ID ATX3_CHICK Reviewed; 363 AA. AC Q9W689; DT 28-FEB-2003, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1999, sequence version 1. DT 24-JAN-2024, entry version 135. DE RecName: Full=Ataxin-3; DE EC=3.4.19.12; DE AltName: Full=Machado-Joseph disease protein 1 homolog; GN Name=ATXN3; Synonyms=MDJ1, MJD; OS Gallus gallus (Chicken). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Archelosauria; Archosauria; Dinosauria; Saurischia; Theropoda; OC Coelurosauria; Aves; Neognathae; Galloanserae; Galliformes; Phasianidae; OC Phasianinae; Gallus. OX NCBI_TaxID=9031; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY. RC STRAIN=SPAFAS; RX PubMed=10023088; DOI=10.1016/s0167-4781(99)00004-4; RA Linhartova I., Repitz M., Draber P., Nemec M., Wiche G., Propst F.; RT "Conserved domains and lack of evidence for polyglutamine length RT polymorphism in the chicken homolog of the Machado-Joseph disease gene RT product ataxin-3."; RL Biochim. Biophys. Acta 1444:299-305(1999). RN [2] RP 3D-STRUCTURE MODELING. RX PubMed=12486728; DOI=10.1002/prot.10280; RA Albrecht M., Hoffmann D., Evert B.O., Schmitt I., Wuellner U., Lengauer T.; RT "Structural modeling of ataxin-3 reveals distant homology to adaptins."; RL Proteins 50:355-370(2003). CC -!- FUNCTION: Deubiquitinating enzyme involved in protein homeostasis CC maintenance, transcription, cytoskeleton regulation, myogenesis and CC degradation of misfolded chaperone substrates (By similarity). Binds CC long polyubiquitin chains and trims them, while it has weak or no CC activity against chains of 4 or less ubiquitins (By similarity). CC Involved in degradation of misfolded chaperone substrates via its CC interaction with STUB1/CHIP: recruited to monoubiquitinated STUB1/CHIP, CC and restricts the length of ubiquitin chain attached to STUB1/CHIP CC substrates and preventing further chain extension (By similarity). CC Interacts with key regulators of transcription and represses CC transcription: acts as a histone-binding protein that regulates CC transcription (By similarity). Acts as a negative regulator of mTORC1 CC signaling in response to amino acid deprivation by mediating CC deubiquitination of RHEB, thereby promoting RHEB inactivation by the CC TSC-TBC complex (By similarity). Regulates autophagy via the CC deubiquitination of 'Lys-402' of BECN1 leading to the stabilization of CC BECN1 (By similarity). {ECO:0000250|UniProtKB:P54252, CC ECO:0000250|UniProtKB:Q9CVD2}. CC -!- CATALYTIC ACTIVITY: CC Reaction=Thiol-dependent hydrolysis of ester, thioester, amide, peptide CC and isopeptide bonds formed by the C-terminal Gly of ubiquitin (a 76- CC residue protein attached to proteins as an intracellular targeting CC signal).; EC=3.4.19.12; Evidence={ECO:0000250|UniProtKB:P54252}; CC -!- SUBCELLULAR LOCATION: Nucleus matrix {ECO:0000250|UniProtKB:P54252}. CC Nucleus {ECO:0000250|UniProtKB:P54252}. Lysosome membrane CC {ECO:0000250|UniProtKB:P54252}; Peripheral membrane protein CC {ECO:0000250|UniProtKB:P54252}. Note=Predominantly nuclear, but not CC exclusively, inner nuclear matrix. Recruited to lysosomal membrane in CC response to amino acid deprivation by the RagA/RRAGA-RagB/RRAGB CC complex. {ECO:0000250|UniProtKB:P54252}. CC -!- TISSUE SPECIFICITY: Widely expressed (PubMed:10023088). CC {ECO:0000269|PubMed:10023088}. CC -!- DOMAIN: The UIM domains bind ubiquitin and interact with various E3 CC ubiquitin-protein ligase, such as STUB1/CHIP (By similarity). They are CC essential to limit the length of ubiquitin chains (By similarity). CC {ECO:0000250|UniProtKB:Q9CVD2}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF085247; AAD21923.1; -; mRNA. DR RefSeq; NP_989688.1; NM_204357.1. DR AlphaFoldDB; Q9W689; -. DR SMR; Q9W689; -. DR STRING; 9031.ENSGALP00000068123; -. DR MEROPS; C86.001; -. DR PaxDb; 9031-ENSGALP00000017488; -. DR Ensembl; ENSGALT00000017509; ENSGALP00000017488; ENSGALG00000010766. DR Ensembl; ENSGALT00010036845.1; ENSGALP00010021465.1; ENSGALG00010015300.1. DR Ensembl; ENSGALT00015041076; ENSGALP00015023940; ENSGALG00015016857. DR GeneID; 378424; -. DR KEGG; gga:378424; -. DR CTD; 4287; -. DR VEuPathDB; HostDB:geneid_378424; -. DR eggNOG; KOG2935; Eukaryota. DR GeneTree; ENSGT00390000001830; -. DR HOGENOM; CLU_031228_1_0_1; -. DR InParanoid; Q9W689; -. DR PhylomeDB; Q9W689; -. DR TreeFam; TF314228; -. DR Reactome; R-GGA-5689877; Josephin domain DUBs. DR PRO; PR:Q9W689; -. DR Proteomes; UP000000539; Chromosome 5. DR Bgee; ENSGALG00000010766; Expressed in testis and 13 other cell types or tissues. DR ExpressionAtlas; Q9W689; baseline and differential. DR GO; GO:0005765; C:lysosomal membrane; ISS:UniProtKB. DR GO; GO:0016363; C:nuclear matrix; IEA:UniProtKB-SubCell. DR GO; GO:0005634; C:nucleus; IBA:GO_Central. DR GO; GO:0004843; F:cysteine-type deubiquitinase activity; ISS:UniProtKB. DR GO; GO:0031625; F:ubiquitin protein ligase binding; ISS:UniProtKB. DR GO; GO:0034198; P:cellular response to amino acid starvation; ISS:UniProtKB. DR GO; GO:0071218; P:cellular response to misfolded protein; ISS:UniProtKB. DR GO; GO:0035520; P:monoubiquitinated protein deubiquitination; ISS:UniProtKB. DR GO; GO:1904262; P:negative regulation of TORC1 signaling; ISS:UniProtKB. DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; ISS:UniProtKB. DR GO; GO:0006515; P:protein quality control for misfolded or incompletely synthesized proteins; ISS:UniProtKB. DR Gene3D; 3.90.70.40; -; 1. DR Gene3D; 1.10.287.10; S15/NS1, RNA-binding; 1. DR InterPro; IPR033865; Ataxin-3. DR InterPro; IPR006155; Josephin. DR InterPro; IPR003903; UIM_dom. DR PANTHER; PTHR14159; ATAXIN-3-RELATED; 1. DR PANTHER; PTHR14159:SF0; ATAXIN-3-RELATED; 1. DR Pfam; PF02099; Josephin; 1. DR Pfam; PF16619; SUIM_assoc; 1. DR Pfam; PF02809; UIM; 3. DR PRINTS; PR01233; JOSEPHIN. DR SMART; SM01246; Josephin; 1. DR SMART; SM00726; UIM; 3. DR PROSITE; PS50957; JOSEPHIN; 1. DR PROSITE; PS50330; UIM; 3. PE 2: Evidence at transcript level; KW Hydrolase; Lysosome; Membrane; Nucleus; Protease; Reference proteome; KW Repeat; Thiol protease; Transcription; Transcription regulation; KW Ubl conjugation pathway. FT CHAIN 1..363 FT /note="Ataxin-3" FT /id="PRO_0000053834" FT DOMAIN 1..180 FT /note="Josephin" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00331" FT DOMAIN 227..246 FT /note="UIM 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00213" FT DOMAIN 247..266 FT /note="UIM 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00213" FT DOMAIN 337..356 FT /note="UIM 3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00213" FT REGION 192..212 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 260..363 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 194..210 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 260..287 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 302..331 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 14 FT /note="Nucleophile" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00331" FT ACT_SITE 119 FT /note="Proton acceptor" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00331" FT ACT_SITE 134 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00331" SQ SEQUENCE 363 AA; 41608 MW; 15C81537096DE8C4 CRC64; MESIFHERQE GSLCAQHCLN NLLQGEYFSP VELSSIAQQL DEEERMRMAE GGVSSEEYRT FLQQPSVNMD DSGFFSIQVI SNALKVWGLE LILFNSPEYQ RLGIDPINEK SFICNYKEHW FTVRKLGKQW FNLNSLLMGP ELISDTYLAL FLAQLQQEGY SIFVVKGDLP DCEADQLLQM IRVQQVQRPK LIGEETAQSR DQRLPRSDVD QAIEVSHPFD GTGMLDEDEE NFQRALALSR QEIDMEDEEA DLRRAIQLSM QGSRQSEFSN SLPQNASQPP HTSQTDSLSS EDLRRRRQAY FEKQQQQLQQ QDLTLNLHDK PTINSSTLEA DPGGDMSEED MLQAAMNMSL ESARNHLSTE EKK //