ID   ATX3_CAEBR              Reviewed;         319 AA.
AC   Q60XN1; A8XTP1;
DT   04-APR-2006, integrated into UniProtKB/Swiss-Prot.
DT   23-NOV-2004, sequence version 1.
DT   27-MAR-2024, entry version 103.
DE   RecName: Full=Ataxin-3 homolog;
DE            EC=3.4.19.12 {ECO:0000250|UniProtKB:O17850};
DE   AltName: Full=Machado-Joseph disease-like protein;
GN   Name=atx-3 {ECO:0000250|UniProtKB:O17850}; ORFNames=CBG18600;
OS   Caenorhabditis briggsae.
OC   Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC   Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC   Caenorhabditis.
OX   NCBI_TaxID=6238;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=AF16;
RX   PubMed=14624247; DOI=10.1371/journal.pbio.0000045;
RA   Stein L.D., Bao Z., Blasiar D., Blumenthal T., Brent M.R., Chen N.,
RA   Chinwalla A., Clarke L., Clee C., Coghlan A., Coulson A., D'Eustachio P.,
RA   Fitch D.H.A., Fulton L.A., Fulton R.E., Griffiths-Jones S., Harris T.W.,
RA   Hillier L.W., Kamath R., Kuwabara P.E., Mardis E.R., Marra M.A.,
RA   Miner T.L., Minx P., Mullikin J.C., Plumb R.W., Rogers J., Schein J.E.,
RA   Sohrmann M., Spieth J., Stajich J.E., Wei C., Willey D., Wilson R.K.,
RA   Durbin R.M., Waterston R.H.;
RT   "The genome sequence of Caenorhabditis briggsae: a platform for comparative
RT   genomics.";
RL   PLoS Biol. 1:166-192(2003).
CC   -!- FUNCTION: Acts as a chain editing deubiquitinating enzyme that binds
CC       and cleaves 'Lys-48'-linked polyubiquitin chains, with a preference for
CC       chains containing four or more ubiquitin molecules thereby modulating
CC       protein degradation by the ubiquitin-proteasome pathway. Probably by
CC       regulating the IGF-1-insulin-like pathway, regulates lifespan.
CC       Regulates germline DNA double-strand-break repair and apoptosis in
CC       response to DNA damage by recruiting E4 ubiquitin-protein ligase ufd-2
CC       to DNA repair foci. Interacts with key regulators of transcription and
CC       represses transcription. Acts as a histone-binding protein that
CC       regulates transcription. {ECO:0000250|UniProtKB:O17850,
CC       ECO:0000250|UniProtKB:P54252}.
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:O17850};
CC   -!- SUBUNIT: Forms a complex composed of deubiquitinating enzyme atx-3,
CC       adapter ubxn-5 and cdc-48.1. Forms a complex composed of
CC       deubiquitinating enzyme atx-3, E4 ubiquitin-protein ligase ufd-2 and
CC       cdc-48.1. Interacts (via RRDR motif) with cdc-48.1 (via N-terminus) and
CC       cdc-48.2 (via N-terminus); the interaction with cdc-48.1 is not
CC       required for atx-3 enzymatic activity. Interacts (via C-terminus) with
CC       ubxn-5. May interact with ned-8. {ECO:0000250|UniProtKB:O17850}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:O17850}. Nucleus
CC       {ECO:0000250|UniProtKB:O17850}. Nucleus, nucleolus
CC       {ECO:0000250|UniProtKB:O17850}. Note=Localizes predominantly in the
CC       cytoplasm. In the germline, following ionizing radiation-induced DNA
CC       damage, localizes to foci within nucleoli where it colocalizes with
CC       cdc-48.1 and/or cdc-48.2 and ufd-2, proteasome alpha subunit and
CC       ubiquitinated proteins. {ECO:0000250|UniProtKB:O17850}.
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DR   EMBL; HE601466; CAP36017.3; -; Genomic_DNA.
DR   RefSeq; XP_002638391.1; XM_002638345.1.
DR   AlphaFoldDB; Q60XN1; -.
DR   SMR; Q60XN1; -.
DR   STRING; 6238.Q60XN1; -.
DR   MEROPS; C86.003; -.
DR   EnsemblMetazoa; CBG18600.1; CBG18600.1; WBGene00037987.
DR   GeneID; 8580388; -.
DR   KEGG; cbr:CBG_18600; -.
DR   CTD; 8580388; -.
DR   WormBase; CBG18600; CBP10927; WBGene00037987; Cbr-atx-3.
DR   eggNOG; KOG2935; Eukaryota.
DR   HOGENOM; CLU_031228_1_1_1; -.
DR   InParanoid; Q60XN1; -.
DR   OMA; WGLEIIH; -.
DR   OrthoDB; 337428at2759; -.
DR   Proteomes; UP000008549; Chromosome V.
DR   GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR   GO; GO:0005730; C:nucleolus; IEA:UniProtKB-SubCell.
DR   GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR   GO; GO:0045202; C:synapse; IEA:GOC.
DR   GO; GO:0004843; F:cysteine-type deubiquitinase activity; IBA:GO_Central.
DR   GO; GO:0007268; P:chemical synaptic transmission; IEA:EnsemblMetazoa.
DR   GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
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; PF02809; UIM; 2.
DR   PRINTS; PR01233; JOSEPHIN.
DR   SMART; SM01246; Josephin; 1.
DR   SMART; SM00726; UIM; 2.
DR   PROSITE; PS50957; JOSEPHIN; 1.
DR   PROSITE; PS50330; UIM; 1.
PE   3: Inferred from homology;
KW   Cytoplasm; Hydrolase; Nucleus; Protease; Reference proteome; Repeat;
KW   Thiol protease; Transcription; Transcription regulation;
KW   Ubl conjugation pathway.
FT   CHAIN           1..319
FT                   /note="Ataxin-3 homolog"
FT                   /id="PRO_0000232395"
FT   DOMAIN          8..179
FT                   /note="Josephin"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00331"
FT   DOMAIN          218..237
FT                   /note="UIM 1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00213"
FT   DOMAIN          242..261
FT                   /note="UIM 2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00213"
FT   REGION          253..319
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          297..300
FT                   /note="Interaction with cdc-48.1 and cdc-48.2"
FT                   /evidence="ECO:0000250|UniProtKB:O17850"
FT   COMPBIAS        256..292
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        293..319
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   ACT_SITE        21
FT                   /note="Nucleophile"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00331"
FT   ACT_SITE        118
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00331"
FT   ACT_SITE        133
FT                   /evidence="ECO:0000250|UniProtKB:P54252,
FT                   ECO:0000255|PROSITE-ProRule:PRU00331"
SQ   SEQUENCE   319 AA;  35834 MW;  AD08AAAF3065CA0C CRC64;
     MSPSDDPISS IFFERQQAAL CAQHALNMLL QDSLFTYENL RDLARQMDQM EHDILGNNAN
     AVGRSENMND SGFFSIQVIE KALETFDLKL INMENPAMAE FKANPLTARA YVLNLREHWF
     VLRKFGNQWF ELNSVKNGPK LLTDTYVKEY LHQFAAENYS IFVVQGILPN SEADDFITLC
     PVVPKPTDFD KKEPNLVQKF FNSVGRRLGG SQEIPDSQED RDLAIAMALS MESKESSESS
     GSDEDQLAKA IEMSLSQDPN IPSTSAAPSE LTETPILGPS TSSETPSGRI PSAEQQRRDR
     AKFLEKLEEE KKSQNVPEE
//