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 24-JAN-2024, entry version 123. 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}; 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; 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 SwissPalm; Q3UN04; -. DR EPD; Q3UN04; -. DR MaxQB; Q3UN04; -. DR PaxDb; 10090-ENSMUSP00000031588; -. DR PeptideAtlas; Q3UN04; -. DR ProteomicsDB; 298460; -. DR Pumba; Q3UN04; -. DR Antibodypedia; 1728; 198 antibodies from 26 providers. DR DNASU; 100756; -. DR Ensembl; ENSMUST00000031588.12; ENSMUSP00000031588.8; ENSMUSG00000029592.12. DR GeneID; 100756; -. DR KEGG; mmu:100756; -. DR UCSC; uc008yzc.1; mouse. DR AGR; MGI:2140991; -. 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; CEREGND; -. DR OrthoDB; 227085at2759; -. 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 77 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 225 other cell types or tissues. DR ExpressionAtlas; Q3UN04; baseline and differential. DR GO; GO:0005829; C:cytosol; IBA:GO_Central. 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:0006508; P:proteolysis; IEA:UniProtKB-KW. DR CDD; cd02662; Peptidase_C19F; 1. DR Gene3D; 3.90.70.10; Cysteine proteinases; 2. 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 PANTHER; PTHR24006; UBIQUITIN CARBOXYL-TERMINAL HYDROLASE; 1. DR PANTHER; PTHR24006:SF650; UBIQUITIN CARBOXYL-TERMINAL HYDROLASE 30; 1. DR Pfam; PF00443; UCH; 1. DR SUPFAM; SSF54001; Cysteine proteinases; 1. DR PROSITE; PS00972; USP_1; 1. DR PROSITE; PS00973; USP_2; 1. DR PROSITE; PS50235; USP_3; 1. DR Genevisible; Q3UN04; MM. 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 //