ID   OTU1_DROME              Reviewed;         347 AA.
AC   Q9VRJ9; Q8T9H3;
DT   03-APR-2007, integrated into UniProtKB/Swiss-Prot.
DT   01-MAY-2000, sequence version 1.
DT   27-MAR-2024, entry version 146.
DE   RecName: Full=Ubiquitin thioesterase Otu1 {ECO:0000305|PubMed:35393473};
DE            EC=3.4.19.12 {ECO:0000250|UniProtKB:Q5VVQ6};
DE   AltName: Full=Yod1 deubiquitinase {ECO:0000312|FlyBase:FBgn0035593};
GN   Name=Yod1 {ECO:0000312|FlyBase:FBgn0035593};
GN   Synonyms=Otu1 {ECO:0000303|PubMed:35393473};
GN   ORFNames=CG4603 {ECO:0000312|FlyBase:FBgn0035593};
OS   Drosophila melanogaster (Fruit fly).
OC   Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC   Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC   Drosophilidae; Drosophila; Sophophora.
OX   NCBI_TaxID=7227;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=Berkeley;
RX   PubMed=10731132; DOI=10.1126/science.287.5461.2185;
RA   Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D.,
RA   Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F.,
RA   George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N.,
RA   Sutton G.G., Wortman J.R., Yandell M.D., Zhang Q., Chen L.X., Brandon R.C.,
RA   Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C.,
RA   Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A.,
RA   An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A.,
RA   Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V.,
RA   Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J.,
RA   Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E.,
RA   Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B.,
RA   Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I.,
RA   Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C.,
RA   Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S.,
RA   Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M.,
RA   Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M.,
RA   Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D.,
RA   Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F.,
RA   Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D.,
RA   Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A.,
RA   Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C.,
RA   McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C.,
RA   Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L.,
RA   Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R.,
RA   Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V.,
RA   Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F.,
RA   Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J.,
RA   Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R.,
RA   Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y.,
RA   Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T.,
RA   Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S.,
RA   Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W.,
RA   Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M.,
RA   Venter J.C.;
RT   "The genome sequence of Drosophila melanogaster.";
RL   Science 287:2185-2195(2000).
RN   [2]
RP   GENOME REANNOTATION.
RC   STRAIN=Berkeley;
RX   PubMed=12537572; DOI=10.1186/gb-2002-3-12-research0083;
RA   Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S.,
RA   Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E.,
RA   Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P.,
RA   Bettencourt B.R., Celniker S.E., de Grey A.D.N.J., Drysdale R.A.,
RA   Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M.,
RA   Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E.;
RT   "Annotation of the Drosophila melanogaster euchromatic genome: a systematic
RT   review.";
RL   Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=Berkeley; TISSUE=Ovary;
RA   Stapleton M., Brokstein P., Hong L., Agbayani A., Carlson J.W., Champe M.,
RA   Chavez C., Dorsett V., Dresnek D., Farfan D., Frise E., George R.A.,
RA   Gonzalez M., Guarin H., Kronmiller B., Li P.W., Liao G., Miranda A.,
RA   Mungall C.J., Nunoo J., Pacleb J.M., Paragas V., Park S., Patel S.,
RA   Phouanenavong S., Wan K.H., Yu C., Lewis S.E., Rubin G.M., Celniker S.E.;
RL   Submitted (JAN-2003) to the EMBL/GenBank/DDBJ databases.
RN   [4]
RP   FUNCTION, AND DISRUPTION PHENOTYPE.
RX   PubMed=35393473; DOI=10.1038/s41598-022-09703-x;
RA   Pahi Z.G., Kovacs L., Szucs D., Borsos B.N., Deak P., Pankotai T.;
RT   "Usp5, Usp34, and Otu1 deubiquitylases mediate DNA repair in Drosophila
RT   melanogaster.";
RL   Sci. Rep. 12:5870-5870(2022).
CC   -!- FUNCTION: Hydrolase that can remove conjugated ubiquitin from proteins
CC       and may therefore play an important regulatory role at the level of
CC       protein turnover by preventing degradation (By similarity). Involved in
CC       the regulation of DNA damage repair (PubMed:35393473).
CC       {ECO:0000250|UniProtKB:P43558, ECO:0000269|PubMed:35393473}.
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:Q5VVQ6};
CC   -!- DISRUPTION PHENOTYPE: When irradiated with X-rays, adults display
CC       increased wing and eye abnormalities (PubMed:35393473). Third instar
CC       larvae exposed to X-rays do not display any changes in pupation or
CC       eclosion (PubMed:35393473). RNAi-mediated knockdown in third instar
CC       larvae results in reduced survival in response to UV radiation
CC       (PubMed:35393473). {ECO:0000269|PubMed:35393473}.
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DR   EMBL; AE014296; AAF50796.1; -; Genomic_DNA.
DR   EMBL; AY069295; AAL39440.1; -; mRNA.
DR   RefSeq; NP_001261436.1; NM_001274507.1.
DR   RefSeq; NP_647951.2; NM_139694.4.
DR   AlphaFoldDB; Q9VRJ9; -.
DR   SMR; Q9VRJ9; -.
DR   BioGRID; 64071; 8.
DR   IntAct; Q9VRJ9; 3.
DR   STRING; 7227.FBpp0303184; -.
DR   MEROPS; C85.007; -.
DR   PaxDb; 7227-FBpp0304189; -.
DR   DNASU; 38603; -.
DR   EnsemblMetazoa; FBtr0077164; FBpp0076867; FBgn0035593.
DR   EnsemblMetazoa; FBtr0331804; FBpp0304189; FBgn0035593.
DR   GeneID; 38603; -.
DR   KEGG; dme:Dmel_CG4603; -.
DR   UCSC; CG4603-RA; d. melanogaster.
DR   AGR; FB:FBgn0035593; -.
DR   CTD; 55432; -.
DR   FlyBase; FBgn0035593; Yod1.
DR   VEuPathDB; VectorBase:FBgn0035593; -.
DR   eggNOG; KOG3288; Eukaryota.
DR   GeneTree; ENSGT00390000009989; -.
DR   HOGENOM; CLU_049327_1_1_1; -.
DR   InParanoid; Q9VRJ9; -.
DR   OMA; TRCILVY; -.
DR   OrthoDB; 5486835at2759; -.
DR   PhylomeDB; Q9VRJ9; -.
DR   Reactome; R-DME-5689896; Ovarian tumor domain proteases.
DR   BioGRID-ORCS; 38603; 0 hits in 1 CRISPR screen.
DR   GenomeRNAi; 38603; -.
DR   PRO; PR:Q9VRJ9; -.
DR   Proteomes; UP000000803; Chromosome 3L.
DR   Bgee; FBgn0035593; Expressed in testis and 11 other cell types or tissues.
DR   ExpressionAtlas; Q9VRJ9; baseline and differential.
DR   GO; GO:0004843; F:cysteine-type deubiquitinase activity; ISS:FlyBase.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0030968; P:endoplasmic reticulum unfolded protein response; IBA:GO_Central.
DR   GO; GO:2000781; P:positive regulation of double-strand break repair; IMP:FlyBase.
DR   GO; GO:0016579; P:protein deubiquitination; ISS:FlyBase.
DR   GO; GO:0030433; P:ubiquitin-dependent ERAD pathway; IBA:GO_Central.
DR   CDD; cd22745; OTU_OTU1; 1.
DR   CDD; cd17059; Ubl_OTU1; 1.
DR   Gene3D; 3.90.70.80; -; 1.
DR   InterPro; IPR048857; OTU1_Ubl.
DR   InterPro; IPR003323; OTU_dom.
DR   InterPro; IPR038765; Papain-like_cys_pep_sf.
DR   InterPro; IPR029071; Ubiquitin-like_domsf.
DR   PANTHER; PTHR13312; HIV-INDUCED PROTEIN-7-LIKE PROTEASE; 1.
DR   PANTHER; PTHR13312:SF0; UBIQUITIN THIOESTERASE OTU1; 1.
DR   Pfam; PF02338; OTU; 1.
DR   Pfam; PF21403; OTU1_UBXL; 1.
DR   SUPFAM; SSF54001; Cysteine proteinases; 1.
DR   SUPFAM; SSF54236; Ubiquitin-like; 1.
DR   PROSITE; PS50802; OTU; 1.
DR   PROSITE; PS00028; ZINC_FINGER_C2H2_1; 1.
DR   Genevisible; Q9VRJ9; DM.
PE   2: Evidence at transcript level;
KW   Hydrolase; Metal-binding; Protease; Reference proteome; Thiol protease;
KW   Ubl conjugation pathway; Zinc; Zinc-finger.
FT   CHAIN           1..347
FT                   /note="Ubiquitin thioesterase Otu1"
FT                   /id="PRO_0000282362"
FT   DOMAIN          5..87
FT                   /note="Ubiquitin-like"
FT   DOMAIN          150..274
FT                   /note="OTU"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00139"
FT   ZN_FING         317..341
FT                   /note="C2H2-type"
FT   REGION          8..89
FT                   /note="UBX-like"
FT                   /evidence="ECO:0000250|UniProtKB:Q5VVQ6"
FT   REGION          155..161
FT                   /note="Cys-loop"
FT                   /evidence="ECO:0000250|UniProtKB:Q5VVQ6"
FT   REGION          213..223
FT                   /note="Variable-loop"
FT                   /evidence="ECO:0000250|UniProtKB:Q5VVQ6"
FT   REGION          263..267
FT                   /note="His-loop"
FT                   /evidence="ECO:0000250|UniProtKB:Q5VVQ6"
FT   REGION          290..295
FT                   /note="S2 site"
FT                   /evidence="ECO:0000250|UniProtKB:Q5VVQ6"
FT   ACT_SITE        158
FT                   /evidence="ECO:0000250|UniProtKB:Q96FW1"
FT   ACT_SITE        161
FT                   /note="Nucleophile"
FT                   /evidence="ECO:0000250|UniProtKB:Q5VVQ6"
FT   ACT_SITE        267
FT                   /evidence="ECO:0000250|UniProtKB:Q5VVQ6"
FT   ACT_SITE        341
FT                   /evidence="ECO:0000250|UniProtKB:Q96FW1"
FT   BINDING         266
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:Q5VVQ6"
FT   CONFLICT        87
FT                   /note="A -> S (in Ref. 3; AAL39440)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   347 AA;  37823 MW;  F8AFA9C679DD77E4 CRC64;
     MTGSFSVKLK SKKGQFIVND LNEHTTLGEL KTKIVQATDI EATQLHVLVG YPPKPLDLSQ
     QQEQRALKAV GINSGETLIV EEKAAPAPAA PVPGGTTVED DEALARRLQA EEEAQLLQET
     AGGPVAQAAD YQLPVAPTES GPNGDFNGIL LKKVVPADNS CLFTSIRFVL NGKVDNEGSE
     MMRHIIAQEV AADPQSYNDA VLGKSNAEYC AWIQKADSWG GAIEVSILSN YYGIEIDVVD
     IQNAIINRFG EDKNFGLRVF LLFDGIHYDP LYMETSPSAA PATIFPVEEL GVYQQAEQLA
     NEAQSSRQYT NVDKFTLRCM QCDVRLVGQV QAQEHAKQTG HKNFGEI
//