UBP30_RAT
ID UBP30_RAT Reviewed; 517 AA.
AC D3ZPG5;
DT 03-SEP-2014, integrated into UniProtKB/Swiss-Prot.
DT 20-APR-2010, sequence version 1.
DT 03-AUG-2022, entry version 79.
DE RecName: Full=Ubiquitin carboxyl-terminal hydrolase 30;
DE EC=3.4.19.12 {ECO:0000250|UniProtKB:Q70CQ3};
DE AltName: Full=Deubiquitinating enzyme 30;
DE AltName: Full=Ubiquitin thioesterase 30;
DE AltName: Full=Ubiquitin-specific-processing protease 30;
DE Short=Ub-specific protease 30;
GN Name=Usp30;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway;
RX PubMed=15057822; DOI=10.1038/nature02426;
RA Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA Mockrin S., Collins F.S.;
RT "Genome sequence of the Brown Norway rat yields insights into mammalian
RT evolution.";
RL Nature 428:493-521(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway;
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP FUNCTION.
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 tethered to the mitochondrial outer
CC membrane that acts as a key inhibitor of mitophagy by counteracting the
CC action of parkin (PRKN): hydrolyzes ubiquitin attached by parkin on
CC target proteins, such as RHOT1/MIRO1 and TOMM20, thereby blocking
CC parkin's ability to drive mitophagy (PubMed:24896179). Preferentially
CC cleaves 'Lys-6'- and 'Lys-11'-linked polyubiquitin chains, 2 types of
CC linkage that participate in mitophagic signaling. Does not cleave
CC efficiently polyubiquitin phosphorylated at 'Ser-65' (By similarity).
CC Acts as negative regulator of mitochondrial fusion by mediating
CC deubiquitination of MFN1 and MFN2 (By similarity).
CC {ECO:0000250|UniProtKB:Q3UN04, ECO:0000250|UniProtKB:Q70CQ3,
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 -!- ACTIVITY REGULATION: Inhibited by the diterpenoid derivative 15-
CC oxospiramilactone (S3). {ECO:0000250|UniProtKB:Q3UN04}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion outer membrane
CC {ECO:0000250|UniProtKB:Q70CQ3}.
CC -!- PTM: Ubiquitinated by parkin (PRKN) at Lys-235 and Lys-289, leading to
CC its degradation. {ECO:0000250|UniProtKB:Q70CQ3}.
CC -!- SIMILARITY: Belongs to the peptidase C19 family. {ECO:0000305}.
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DR EMBL; AABR06072514; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH473973; EDM13952.1; -; Genomic_DNA.
DR RefSeq; NP_001100623.1; NM_001107153.1.
DR AlphaFoldDB; D3ZPG5; -.
DR SMR; D3ZPG5; -.
DR STRING; 10116.ENSRNOP00000034698; -.
DR PaxDb; D3ZPG5; -.
DR PeptideAtlas; D3ZPG5; -.
DR Ensembl; ENSRNOT00000030891; ENSRNOP00000034698; ENSRNOG00000028556.
DR GeneID; 304579; -.
DR KEGG; rno:304579; -.
DR UCSC; RGD:1307949; rat.
DR CTD; 84749; -.
DR RGD; 1307949; Usp30.
DR eggNOG; KOG1867; Eukaryota.
DR GeneTree; ENSGT00550000075075; -.
DR HOGENOM; CLU_008279_14_2_1; -.
DR InParanoid; D3ZPG5; -.
DR OMA; CNETTTH; -.
DR OrthoDB; 1437269at2759; -.
DR PhylomeDB; D3ZPG5; -.
DR TreeFam; TF105781; -.
DR Reactome; R-RNO-5689880; Ub-specific processing proteases.
DR Reactome; R-RNO-9664873; Pexophagy.
DR PRO; PR:D3ZPG5; -.
DR Proteomes; UP000002494; Chromosome 12.
DR Proteomes; UP000234681; Chromosome 12.
DR Bgee; ENSRNOG00000028556; Expressed in testis and 20 other tissues.
DR ExpressionAtlas; D3ZPG5; baseline and differential.
DR Genevisible; D3ZPG5; RN.
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; ISO:RGD.
DR GO; GO:0005739; C:mitochondrion; ISO:RGD.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0004843; F:cysteine-type deubiquitinase activity; ISO:RGD.
DR GO; GO:0004197; F:cysteine-type endopeptidase activity; ISO:RGD.
DR GO; GO:0000422; P:autophagy of mitochondrion; ISO:RGD.
DR GO; GO:0008053; P:mitochondrial fusion; ISO:RGD.
DR GO; GO:1901525; P:negative regulation of mitophagy; IMP:RGD.
DR GO; GO:0016579; P:protein deubiquitination; ISO:RGD.
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: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; 1.
DR SUPFAM; SSF54001; SSF54001; 1.
DR PROSITE; PS00972; USP_1; 1.
DR PROSITE; PS00973; USP_2; 1.
DR PROSITE; PS50235; USP_3; 1.
PE 3: Inferred from homology;
KW Hydrolase; Isopeptide bond; Membrane; Mitochondrion;
KW Mitochondrion outer membrane; Protease; Reference proteome; Thiol protease;
KW Transmembrane; Transmembrane helix; Ubl conjugation;
KW Ubl conjugation pathway.
FT CHAIN 1..517
FT /note="Ubiquitin carboxyl-terminal hydrolase 30"
FT /id="PRO_0000430251"
FT TOPO_DOM 1..35
FT /note="Mitochondrial intermembrane"
FT /evidence="ECO:0000255"
FT TRANSMEM 36..56
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 57..517
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 68..502
FT /note="USP"
FT REGION 364..395
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 77
FT /note="Nucleophile"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10092,
FT ECO:0000255|PROSITE-ProRule:PRU10093"
FT ACT_SITE 452
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10092,
FT ECO:0000255|PROSITE-ProRule:PRU10093"
FT CROSSLNK 235
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:Q70CQ3"
FT CROSSLNK 289
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:Q70CQ3"
SQ SEQUENCE 517 AA; 58206 MW; 39E95857B6959226 CRC64;
MLSSRAQAAR TAADKALQRF LRTGAAVRYK VMKNWGVIGG IAAALAAGIY VIWGPITERK
KRRKGLVPGL VNLGNTCFMN SLLQGLSACP AFVKWLEEFT TQYSRDQQGP HTHQCLSLTL
LSLLKALSCQ EVTEEEVLDA SCLLDVLRMY RWQISSFEEQ DAHELFHVIT SSLEDERDRQ
PRVTHLFDVH SLEQQSEMAP RQVTCHTRGS PHPTTNPWKS QHPFHGRLSS NMVCKHCEHQ
SPVRFDTFDS LSLSIPAATW GHPLTLDHCL HHFISSESVR DVVCDNCTKI EAKGTQNGEK
VEHQRTTFVK QLKLGKLPQC LCIHLQRLSW SSQGTPLKRH EHVQFNEFLM MDFYKYRLLG
HKPSQHGPKA TESPGSALGV QDTQAAPKPG LSQPAAPKTQ FFMNGACSPS LLPALPSPMA
FPLPVAPDYS SSMYLFRLMA VVVHHGDMHS GHFVTYRRSP PSAKNPLSTS NQWLWISDDT
VRKASLQEVL SSSAYLLFYE RVLSRVQQQG REYRSEE
