Detail Information for IndEnz0002018531
IED ID IndEnz0002018531
Enzyme Type ID protease018531
Protein Name Ataxin-3
EC 3.4.19.12
Machado-Joseph disease protein 1
Spinocerebellar ataxia type 3 protein
Gene Name ATXN3 ATX3 MJD MJD1 SCA3
Organism Homo sapiens (Human)
Taxonomic Lineage cellular organisms Eukaryota Opisthokonta Metazoa Eumetazoa Bilateria Deuterostomia Chordata Craniata Vertebrata Gnathostomata (jawed vertebrates) Teleostomi Euteleostomi Sarcopterygii Dipnotetrapodomorpha Tetrapoda Amniota Mammalia Theria Eutheria Boreoeutheria Euarchontoglires Primates Haplorrhini Simiiformes Catarrhini Hominoidea (apes) Hominidae (great apes) Homininae Homo Homo sapiens (Human)
Enzyme Sequence MESIFHEKQEGSLCAQHCLNNLLQGEYFSPVELSSIAHQLDEEERMRMAEGGVTSEDYRTFLQQPSGNMDDSGFFSIQVISNALKVWGLELILFNSPEYQRLRIDPINERSFICNYKEHWFTVRKLGKQWFNLNSLLTGPELISDTYLALFLAQLQQEGYSIFVVKGDLPDCEADQLLQMIRVQQMHRPKLIGEELAQLKEQRVHKTDLERVLEANDGSGMLDEDEEDLQRALALSRQEIDMEDEEADLRRAIQLSMQGSSRNISQDMTQTSGTNLTSEELRKRREAYFEKQQQKQQQQQQQQQQGDLSGQSSHPCERPATSSGALGSDLGDAMSEEDMLQAAVTMSLETVRNDLKTEGKK
Enzyme Length 361
Uniprot Accession Number P54252
Absorption
Active Site ACT_SITE 14; /note="Nucleophile"; /evidence="ECO:0000269|PubMed:23625928"; ACT_SITE 119; /note="Proton acceptor"; /evidence="ECO:0000305|PubMed:16020535, ECO:0000305|PubMed:16118278"; ACT_SITE 134; /evidence="ECO:0000305|PubMed:16020535, ECO:0000305|PubMed:16118278"
Activity Regulation
Binding Site
Calcium Binding
catalytic Activity CATALYTIC ACTIVITY: Reaction=Thiol-dependent hydrolysis of ester, thioester, amide, peptide and isopeptide bonds formed by the C-terminal Gly of ubiquitin (a 76-residue protein attached to proteins as an intracellular targeting signal).; EC=3.4.19.12; Evidence={ECO:0000269|PubMed:17696782};
DNA Binding
EC Number 3.4.19.12
Enzyme Function FUNCTION: Deubiquitinating enzyme involved in protein homeostasis maintenance, transcription, cytoskeleton regulation, myogenesis and degradation of misfolded chaperone substrates (PubMed:12297501, PubMed:17696782, PubMed:23625928, PubMed:28445460, PubMed:16118278). Binds long polyubiquitin chains and trims them, while it has weak or no activity against chains of 4 or less ubiquitins (PubMed:17696782). 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 (By similarity). Interacts with key regulators of transcription and represses transcription: acts as a histone-binding protein that regulates transcription (PubMed:12297501). Regulates autophagy via the deubiquitination of 'Lys-402' of BECN1 leading to the stabilization of BECN1 (PubMed:28445460). {ECO:0000250|UniProtKB:Q9CVD2, ECO:0000269|PubMed:12297501, ECO:0000269|PubMed:16118278, ECO:0000269|PubMed:17696782, ECO:0000269|PubMed:23625928, ECO:0000269|PubMed:28445460}.
Temperature Dependency
PH Dependency
Pathway
nucleotide Binding
Features Active site (3); Alternative sequence (4); Beta strand (10); Chain (1); Compositional bias (2); Cross-link (2); Domain (4); Helix (12); Modified residue (4); Mutagenesis (4); Natural variant (3); Region (1); Sequence conflict (3); Turn (3)
Keywords 3D-structure;Alternative splicing;Hydrolase;Isopeptide bond;Neurodegeneration;Nucleus;Phosphoprotein;Protease;Reference proteome;Repeat;Spinocerebellar ataxia;Thiol protease;Transcription;Transcription regulation;Triplet repeat expansion;Ubl conjugation;Ubl conjugation pathway
Interact With Q9H7C9; Q6PCB6; Q6UY14-3; O43488; Q9NP61; Q14CB8; Q9Y575-3; Q96FT7-4; P06276; Q96G97-4; Q6UWD8; Q8N865; P29466-3; P42574; Q96LX7-5; P40227; Q5VV42; Q16740; Q02930-3; Q8IUI8; Q9H816; Q9P1A6-3; P50570-2; Q3B7T1; Q01844; Q01844-3; Q01844-4; O15287; P23142-4; Q9UHY8; Q3SYB3; P06241-3; Q8TB36; Q9H8Y8; O75409; P68431; Q969S8; O75330-3; P22692; Q16891; Q9Y2M5; Q9BYZ2; Q9UPM6; Q9UDY8-2; Q9H8H3; O94851; A4FUJ8; Q13064; Q9Y483-4; Q8WY64; Q15466; Q8NFH3; Q96DC9; Q96DC9-2; Q9BWI9; Q8N3R9; Q9NVD7; Q9HBE1-4; O15530-4; Q9BSU1; O75925; P42336; Q03405-2; Q8NBT0; P17612; P51665; P54725; Q9NS23-4; Q93062-3; Q6ZNA4-2; Q96EP0; Q8N5Z7; Q8TBK5; Q66K80; P16581; P50454; Q8IVP1; Q9NQ40; O95416; Q99932-2; Q8IUW3; Q9NRP7; Q8TDW5-2; Q9Y458; O95551; Q9Y4R8; Q15554-4; Q8IYF3-3; Q8NA77; P37173; Q9BXR5; Q9UMX0; P13051-2; Q92995; P55072; Q8NEZ2; Q15007-2; Q9H0M0; Q9H4I2-2; Q96NC0; Q8N895; Itself; Q14457; P54257; P0CG48; P55072; O60260
Induction
Subcellular Location SUBCELLULAR LOCATION: Nucleus matrix {ECO:0000269|PubMed:9580663}. Nucleus {ECO:0000269|PubMed:30455355}. Note=Predominantly nuclear, but not exclusively, inner nuclear matrix.
Modified Residue MOD_RES 219; /note=Phosphoserine; /evidence=ECO:0000250|UniProtKB:Q9CVD2; MOD_RES 265; /note=Phosphoserine; /evidence=ECO:0007744|PubMed:23186163; MOD_RES 272; /note=Phosphoserine; /evidence=ECO:0000250|UniProtKB:Q9CVD2; MOD_RES 328; /note=Phosphoserine; /evidence=ECO:0000250|UniProtKB:Q9CVD2
Post Translational Modification PTM: Monoubiquitinated N-terminally by UBE2W, possibly leading to activate the deubiquitinating enzyme activity (PubMed:23696636). {ECO:0000269|PubMed:23696636}.
Signal Peptide
Structure 3D NMR spectroscopy (5); X-ray crystallography (2)
Cross Reference PDB 1YZB; 2AGA; 2DOS; 2JRI; 2KLZ; 4WTH; 4YS9;
Mapped Pubmed ID 10915768; 12239572; 12914917; 12944474; 14559776; 15140190; 15544810; 15630566; 16525503; 16712842; 16713569; 17082820; 17434145; 18391950; 18391951; 18599482; 19153604; 19615732; 20414249; 20711500; 20940148; 21386698; 21536589; 21900206; 22129356; 24040102; 25260751; 25448680; 26496610; 26880203; 27047745; 27547294; 31379806;
Motif
Gene Encoded By
Mass 41,250
Kinetics
Metal Binding
Rhea ID
Cross Reference Brenda