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Protein

Ubiquitin carboxyl-terminal hydrolase 30

Gene

USP30

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Deubiquitinating enzyme that acts as a key inhibitor of mitophagy by counteracting the action of parkin (PARK2): hydrolyzes ubiquitin attached by parkin on target proteins, such as RHOT1/MIRO1 and TOMM20, thereby blocking parkin's ability to drive mitophagy (PubMed:24896179). Acts as negative regulator of mitochondrial fusion by mediating deubiquitination of MFN1 and MFN2.2 Publications

Catalytic activityi

Thiol-dependent hydrolysis of ester, thioester, amide, peptide and isopeptide bonds formed by the C-terminal Gly of ubiquitin (a 76-residue protein attached to proteins as an intracellular targeting signal).1 Publication

Enzyme regulationi

Inhibited by the diterpenoid derivative 15-oxospiramilactone (S3).By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Active sitei77 – 771Nucleophile
Active sitei452 – 4521Proton acceptorPROSITE-ProRule annotation

GO - Molecular functioni

  1. cysteine-type endopeptidase activity Source: UniProtKB
  2. ubiquitin-specific protease activity Source: UniProtKB
  3. ubiquitin thiolesterase activity Source: UniProtKB

GO - Biological processi

  1. mitochondrial fusion Source: UniProtKB
  2. mitochondrion degradation Source: UniProtKB
  3. proteasome-mediated ubiquitin-dependent protein catabolic process Source: GO_Central
  4. protein deubiquitination Source: UniProtKB
  5. regulation of proteasomal protein catabolic process Source: GO_Central
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Protease, Thiol protease

Keywords - Biological processi

Ubl conjugation pathway

Protein family/group databases

MEROPSiC19.060.

Names & Taxonomyi

Protein namesi
Recommended name:
Ubiquitin carboxyl-terminal hydrolase 30 (EC:3.4.19.12)
Alternative name(s):
Deubiquitinating enzyme 30
Ubiquitin thioesterase 30
Ubiquitin-specific-processing protease 30
Short name:
Ub-specific protease 30
Gene namesi
Name:USP30
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 12

Organism-specific databases

HGNCiHGNC:20065. USP30.

Subcellular locationi

Mitochondrion outer membrane 2 Publications

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 3535Mitochondrial intermembraneSequence AnalysisAdd
BLAST
Transmembranei36 – 5621HelicalSequence AnalysisAdd
BLAST
Topological domaini57 – 517461CytoplasmicSequence AnalysisAdd
BLAST

GO - Cellular componenti

  1. integral component of membrane Source: UniProtKB-KW
  2. mitochondrial outer membrane Source: UniProtKB
  3. mitochondrion Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Membrane, Mitochondrion, Mitochondrion outer membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi28 – 281R → T: No change in mitochondrial subcellular location; when associated with N-30 and N-33. 1 Publication
Mutagenesisi30 – 301K → N: No effect on subcellular location; when associated with N-28 and N-33. 1 Publication
Mutagenesisi33 – 331K → N: No effect on subcellular location; when associated with N-28 and N-30. 1 Publication
Mutagenesisi59 – 646RKKRRK → NNASNN: Loss of mitochondrial subcellular location. Located in the endoplasmic reticulum. 1 Publication
Mutagenesisi77 – 771C → S: Loss of deubiquitinase activity and impaired ability to inhibit mitophagy. Increased TOMM20 ubiquitination. 2 Publications

Organism-specific databases

PharmGKBiPA134971149.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 517517Ubiquitin carboxyl-terminal hydrolase 30PRO_0000080662Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Cross-linki235 – 235Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Cross-linki289 – 289Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication

Post-translational modificationi

Ubiquitinated by parkin (PARK2) at Lys-235 and Lys-289, leading to its degradation.1 Publication

Keywords - PTMi

Isopeptide bond, Ubl conjugation

Proteomic databases

MaxQBiQ70CQ3.
PaxDbiQ70CQ3.
PRIDEiQ70CQ3.

PTM databases

PhosphoSiteiQ70CQ3.

Expressioni

Tissue specificityi

Expressed in skeletal muscle, pancreas, liver and kidney.1 Publication

Gene expression databases

BgeeiQ70CQ3.
CleanExiHS_USP30.
ExpressionAtlasiQ70CQ3. baseline and differential.
GenevestigatoriQ70CQ3.

Organism-specific databases

HPAiHPA016952.

Interactioni

Protein-protein interaction databases

BioGridi124238. 10 interactions.
DIPiDIP-53578N.
IntActiQ70CQ3. 6 interactions.
STRINGi9606.ENSP00000257548.

Structurei

3D structure databases

ProteinModelPortaliQ70CQ3.
SMRiQ70CQ3. Positions 61-354, 426-501.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini68 – 502435USPAdd
BLAST

Sequence similaritiesi

Belongs to the peptidase C19 family.Curated
Contains 1 USP domain.Curated

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG259866.
GeneTreeiENSGT00550000075075.
HOGENOMiHOG000065744.
HOVERGENiHBG079301.
InParanoidiQ70CQ3.
KOiK11851.
OMAiMKNWGVL.
PhylomeDBiQ70CQ3.
TreeFamiTF105781.

Family and domain databases

InterProiIPR001394. Peptidase_C19_UCH.
IPR018200. USP_CS.
IPR028889. USP_dom.
[Graphical view]
PfamiPF00443. UCH. 1 hit.
[Graphical view]
PROSITEiPS00972. USP_1. 1 hit.
PS00973. USP_2. 1 hit.
PS50235. USP_3. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q70CQ3-1 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
MLSSRAEAAM TAADRAIQRF LRTGAAVRYK VMKNWGVIGG IAAALAAGIY
60 70 80 90 100
VIWGPITERK KRRKGLVPGL VNLGNTCFMN SLLQGLSACP AFIRWLEEFT
110 120 130 140 150
SQYSRDQKEP PSHQYLSLTL LHLLKALSCQ EVTDDEVLDA SCLLDVLRMY
160 170 180 190 200
RWQISSFEEQ DAHELFHVIT SSLEDERDRQ PRVTHLFDVH SLEQQSEITP
210 220 230 240 250
KQITCRTRGS PHPTSNHWKS QHPFHGRLTS NMVCKHCEHQ SPVRFDTFDS
260 270 280 290 300
LSLSIPAATW GHPLTLDHCL HHFISSESVR DVVCDNCTKI EAKGTLNGEK
310 320 330 340 350
VEHQRTTFVK QLKLGKLPQC LCIHLQRLSW SSHGTPLKRH EHVQFNEFLM
360 370 380 390 400
MDIYKYHLLG HKPSQHNPKL NKNPGPTLEL QDGPGAPTPV LNQPGAPKTQ
410 420 430 440 450
IFMNGACSPS LLPTLSAPMP FPLPVVPDYS SSTYLFRLMA VVVHHGDMHS
460 470 480 490 500
GHFVTYRRSP PSARNPLSTS NQWLWVSDDT VRKASLQEVL SSSAYLLFYE
510
RVLSRMQHQS QECKSEE
Length:517
Mass (Da):58,503
Last modified:July 5, 2004 - v1
Checksum:i68FA9B9BEBCFF8DF
GO

Sequence cautioni

The sequence AAH04868.1 differs from that shown. Reason: Erroneous initiation. Curated
The sequence BAB55392.1 differs from that shown. Reason: Erroneous initiation. Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti357 – 3571H → R.
Corresponds to variant rs16939904 [ dbSNP | Ensembl ].
VAR_059751

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ586136 mRNA. Translation: CAE51936.1.
BC004868 mRNA. Translation: AAH04868.1. Different initiation.
BC022094 mRNA. Translation: AAH22094.2.
AK027820 mRNA. Translation: BAB55392.1. Different initiation.
CCDSiCCDS9123.2.
RefSeqiNP_001288104.1. NM_001301175.1.
NP_116052.2. NM_032663.4.
XP_006719715.1. XM_006719652.1.
XP_006719716.1. XM_006719653.1.
UniGeneiHs.486434.
Hs.660996.

Genome annotation databases

EnsembliENST00000257548; ENSP00000257548; ENSG00000135093.
GeneIDi84749.
KEGGihsa:84749.
UCSCiuc001tnu.4. human.

Polymorphism databases

DMDMi52000872.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ586136 mRNA. Translation: CAE51936.1.
BC004868 mRNA. Translation: AAH04868.1. Different initiation.
BC022094 mRNA. Translation: AAH22094.2.
AK027820 mRNA. Translation: BAB55392.1. Different initiation.
CCDSiCCDS9123.2.
RefSeqiNP_001288104.1. NM_001301175.1.
NP_116052.2. NM_032663.4.
XP_006719715.1. XM_006719652.1.
XP_006719716.1. XM_006719653.1.
UniGeneiHs.486434.
Hs.660996.

3D structure databases

ProteinModelPortaliQ70CQ3.
SMRiQ70CQ3. Positions 61-354, 426-501.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi124238. 10 interactions.
DIPiDIP-53578N.
IntActiQ70CQ3. 6 interactions.
STRINGi9606.ENSP00000257548.

Protein family/group databases

MEROPSiC19.060.

PTM databases

PhosphoSiteiQ70CQ3.

Polymorphism databases

DMDMi52000872.

Proteomic databases

MaxQBiQ70CQ3.
PaxDbiQ70CQ3.
PRIDEiQ70CQ3.

Protocols and materials databases

DNASUi84749.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000257548; ENSP00000257548; ENSG00000135093.
GeneIDi84749.
KEGGihsa:84749.
UCSCiuc001tnu.4. human.

Organism-specific databases

CTDi84749.
GeneCardsiGC12P109460.
HGNCiHGNC:20065. USP30.
HPAiHPA016952.
MIMi612492. gene.
neXtProtiNX_Q70CQ3.
PharmGKBiPA134971149.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG259866.
GeneTreeiENSGT00550000075075.
HOGENOMiHOG000065744.
HOVERGENiHBG079301.
InParanoidiQ70CQ3.
KOiK11851.
OMAiMKNWGVL.
PhylomeDBiQ70CQ3.
TreeFamiTF105781.

Miscellaneous databases

ChiTaRSiUSP30. human.
GenomeRNAii84749.
NextBioi74888.
PROiQ70CQ3.
SOURCEiSearch...

Gene expression databases

BgeeiQ70CQ3.
CleanExiHS_USP30.
ExpressionAtlasiQ70CQ3. baseline and differential.
GenevestigatoriQ70CQ3.

Family and domain databases

InterProiIPR001394. Peptidase_C19_UCH.
IPR018200. USP_CS.
IPR028889. USP_dom.
[Graphical view]
PfamiPF00443. UCH. 1 hit.
[Graphical view]
PROSITEiPS00972. USP_1. 1 hit.
PS00973. USP_2. 1 hit.
PS50235. USP_3. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Cloning and enzymatic analysis of 22 novel human ubiquitin-specific proteases."
    Quesada V., Diaz-Perales A., Gutierrez-Fernandez A., Garabaya C., Cal S., Lopez-Otin C.
    Biochem. Biophys. Res. Commun. 314:54-62(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, CATALYTIC ACTIVITY.
  2. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Lung and Skin.
  3. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
    Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
    , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
    Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 24-517.
    Tissue: Placenta.
  4. "Regulation of mitochondrial morphology by USP30, a deubiquitinating enzyme present in the mitochondrial outer membrane."
    Nakamura N., Hirose S.
    Mol. Biol. Cell 19:1903-1911(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBCELLULAR LOCATION, MUTAGENESIS OF ARG-28; LYS-30; LYS-33; 59-ARG--LYS-64 AND CYS-77.
  5. "The mitochondrial deubiquitinase USP30 opposes parkin-mediated mitophagy."
    Bingol B., Tea J.S., Phu L., Reichelt M., Bakalarski C.E., Song Q., Foreman O., Kirkpatrick D.S., Sheng M.
    Nature 510:370-375(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBCELLULAR LOCATION, MUTAGENESIS OF CYS-77, UBIQUITINATION AT LYS-235 AND LYS-289.

Entry informationi

Entry nameiUBP30_HUMAN
AccessioniPrimary (citable) accession number: Q70CQ3
Secondary accession number(s): Q8WTU7, Q96JX4, Q9BSS3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: September 13, 2004
Last sequence update: July 5, 2004
Last modified: February 4, 2015
This is version 104 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 12
    Human chromosome 12: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. Peptidase families
    Classification of peptidase families and list of entries
  6. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.