ATX3L_HUMAN
ID ATX3L_HUMAN Reviewed; 355 AA.
AC Q9H3M9; B2RNY8;
DT 09-JAN-2007, integrated into UniProtKB/Swiss-Prot.
DT 09-JAN-2007, sequence version 2.
DT 03-AUG-2022, entry version 141.
DE RecName: Full=Ataxin-3-like protein {ECO:0000305};
DE EC=3.4.19.12;
DE AltName: Full=Machado-Joseph disease protein 1-like;
GN Name=ATXN3L {ECO:0000312|HGNC:HGNC:24173}; Synonyms=ATX3L, MJDL;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15772651; DOI=10.1038/nature03440;
RA Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D.,
RA Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L.,
RA Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C.,
RA Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A.,
RA Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P.,
RA Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D.,
RA Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D.,
RA Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L.,
RA Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P.,
RA Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G.,
RA Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J.,
RA Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D.,
RA Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L.,
RA Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z.,
RA Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S.,
RA Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S.,
RA Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O.,
RA Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H.,
RA Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T.,
RA Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L.,
RA Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R.,
RA Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y.,
RA Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K.,
RA Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J.,
RA Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L.,
RA Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S.,
RA Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A.,
RA Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L.,
RA Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D.,
RA Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H.,
RA McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S.,
RA Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C.,
RA Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S.,
RA Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V.,
RA Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K.,
RA Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K.,
RA Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D.,
RA Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R.,
RA Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B.,
RA Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C.,
RA d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q.,
RA Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N.,
RA Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A.,
RA Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J.,
RA Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A.,
RA Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F.,
RA Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L.,
RA Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S.,
RA Rogers J., Bentley D.R.;
RT "The DNA sequence of the human X chromosome.";
RL Nature 434:325-337(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT ASP-332.
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ASP-332.
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 10-355, AND VARIANT ASP-332.
RX PubMed=11450850; DOI=10.1007/s100380170060;
RA Ichikawa Y., Goto J., Hattori M., Toyoda A., Ishii K., Jeong S.-Y.,
RA Hashida H., Masuda N., Ogata K., Kasai F., Hirai M., Maciel P.,
RA Rouleau G.A., Sakaki Y., Kanazawa I.;
RT "The genomic structure and expression of MJD, the Machado-Joseph disease
RT gene.";
RL J. Hum. Genet. 46:413-422(2001).
RN [5]
RP X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 1-190 IN COMPLEX WITH UBIQUITIN,
RP CATALYTIC ACTIVITY, AND ACTIVE SITE.
RX PubMed=21118805; DOI=10.1074/jbc.m110.177360;
RA Weeks S.D., Grasty K.C., Hernandez-Cuebas L., Loll P.J.;
RT "Crystal structure of a Josephin-ubiquitin complex: evolutionary restraints
RT on ataxin-3 deubiquitinating activity.";
RL J. Biol. Chem. 286:4555-4565(2011).
CC -!- FUNCTION: Deubiquitinating enzyme that cleaves both 'Lys-48'-linked and
CC 'Lys-63'-linked poly-ubiquitin chains (in vitro).
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:21118805};
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250}.
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DR EMBL; AC004674; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471074; EAW98819.1; -; Genomic_DNA.
DR EMBL; BC137186; AAI37187.1; -; mRNA.
DR EMBL; BC137187; AAI37188.1; -; mRNA.
DR EMBL; AB050195; BAB18799.1; -; mRNA.
DR CCDS; CCDS48080.1; -.
DR RefSeq; NP_001129467.1; NM_001135995.1.
DR PDB; 3O65; X-ray; 2.70 A; A/C/E/G=1-190.
DR PDBsum; 3O65; -.
DR AlphaFoldDB; Q9H3M9; -.
DR SMR; Q9H3M9; -.
DR BioGRID; 124954; 11.
DR IntAct; Q9H3M9; 2.
DR STRING; 9606.ENSP00000369996; -.
DR BindingDB; Q9H3M9; -.
DR ChEMBL; CHEMBL4630855; -.
DR MEROPS; C86.002; -.
DR iPTMnet; Q9H3M9; -.
DR PhosphoSitePlus; Q9H3M9; -.
DR BioMuta; ATXN3L; -.
DR DMDM; 122055954; -.
DR MassIVE; Q9H3M9; -.
DR PaxDb; Q9H3M9; -.
DR PeptideAtlas; Q9H3M9; -.
DR PRIDE; Q9H3M9; -.
DR Antibodypedia; 23827; 55 antibodies from 15 providers.
DR DNASU; 92552; -.
DR Ensembl; ENST00000380622.5; ENSP00000369996.2; ENSG00000123594.7.
DR GeneID; 92552; -.
DR KEGG; hsa:92552; -.
DR MANE-Select; ENST00000380622.5; ENSP00000369996.2; NM_001135995.2; NP_001129467.1.
DR UCSC; uc010ned.4; human.
DR CTD; 92552; -.
DR DisGeNET; 92552; -.
DR GeneCards; ATXN3L; -.
DR HGNC; HGNC:24173; ATXN3L.
DR HPA; ENSG00000123594; Tissue enriched (testis).
DR MIM; 300920; gene.
DR neXtProt; NX_Q9H3M9; -.
DR OpenTargets; ENSG00000123594; -.
DR PharmGKB; PA134884147; -.
DR VEuPathDB; HostDB:ENSG00000123594; -.
DR eggNOG; KOG2935; Eukaryota.
DR GeneTree; ENSGT00390000001830; -.
DR HOGENOM; CLU_031228_1_0_1; -.
DR InParanoid; Q9H3M9; -.
DR OMA; EHRVYKT; -.
DR OrthoDB; 1482722at2759; -.
DR PhylomeDB; Q9H3M9; -.
DR TreeFam; TF314228; -.
DR PathwayCommons; Q9H3M9; -.
DR Reactome; R-HSA-5689877; Josephin domain DUBs.
DR SignaLink; Q9H3M9; -.
DR BioGRID-ORCS; 92552; 9 hits in 700 CRISPR screens.
DR GenomeRNAi; 92552; -.
DR Pharos; Q9H3M9; Tbio.
DR PRO; PR:Q9H3M9; -.
DR Proteomes; UP000005640; Chromosome X.
DR RNAct; Q9H3M9; protein.
DR Bgee; ENSG00000123594; Expressed in sperm and 16 other tissues.
DR ExpressionAtlas; Q9H3M9; baseline and differential.
DR Genevisible; Q9H3M9; HS.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0004843; F:cysteine-type deubiquitinase activity; IDA:UniProtKB.
DR GO; GO:0016579; P:protein deubiquitination; IDA:UniProtKB.
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; 2.
DR PROSITE; PS50957; JOSEPHIN; 1.
DR PROSITE; PS50330; UIM; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Hydrolase; Nucleus; Protease; Reference proteome; Repeat;
KW Thiol protease; Transcription; Transcription regulation;
KW Ubl conjugation pathway.
FT CHAIN 1..355
FT /note="Ataxin-3-like protein"
FT /id="PRO_0000271099"
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..258
FT /note="UIM 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00213"
FT REGION 209..230
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 253..331
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 253..276
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 278..292
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 293..323
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"
FT VARIANT 266
FT /note="L -> F (in dbSNP:rs16999010)"
FT /id="VAR_029861"
FT VARIANT 332
FT /note="G -> D (in dbSNP:rs4830842)"
FT /evidence="ECO:0000269|PubMed:11450850,
FT ECO:0000269|PubMed:15489334, ECO:0000269|Ref.2"
FT /id="VAR_029862"
FT CONFLICT 101
FT /note="K -> M (in Ref. 4; BAB18799)"
FT /evidence="ECO:0000305"
FT CONFLICT 314
FT /note="P -> A (in Ref. 4; BAB18799)"
FT /evidence="ECO:0000305"
FT HELIX 14..23
FT /evidence="ECO:0007829|PDB:3O65"
FT HELIX 30..48
FT /evidence="ECO:0007829|PDB:3O65"
FT HELIX 49..51
FT /evidence="ECO:0007829|PDB:3O65"
FT HELIX 56..62
FT /evidence="ECO:0007829|PDB:3O65"
FT STRAND 67..69
FT /evidence="ECO:0007829|PDB:3O65"
FT HELIX 77..85
FT /evidence="ECO:0007829|PDB:3O65"
FT TURN 86..88
FT /evidence="ECO:0007829|PDB:3O65"
FT STRAND 90..93
FT /evidence="ECO:0007829|PDB:3O65"
FT HELIX 97..101
FT /evidence="ECO:0007829|PDB:3O65"
FT HELIX 106..108
FT /evidence="ECO:0007829|PDB:3O65"
FT STRAND 111..118
FT /evidence="ECO:0007829|PDB:3O65"
FT STRAND 120..126
FT /evidence="ECO:0007829|PDB:3O65"
FT STRAND 129..132
FT /evidence="ECO:0007829|PDB:3O65"
FT STRAND 137..139
FT /evidence="ECO:0007829|PDB:3O65"
FT STRAND 141..143
FT /evidence="ECO:0007829|PDB:3O65"
FT HELIX 145..152
FT /evidence="ECO:0007829|PDB:3O65"
FT HELIX 153..156
FT /evidence="ECO:0007829|PDB:3O65"
FT STRAND 160..167
FT /evidence="ECO:0007829|PDB:3O65"
FT HELIX 173..178
FT /evidence="ECO:0007829|PDB:3O65"
SQ SEQUENCE 355 AA; 40747 MW; EE5097A6E4476D75 CRC64;
MDFIFHEKQE GFLCAQHCLN NLLQGEYFSP VELASIAHQL DEEERMRMAE GGVTSEEYLA
FLQQPSENMD DTGFFSIQVI SNALKFWGLE IIHFNNPEYQ KLGIDPINER SFICNYKQHW
FTIRKFGKHW FNLNSLLAGP ELISDTCLAN FLARLQQQAY SVFVVKGDLP DCEADQLLQI
ISVEEMDTPK LNGKKLVKQK EHRVYKTVLE KVSEESDESG TSDQDEEDFQ RALELSRQET
NREDEHLRST IELSMQGSSG NTSQDLPKTS CVTPASEQPK KIKEDYFEKH QQEQKQQQQQ
SDLPGHSSYL HERPTTSSRA IESDLSDDIS EGTVQAAVDT ILEIMRKNLK IKGEK
