USP30

USP30, a member of the ubiquitin-specific protease family (see USP1, MIM 603478), is a novel mitochondrial deubiquitinating (DUB) enzyme (Nakamura and Hirose, 2008 [PubMed 18287522]).

Full Name

ubiquitin specific peptidase 30

Function

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 in 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).

Biological Process

Biological Process autophagy of mitochondrion Source:UniProtKB1 Publication
Biological Process mitochondrial fusion Source:UniProtKB
Biological Process negative regulation of mitophagy Source:Ensembl
Biological Process pexophagy Source:Reactome
Biological Process protein deubiquitination Source:UniProtKB1 Publication
Biological Process protein K11-linked deubiquitination Source:UniProtKB1 Publication
Biological Process protein K6-linked deubiquitination Source:UniProtKB1 Publication
Biological Process ubiquitin-dependent protein catabolic process Source:InterPro

Cellular Location

Mitochondrion outer membrane

Topology

Mitochondrial intermembrane: 1-35
Helical: 36-56
Cytoplasmic: 57-517

PTM

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