ID   UCHL_DROME              Reviewed;         227 AA.
AC   P35122; Q4PIX7; Q9TWA0; Q9V417;
DT   01-FEB-1994, integrated into UniProtKB/Swiss-Prot.
DT   30-AUG-2005, sequence version 2.
DT   02-SEP-2026, entry version 170.
DE   RecName: Full=Ubiquitin carboxyl-terminal hydrolase;
DE            EC=3.4.19.12;
DE   AltName: Full=Ubiquitin thioesterase;
GN   Name=Uch; Synonyms=ubc-D; ORFNames=CG4265;
OS   Drosophila melanogaster (Fruit fly).
OC   Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Altocrustacea; Allotriocarida;
OC   Hexapoda; Insecta; Pterygota; Neoptera; Eumetabola; Endopterygota;
OC   Aparaglossata; Panorpida; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC   Drosophilidae; Drosophila; Sophophora.
OX   NCBI_TaxID=7227;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=1426603; DOI=10.1042/bst0200631;
RA   Wilkinson K.D., Deshpande S., Larsen C.N.;
RT   "Comparisons of neuronal (PGP 9.5) and non-neuronal ubiquitin C-terminal
RT   hydrolases.";
RL   Biochem. Soc. Trans. 20:631-637(1992).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], FUNCTION, AND DEVELOPMENTAL
RP   STAGE.
RC   STRAIN=Oregon-R;
RX   PubMed=7683284; DOI=10.1006/dbio.1993.1125;
RA   Zhang N., Wilkinson K., Bownes M.;
RT   "Cloning and analysis of expression of a ubiquitin carboxyl terminal
RT   hydrolase expressed during oogenesis in Drosophila melanogaster.";
RL   Dev. Biol. 157:214-223(1993).
RN   [3]
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   [4]
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   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=Berkeley; TISSUE=Head;
RX   PubMed=10731138; DOI=10.1126/science.287.5461.2222;
RA   Rubin G.M., Hong L., Brokstein P., Evans-Holm M., Frise E., Stapleton M.,
RA   Harvey D.A.;
RT   "A Drosophila complementary DNA resource.";
RL   Science 287:2222-2224(2000).
CC   -!- FUNCTION: Ubiquitin-protein hydrolase is involved both in the
CC       processing of ubiquitin precursors and of ubiquitinated proteins. This
CC       enzyme is a thiol protease that recognizes and hydrolyzes a peptide
CC       bond at the C-terminal glycine of ubiquitin.
CC       {ECO:0000269|PubMed:7683284}.
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;
CC   -!- DEVELOPMENTAL STAGE: Expressed both maternally and zygotically.
CC       {ECO:0000269|PubMed:7683284}.
CC   -!- SIMILARITY: Belongs to the peptidase C12 family. {ECO:0000305}.
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DR   EMBL; S60346; AAA15411.1; -; Genomic_DNA.
DR   EMBL; X69678; CAA49358.1; -; mRNA.
DR   EMBL; X69679; CAA49359.1; -; Genomic_DNA.
DR   EMBL; AE014134; AAF51291.1; -; Genomic_DNA.
DR   EMBL; AF145600; AAD38575.1; -; mRNA.
DR   PIR; S33956; S33956.
DR   RefSeq; NP_001188681.1; NM_001201752.2.
DR   RefSeq; NP_476940.1; NM_057592.4.
DR   AlphaFoldDB; P35122; -.
DR   SMR; P35122; -.
DR   BioGRID; 59626; 68.
DR   FunCoup; P35122; 759.
DR   IntAct; P35122; 178.
DR   STRING; 7227.FBpp0077516; -.
DR   MEROPS; C12.008; -.
DR   PaxDb; 7227-FBpp0077516; -.
DR   PeptideAtlas; P35122; -.
DR   DNASU; 33397; -.
DR   EnsemblMetazoa; FBtr0077844; FBpp0077516; FBgn0010288.
DR   EnsemblMetazoa; FBtr0303459; FBpp0292511; FBgn0010288.
DR   GeneID; 33397; -.
DR   KEGG; dme:Dmel_CG4265; -.
DR   AGR; FB:FBgn0010288; -.
DR   CTD; 33397; -.
DR   FlyBase; FBgn0010288; Uch.
DR   VEuPathDB; VectorBase:FBgn0010288; -.
DR   eggNOG; KOG1415; Eukaryota.
DR   InParanoid; P35122; -.
DR   OMA; IDLHYVC; -.
DR   OrthoDB; 427186at2759; -.
DR   PhylomeDB; P35122; -.
DR   Reactome; R-DME-5689603; UCH proteinases.
DR   Reactome; R-DME-8866652; Synthesis of active ubiquitin: roles of E1 and E2 enzymes.
DR   Reactome; R-DME-8951664; Neddylation.
DR   BioGRID-ORCS; 33397; 0 hits in 3 CRISPR screens.
DR   GenomeRNAi; 33397; -.
DR   PRO; PR:P35122; -.
DR   Proteomes; UP000000803; Chromosome 2L.
DR   Bgee; FBgn0010288; Expressed in early elongation stage spermatid (Drosophila) in testis and 156 other cell types or tissues.
DR   ExpressionAtlas; P35122; baseline and differential.
DR   GO; GO:0004843; F:cysteine-type deubiquitinase activity; IDA:FlyBase.
DR   GO; GO:0045821; P:positive regulation of glycolytic process; IGI:FlyBase.
DR   GO; GO:0030163; P:protein catabolic process; IBA:GO_Central.
DR   GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IEA:InterPro.
DR   CDD; cd09616; Peptidase_C12_UCH_L1_L3; 1.
DR   FunFam; 3.40.532.10:FF:000006; Ubiquitin carboxyl-terminal hydrolase; 1.
DR   Gene3D; 3.40.532.10; Peptidase C12, ubiquitin carboxyl-terminal hydrolase; 1.
DR   InterPro; IPR038765; Papain-like_cys_pep_sf.
DR   InterPro; IPR001578; Peptidase_C12_UCH.
DR   InterPro; IPR036959; Peptidase_C12_UCH_sf.
DR   InterPro; IPR057254; UCH_AS.
DR   PANTHER; PTHR10589; UBIQUITIN CARBOXYL-TERMINAL HYDROLASE; 1.
DR   PANTHER; PTHR10589:SF17; UBIQUITIN CARBOXYL-TERMINAL HYDROLASE; 1.
DR   Pfam; PF01088; Peptidase_C12; 1.
DR   PRINTS; PR00707; UBCTHYDRLASE.
DR   SUPFAM; SSF54001; Cysteine proteinases; 1.
DR   PROSITE; PS00140; UCH_1; 1.
DR   PROSITE; PS52048; UCH_DOMAIN; 1.
PE   2: Evidence at transcript level;
KW   Hydrolase; Protease; Reference proteome; Thiol protease;
KW   Ubl conjugation pathway.
FT   CHAIN           1..227
FT                   /note="Ubiquitin carboxyl-terminal hydrolase"
FT                   /id="PRO_0000211072"
FT   DOMAIN          3..224
FT                   /note="UCH catalytic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01393"
FT   ACT_SITE        93
FT                   /note="Nucleophile"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01393,
FT                   ECO:0000255|PROSITE-ProRule:PRU10091"
FT   ACT_SITE        164
FT                   /note="Proton donor"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01393"
FT   SITE            87
FT                   /note="Transition state stabilizer"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01393"
FT   SITE            179
FT                   /note="Important for enzyme activity"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01393"
FT   CONFLICT        22
FT                   /note="G -> A (in Ref. 2; AAA15411/CAA49358/CAA49359)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        65
FT                   /note="A -> T (in Ref. 1 and 2)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        107
FT                   /note="E -> G (in Ref. 1)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   227 AA;  25850 MW;  298A025569C3D409 CRC64;
     MLTWTPLESN PEVLTKYIHK LGVSPAWSVT DVIGLEDDTL EWIPRPVKAF ILLFPCSETY
     EKHRAEEHDR IKEVEEQHPE DLFYMRQFTH NACGTVALIH SVANNKEVDI DRGVLKDFLE
     KTASLSPEER GRALEKDEKF TADHEALAQE GQTNAANHEK VIHHFIALVN KEGTLYELDG
     RKSFPIKHGP TSEETFVKDA AKVCKEFMAR DPNEVRFTVL ALTAAQQ
//