PARK2 Functions within a multiprotein E3 ubiquitin ligase complex, catalyzing the covalent attachment of ubiquitin moieties onto substrate proteins, such as BCL2, SYT11, CCNE1, GPR37, RHOT1/MIRO1, MFN1, MFN2, STUB1, SNCAIP, SEPTIN5, TOMM20, USP30, ZNF746 and AIMP2. Mediates monoubiquitination as well as 'Lys-6', 'Lys-11', 'Lys-48'-linked and 'Lys-63'-linked polyubiquitination of substrates depending on the context. Participates in the removal and/or detoxification of abnormally folded or damaged protein by mediating 'Lys-63'-linked polyubiquitination of misfolded proteins such as PARK7: 'Lys-63'-linked polyubiquitinated misfolded proteins are then recognized by HDAC6, leading to their recruitment to aggresomes, followed by degradation. Mediates 'Lys-63'-linked polyubiquitination of a 22 kDa O-linked glycosylated isoform of SNCAIP, possibly playing a role in Lewy-body formation. Mediates monoubiquitination of BCL2, thereby acting as a positive regulator of autophagy. Promotes the autophagic degradation of dysfunctional depolarized mitochondria (mitophagy) by promoting the ubiquitination of mitochondrial proteins such as TOMM20, RHOT1/MIRO1 and USP30. Preferentially assembles 'Lys-6'-, 'Lys-11'- and 'Lys-63'-linked polyubiquitin chains following mitochondrial damage, leading to mitophagy. Mediates 'Lys-48'-linked polyubiquitination of ZNF746, followed by degradation of ZNF746 by the proteasome; possibly playing a role in the regulation of neuron death. Limits the production of reactive oxygen species (ROS). Regulates cyclin-E during neuronal apoptosis. In collaboration with CHPF isoform 2, may enhance cell viability and protect cells from oxidative stress. Independently of its ubiquitin ligase activity, protects from apoptosis by the transcriptional repression of p53/TP53. May protect neurons against alpha synuclein toxicity, proteasomal dysfunction, GPR37 accumulation, and kainate-induced excitotoxicity. May play a role in controlling neurotransmitter trafficking at the presynaptic terminal and in calcium-dependent exocytosis. May represent a tumor suppressor gene. Belongs to the RBR family. Parkin subfamily. Highly expressed in the brain including the substantia nigra. Expressed in heart, testis and skeletal muscle. Expression is down-regulated or absent in tumor biopsies, and absent in the brain of PARK2 patients. Overexpression protects dopamine neurons from kainate-mediated apoptosis. Found in serum (at protein level). 8 alternatively spliced human isoforms have been reported. Note: This description may include information from UniProtKB.
Protein type: EC 6.3.2.-; EC; Ligase; Translation; Translation regulation; Ubiquitin conjugating system; Ubiquitin ligase
Chromosomal Location of human Ortholog: 6q26
Cellular Component:  aggresome; cytoplasm; cytosol; dopaminergic synapse; endoplasmic reticulum; Golgi apparatus; Lewy body; mitochondrial outer membrane; mitochondrion; mitochondrion-derived vesicle; neuron projection; nuclear speck; nucleus; Parkin-FBXW7-Cul1 ubiquitin ligase complex; perinuclear region of cytoplasm; postsynaptic density; presynapse; SCF ubiquitin ligase complex; ubiquitin ligase complex
Molecular Function:  actin binding; beta-catenin binding; cullin family protein binding; enzyme binding; F-box domain binding; G protein-coupled receptor binding; heat shock protein binding; histone deacetylase binding; Hsp70 protein binding; identical protein binding; kinase binding; PDZ domain binding; phospholipase binding; protein binding; protein kinase binding; protein-containing complex binding; protein-folding chaperone binding; SH3 domain binding; transcription corepressor activity; tubulin binding; ubiquitin binding; ubiquitin conjugating enzyme binding; ubiquitin protein ligase activity; ubiquitin protein ligase binding; ubiquitin-protein transferase activity; ubiquitin-specific protease binding; zinc ion binding
Biological Process:  adult locomotory behavior; aggresome assembly; amyloid fibril formation; autophagy of mitochondrion; cellular response to dopamine; cellular response to manganese ion; cellular response to oxidative stress; cellular response to toxic substance; cellular response to unfolded protein; central nervous system development; dopamine metabolic process; dopamine uptake involved in synaptic transmission; ERAD pathway; free ubiquitin chain polymerization; learning; macroautophagy; mitochondrial fission; mitochondrion organization; mitochondrion to lysosome transport; mitophagy; negative regulation by host of viral genome replication; negative regulation of actin filament bundle assembly; negative regulation of canonical Wnt signaling pathway; negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway; negative regulation of endoplasmic reticulum stress-induced neuron intrinsic apoptotic signaling pathway; negative regulation of exosomal secretion; negative regulation of gene expression; negative regulation of glucokinase activity; negative regulation of insulin secretion; negative regulation of intralumenal vesicle formation; negative regulation of intrinsic apoptotic signaling pathway by p53 class mediator; negative regulation of JNK cascade; negative regulation of mitochondrial fusion; negative regulation of neuron apoptotic process; negative regulation of neuron death; negative regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway; negative regulation of primary amine oxidase activity; negative regulation of protein phosphorylation; negative regulation of reactive oxygen species metabolic process; negative regulation of release of cytochrome c from mitochondria; negative regulation of spontaneous neurotransmitter secretion; negative regulation of transcription by RNA polymerase II; neuron cellular homeostasis; norepinephrine metabolic process; parkin-mediated stimulation of mitophagy in response to mitochondrial depolarization; positive regulation of autophagy of mitochondrion; positive regulation of dendrite extension; positive regulation of DNA binding; positive regulation of gene expression; positive regulation of I-kappaB kinase/NF-kappaB signaling; positive regulation of mitochondrial fission; positive regulation of mitochondrial fusion; positive regulation of mitophagy in response to mitochondrial depolarization; positive regulation of neurotransmitter uptake; positive regulation of proteasomal protein catabolic process; positive regulation of proteasomal ubiquitin-dependent protein catabolic process; positive regulation of protein binding; positive regulation of protein catabolic process; positive regulation of protein linear polyubiquitination; positive regulation of protein localization to membrane; positive regulation of retrograde transport, endosome to Golgi; positive regulation of transcription by RNA polymerase II; positive regulation of tumor necrosis factor-mediated signaling pathway; proteasomal protein catabolic process; proteasome-mediated ubiquitin-dependent protein catabolic process; protein autoubiquitination; protein catabolic process; protein destabilization; protein deubiquitination; protein K11-linked ubiquitination; protein K27-linked ubiquitination; protein K29-linked ubiquitination; protein K48-linked ubiquitination; protein K6-linked ubiquitination; protein K63-linked ubiquitination; protein localization to mitochondrion; protein monoubiquitination; protein polyubiquitination; protein stabilization; protein ubiquitination; regulation of apoptotic process; regulation of autophagy; regulation of canonical Wnt signaling pathway; regulation of cellular response to oxidative stress; regulation of dopamine metabolic process; regulation of dopamine secretion; regulation of glucose metabolic process; regulation of lipid transport; regulation of mitochondrial membrane potential; regulation of mitochondrion organization; regulation of necroptotic process; regulation of protein stability; regulation of protein targeting to mitochondrion; regulation of protein ubiquitination; regulation of reactive oxygen species metabolic process; regulation of synaptic vesicle endocytosis; regulation of synaptic vesicle transport; regulation protein catabolic process at presynapse; response to endoplasmic reticulum stress; response to oxidative stress; startle response; synaptic transmission, glutamatergic; ubiquitin-dependent protein catabolic process
Disease: Lung Cancer; Parkinson Disease 2, Autosomal Recessive Juvenile
Reference #:  O60260 (UniProtKB)
Alt. Names/Synonyms: AR-JP; E3 ubiquitin-protein ligase parkin; LPRS2; PARK2; parkin; parkin 2; parkin RBR E3 ubiquitin protein ligase; Parkin RBR E3 ubiquitin-protein ligase; Parkinson disease (autosomal recessive, juvenile) 2, parkin; Parkinson disease protein 2; Parkinson juvenile disease protein 2; parkinson protein 2 E3 ubiquitin protein ligase; parkinson protein 2, E3 ubiquitin protein ligase (parkin); PDJ; PRKN; PRKN2
Gene Symbols: PRKN
Molecular weight: 51,641 Da
Basal Isoelectric point: 6.71  Predict pI for various phosphorylation states
CST Pathways:  Parkinson's Disease
Protein-Specific Antibodies, siRNAs or Recombinant Proteins from Cell Signaling Technology® Total Proteins
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Protein Structure Not Found.

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