Parkin (protein)

PRKN
Available structures
PDB	Ortholog search: PDBe RCSB
List of PDB id codes
	1IYF, 2JMO, 4I1F, 4I1H, 4BM9, 5C1Z, 5C23, 5C9V
Identifiers
Aliases	PRKN, parkin RBR E3 ubiquitin protein ligase, AR-JP, LPRS2, PDJ, PARK2, Parkin
External IDs	OMIM: 602544; MGI: 1355296; HomoloGene: 3355; GeneCards: PRKN; OMA:PRKN - orthologs
Gene location (Human)
Chr.	Chromosome 6 (human)
End	162,727,775 bp
Gene location (Mouse)
Chr.	Chromosome 17 (mouse)
End	12,282,248 bp
RNA expression pattern
	Top expressed in
	sural nerve; ; testicle; ; muscle of thigh; ; sperm; ; Achilles tendon; ; gastrocnemius muscle; ; gonad; ; prefrontal cortex; ; right auricle of heart; ; left testis;
	Top expressed in
	muscle of thigh; ; embryo; ; spermatocyte; ; embryo; ; spermatid; ; zygote; ; soleus muscle; ; knee joint; ; morula; ; right kidney;
	More reference expression data
	More reference expression data
Gene ontology
Molecular function	phospholipase binding; DNA-binding transcription factor activity; SH3 domain binding; histone deacetylase binding; tubulin binding; cullin family protein binding; PDZ domain binding; heat shock protein binding; metal ion binding; Hsp70 protein binding; kinase binding; enzyme binding; beta-catenin binding; zinc ion binding; protein binding; ubiquitin conjugating enzyme binding; protein kinase binding; chaperone binding; transcription cis-regulatory region binding; ubiquitin-protein transferase activity; F-box domain binding; ubiquitin binding; identical protein binding; actin binding; ubiquitin-specific protease binding; G protein-coupled receptor binding; ubiquitin protein ligase binding; transferase activity; ubiquitin protein ligase activity; DNA-binding transcription repressor activity, RNA polymerase II-specific; protein-containing complex binding;
Cellular component	cytoplasm; cytosol; mitochondrion; perinuclear region of cytoplasm; nucleus; Lewy body; SCF ubiquitin ligase complex; aggresome; endoplasmic reticulum; Golgi apparatus; Parkin-FBXW7-Cul1 ubiquitin ligase complex; ubiquitin ligase complex; LUBAC complex; presynapse; neuron projection; mitochondrion-derived vesicle; nuclear speck; protein-containing complex;
Biological process	negative regulation of neuron apoptotic process; protein K29-linked ubiquitination; negative regulation of insulin secretion; ERAD pathway; positive regulation of mitochondrial fission; positive regulation of mitophagy in response to mitochondrial depolarization; positive regulation of protein catabolic process; synaptic transmission, glutamatergic; positive regulation of tumor necrosis factor-mediated signaling pathway; neuron cellular homeostasis; regulation of protein ubiquitination; cellular response to toxic substance; modulation of chemical synaptic transmission; regulation of synaptic vesicle transport; learning; protein monoubiquitination; synaptic transmission, dopaminergic; positive regulation of neurotransmitter uptake; regulation of glucose metabolic process; protein K6-linked ubiquitination; negative regulation of intrinsic apoptotic signaling pathway by p53 class mediator; negative regulation of spontaneous neurotransmitter secretion; negative regulation by host of viral genome replication; positive regulation of DNA binding; macroautophagy; negative regulation of canonical Wnt signaling pathway; Unfolded Protein Response; aggresome assembly; proteasome-mediated ubiquitin-dependent protein catabolic process; regulation of dopamine secretion; zinc ion homeostasis; free ubiquitin chain polymerization; regulation of transcription, DNA-templated; locomotory behavior; norepinephrine metabolic process; negative regulation of endoplasmic reticulum stress-induced neuron intrinsic apoptotic signaling pathway; adult locomotory behavior; protein metabolic process; negative regulation of cell death; response to oxidative stress; protein K27-linked ubiquitination; negative regulation of gene expression; transcription, DNA-templated; response to endoplasmic reticulum stress; protein K11-linked ubiquitination; central nervous system development; negative regulation of oxidative stress-induced cell death; positive regulation of mitochondrial fusion; protein localization to mitochondrion; proteasomal protein catabolic process; cellular response to manganese ion; negative regulation of mitochondrial fusion; protein autoubiquitination; negative regulation of neuron death; negative regulation of protein phosphorylation; negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway; negative regulation of primary amine oxidase activity; startle response; mitochondrial fission; regulation of mitochondrion organization; regulation of canonical Wnt signaling pathway; negative regulation of release of cytochrome c from mitochondria; protein stabilization; mitochondrion organization; protein polyubiquitination; negative regulation of transcription by RNA polymerase II; regulation of reactive oxygen species metabolic process; regulation of neurotransmitter secretion; positive regulation of protein linear polyubiquitination; protein K48-linked ubiquitination; dopamine uptake involved in synaptic transmission; regulation of autophagy; regulation of protein targeting to mitochondrion; protein destabilization; negative regulation of glucokinase activity; positive regulation of proteasomal protein catabolic process; protein K63-linked ubiquitination; cellular response to dopamine; regulation of lipid transport; negative regulation of actin filament bundle assembly; regulation of dopamine metabolic process; regulation of mitochondrial membrane potential; autophagy; negative regulation of JNK cascade; dopamine metabolic process; positive regulation of gene expression; positive regulation of I-kappaB kinase/NF-kappaB signaling; positive regulation of dendrite extension; negative regulation of reactive oxygen species metabolic process; positive regulation of transcription by RNA polymerase II; mitophagy; protein ubiquitination; parkin-mediated stimulation of mitophagy in response to mitochondrial depolarization; positive regulation of proteasomal ubiquitin-dependent protein catabolic process; protein deubiquitination; regulation of protein stability; positive regulation of protein binding; mitochondrion to lysosome transport; regulation of cellular response to oxidative stress; negative regulation of exosomal secretion; positive regulation of retrograde transport, endosome to Golgi; negative regulation of intralumenal vesicle formation; positive regulation of protein localization to membrane; autophagy of mitochondrion; negative regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway; positive regulation of autophagy of mitochondrion; ubiquitin-dependent protein catabolic process; regulation of apoptotic process;
	Sources:Amigo / QuickGO
Orthologs
	5071
	50873
	ENSG00000185345
	ENSMUSG00000023826
	O60260
	Q9WVS6
	NM_004562; NM_013987; NM_013988
	NM_016694; NM_001317726
	NP_004553; NP_054642; NP_054643
	NP_001304655; NP_057903
	Wikidata
View/Edit Human	View/Edit Mouse

Parkin is a 465-amino acid residue E3 ubiquitin ligase, a protein that in humans and mice is encoded by the PARK2 gene. Parkin plays a critical role in ubiquitination – the process whereby molecules are covalently labelled with ubiquitin (Ub) and directed towards degradation in proteasomes or lysosomes. Ubiquitination involves the sequential action of three enzymes. First, an E1 ubiquitin-activating enzyme binds to inactive Ub in eukaryotic cells via a thioester bond and mobilises it in an ATP-dependent process. Ub is then transferred to an E2 ubiquitin-conjugating enzyme before being conjugated to the target protein via an E3 ubiquitin ligase. There exists a multitude of E3 ligases, which differ in structure and substrate specificity to allow selective targeting of proteins to intracellular degradation.

In particular, parkin recognises proteins on the outer membrane of mitochondria upon cellular insult and mediates the clearance of damaged mitochondria via autophagy and proteasomal mechanisms. Parkin also enhances cell survival by suppressing both mitochondria-dependent and -independent apoptosis. Mutations are associated with mitochondrial dysfunction, leading to neuronal death in Parkinson's disease and aberrant metabolism in tumourigenesis.