ATX3_MOUSE
ID ATX3_MOUSE Reviewed; 355 AA.
AC Q9CVD2;
DT 28-FEB-2003, integrated into UniProtKB/Swiss-Prot.
DT 28-FEB-2003, sequence version 2.
DT 03-AUG-2022, entry version 163.
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;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=NOD; TISSUE=Stomach, and Thymus;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-219, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic brain;
RX PubMed=15345747; DOI=10.1074/mcp.m400085-mcp200;
RA Ballif B.A., Villen J., Beausoleil S.A., Schwartz D., Gygi S.P.;
RT "Phosphoproteomic analysis of the developing mouse brain.";
RL Mol. Cell. Proteomics 3:1093-1101(2004).
RN [3]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-268 AND SER-273, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=17242355; DOI=10.1073/pnas.0609836104;
RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
RT "Large-scale phosphorylation analysis of mouse liver.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
RN [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-219; SER-268; SER-272;
RP SER-273 AND SER-321, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RC TISSUE=Brown adipose tissue, Heart, Kidney, Lung, Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [5]
RP FUNCTION, INTERACTION WITH STUB1, UBIQUITINATION, AND MUTAGENESIS OF
RP CYS-14.
RX PubMed=21855799; DOI=10.1016/j.molcel.2011.05.036;
RA Scaglione K.M., Zavodszky E., Todi S.V., Patury S., Xu P.,
RA Rodriguez-Lebron E., Fischer S., Konen J., Djarmati A., Peng J.,
RA Gestwicki J.E., Paulson H.L.;
RT "Ube2w and ataxin-3 coordinately regulate the ubiquitin ligase CHIP.";
RL Mol. Cell 43:599-612(2011).
RN [6]
RP INTERACTION WITH BECN1, FUNCTION, AND DOMAIN.
RX PubMed=28445460; DOI=10.1038/nature22078;
RA Ashkenazi A., Bento C.F., Ricketts T., Vicinanza M., Siddiqi F., Pavel M.,
RA Squitieri F., Hardenberg M.C., Imarisio S., Menzies F.M., Rubinsztein D.C.;
RT "Polyglutamine tracts regulate beclin 1-dependent autophagy.";
RL Nature 545:108-111(2017).
RN [7]
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 (PubMed:21855799).
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 (PubMed:28445460). {ECO:0000250|UniProtKB:P54252,
CC ECO:0000269|PubMed:21855799, ECO:0000269|PubMed:28445460}.
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:0000305|PubMed:21855799,
CC ECO:0000305|PubMed:28445460};
CC -!- SUBUNIT: Interacts with STUB1/CHIP (when monoubiquitinated)
CC (PubMed:21855799). Interacts with DNA repair proteins RAD23A and RAD23B
CC (By similarity). Interacts with BECN1 (via its poly-Gln domain)
CC (PubMed:28445460). Interacts with PRKN, UBR2, VCP and tubulin (By
CC similarity). {ECO:0000250|UniProtKB:P54252,
CC ECO:0000269|PubMed:21855799, ECO:0000269|PubMed:28445460}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:P54252}.
CC -!- DOMAIN: The UIM domains bind ubiquitin and interact with various E3
CC ubiquitin-protein ligase, such as STUB1/CHIP. They are essential to
CC limit the length of ubiquitin chains (PubMed:21855799).
CC {ECO:0000269|PubMed:21855799}.
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; AK008675; BAB25825.3; -; mRNA.
DR EMBL; AK030842; BAC27155.1; -; mRNA.
DR CCDS; CCDS26115.1; -.
DR RefSeq; NP_083981.2; NM_029705.3.
DR AlphaFoldDB; Q9CVD2; -.
DR BMRB; Q9CVD2; -.
DR SMR; Q9CVD2; -.
DR BioGRID; 225755; 17.
DR IntAct; Q9CVD2; 2.
DR MINT; Q9CVD2; -.
DR STRING; 10090.ENSMUSP00000021606; -.
DR MEROPS; C86.001; -.
DR iPTMnet; Q9CVD2; -.
DR PhosphoSitePlus; Q9CVD2; -.
DR EPD; Q9CVD2; -.
DR MaxQB; Q9CVD2; -.
DR PaxDb; Q9CVD2; -.
DR PRIDE; Q9CVD2; -.
DR ProteomicsDB; 277208; -.
DR Antibodypedia; 13668; 334 antibodies from 32 providers.
DR DNASU; 110616; -.
DR Ensembl; ENSMUST00000021606; ENSMUSP00000021606; ENSMUSG00000021189.
DR GeneID; 110616; -.
DR KEGG; mmu:110616; -.
DR UCSC; uc007otv.2; mouse.
DR CTD; 4287; -.
DR MGI; MGI:1099442; Atxn3.
DR VEuPathDB; HostDB:ENSMUSG00000021189; -.
DR eggNOG; KOG2935; Eukaryota.
DR GeneTree; ENSGT00390000001830; -.
DR InParanoid; Q9CVD2; -.
DR OMA; QQIQRPK; -.
DR OrthoDB; 1482722at2759; -.
DR PhylomeDB; Q9CVD2; -.
DR TreeFam; TF314228; -.
DR BRENDA; 3.4.19.12; 3474.
DR Reactome; R-MMU-5689877; Josephin domain DUBs.
DR Reactome; R-MMU-9615017; FOXO-mediated transcription of oxidative stress, metabolic and neuronal genes.
DR BioGRID-ORCS; 110616; 2 hits in 73 CRISPR screens.
DR ChiTaRS; Atxn3; mouse.
DR PRO; PR:Q9CVD2; -.
DR Proteomes; UP000000589; Chromosome 12.
DR RNAct; Q9CVD2; protein.
DR Bgee; ENSMUSG00000021189; Expressed in spermatid and 224 other tissues.
DR ExpressionAtlas; Q9CVD2; baseline and differential.
DR Genevisible; Q9CVD2; MM.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0005829; C:cytosol; ISS:ParkinsonsUK-UCL.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; ISO:MGI.
DR GO; GO:0005759; C:mitochondrial matrix; IDA:MGI.
DR GO; GO:0031966; C:mitochondrial membrane; IDA:MGI.
DR GO; GO:0042405; C:nuclear inclusion body; IDA:MGI.
DR GO; GO:0005730; C:nucleolus; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0051117; F:ATPase binding; ISS:ParkinsonsUK-UCL.
DR GO; GO:0004843; F:cysteine-type deubiquitinase activity; IDA:UniProtKB.
DR GO; GO:0004407; F:histone deacetylase activity; ISO:MGI.
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; ISO:MGI.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; IPI:UniProtKB.
DR GO; GO:0030036; P:actin cytoskeleton organization; ISS:ParkinsonsUK-UCL.
DR GO; GO:0034605; P:cellular response to heat; IMP:MGI.
DR GO; GO:0071218; P:cellular response to misfolded protein; IMP:UniProtKB.
DR GO; GO:0035640; P:exploration behavior; IMP:MGI.
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; IDA:UniProtKB.
DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; IMP:UniProtKB.
DR GO; GO:0016579; P:protein deubiquitination; IBA:GO_Central.
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:0006515; P:protein quality control for misfolded or incompletely synthesized proteins; IMP:UniProtKB.
DR GO; GO:0010810; P:regulation of cell-substrate adhesion; IMP:MGI.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IMP:MGI.
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; 3.
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_0000053832"
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..355
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..291
FT /note="Basic and acidic 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 219
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:15345747,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 268
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17242355,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 272
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 273
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17242355,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 321
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
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: Abolishes deubiquitinating activity."
FT /evidence="ECO:0000269|PubMed:21855799"
SQ SEQUENCE 355 AA; 40533 MW; D148DD10EA481D5B CRC64;
MESIFHEKQE GSLCAQHCLN NLLQGEYFSP VELSSIAHQL DEEERLRMAE GGVTSEDYRT
FLQQPSGNMD DSGFFSIQVI SNALKVWGLE LILFNSPEYQ RLRIDPINER SFICNYKEHW
FTVRKLGKQW FNLNSLLTGP ELISDTYLAL FLAQLQQEGY SIFVVKGDLP DCEADQLLQM
IKVQQMHRPK LIGEELAHLK EQSALKADLE RVLEAADGSG IFDEDEDDLQ RALAISRQEI
DMEDEEADLR RAIQLSMQGS SRSMCENSPQ TSSPDLSSEE LRRRREAYFE KQQQQQQEVD
RPGPLSYPRE RPTTSSGGRR SDQGGDAVSE EDMLRAAVTM SLETAKDNLK AERKK
