UBP32_DROME
ID UBP32_DROME Reviewed; 1715 AA.
AC M9PD06; M9PFQ1; M9PFZ0; M9PG46;
DT 25-OCT-2017, integrated into UniProtKB/Swiss-Prot.
DT 26-JUN-2013, sequence version 1.
DT 03-AUG-2022, entry version 71.
DE RecName: Full=Ubiquitin carboxyl-terminal hydrolase 32 {ECO:0000305};
DE EC=3.4.19.12 {ECO:0000250|UniProtKB:Q8NFA0};
GN Name=Usp32 {ECO:0000312|FlyBase:FBgn0036913};
GN Synonyms=Usp15 {ECO:0000303|PubMed:24852371};
GN ORFNames=CG8334 {ECO:0000312|FlyBase:FBgn0036913};
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 {ECO:0000312|Proteomes:UP000000803};
RN [1] {ECO:0000312|Proteomes:UP000000803}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley {ECO:0000312|Proteomes:UP000000803};
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] {ECO:0000312|Proteomes:UP000000803}
RP GENOME REANNOTATION.
RC STRAIN=Berkeley {ECO:0000312|Proteomes:UP000000803};
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] {ECO:0000305}
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=24852371; DOI=10.1093/hmg/ddu244;
RA Cornelissen T., Haddad D., Wauters F., Van Humbeeck C., Mandemakers W.,
RA Koentjoro B., Sue C., Gevaert K., De Strooper B., Verstreken P.,
RA Vandenberghe W.;
RT "The deubiquitinase USP15 antagonizes Parkin-mediated mitochondrial
RT ubiquitination and mitophagy.";
RL Hum. Mol. Genet. 23:5227-5242(2014).
CC -!- FUNCTION: Deubiquitinating enzyme that acts as an inhibitor of
CC mitophagy probably by counteracting the action of park. Possibly
CC functions by hydrolyzing ubiquitin attached by park on target proteins,
CC thereby reducing park's ability to drive mitophagy.
CC {ECO:0000269|PubMed:24852371}.
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:Q8NFA0};
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=B {ECO:0000312|FlyBase:FBgn0036913};
CC IsoId=M9PD06-1; Sequence=Displayed;
CC Name=C {ECO:0000312|FlyBase:FBgn0036913};
CC IsoId=M9PD06-2; Sequence=VSP_059180;
CC Name=D {ECO:0000312|FlyBase:FBgn0036913};
CC IsoId=M9PD06-3; Sequence=VSP_059180, VSP_059181;
CC Name=E {ECO:0000312|FlyBase:FBgn0036913};
CC IsoId=M9PD06-4; Sequence=VSP_059181;
CC -!- DISRUPTION PHENOTYPE: RNAi-mediated knockdown has no effect on the
CC number of mitochondrial clumps and mitochondrial membrane potential in
CC the indirect flight muscles, and there is also no effect on climbing
CC performance. However RNAi-mediated knockdown rescues the defective
CC mitophagy phenotypes caused by mutations in park; reducing the number
CC of mitochondrial clumps, and improving mitochondrial membrane potential
CC and climbing performance in park-deficient flies.
CC {ECO:0000269|PubMed:24852371}.
CC -!- SIMILARITY: Belongs to the peptidase C19 family. USP20/USP33 subfamily.
CC {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AE014296; AGB94767.1; -; Genomic_DNA.
DR EMBL; AE014296; AGB94768.1; -; Genomic_DNA.
DR EMBL; AE014296; AGB94769.1; -; Genomic_DNA.
DR EMBL; AE014296; AGB94770.1; -; Genomic_DNA.
DR RefSeq; NP_001262074.1; NM_001275145.2.
DR RefSeq; NP_001262075.1; NM_001275146.2.
DR RefSeq; NP_001262076.1; NM_001275147.2.
DR RefSeq; NP_001262077.1; NM_001275148.2.
DR AlphaFoldDB; M9PD06; -.
DR SMR; M9PD06; -.
DR STRING; 7227.FBpp0074659; -.
DR MEROPS; C19.A48; -.
DR PaxDb; M9PD06; -.
DR PRIDE; M9PD06; -.
DR EnsemblMetazoa; FBtr0479916; FBpp0428248; FBgn0036913.
DR GeneID; 40169; -.
DR KEGG; dme:Dmel_CG8334; -.
DR CTD; 84669; -.
DR FlyBase; FBgn0036913; Usp32.
DR VEuPathDB; VectorBase:FBgn0036913; -.
DR eggNOG; KOG1870; Eukaryota.
DR OMA; TQTYRRK; -.
DR BioGRID-ORCS; 40169; 0 hits in 3 CRISPR screens.
DR GenomeRNAi; 40169; -.
DR PRO; PR:M9PD06; -.
DR Proteomes; UP000000803; Chromosome 3L.
DR Bgee; FBgn0036913; Expressed in cleaving embryo and 24 other tissues.
DR ExpressionAtlas; M9PD06; baseline and differential.
DR GO; GO:0005794; C:Golgi apparatus; IBA:GO_Central.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0004843; F:cysteine-type deubiquitinase activity; IBA:GO_Central.
DR GO; GO:0016579; P:protein deubiquitination; ISS:FlyBase.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IEA:InterPro.
DR CDD; cd00051; EFh; 1.
DR Gene3D; 3.30.2230.10; -; 1.
DR InterPro; IPR035927; DUSP-like_sf.
DR InterPro; IPR011992; EF-hand-dom_pair.
DR InterPro; IPR018247; EF_Hand_1_Ca_BS.
DR InterPro; IPR002048; EF_hand_dom.
DR InterPro; IPR038765; Papain-like_cys_pep_sf.
DR InterPro; IPR006615; Pept_C19_DUSP.
DR InterPro; IPR001394; Peptidase_C19_UCH.
DR InterPro; IPR018200; USP_CS.
DR InterPro; IPR028889; USP_dom.
DR Pfam; PF06337; DUSP; 1.
DR Pfam; PF13202; EF-hand_5; 2.
DR Pfam; PF00443; UCH; 1.
DR SMART; SM00695; DUSP; 1.
DR SMART; SM00054; EFh; 2.
DR SUPFAM; SSF143791; SSF143791; 1.
DR SUPFAM; SSF47473; SSF47473; 1.
DR SUPFAM; SSF54001; SSF54001; 1.
DR PROSITE; PS51283; DUSP; 1.
DR PROSITE; PS00018; EF_HAND_1; 1.
DR PROSITE; PS50222; EF_HAND_2; 2.
DR PROSITE; PS00972; USP_1; 1.
DR PROSITE; PS00973; USP_2; 1.
DR PROSITE; PS50235; USP_3; 1.
PE 3: Inferred from homology;
KW Alternative splicing; Calcium; Hydrolase; Metal-binding; Phosphoprotein;
KW Protease; Reference proteome; Repeat; Thiol protease;
KW Ubl conjugation pathway.
FT CHAIN 1..1715
FT /note="Ubiquitin carboxyl-terminal hydrolase 32"
FT /evidence="ECO:0000255"
FT /id="PRO_0000442142"
FT DOMAIN 161..196
FT /note="EF-hand 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DOMAIN 197..232
FT /note="EF-hand 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DOMAIN 314..492
FT /note="DUSP"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00613"
FT DOMAIN 677..1675
FT /note="USP"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01035"
FT REGION 393..429
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1103..1213
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1536..1569
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 393..416
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1103..1126
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1142..1165
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1186..1206
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1548..1569
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 686
FT /note="Nucleophile"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01035"
FT ACT_SITE 1633
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01035"
FT BINDING 174
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 176
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 178
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 180
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 185
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 210
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000305"
FT BINDING 212
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000305"
FT BINDING 214
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000305"
FT BINDING 221
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000305"
FT VAR_SEQ 1053..1071
FT /note="Missing (in isoform C and isoform D)"
FT /id="VSP_059180"
FT VAR_SEQ 1288..1290
FT /note="Missing (in isoform D and isoform E)"
FT /id="VSP_059181"
SQ SEQUENCE 1715 AA; 191844 MW; ED150C4CADE2BEAB CRC64;
MLYAACGGTQ RGISFNDLLC GLVLITRGTQ AEKTKFLWNL YCNDAGTFII KSDYVRNVNL
APFESVSLFA QSERVNFEQF QDWIIKHRNA TVLSKWLLSD NCVSLTSELE TPTFYQSLAG
VTHLEEKDIG DLEKEFWRLK NTSQNGQIDL QFLGPLISPP IPKNALAGLF NAFDENRDGH
IDFKELCCGV SAACRGPGVE RTRFCFKIFD VDRDGVLSHD ETLQMINVLL LVAKENQESQ
QYKDLTKQLV ISDLLEFGQR RSPDGTPSKL TRDNVSLTAE DFMLWTVQCD LRLMQPLLDL
IFELCHIVFG LWPQCKHMEN DIVRGWLRRE ERRPYRVGQF WYLITHDWWL SWMQYTQHTT
HTCDYCKRTA SQRTAVDEAL VCDESFNTHS LEQHDSYSLG SGTGSASGSG SASSGISAGR
HCGPVRPGPI DNSNLITANP FRNVRTLTGE GGHLKRDTPL VQNHDFELVP KSLWKALNRW
YGDNLPLPRQ VIQPPNSDVE LELYPLNLRI LLHQAQPSQT GVGGGTQLGS WGSTVSGGYG
VLASGGGYAA IAVSSVLQPP KRYLAYTAAF SRLATVRQVG EFLCEQLRLK SEDIRLWHVP
QLDNGAILLE EDAMCLKELL IRDNDQLLLE IRNKDLTWPE ELGSLATAQC GQGAGTPGDR
RRLTRSSIMS VHAPGATGLH NLGNTCFMNA ALQVLFNTQP LAQYFQREMH RFEVNAANKL
GTKGQLAMRY AELLKEVWTA TTRSVAPLKL RFCVNKYAPQ FAGGGQHDSQ ELLEWLLDAL
HEDLNRVMEK PYSELKDSNG RPDKIVAAEA WSQHHARNQS IIIDLFYGQL KSKVSCLGCG
HESVRFDPFS LLSLPLPVEN YIYFEVLVIL LDGSVPIKYG FRLNSDCKYS HLKHKLSTMC
SLPPNLMLVC ELWNSQIRQV LNDDEKLRTQ SAKELYVYQL PEQSMRTRSN SGLSMHIEQG
LKDIQRSSAL ITSAQDSLSS LSTLQTSSHR ASSRVLCNGH VSGLDVEGEA EVGTDVSQCN
SNSNYNPIVS TYSGNGSGDN QVHELLPDEA GKVSRCFGKR ECMPHSLFCF KESLILSSSP
ENTFMHGAAA QQKRVSSAKL LHTESNTSSM SYTNHSGENS MESSLTEPIP LADLEPVSSR
NGSGGEDCSY RTSPNDSSGL STGHTLGASL DVDEQAEEGN AEDHDQPDQI TTSQPETSSG
VYSRRSSQPP HKAGKYLVAV HRKITRHDSY FLSYHKTRPS LFGVPLLIPN SEGGTHKDLY
CAVWLQVSRL LSPLPATTEQ ANHAADCDDS LGYDFPFTLR AVKADGLTCA ICPWSSFCRG
CEIRCNNDYV LQGALPPINA AASNTSTPKM NAKFPSLPNL EAKRTPEYTA SLSYTPTTKY
FEDFTIAIDW DPTALHLRYQ STLERLWVDH ETIAISRREQ VEPVDLNHCL RAFTSEEKLE
QWYHCSHCKG KKPATKKLQI WKLPPILIVH LKRFNCVNGK WVKSQKVVHF PFDDFDPTPY
LASVPQETIL RHKELLELKN DAEMTMATNE VVSELDEIDA PSKEVKEELP NQTGSTKATA
SPPPTGNILR QSKTKNAVRR QRLISTSLTK TPIVDGEFED YHQHRLKPDV DQFDPRYRLY
AVVSHSGMLN GGHYISYASN ATGSWYCYND SSCREISQKP VIDPSAAYLL FYERKGLDYE
PYLPNIEGRT LPNTASVPLE VDETEGELKK LCSIS
