UniProt:P54252 ATXN3

chain
  • chain:1-361
checksum 90C3EF73BB26CAFD
comment
  • FUNCTION Deubiquitinating enzyme involved in protein homeostasis maintenance, transcription, cytoskeleton regulation, myogenesis and degradation of misfolded chaperone substrates (PubMed:12297501, PubMed:16118278, PubMed:17696782, PubMed:23625928, PubMed:28445460, PubMed:33157014). 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). Acts as a negative regulator of mTORC1 signaling in response to amino acid deprivation by mediating deubiquitination of RHEB, thereby promoting RHEB inactivation by the TSC-TBC complex (PubMed:33157014). Regulates autophagy via the deubiquitination of 'Lys-402' of BECN1 leading to the stabilization of BECN1 (PubMed:28445460).CATALYTIC ACTIVITY 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).SUBUNIT Interacts with STUB1/CHIP (when monoubiquitinated) (By similarity). Interacts with DNA repair proteins RAD23A and RAD23B (PubMed:16020535, PubMed:30455355). Interacts with BECN1 (via its poly-Gln domain) (PubMed:28445460). Interacts with PRKN, UBR2, VCP and tubulin. Short isoform 1 interacts with CASP7 (PubMed:30455355).INTERACTION Predominantly nuclear, but not exclusively, inner nuclear matrix (PubMed:9580663). Recruited to lysosomal membrane in response to amino acid deprivation by the RagA/RRAGA-RagB/RRAGB complex (PubMed:33157014).ALTERNATIVE PRODUCTS Ubiquitous.DOMAIN The UIM domains bind ubiquitin and interact with various E3 ubiquitin-protein ligase, such as STUB1/CHIP. They are essential to limit the length of ubiquitin chains (By similarity).DOMAIN The poly-Gln domain is involved in the interaction with BECN1 and subsequent starvation-induced autophagy (PubMed:28445460).PTM Monoubiquitinated N-terminally by UBE2W, possibly leading to activate the deubiquitinating enzyme activity (PubMed:23696636).POLYMORPHISM The poly-Gln region of ATXN3 is highly polymorphic (14 to 41 repeats) in the normal population and is expanded to about 55-82 repeats in spinocerebellar ataxia 3 (SCA3) patients (PubMed:7874163, PubMed:9274833).DISEASE The disease is caused by variants affecting the gene represented in this entry.
crossReference
databaseName UniProt
dbId 59281
description
  • recommendedName: Ataxin-3 ecNumber evidence="10 15"3.4.19.12 alternativeName: Machado-Joseph disease protein 1 alternativeName: Spinocerebellar ataxia type 3 protein
displayName UniProt:P54252 ATXN3
geneName
  • ATXN3
  • ATX3
  • MJD
  • MJD1
  • SCA3
identifier P54252
isSequenceChanged false
keyword
  • 3D-structure
  • Alternative splicing
  • Hydrolase
  • Isopeptide bond
  • Lysosome
  • Membrane
  • Neurodegeneration
  • Nucleus
  • Phosphoprotein
  • Protease
  • Proteomics identification
  • Reference proteome
  • Repeat
  • Spinocerebellar ataxia
  • Thiol protease
  • Transcription
  • Transcription regulation
  • Triplet repeat expansion
  • Ubl conjugation
  • Ubl conjugation pathway
modified [InstanceEdit:9926675] Weiser, Joel, 2024-11-03
moleculeType Protein
name
  • ATXN3
physicalEntity
referenceDatabase [ReferenceDatabase:2] UniProt
referenceGene
referenceTranscript
schemaClass ReferenceGeneProduct
secondaryIdentifier
  • ATX3_HUMAN
  • A7LFZ5
  • D6RDL9
  • E9PB63
  • O15284
  • O15285
  • O15286
  • Q8N189
  • Q96TC3
  • Q96TC4
  • Q9H3N0
sequenceLength 361
species [Species:48887] Homo sapiens
stId uniprot:P54252
url http://purl.uniprot.org/uniprot/P54252

Referrals

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