OTU1_HUMAN
ID OTU1_HUMAN Reviewed; 348 AA.
AC Q5VVQ6; B2RNX3; Q5VVQ5; Q6ZRS6; Q86T63; Q9P1L8;
DT 03-APR-2007, integrated into UniProtKB/Swiss-Prot.
DT 07-DEC-2004, sequence version 1.
DT 03-AUG-2022, entry version 143.
DE RecName: Full=Ubiquitin thioesterase OTU1;
DE EC=3.4.19.12 {ECO:0000269|PubMed:19818707, ECO:0000269|PubMed:23827681};
DE AltName: Full=DUBA-8;
DE AltName: Full=HIV-1-induced protease 7;
DE Short=HIN-7;
DE Short=HsHIN7;
DE AltName: Full=OTU domain-containing protein 2;
GN Name=YOD1; Synonyms=DUBA8, HIN7, OTUD2; ORFNames=PRO0907;
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 MRNA] (ISOFORM 2).
RC TISSUE=Testis;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
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 (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain, and Testis;
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 8-348.
RC TISSUE=Spinal cord;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 267-348.
RC TISSUE=Fetal liver;
RX PubMed=11483580; DOI=10.1101/gr.175501;
RA Yu Y., Zhang C., Zhou G., Wu S., Qu X., Wei H., Xing G., Dong C., Zhai Y.,
RA Wan J., Ouyang S., Li L., Zhang S., Zhou K., Zhang Y., Wu C., He F.;
RT "Gene expression profiling in human fetal liver and identification of
RT tissue- and developmental-stage-specific genes through compiled expression
RT profiles and efficient cloning of full-length cDNAs.";
RL Genome Res. 11:1392-1403(2001).
RN [7]
RP FUNCTION, ENZYME ACTIVITY, INTERACTION WITH FAF2; DERL1 AND VCP, AND
RP MUTAGENESIS OF CYS-160.
RX PubMed=19818707; DOI=10.1016/j.molcel.2009.09.016;
RA Ernst R., Mueller B., Ploegh H.L., Schlieker C.;
RT "The otubain YOD1 is a deubiquitinating enzyme that associates with p97 to
RT facilitate protein dislocation from the ER.";
RL Mol. Cell 36:28-38(2009).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [9]
RP FUNCTION, INTERACTION WITH PLAA; UBXN6 AND VCP, SUBCELLULAR LOCATION, AND
RP MUTAGENESIS OF CYS-160.
RX PubMed=27753622; DOI=10.15252/embj.201695148;
RA Papadopoulos C., Kirchner P., Bug M., Grum D., Koerver L., Schulze N.,
RA Poehler R., Dressler A., Fengler S., Arhzaouy K., Lux V., Ehrmann M.,
RA Weihl C.C., Meyer H.;
RT "VCP/p97 cooperates with YOD1, UBXD1 and PLAA to drive clearance of
RT ruptured lysosomes by autophagy.";
RL EMBO J. 36:135-150(2017).
RN [10]
RP X-RAY CRYSTALLOGRAPHY (1.47 ANGSTROMS) OF 132-314 IN COMPLEX WITH
RP UBIQUITINATED SUBSTRATE, FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF
RP ILE-292; VAL-295; HIS-336 AND HIS-342.
RX PubMed=23827681; DOI=10.1016/j.cell.2013.05.046;
RA Mevissen T.E., Hospenthal M.K., Geurink P.P., Elliott P.R., Akutsu M.,
RA Arnaudo N., Ekkebus R., Kulathu Y., Wauer T., El Oualid F., Freund S.M.,
RA Ovaa H., Komander D.;
RT "OTU deubiquitinases reveal mechanisms of linkage specificity and enable
RT ubiquitin chain restriction analysis.";
RL Cell 154:169-184(2013).
CC -!- FUNCTION: Hydrolase that can remove conjugated ubiquitin from proteins
CC and participates in endoplasmic reticulum-associated degradation (ERAD)
CC for misfolded lumenal proteins. May act by triming the ubiquitin chain
CC on the associated substrate to facilitate their threading through the
CC VCP/p97 pore. Ubiquitin moieties on substrates may present a steric
CC impediment to the threading process when the substrate is transferred
CC to the VCP pore and threaded through VCP's axial channel. Mediates
CC deubiquitination of 'Lys-27'-, 'Lys-29'- and 'Lys-33'-linked
CC polyubiquitin chains. Also able to hydrolyze 'Lys-11'-linked ubiquitin
CC chains. Cleaves both polyubiquitin and di-ubiquitin. May play a role in
CC macroautophagy, regulating for instance the clearance of damaged
CC lysosomes. May recruit PLAA, UBXN6 and VCP to damaged lysosome
CC membranes decorated with K48-linked ubiquitin chains and remove these
CC chains allowing autophagosome formation (PubMed:27753622).
CC {ECO:0000269|PubMed:19818707, ECO:0000269|PubMed:23827681,
CC ECO:0000269|PubMed:27753622}.
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:19818707,
CC ECO:0000269|PubMed:23827681};
CC -!- SUBUNIT: Interacts with VCP; the interaction is direct. Interacts with
CC FAF2/UBXD8. Interacts with DERL1; however interaction is dependent on
CC the UBAX-like region, suggesting that it may be indirect. Interacts
CC with PLAA, UBXN6 and VCP; may form a complex involved in macroautophagy
CC (PubMed:27753622). {ECO:0000269|PubMed:19818707,
CC ECO:0000269|PubMed:23827681, ECO:0000269|PubMed:27753622}.
CC -!- INTERACTION:
CC Q5VVQ6; Q15038: DAZAP2; NbExp=7; IntAct=EBI-2510804, EBI-724310;
CC Q5VVQ6; Q96D03: DDIT4L; NbExp=3; IntAct=EBI-2510804, EBI-742054;
CC Q5VVQ6; Q92567-2: FAM168A; NbExp=5; IntAct=EBI-2510804, EBI-11978259;
CC Q5VVQ6; Q0VD86: INCA1; NbExp=3; IntAct=EBI-2510804, EBI-6509505;
CC Q5VVQ6; P25791-3: LMO2; NbExp=3; IntAct=EBI-2510804, EBI-11959475;
CC Q5VVQ6; Q9UHC7: MKRN1; NbExp=5; IntAct=EBI-2510804, EBI-373524;
CC Q5VVQ6; Q9NPE2: NGRN; NbExp=3; IntAct=EBI-2510804, EBI-2683432;
CC Q5VVQ6; Q96CS7: PLEKHB2; NbExp=5; IntAct=EBI-2510804, EBI-373552;
CC Q5VVQ6; Q9NRQ2: PLSCR4; NbExp=3; IntAct=EBI-2510804, EBI-769257;
CC Q5VVQ6; O14818: PSMA7; NbExp=5; IntAct=EBI-2510804, EBI-603272;
CC Q5VVQ6; P35250-2: RFC2; NbExp=3; IntAct=EBI-2510804, EBI-12936957;
CC Q5VVQ6; Q9NWF9: RNF216; NbExp=3; IntAct=EBI-2510804, EBI-723313;
CC Q5VVQ6; Q99942: RNF5; NbExp=3; IntAct=EBI-2510804, EBI-348482;
CC Q5VVQ6; Q8N0X7: SPART; NbExp=3; IntAct=EBI-2510804, EBI-2643803;
CC Q5VVQ6; Q9Y458: TBX22; NbExp=3; IntAct=EBI-2510804, EBI-6427217;
CC Q5VVQ6; Q05BL1: TP53BP2; NbExp=3; IntAct=EBI-2510804, EBI-11952721;
CC Q5VVQ6; Q9Y4K3: TRAF6; NbExp=5; IntAct=EBI-2510804, EBI-359276;
CC Q5VVQ6; Q9BZR9: TRIM8; NbExp=3; IntAct=EBI-2510804, EBI-2340370;
CC Q5VVQ6; P0CG48: UBC; NbExp=3; IntAct=EBI-2510804, EBI-3390054;
CC Q5VVQ6; Q9BZV1: UBXN6; NbExp=3; IntAct=EBI-2510804, EBI-1993899;
CC Q5VVQ6; P55072: VCP; NbExp=3; IntAct=EBI-2510804, EBI-355164;
CC Q5VVQ6; Q9NU63-3: ZFP57; NbExp=3; IntAct=EBI-2510804, EBI-12879708;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:27753622}.
CC Note=Recruited to damaged lysosomes decorated with K48-linked ubiquitin
CC chains. {ECO:0000269|PubMed:27753622}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q5VVQ6-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q5VVQ6-2; Sequence=VSP_024122;
CC -!- DOMAIN: The UBAX-like region mediates the interaction with VCP.
CC According to PubMed:19818707, it corresponds to a UBX domain, which is
CC a hallmark for VCP-associated proteins. However, no canonical UBX is
CC detected by prediction tools such as Pfam or PROSITE.
CC -!- DOMAIN: The C2H2-type zinc finger mediates specificity for 'Lys-27'-,
CC 'Lys-29'- and 'Lys-33'-linked polyubiquitin chains but not for 'Lys-
CC 11'-linked ubiquitin chains. Selectivity for 'Lys-11'-linked ubiquitin
CC chains is provided by recognition of the sequence surrounding 'Lys-11'
CC in ubiquitin. The S2 site region provides specificity for longer 'Lys-
CC 11'-linked ubiquitin chains (PubMed:23827681).
CC {ECO:0000269|PubMed:23827681}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAF71033.1; Type=Erroneous translation; Note=Wrong choice of frame.; Evidence={ECO:0000305};
CC Sequence=EAW93510.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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DR EMBL; AK128014; BAC87233.1; -; mRNA.
DR EMBL; AL445493; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471100; EAW93509.1; -; Genomic_DNA.
DR EMBL; CH471100; EAW93510.1; ALT_SEQ; Genomic_DNA.
DR EMBL; BC137166; AAI37167.1; -; mRNA.
DR EMBL; BC137167; AAI37168.1; -; mRNA.
DR EMBL; AL833081; CAD89975.1; -; mRNA.
DR EMBL; AF116608; AAF71033.1; ALT_SEQ; mRNA.
DR CCDS; CCDS31002.1; -. [Q5VVQ6-1]
DR CCDS; CCDS60402.1; -. [Q5VVQ6-2]
DR RefSeq; NP_001263249.1; NM_001276320.1. [Q5VVQ6-2]
DR RefSeq; NP_061036.3; NM_018566.3. [Q5VVQ6-1]
DR PDB; 4BOQ; X-ray; 1.47 A; A=132-314.
DR PDB; 4BOS; X-ray; 2.35 A; A/B=147-314.
DR PDB; 4BOZ; X-ray; 3.03 A; A/D=132-314.
DR PDBsum; 4BOQ; -.
DR PDBsum; 4BOS; -.
DR PDBsum; 4BOZ; -.
DR AlphaFoldDB; Q5VVQ6; -.
DR SMR; Q5VVQ6; -.
DR BioGRID; 120666; 77.
DR IntAct; Q5VVQ6; 32.
DR STRING; 9606.ENSP00000326813; -.
DR BindingDB; Q5VVQ6; -.
DR ChEMBL; CHEMBL4630833; -.
DR MEROPS; C85.007; -.
DR iPTMnet; Q5VVQ6; -.
DR PhosphoSitePlus; Q5VVQ6; -.
DR BioMuta; YOD1; -.
DR DMDM; 74747276; -.
DR EPD; Q5VVQ6; -.
DR jPOST; Q5VVQ6; -.
DR MassIVE; Q5VVQ6; -.
DR MaxQB; Q5VVQ6; -.
DR PaxDb; Q5VVQ6; -.
DR PeptideAtlas; Q5VVQ6; -.
DR PRIDE; Q5VVQ6; -.
DR ProteomicsDB; 65481; -. [Q5VVQ6-1]
DR ProteomicsDB; 65482; -. [Q5VVQ6-2]
DR Antibodypedia; 34591; 167 antibodies from 27 providers.
DR DNASU; 55432; -.
DR Ensembl; ENST00000315927.9; ENSP00000326813.4; ENSG00000180667.11. [Q5VVQ6-1]
DR Ensembl; ENST00000367084.1; ENSP00000356051.1; ENSG00000180667.11. [Q5VVQ6-2]
DR GeneID; 55432; -.
DR KEGG; hsa:55432; -.
DR MANE-Select; ENST00000315927.9; ENSP00000326813.4; NM_018566.4; NP_061036.3.
DR UCSC; uc001hfe.1; human. [Q5VVQ6-1]
DR CTD; 55432; -.
DR DisGeNET; 55432; -.
DR GeneCards; YOD1; -.
DR HGNC; HGNC:25035; YOD1.
DR HPA; ENSG00000180667; Tissue enhanced (bone).
DR MIM; 612023; gene.
DR neXtProt; NX_Q5VVQ6; -.
DR NIAGADS; ENSG00000180667; -.
DR OpenTargets; ENSG00000180667; -.
DR PharmGKB; PA142670552; -.
DR VEuPathDB; HostDB:ENSG00000180667; -.
DR eggNOG; KOG3288; Eukaryota.
DR GeneTree; ENSGT00390000009989; -.
DR HOGENOM; CLU_049327_1_0_1; -.
DR InParanoid; Q5VVQ6; -.
DR OMA; NEEYCDW; -.
DR OrthoDB; 1327072at2759; -.
DR PhylomeDB; Q5VVQ6; -.
DR TreeFam; TF323700; -.
DR BRENDA; 3.4.19.12; 2681.
DR PathwayCommons; Q5VVQ6; -.
DR Reactome; R-HSA-5689896; Ovarian tumor domain proteases.
DR SignaLink; Q5VVQ6; -.
DR BioGRID-ORCS; 55432; 4 hits in 1117 CRISPR screens.
DR ChiTaRS; YOD1; human.
DR GenomeRNAi; 55432; -.
DR Pharos; Q5VVQ6; Tbio.
DR PRO; PR:Q5VVQ6; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q5VVQ6; protein.
DR Bgee; ENSG00000180667; Expressed in amniotic fluid and 178 other tissues.
DR Genevisible; Q5VVQ6; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0004843; F:cysteine-type deubiquitinase activity; IDA:UniProtKB.
DR GO; GO:0101005; F:deubiquitinase activity; TAS:ParkinsonsUK-UCL.
DR GO; GO:1990380; F:Lys48-specific deubiquitinase activity; IDA:ParkinsonsUK-UCL.
DR GO; GO:0061578; F:Lys63-specific deubiquitinase activity; TAS:ParkinsonsUK-UCL.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; IPI:ParkinsonsUK-UCL.
DR GO; GO:0030968; P:endoplasmic reticulum unfolded protein response; IMP:UniProtKB.
DR GO; GO:0016236; P:macroautophagy; IMP:UniProtKB.
DR GO; GO:1904153; P:negative regulation of retrograde protein transport, ER to cytosol; IMP:ParkinsonsUK-UCL.
DR GO; GO:0016579; P:protein deubiquitination; IBA:GO_Central.
DR GO; GO:0035871; P:protein K11-linked deubiquitination; IDA:UniProtKB.
DR GO; GO:1990167; P:protein K27-linked deubiquitination; IDA:UniProtKB.
DR GO; GO:0035523; P:protein K29-linked deubiquitination; IDA:UniProtKB.
DR GO; GO:1990168; P:protein K33-linked deubiquitination; IDA:UniProtKB.
DR GO; GO:0071108; P:protein K48-linked deubiquitination; IDA:UniProtKB.
DR GO; GO:0070536; P:protein K63-linked deubiquitination; IDA:UniProtKB.
DR GO; GO:0030433; P:ubiquitin-dependent ERAD pathway; IMP:UniProtKB.
DR InterPro; IPR039138; OTU1_2_3.
DR InterPro; IPR003323; OTU_dom.
DR InterPro; IPR038765; Papain-like_cys_pep_sf.
DR InterPro; IPR029071; Ubiquitin-like_domsf.
DR InterPro; IPR013087; Znf_C2H2_type.
DR PANTHER; PTHR13312; PTHR13312; 1.
DR Pfam; PF02338; OTU; 1.
DR SUPFAM; SSF54001; SSF54001; 1.
DR SUPFAM; SSF54236; SSF54236; 1.
DR PROSITE; PS50802; OTU; 1.
DR PROSITE; PS00028; ZINC_FINGER_C2H2_1; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cytoplasm; Hydrolase; Metal-binding;
KW Protease; Reference proteome; Thiol protease; Ubl conjugation pathway;
KW Unfolded protein response; Zinc; Zinc-finger.
FT CHAIN 1..348
FT /note="Ubiquitin thioesterase OTU1"
FT /id="PRO_0000282356"
FT DOMAIN 149..274
FT /note="OTU"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00139"
FT ZN_FING 318..342
FT /note="C2H2-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT REGION 1..39
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 50..128
FT /note="UBX-like"
FT /evidence="ECO:0000305|PubMed:23827681"
FT REGION 154..160
FT /note="Cys-loop"
FT /evidence="ECO:0000305|PubMed:23827681"
FT REGION 213..223
FT /note="Variable-loop"
FT /evidence="ECO:0000305|PubMed:23827681"
FT REGION 263..267
FT /note="His-loop"
FT /evidence="ECO:0000305|PubMed:23827681"
FT REGION 291..296
FT /note="S2 site"
FT /evidence="ECO:0000305|PubMed:23827681"
FT ACT_SITE 157
FT /evidence="ECO:0000250|UniProtKB:Q96FW1"
FT ACT_SITE 160
FT /note="Nucleophile"
FT /evidence="ECO:0000305|PubMed:23827681"
FT ACT_SITE 267
FT /evidence="ECO:0000305|PubMed:23827681"
FT ACT_SITE 342
FT /evidence="ECO:0000250|UniProtKB:Q96FW1"
FT BINDING 266
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:23827681,
FT ECO:0007744|PDB:4BOS"
FT VAR_SEQ 1..61
FT /note="MFGPAKGRHFGVHPAPGFPGGVSQQAAGTKAGPAGAWPVGSRTDTMWRLRCK
FT AKDGTHVLQ -> METLHIIYSEAKSFTVE (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_024122"
FT MUTAGEN 160
FT /note="C->S: Abolishes deubiquitinase activity without
FT affecting interaction with VCP. Specifically blocks a step
FT in the course of dislocation and/or degradation of
FT endoplasmic reticulum-resident proteins destined for
FT proteasomal degradation. Prevents the macroautophagy of
FT damaged lysosome membranes decorated with K48-linked
FT ubiquitin chains."
FT /evidence="ECO:0000269|PubMed:19818707,
FT ECO:0000269|PubMed:27753622"
FT MUTAGEN 292
FT /note="I->Q: Does not affect activity or specificity.
FT Impairs ability to cleave longer 'Lys-11'-linked ubiquitin
FT chains; when associated with Q-295."
FT /evidence="ECO:0000269|PubMed:23827681"
FT MUTAGEN 295
FT /note="V->Q: Does not affect activity or specificity.
FT Impairs ability to cleave longer 'Lys-11'-linked ubiquitin
FT chains; when associated with Q-292."
FT /evidence="ECO:0000269|PubMed:23827681"
FT MUTAGEN 336
FT /note="H->A: Reduced activity toward 'Lys-27'-, 'Lys-
FT 29'- and 'Lys-33'-linked ubiquitin without affecting
FT activity toward 'Lys-11'-linked ubiquitin; when associated
FT with A-342."
FT /evidence="ECO:0000269|PubMed:23827681"
FT MUTAGEN 342
FT /note="H->A: Reduced activity toward 'Lys-27'-, 'Lys-
FT 29'- and 'Lys-33'-linked ubiquitin without affecting
FT activity toward 'Lys-11'-linked ubiquitin; when associated
FT with A-336."
FT /evidence="ECO:0000269|PubMed:23827681"
FT CONFLICT 8
FT /note="R -> G (in Ref. 5; CAD89975)"
FT /evidence="ECO:0000305"
FT CONFLICT 90
FT /note="L -> F (in Ref. 1; BAC87233)"
FT /evidence="ECO:0000305"
FT HELIX 138..140
FT /evidence="ECO:0007829|PDB:4BOQ"
FT STRAND 148..151
FT /evidence="ECO:0007829|PDB:4BOQ"
FT HELIX 160..169
FT /evidence="ECO:0007829|PDB:4BOQ"
FT HELIX 176..178
FT /evidence="ECO:0007829|PDB:4BOS"
FT HELIX 179..192
FT /evidence="ECO:0007829|PDB:4BOQ"
FT TURN 194..196
FT /evidence="ECO:0007829|PDB:4BOQ"
FT HELIX 199..202
FT /evidence="ECO:0007829|PDB:4BOQ"
FT HELIX 206..213
FT /evidence="ECO:0007829|PDB:4BOQ"
FT STRAND 215..217
FT /evidence="ECO:0007829|PDB:4BOQ"
FT HELIX 222..232
FT /evidence="ECO:0007829|PDB:4BOQ"
FT STRAND 234..240
FT /evidence="ECO:0007829|PDB:4BOQ"
FT TURN 241..244
FT /evidence="ECO:0007829|PDB:4BOQ"
FT STRAND 245..249
FT /evidence="ECO:0007829|PDB:4BOQ"
FT TURN 250..252
FT /evidence="ECO:0007829|PDB:4BOQ"
FT STRAND 256..263
FT /evidence="ECO:0007829|PDB:4BOQ"
FT STRAND 268..274
FT /evidence="ECO:0007829|PDB:4BOQ"
FT STRAND 276..280
FT /evidence="ECO:0007829|PDB:4BOQ"
FT STRAND 285..287
FT /evidence="ECO:0007829|PDB:4BOZ"
FT HELIX 292..308
FT /evidence="ECO:0007829|PDB:4BOQ"
SQ SEQUENCE 348 AA; 38322 MW; 91DBD25BE85B1CCC CRC64;
MFGPAKGRHF GVHPAPGFPG GVSQQAAGTK AGPAGAWPVG SRTDTMWRLR CKAKDGTHVL
QGLSSRTRVR ELQGQIAAIT GIAPGGQRIL VGYPPECLDL SNGDTILEDL PIQSGDMLII
EEDQTRPRSS PAFTKRGASS YVRETLPVLT RTVVPADNSC LFTSVYYVVE GGVLNPACAP
EMRRLIAQIV ASDPDFYSEA ILGKTNQEYC DWIKRDDTWG GAIEISILSK FYQCEICVVD
TQTVRIDRFG EDAGYTKRVL LIYDGIHYDP LQRNFPDPDT PPLTIFSSND DIVLVQALEL
ADEARRRRQF TDVNRFTLRC MVCQKGLTGQ AEAREHAKET GHTNFGEV
