UBP30_DROME
ID UBP30_DROME Reviewed; 558 AA.
AC Q9W462;
DT 03-SEP-2014, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 164.
DE RecName: Full=Ubiquitin carboxyl-terminal hydrolase 30 homolog;
DE Short=dUSP30;
DE EC=3.4.19.12;
DE AltName: Full=Deubiquitinating enzyme 30 homolog;
DE AltName: Full=Ubiquitin thioesterase 30 homolog;
DE AltName: Full=Ubiquitin-specific-processing protease 30 homolog;
DE Short=Ub-specific protease 30 homolog;
GN Name=Usp30 {ECO:0000312|FlyBase:FBgn0029819};
GN ORFNames=CG3016 {ECO:0000312|FlyBase:FBgn0029819};
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=Embryo;
RX PubMed=12537569; DOI=10.1186/gb-2002-3-12-research0080;
RA Stapleton M., Carlson J.W., Brokstein P., Yu C., Champe M., George R.A.,
RA Guarin H., Kronmiller B., Pacleb J.M., Park S., Wan K.H., Rubin G.M.,
RA Celniker S.E.;
RT "A Drosophila full-length cDNA resource.";
RL Genome Biol. 3:RESEARCH0080.1-RESEARCH0080.8(2002).
RN [4]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=24896179; DOI=10.1038/nature13418;
RA Bingol B., Tea J.S., Phu L., Reichelt M., Bakalarski C.E., Song Q.,
RA Foreman O., Kirkpatrick D.S., Sheng M.;
RT "The mitochondrial deubiquitinase USP30 opposes parkin-mediated
RT mitophagy.";
RL Nature 510:370-375(2014).
CC -!- FUNCTION: Deubiquitinating enzyme that acts as a key inhibitor of
CC mitophagy by counteracting the action of parkin (park).
CC {ECO:0000269|PubMed:24896179}.
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:Q70CQ3};
CC -!- SUBCELLULAR LOCATION: Mitochondrion outer membrane
CC {ECO:0000250|UniProtKB:Q70CQ3}.
CC -!- DISRUPTION PHENOTYPE: RNAi-mediated knockdown rescues the defective
CC mitophagy caused by mutations in parkin and improves mitochondrial
CC integrity in park- or PINK1-deficient flies. Moreover, knockdown in
CC dopaminergic neurons protects flies against paraquat herbicide toxicity
CC in vivo, ameliorating defects in dopamine levels, motor function and
CC organismal survival. {ECO:0000269|PubMed:24896179}.
CC -!- SIMILARITY: Belongs to the peptidase C19 family. {ECO:0000305}.
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DR EMBL; AE014298; AAF46096.1; -; Genomic_DNA.
DR EMBL; AY069649; AAL39794.1; -; mRNA.
DR EMBL; AE014298; AHN59383.1; -; Genomic_DNA.
DR RefSeq; NP_001284912.1; NM_001297983.1.
DR RefSeq; NP_572274.1; NM_132046.3.
DR AlphaFoldDB; Q9W462; -.
DR SMR; Q9W462; -.
DR BioGRID; 58018; 9.
DR IntAct; Q9W462; 4.
DR STRING; 7227.FBpp0070793; -.
DR PaxDb; Q9W462; -.
DR PRIDE; Q9W462; -.
DR DNASU; 31519; -.
DR EnsemblMetazoa; FBtr0070828; FBpp0070793; FBgn0029819.
DR EnsemblMetazoa; FBtr0343537; FBpp0310141; FBgn0029819.
DR GeneID; 31519; -.
DR KEGG; dme:Dmel_CG3016; -.
DR UCSC; CG3016-RA; d. melanogaster.
DR CTD; 84749; -.
DR FlyBase; FBgn0029819; Usp30.
DR VEuPathDB; VectorBase:FBgn0029819; -.
DR eggNOG; KOG1867; Eukaryota.
DR GeneTree; ENSGT00550000075075; -.
DR HOGENOM; CLU_008279_14_0_1; -.
DR InParanoid; Q9W462; -.
DR OMA; CNETTTH; -.
DR OrthoDB; 1437269at2759; -.
DR PhylomeDB; Q9W462; -.
DR Reactome; R-DME-5689880; Ub-specific processing proteases.
DR Reactome; R-DME-9664873; Pexophagy.
DR BioGRID-ORCS; 31519; 0 hits in 1 CRISPR screen.
DR GenomeRNAi; 31519; -.
DR PRO; PR:Q9W462; -.
DR Proteomes; UP000000803; Chromosome X.
DR Bgee; FBgn0029819; Expressed in eye disc (Drosophila) and 22 other tissues.
DR Genevisible; Q9W462; DM.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005741; C:mitochondrial outer membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0004843; F:cysteine-type deubiquitinase activity; ISS:FlyBase.
DR GO; GO:0004197; F:cysteine-type endopeptidase activity; IBA:GO_Central.
DR GO; GO:0016579; P:protein deubiquitination; ISS:FlyBase.
DR GO; GO:0035871; P:protein K11-linked deubiquitination; ISS:UniProtKB.
DR GO; GO:0044313; P:protein K6-linked deubiquitination; ISS:UniProtKB.
DR GO; GO:1901562; P:response to paraquat; IMP:FlyBase.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IEA:InterPro.
DR InterPro; IPR038765; Papain-like_cys_pep_sf.
DR InterPro; IPR001394; Peptidase_C19_UCH.
DR InterPro; IPR018200; USP_CS.
DR InterPro; IPR028889; USP_dom.
DR Pfam; PF00443; UCH; 2.
DR SUPFAM; SSF54001; SSF54001; 1.
DR PROSITE; PS00973; USP_2; 1.
DR PROSITE; PS50235; USP_3; 1.
PE 2: Evidence at transcript level;
KW Hydrolase; Membrane; Mitochondrion; Mitochondrion outer membrane; Protease;
KW Reference proteome; Thiol protease; Transmembrane; Transmembrane helix;
KW Ubl conjugation pathway.
FT CHAIN 1..558
FT /note="Ubiquitin carboxyl-terminal hydrolase 30 homolog"
FT /id="PRO_0000430252"
FT TRANSMEM 6..26
FT /note="Helical"
FT /evidence="ECO:0000255"
FT DOMAIN 39..550
FT /note="USP"
FT REGION 267..300
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 279..300
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 48
FT /note="Nucleophile"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10093"
FT ACT_SITE 506
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10093"
SQ SEQUENCE 558 AA; 60880 MW; 86E46CC71D09EE75 CRC64;
MESEKILMAA GVTVAAVVGA FVFWGPSGSR LRQRRGQIAG LHNFGLTCFL NTLLQAMAAC
PQFIAWLQLY NNASPDRKSL ITSMLNTLEV VNGTHATLRG DPYSPGAVLR ALNALGWVIP
QEEHDAHELF HVLLTCLEEE AIRPQPLGCL SDALPTDNDD NSSLAGTATP VGGFRSFSSM
AAGLGASQRI GDQPNRPSSA MLTDFLNMEY DESTSLQRLV RSEAHTPDSP ASVCERDGND
RLGSVLLDAV SPGTPFGFPL VSNPDSLATP MLGGERSSRP RLPQSQQQQD EGLNRRVSSS
CRSLERLHRG PGRVSIWSNM MPSQVAHPFQ GAMGAQIVCN GCGSKSAVRY DKFDSITLNL
PPQRRTGLSL GHLLSEYITS EDLSDVKCDS CNETTTHTKS VTFAKLPACL CIHVARTVWL
PTGQVCKRKD YVHFPESLSM APYSFVQPHL NSQAGTPWGS TMSLYSSSLP MNNGVGGGEG
FGTMFPKNLY RLLAVVVHSG EANSGHFVTY RRGSLRNAHR WYYTSDTIVR EVSIDEVLSV
PAYLLFYDRG QQRQLNLR
