012; F:RNA polymerase II regulatory region DNA binding; IEA:Compara.
GO:0031625; F:ubiquitin protein ligase binding; ISS:UniProtKB.
GO:0004221; F:ubiquitin thiolesterase activity; ISS:UniProtKB.
GO:0004843; F:ubiquitin-specific protease activity; ISS:UniProtKB.
GO:0030036; P:actin cytoskeleton organization; IMP:MGI.
GO:0008219; P:cell death; IEA:UniProtKB-KW.
GO:0034605; P:cellular response to heat; IEA:Compara.
GO:0071218; P:cellular response to misfolded protein; ISS:UniProtKB.
GO:0035640; P:exploration behavior; IEA:Compara.
GO:0070932; P:histone H3 deacetylation; IEA:Compara.
GO:0045104; P:intermediate filament cytoskeleton organization; IMP:MGI.
GO:0000226; P:microtubule cytoskeleton organization; IMP:MGI.
GO:0006515; P:misfolded or incompletely synthesized protein catabolic process; ISS:UniProtKB.
GO:0035520; P:monoubiquitinated protein deubiquitination; ISS:UniProtKB.
GO:0007399; P:nervous system development; TAS:ProtInc.
GO:0006289; P:nucleotide-excision repair; TAS:ProtInc.
GO:0043161; P:proteasomal ubiquitin-dependent protein catabolic process; ISS:UniProtKB.
GO:0010810; P:regulation of cell-substrate adhesion; IMP:MGI.
GO:0006355; P:regulation of transcription, DNA-dependent; IEA:UniProtKB-KW.
GO:0007268; P:synaptic transmission; TAS:ProtInc.
GO:0006351; P:transcription, DNA-dependent; IEA:UniProtKB-KW.

IPR006155; Josephin.
IPR003903; Ubiquitin-int_motif.

PF02099; Josephin
PF02809; UIM

PS50957; JOSEPHIN
PS50330; UIM