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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 tethered to the mitochondrial outer membrane that acts as a key inhibitor of mitophagy by counteracting the action of parkin (PRKN): hydrolyzes ubiquitin attached by parkin on target proteins, such as RHOT1/MIRO1 and TOMM20, thereby blocking parkin's ability to drive mitophagy (PubMed:18287522, PubMed:24896179, PubMed:25527291, PubMed:25621951). Preferentially cleaves 'Lys-6'- and 'Lys-11'-linked polyubiquitin chains, 2 types of linkage that participate to mitophagic signaling (PubMed:25621951). Does not cleave efficiently polyubiquitin phosphorylated at 'Ser-65' (PubMed:25527291). Acts as negative regulator of mitochondrial fusion by mediating deubiquitination of MFN1 and MFN2 (By similarity).By similarity4 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)DescriptionActionsGraphical viewLength
Active sitei77Nucleophile3 Publications1
Active sitei452Proton acceptorPROSITE-ProRule annotation1

GO - Molecular functioni

  • cysteine-type endopeptidase activity Source: UniProtKB
  • thiol-dependent ubiquitin-specific protease activity Source: UniProtKB
  • thiol-dependent ubiquitinyl hydrolase activity Source: UniProtKB

GO - Biological processi

  • autophagy of mitochondrion Source: UniProtKB
  • mitochondrial fusion Source: UniProtKB
  • protein deubiquitination Source: UniProtKB
  • protein K11-linked deubiquitination Source: UniProtKB
  • protein K6-linked deubiquitination Source: UniProtKB
  • ubiquitin-dependent protein catabolic process Source: InterPro

Keywordsi

Molecular functionHydrolase, Protease, Thiol protease
Biological processUbl conjugation pathway

Enzyme and pathway databases

ReactomeiR-HSA-5689880. Ub-specific processing proteases.

Protein family/group databases

MEROPSiC19.060.

Names & Taxonomyi

Protein namesi
Recommended name:
Ubiquitin carboxyl-terminal hydrolase 30 (EC:3.4.19.121 Publication)
Alternative name(s):
Deubiquitinating enzyme 30
Ubiquitin thioesterase 30
Ubiquitin-specific-processing protease 30
Short name:
Ub-specific protease 30
Gene namesi
Name:USP30Imported
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 12

Organism-specific databases

EuPathDBiHostDB:ENSG00000135093.12.
HGNCiHGNC:20065. USP30.

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 35Mitochondrial intermembraneSequence analysisAdd BLAST35
Transmembranei36 – 56HelicalSequence analysisAdd BLAST21
Topological domaini57 – 517CytoplasmicSequence analysisAdd BLAST461

Keywords - Cellular componenti

Membrane, Mitochondrion, Mitochondrion outer membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi28R → T: No change in mitochondrial subcellular location; when associated with N-30 and N-33. 1 Publication1
Mutagenesisi30K → N: No effect on subcellular location; when associated with N-28 and N-33. 1 Publication1
Mutagenesisi33K → N: No effect on subcellular location; when associated with N-28 and N-30. 1 Publication1
Mutagenesisi59 – 64RKKRRK → NNASNN: Loss of mitochondrial subcellular location. Located in the endoplasmic reticulum. 1 Publication6
Mutagenesisi77C → S: Loss of deubiquitinase activity and impaired ability to inhibit mitophagy. Increased TOMM20 ubiquitination. 3 Publications1

Organism-specific databases

DisGeNETi84749.
OpenTargetsiENSG00000135093.
PharmGKBiPA134971149.

Polymorphism and mutation databases

BioMutaiUSP30.
DMDMi52000872.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000806621 – 517Ubiquitin carboxyl-terminal hydrolase 30Add BLAST517

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Cross-linki235Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Cross-linki289Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication

Post-translational modificationi

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

Keywords - PTMi

Isopeptide bond, Ubl conjugation

Proteomic databases

EPDiQ70CQ3.
MaxQBiQ70CQ3.
PaxDbiQ70CQ3.
PeptideAtlasiQ70CQ3.
PRIDEiQ70CQ3.

PTM databases

iPTMnetiQ70CQ3.
PhosphoSitePlusiQ70CQ3.

Expressioni

Tissue specificityi

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

Gene expression databases

BgeeiENSG00000135093.
CleanExiHS_USP30.
ExpressionAtlasiQ70CQ3. baseline and differential.
GenevisibleiQ70CQ3. HS.

Organism-specific databases

HPAiHPA016952.

Interactioni

Protein-protein interaction databases

BioGridi124238. 34 interactors.
DIPiDIP-53578N.
IntActiQ70CQ3. 7 interactors.
STRINGi9606.ENSP00000257548.

Structurei

3D structure databases

ProteinModelPortaliQ70CQ3.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini68 – 502USPAdd BLAST435

Sequence similaritiesi

Belongs to the peptidase C19 family.Curated

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG1867. Eukaryota.
ENOG410XQQ0. LUCA.
GeneTreeiENSGT00550000075075.
HOGENOMiHOG000065744.
HOVERGENiHBG079301.
InParanoidiQ70CQ3.
KOiK11851.
OMAiCNETTTH.
OrthoDBiEOG091G0D1P.
PhylomeDBiQ70CQ3.
TreeFamiTF105781.

Family and domain databases

InterProiView protein in InterPro
IPR001394. Peptidase_C19_UCH.
IPR018200. USP_CS.
IPR028889. USP_dom.
PfamiView protein in Pfam
PF00443. UCH. 1 hit.
PROSITEiView protein in PROSITE
PS00972. USP_1. 1 hit.
PS00973. USP_2. 1 hit.
PS50235. USP_3. 1 hit.

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

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_059751357H → R. Corresponds to variant dbSNP:rs16939904Ensembl.1

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_006719716.1. XM_006719653.3.
UniGeneiHs.486434.
Hs.660996.

Genome annotation databases

EnsembliENST00000257548; ENSP00000257548; ENSG00000135093.
GeneIDi84749.
KEGGihsa:84749.
UCSCiuc010sxi.3. human.

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Entry informationi

Entry nameiUBP30_HUMAN
AccessioniPrimary (citable) accession number: Q70CQ3
Secondary accession number(s): Q8WTU7, Q96JX4, Q9BSS3
Entry historyiIntegrated into UniProtKB/Swiss-Prot: September 13, 2004
Last sequence update: July 5, 2004
Last modified: September 27, 2017
This is version 127 of the entry and version 1 of the sequence. See 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