UBP30_MOUSE
ID UBP30_MOUSE Reviewed; 517 AA.
AC Q3UN04; Q3TS48; Q3TSB9; Q8BVI3; Q8CHW7;
DT 16-JUN-2009, integrated into UniProtKB/Swiss-Prot.
DT 11-OCT-2005, sequence version 1.
DT 03-AUG-2022, entry version 115.
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 Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Embryo, Lung, and Medulla oblongata;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Salivary gland;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP FUNCTION, ACTIVITY REGULATION, ACTIVE SITE, SUBCELLULAR LOCATION, AND
RP MUTAGENESIS OF CYS-77; CYS-234; CYS-284 AND HIS-452.
RX PubMed=24513856; DOI=10.1038/cr.2014.20;
RA Yue W., Chen Z., Liu H., Yan C., Chen M., Feng D., Yan C., Wu H., Du L.,
RA Wang Y., Liu J., Huang X., Xia L., Liu L., Wang X., Jin H., Wang J.,
RA Song Z., Hao X., Chen Q.;
RT "A small natural molecule promotes mitochondrial fusion through inhibition
RT of the deubiquitinase USP30.";
RL Cell Res. 24:482-496(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. Preferentially cleaves 'Lys-
CC 6'- and 'Lys-11'-linked polyubiquitin chains, 2 types of linkage that
CC participate in mitophagic signaling. Does not cleave efficiently
CC polyubiquitin phosphorylated at 'Ser-65' (By similarity). Acts as
CC negative regulator of mitochondrial fusion by mediating
CC deubiquitination of MFN1 and MFN2 (PubMed:24513856).
CC {ECO:0000250|UniProtKB:Q70CQ3, ECO:0000269|PubMed:24513856}.
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:0000269|PubMed:24513856}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion outer membrane
CC {ECO:0000269|PubMed:24513856}.
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}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH38606.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AK078164; BAC37154.1; -; mRNA.
DR EMBL; AK144578; BAE25944.1; -; mRNA.
DR EMBL; AK162153; BAE36756.1; -; mRNA.
DR EMBL; AK162269; BAE36827.1; -; mRNA.
DR EMBL; BC038606; AAH38606.1; ALT_INIT; mRNA.
DR CCDS; CCDS19558.1; -.
DR RefSeq; NP_001028374.1; NM_001033202.3.
DR AlphaFoldDB; Q3UN04; -.
DR SMR; Q3UN04; -.
DR BioGRID; 221523; 2.
DR STRING; 10090.ENSMUSP00000031588; -.
DR ChEMBL; CHEMBL4680032; -.
DR iPTMnet; Q3UN04; -.
DR PhosphoSitePlus; Q3UN04; -.
DR EPD; Q3UN04; -.
DR MaxQB; Q3UN04; -.
DR PaxDb; Q3UN04; -.
DR PeptideAtlas; Q3UN04; -.
DR PRIDE; Q3UN04; -.
DR ProteomicsDB; 298460; -.
DR Antibodypedia; 1728; 179 antibodies from 26 providers.
DR DNASU; 100756; -.
DR Ensembl; ENSMUST00000031588; ENSMUSP00000031588; ENSMUSG00000029592.
DR GeneID; 100756; -.
DR KEGG; mmu:100756; -.
DR UCSC; uc008yzc.1; mouse.
DR CTD; 84749; -.
DR MGI; MGI:2140991; Usp30.
DR VEuPathDB; HostDB:ENSMUSG00000029592; -.
DR eggNOG; KOG1867; Eukaryota.
DR GeneTree; ENSGT00550000075075; -.
DR HOGENOM; CLU_008279_14_2_1; -.
DR InParanoid; Q3UN04; -.
DR OMA; CNETTTH; -.
DR OrthoDB; 1437269at2759; -.
DR PhylomeDB; Q3UN04; -.
DR TreeFam; TF105781; -.
DR Reactome; R-MMU-5689880; Ub-specific processing proteases.
DR Reactome; R-MMU-9664873; Pexophagy.
DR BioGRID-ORCS; 100756; 7 hits in 72 CRISPR screens.
DR ChiTaRS; Usp30; mouse.
DR PRO; PR:Q3UN04; -.
DR Proteomes; UP000000589; Chromosome 5.
DR RNAct; Q3UN04; protein.
DR Bgee; ENSMUSG00000029592; Expressed in animal zygote and 223 other tissues.
DR ExpressionAtlas; Q3UN04; baseline and differential.
DR Genevisible; Q3UN04; MM.
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; ISS:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0004843; F:cysteine-type deubiquitinase activity; IMP:UniProtKB.
DR GO; GO:0004197; F:cysteine-type endopeptidase activity; ISS:UniProtKB.
DR GO; GO:0000422; P:autophagy of mitochondrion; ISS:UniProtKB.
DR GO; GO:0008053; P:mitochondrial fusion; IMP:UniProtKB.
DR GO; GO:1901525; P:negative regulation of mitophagy; ISO:MGI.
DR GO; GO:0016579; P:protein deubiquitination; IMP:UniProtKB.
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 1: Evidence at protein level;
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_0000377537"
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 198..221
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
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 ECO:0000269|PubMed:24513856"
FT ACT_SITE 452
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10092,
FT ECO:0000255|PROSITE-ProRule:PRU10093,
FT ECO:0000269|PubMed:24513856"
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"
FT MUTAGEN 77
FT /note="C->S: Loss of deubiquitinase activity and binding to
FT diterpenoid derivative 15-oxospiramilactone (S3)
FT inhibitor."
FT /evidence="ECO:0000269|PubMed:24513856"
FT MUTAGEN 234
FT /note="C->S: Does not affect binding to diterpenoid
FT derivative 15-oxospiramilactone (S3) inhibitor."
FT /evidence="ECO:0000269|PubMed:24513856"
FT MUTAGEN 284
FT /note="C->S: Does not affect binding to diterpenoid
FT derivative 15-oxospiramilactone (S3) inhibitor."
FT /evidence="ECO:0000269|PubMed:24513856"
FT MUTAGEN 452
FT /note="H->A: Does not affect binding to diterpenoid
FT derivative 15-oxospiramilactone (S3) inhibitor."
FT /evidence="ECO:0000269|PubMed:24513856"
SQ SEQUENCE 517 AA; 58221 MW; 561866EF23103048 CRC64;
MLSSRAQAAR TAADKALQRF LRTGAAVRYK VMKNWGVIGG IAAALAAGIY VIWGPITERK
KRRKGLVPGL VNLGNTCFMN SLLQGLSACP AFVKWLEEFT TQYSRDQQGP HTHQCLSLTL
LNLLKALSCQ EVTEDEVLDA SCLLDVLRMY RWQISSFEEQ DAHELFHVIT SSLEDERDRQ
PRVTHLFDVH SLEQQSEMAP RQVTCHTRGS PHPTTNHWKS QHPFHGRLTS NMVCKHCEHQ
SPVRFDTFDS LSLSIPAATW GHPLTLDHCL HHFISSESVR DVVCDNCTKI EARGTLTGEK
VEHQRSTFVK QLKLGKLPQC LCIHLQRLSW SSHGTPLKRH EHVQFNEFLM MDFYKYRLLG
HKPSQHGPKA TENPGSAPEV QDAQAAPKPG LSQPGAPKTQ IFLNGACSPS LLPALPSPVA
FPLPVVPDYS SSTYLFRLMA VVVHHGDMHS GHFVTYRRSP PSAKNPLSTS NQWLWISDDT
VRKASLQEVL SSSAYLLFYE RVLSRVQQQG REYRSEE
