ATX3_RAT
ID ATX3_RAT Reviewed; 355 AA.
AC O35815;
DT 28-FEB-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1998, sequence version 1.
DT 03-AUG-2022, entry version 151.
DE RecName: Full=Ataxin-3;
DE EC=3.4.19.12;
DE AltName: Full=Machado-Joseph disease protein 1 homolog;
GN Name=Atxn3; Synonyms=Mjd, Sca3;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RC TISSUE=Brain, and Testis;
RX PubMed=10732811; DOI=10.1007/s100480050015;
RA Schmitt I., Brattig T., Gossen M., Riess O.;
RT "Characterization of the rat spinocerebellar ataxia type 3 gene.";
RL Neurogenetics 1:103-112(1997).
RN [2]
RP CATALYTIC ACTIVITY, MUTAGENESIS OF CYS-14; HIS-119 AND ASN-134, AND
RP FUNCTION.
RX PubMed=17696782; DOI=10.1515/bc.2007.107;
RA Tzvetkov N., Breuer P.;
RT "Josephin domain-containing proteins from a variety of species are active
RT de-ubiquitination enzymes.";
RL Biol. Chem. 388:973-978(2007).
RN [3]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
RN [4]
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 (PubMed:17696782). 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). 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, ECO:0000269|PubMed:17696782}.
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:0000269|PubMed:17696782};
CC -!- SUBUNIT: Interacts with STUB1/CHIP (when monoubiquitinated) (By
CC similarity). Interacts with DNA repair proteins RAD23A and RAD23B.
CC Interacts with BECN1 (via its poly-Gln domain) (By similarity).
CC Interacts with PRKN, UBR2, VCP and tubulin (By similarity).
CC {ECO:0000250|UniProtKB:P54252, ECO:0000250|UniProtKB:Q9CVD2}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:P54252}.
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed (PubMed:10732811).
CC {ECO:0000269|PubMed:10732811}.
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 -!- PTM: Monoubiquitinated by UBE2W, possibly leading to activate the
CC deubiquitinating enzyme activity (By similarity).
CC {ECO:0000250|UniProtKB:P54252}.
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DR EMBL; Y12319; CAA72986.1; -; mRNA.
DR RefSeq; NP_067734.1; NM_021702.1.
DR AlphaFoldDB; O35815; -.
DR BMRB; O35815; -.
DR SMR; O35815; -.
DR BioGRID; 248780; 2.
DR STRING; 10116.ENSRNOP00000007505; -.
DR MEROPS; C86.001; -.
DR iPTMnet; O35815; -.
DR PhosphoSitePlus; O35815; -.
DR jPOST; O35815; -.
DR PaxDb; O35815; -.
DR Ensembl; ENSRNOT00000007505; ENSRNOP00000007505; ENSRNOG00000005470.
DR GeneID; 60331; -.
DR KEGG; rno:60331; -.
DR UCSC; RGD:621567; rat.
DR CTD; 4287; -.
DR RGD; 621567; Atxn3.
DR eggNOG; KOG2935; Eukaryota.
DR GeneTree; ENSGT00390000001830; -.
DR HOGENOM; CLU_031228_1_0_1; -.
DR InParanoid; O35815; -.
DR OMA; QQIQRPK; -.
DR OrthoDB; 1482722at2759; -.
DR PhylomeDB; O35815; -.
DR TreeFam; TF314228; -.
DR Reactome; R-RNO-5689877; Josephin domain DUBs.
DR Reactome; R-RNO-9615017; FOXO-mediated transcription of oxidative stress, metabolic and neuronal genes.
DR PRO; PR:O35815; -.
DR Proteomes; UP000002494; Chromosome 6.
DR Bgee; ENSRNOG00000005470; Expressed in testis and 19 other tissues.
DR Genevisible; O35815; RN.
DR GO; GO:0005737; C:cytoplasm; ISO:RGD.
DR GO; GO:0005829; C:cytosol; ISS:ParkinsonsUK-UCL.
DR GO; GO:0005759; C:mitochondrial matrix; ISO:RGD.
DR GO; GO:0031966; C:mitochondrial membrane; ISO:RGD.
DR GO; GO:0042405; C:nuclear inclusion body; ISO:RGD.
DR GO; GO:0005634; C:nucleus; IDA:RGD.
DR GO; GO:0051117; F:ATPase binding; ISS:ParkinsonsUK-UCL.
DR GO; GO:0004843; F:cysteine-type deubiquitinase activity; ISS:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; ISS:ParkinsonsUK-UCL.
DR GO; GO:1990380; F:Lys48-specific deubiquitinase activity; ISS:ParkinsonsUK-UCL.
DR GO; GO:0061578; F:Lys63-specific deubiquitinase activity; ISS:ParkinsonsUK-UCL.
DR GO; GO:0000977; F:RNA polymerase II transcription regulatory region sequence-specific DNA binding; IDA:RGD.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; ISS:UniProtKB.
DR GO; GO:0030036; P:actin cytoskeleton organization; ISS:ParkinsonsUK-UCL.
DR GO; GO:0034605; P:cellular response to heat; ISO:RGD.
DR GO; GO:0071218; P:cellular response to misfolded protein; ISS:UniProtKB.
DR GO; GO:0035640; P:exploration behavior; ISO:RGD.
DR GO; GO:0070932; P:histone H3 deacetylation; IEP:RGD.
DR GO; GO:0045104; P:intermediate filament cytoskeleton organization; ISS:ParkinsonsUK-UCL.
DR GO; GO:0000226; P:microtubule cytoskeleton organization; ISS:ParkinsonsUK-UCL.
DR GO; GO:0035520; P:monoubiquitinated protein deubiquitination; ISS:UniProtKB.
DR GO; GO:1904294; P:positive regulation of ERAD pathway; ISO:RGD.
DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; ISS:UniProtKB.
DR GO; GO:0016579; P:protein deubiquitination; ISO:RGD.
DR GO; GO:0071108; P:protein K48-linked deubiquitination; ISS:ParkinsonsUK-UCL.
DR GO; GO:0070536; P:protein K63-linked deubiquitination; ISS:ParkinsonsUK-UCL.
DR GO; GO:1904379; P:protein localization to cytosolic proteasome complex involved in ERAD pathway; ISO:RGD.
DR GO; GO:0006515; P:protein quality control for misfolded or incompletely synthesized proteins; ISS:UniProtKB.
DR GO; GO:0010810; P:regulation of cell-substrate adhesion; ISS:ParkinsonsUK-UCL.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; ISO:RGD.
DR InterPro; IPR033865; Ataxin-3.
DR InterPro; IPR006155; Josephin.
DR InterPro; IPR003903; UIM_dom.
DR PANTHER; PTHR14159; PTHR14159; 1.
DR Pfam; PF02099; Josephin; 1.
DR Pfam; PF02809; UIM; 2.
DR SMART; SM01246; Josephin; 1.
DR SMART; SM00726; UIM; 3.
DR PROSITE; PS50957; JOSEPHIN; 1.
DR PROSITE; PS50330; UIM; 2.
PE 1: Evidence at protein level;
KW Hydrolase; Isopeptide bond; Nucleus; Phosphoprotein; Protease;
KW Reference proteome; Repeat; Thiol protease; Transcription;
KW Transcription regulation; Ubl conjugation; Ubl conjugation pathway.
FT CHAIN 1..355
FT /note="Ataxin-3"
FT /id="PRO_0000053833"
FT DOMAIN 1..180
FT /note="Josephin"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00331"
FT DOMAIN 224..243
FT /note="UIM 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00213"
FT DOMAIN 244..263
FT /note="UIM 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00213"
FT DOMAIN 329..348
FT /note="UIM 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00213"
FT REGION 257..333
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 257..276
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 277..297
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 309..328
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 14
FT /note="Nucleophile"
FT /evidence="ECO:0000250|UniProtKB:P54252"
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"
FT MOD_RES 268
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9CVD2"
FT MOD_RES 272
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9CVD2"
FT MOD_RES 273
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9CVD2"
FT MOD_RES 321
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9CVD2"
FT CROSSLNK 1
FT /note="Peptide (Met-Gly) (interchain with G-Cter in
FT ubiquitin)"
FT /evidence="ECO:0000250"
FT CROSSLNK 200
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:P54252"
FT MUTAGEN 14
FT /note="C->A,S: Loss of enzyme activity."
FT /evidence="ECO:0000269|PubMed:17696782"
FT MUTAGEN 119
FT /note="H->A: Loss of enzyme activity."
FT /evidence="ECO:0000269|PubMed:17696782"
FT MUTAGEN 134
FT /note="N->A: Loss of enzyme activity."
FT /evidence="ECO:0000269|PubMed:17696782"
SQ SEQUENCE 355 AA; 40446 MW; 87B6A6EE54FF29F5 CRC64;
MESIFHEKQE GSLCAQHCLN NLLQGEYFSP VELSSIAHQL DEEERLRMAE GGVTSEDYRT
FLQQPSGNMD DSGFFSIQVI SNALKVWGLE LILFNSPEYQ RLRIDPINER SFICNYKEHW
FTVRKLGKQW FNLNSLLTGP ELISDTYLAL FLAQLQQEGY SIFVVKGDLP DCEADQLLQM
IKVQQMHRPK LIGEELAHLK EQSALKADLE RVLEAADGPG MFDDDEDDLQ RALAMSRQEI
DMEDEEADLR RAIQLSMQGS SRGMCEDSPQ TSSTDLSSEE LRKRREAYFE KQQHQQQEAD
RPGYLSYPCE RPTTSSGGLR SNQAGNAMSE EDVLRATVTV SLETAKDSLK AERKK
