PARK2
Gene Information
- Official Symbol: PRKN
- Official Name: parkin RBR E3 ubiquitin protein ligase
- Aliases and Previous Symbols: N/A
- Entrez ID: 5071
- UniProt: O60260
- Interactions: BioGRID
- PubMed articles: Open PubMed
- OMIM: Open OMIM
Function Summary
- Entrez Summary: The precise function of this gene is unknown; however, the encoded protein is a component of a multiprotein E3 ubiquitin ligase complex that mediates the targeting of substrate proteins for proteasomal degradation. Mutations in this gene are known to cause Parkinson disease and autosomal recessive juvenile Parkinson disease. Alternative splicing of this gene produces multiple transcript variants encoding distinct isoforms. Additional splice variants of this gene have been described but currently lack transcript support. [provided by RefSeq, Jul 2008].
- UniProt Summary: N/A
Pfam Domains GO Terms
Pfam Domains
| ubiquitin |
| Rad60-SLD |
| IBR |
GO Terms
| negative regulation of endosome organization |
| negative regulation of endoplasmic reticulum stress-induced neuron intrinsic apoptotic signaling pathway |
| positive regulation of retrograde transport, endosome to Golgi |
| regulation of protein linear polyubiquitination |
| negative regulation of spontaneous neurotransmitter secretion |
| regulation of endoplasmic reticulum stress-induced neuron intrinsic apoptotic signaling pathway |
| positive regulation of protein linear polyubiquitination |
| regulation of intralumenal vesicle formation |
| negative regulation of intralumenal vesicle formation |
| negative regulation of primary amine oxidase activity |
| F-box domain binding |
| mitochondrion-derived vesicle |
| Parkin-FBXW7-Cul1 ubiquitin ligase complex |
| mitochondrion to lysosome transport |
| positive regulation of mitochondrial fusion |
| negative regulation of exosomal secretion |
| mitochondrion-derived vesicle mediated transport |
| regulation of spontaneous neurotransmitter secretion |
| dopamine uptake involved in synaptic transmission |
| regulation of retrograde transport, endosome to Golgi |
| catecholamine uptake involved in synaptic transmission |
| regulation of endosome organization |
| protein K27-linked ubiquitination |
| negative regulation of glucokinase activity |
| negative regulation of hexokinase activity |
| regulation of spontaneous synaptic transmission |
| negative regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway |
| parkin-mediated stimulation of mitophagy in response to mitochondrial depolarization |
| Lewy body |
| free ubiquitin chain polymerization |
| positive regulation of neurotransmitter uptake |
| mitophagy |
| negative regulation of mitochondrial fusion |
| protein K29-linked ubiquitination |
| aggresome assembly |
| negative regulation by host of viral genome replication |
| regulation of synaptic vesicle transport |
| inclusion body assembly |
| protein K6-linked ubiquitination |
| dopamine uptake |
| catecholamine uptake |
| regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway |
| ubiquitin recycling |
| positive regulation of mitophagy in response to mitochondrial depolarization |
| positive regulation of mitophagy |
| regulation of mitochondrial fusion |
| positive regulation of tumor necrosis factor-mediated signaling pathway |
| regulation of glucokinase activity |
| dopamine transport |
| negative regulation by host of viral process |
| regulation of hexokinase activity |
| positive regulation of protein polyubiquitination |
| negative regulation of neurotransmitter secretion |
| positive regulation of autophagy of mitochondrion in response to mitochondrial depolarization |
| cellular response to manganese ion |
| norepinephrine metabolic process |
| regulation of autophagy of mitochondrion in response to mitochondrial depolarization |
| positive regulation of cytoplasmic transport |
| catecholamine transport |
| modulation by host of viral genome replication |
| neurotransmitter reuptake |
| positive regulation of mitochondrial fission |
| phospholipase binding |
| regulation of mitophagy |
| ubiquitin-specific protease binding |
| mitochondrial fission |
| regulation of exosomal secretion |
| cullin family protein binding |
| response to manganese ion |
| negative regulation of oxidative stress-induced intrinsic apoptotic signaling pathway |
| positive regulation of autophagy of mitochondrion |
| response to mitochondrial depolarisation |
| negative regulation of release of cytochrome c from mitochondria |
| synaptic transmission, dopaminergic |
| regulation of catecholamine metabolic process |
| regulation of dopamine metabolic process |
| negative regulation of oxidative stress-induced neuron death |
| negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway |
| regulation of neurotransmitter uptake |
| monoamine transport |
| selective autophagy |
| regulation of protein polyubiquitination |
| negative regulation of intrinsic apoptotic signaling pathway by p53 class mediator |
| negative regulation of neurotransmitter transport |
| regulation of mitochondrial fission |
| positive regulation of dendrite extension |
| negative regulation of oxidoreductase activity |
| negative regulation of actin filament bundle assembly |
| regulation of cytoplasmic transport |
| regulation of dendrite extension |
| regulation of oxidative stress-induced neuron death |
| startle response |
| regulation of oxidative stress-induced intrinsic apoptotic signaling pathway |
| modulation by host of viral process |
| synaptic transmission, glutamatergic |
| neurotransmitter uptake |
| dopamine metabolic process |
| protein K11-linked ubiquitination |
| regulation of intrinsic apoptotic signaling pathway by p53 class mediator |
| regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway |
| ubiquitin conjugating enzyme binding |
| negative regulation of signal transduction by p53 class mediator |
| negative regulation of exocytosis |
| neuron cellular homeostasis |
| negative regulation of JNK cascade |
| zinc ion homeostasis |
| positive regulation of neurotransmitter transport |
| negative regulation of insulin secretion |
| autophagy of mitochondrion |
| protein K63-linked ubiquitination |
| mitochondrion disassembly |
| regulation of dopamine secretion |
| Hsp70 protein binding |
| negative regulation of cellular carbohydrate metabolic process |
| regulation of autophagy of mitochondrion |
| aggresome |
| catecholamine metabolic process |
| negative regulation of response to endoplasmic reticulum stress |
| regulation of protein targeting to mitochondrion |
| catechol-containing compound metabolic process |
| negative regulation of stress-activated protein kinase signaling cascade |
| negative regulation of cellular response to oxidative stress |
| negative regulation of oxidative stress-induced cell death |
| negative regulation of stress-activated MAPK cascade |
| negative regulation of peptide hormone secretion |
| protein destabilization |
| negative regulation of response to oxidative stress |
| regulation of release of cytochrome c from mitochondria |
| negative regulation of carbohydrate metabolic process |
| positive regulation of cytokine-mediated signaling pathway |
| ammonium transport |
| negative regulation of mitochondrion organization |
| protein K48-linked ubiquitination |
| tubulin binding |
| negative regulation of reactive oxygen species metabolic process |
| positive regulation of DNA binding |
| negative regulation of viral genome replication |
| positive regulation of response to cytokine stimulus |
| regulation of tumor necrosis factor-mediated signaling pathway |
| heat shock protein binding |
| negative regulation of synaptic transmission |
| protein monoubiquitination |
| regulation of catecholamine secretion |
| negative regulation of hormone secretion |
| regulation of oxidative stress-induced cell death |
| SCF ubiquitin ligase complex |
| organelle disassembly |
| protein autoubiquitination |
| G protein-coupled receptor binding |
| positive regulation of macroautophagy |
| regulation of mitochondrial membrane potential |
| modification by host of symbiont morphology or physiology |
| regulation of establishment of protein localization to mitochondrion |
| regulation of cellular response to oxidative stress |
| transcription regulatory region sequence-specific DNA binding |
| interaction with symbiont |
| adult locomotory behavior |
| protein localization to mitochondrion |
| regulation of cellular amine metabolic process |
| ubiquitin binding |
| negative regulation of viral life cycle |
| positive regulation of proteasomal ubiquitin-dependent protein catabolic process |
| regulation of protein targeting |
| phenol-containing compound metabolic process |
| regulation of response to endoplasmic reticulum stress |
| beta-catenin binding |
| regulation of response to oxidative stress |
| cellular response to dopamine |
| protein polymerization |
| response to dopamine |
| PDZ domain binding |
| ERAD pathway |
| regulation of actin filament bundle assembly |
| kinase binding |
| positive regulation of protein binding |
| regulation of viral genome replication |
| regulation of amine transport |
| presynapse |
| negative regulation of intrinsic apoptotic signaling pathway |
| regulation of oxidoreductase activity |
| negative regulation of viral process |
| positive regulation of ubiquitin-dependent protein catabolic process |
| regulation of response to drug |
| cellular response to catecholamine stimulus |
| cellular response to monoamine stimulus |
| chaperone binding |
| positive regulation of proteasomal protein catabolic process |
| regulation of neurotransmitter secretion |
| ubiquitin ligase complex |
| response to catecholamine |
| response to monoamine |
| lysosomal transport |
| regulation of lipid transport |
| neuromuscular process |
| modification of morphology or physiology of other organism involved in symbiotic interaction |
| histone deacetylase binding |
| regulation of glucose metabolic process |
| positive regulation of protein ubiquitination |
| positive regulation of mitochondrion organization |
| positive regulation of autophagy |
| positive regulation of proteolysis involved in cellular protein catabolic process |
| positive regulation of protein localization to membrane |
| regulation of proteasomal ubiquitin-dependent protein catabolic process |
| regulation of DNA binding |
| cellular response to unfolded protein |
| cellular response to ammonium ion |
| SH3 domain binding |
| negative regulation of supramolecular fiber organization |
| transition metal ion homeostasis |
| negative regulation of protein secretion |
| positive regulation of protein modification by small protein conjugation or removal |
| regulation of lipid localization |
| organic hydroxy compound transport |
| negative regulation of peptide secretion |
| regulation of cellular carbohydrate metabolic process |
| negative regulation of cytoskeleton organization |
| positive regulation of cellular protein catabolic process |
| vacuolar transport |
| regulation of neurotransmitter transport |
| regulation of viral life cycle |
| adult behavior |
| negative regulation of neuron apoptotic process |
| learning |
| cellular response to topologically incorrect protein |
| drug transport |
| regulation of ubiquitin-dependent protein catabolic process |
| modification of morphology or physiology of other organism |
| regulation of intrinsic apoptotic signaling pathway |
| macroautophagy |
| response to unfolded protein |
| positive regulation of cell growth |
| regulation of cytokine-mediated signaling pathway |
| negative regulation of MAPK cascade |
| positive regulation of developmental growth |
| regulation of macroautophagy |
| negative regulation of canonical Wnt signaling pathway |
| regulation of response to cytokine stimulus |
| regulation of insulin secretion |
| protein stabilization |
| positive regulation of binding |
| neurotransmitter transport |
| regulation of reactive oxygen species metabolic process |
| regulation of signal transduction by p53 class mediator |
| regulation of mitochondrion organization |
| negative regulation of protein transport |
| regulation of proteasomal protein catabolic process |
| response to ammonium ion |
| positive regulation of I-kappaB kinase/NF-kappaB signaling |
| negative regulation of establishment of protein localization |
| regulation of JNK cascade |
| response to topologically incorrect protein |
| regulation of protein localization to membrane |
| cellular response to metal ion |
| ammonium ion metabolic process |
| locomotory behavior |
| regulation of protein ubiquitination |
| negative regulation of secretion by cell |
| regulation of carbohydrate metabolic process |
| regulation of viral process |
| negative regulation of neuron death |
| regulation of neuron apoptotic process |
| positive regulation of intracellular transport |
| regulation of peptide hormone secretion |
| negative regulation of Wnt signaling pathway |
| cellular response to toxic substance |
| mitochondrial transport |
| negative regulation of multi-organism process |
| positive regulation of protein catabolic process |
| regulation of proteolysis involved in cellular protein catabolic process |
| regulation of protein binding |
| regulation of symbiosis, encompassing mutualism through parasitism |
| cellular response to inorganic substance |
| ubiquitin protein ligase activity |
| regulation of exocytosis |
| negative regulation of apoptotic signaling pathway |
| regulation of protein modification by small protein conjugation or removal |
| regulation of intracellular protein transport |
| negative regulation of secretion |
| regulation of stress-activated MAPK cascade |
| regulation of I-kappaB kinase/NF-kappaB signaling |
| regulation of stress-activated protein kinase signaling cascade |
| DNA-binding transcription repressor activity, RNA polymerase II-specific |
| negative regulation of kinase activity |
| ubiquitin-protein transferase activity |
| regulation of cellular protein catabolic process |
| response to endoplasmic reticulum stress |
| learning or memory |
| positive regulation of growth |
| regulation of actin filament organization |
| autophagy |
| process utilizing autophagic mechanism |
| protein-containing complex binding |
| regulation of hormone secretion |
| actin binding |
| negative regulation of transferase activity |
| positive regulation of neuron projection development |
| regulation of canonical Wnt signaling pathway |
| protein deubiquitination |
| regulation of protein stability |
| ubiquitin protein ligase binding |
| protein modification by small protein removal |
| cognition |
| protein polyubiquitination |
| regulation of neuron death |
| organelle fission |
| neuron projection |
| proteasome-mediated ubiquitin-dependent protein catabolic process |
| positive regulation of cellular protein localization |
| regulation of developmental growth |
| regulation of autophagy |
| anatomical structure homeostasis |
| regulation of actin cytoskeleton organization |
| enzyme binding |
| proteasomal protein catabolic process |
| regulation of intracellular transport |
| regulation of supramolecular fiber organization |
| regulation of neurotransmitter levels |
| positive regulation of proteolysis |
| regulation of Wnt signaling pathway |
| positive regulation of cellular catabolic process |
| positive regulation of neuron differentiation |
| response to metal ion |
| negative regulation of organelle organization |
| regulation of binding |
| positive regulation of cell projection organization |
| regulation of protein catabolic process |
| response to oxidative stress |
| regulation of actin filament-based process |
| regulation of apoptotic signaling pathway |
| cellular component disassembly |
| nuclear speck |
| cellular response to drug |
| negative regulation of protein phosphorylation |
| regulation of cell growth |
| chemical synaptic transmission |
| anterograde trans-synaptic signaling |
| regulation of small molecule metabolic process |
| regulation of membrane potential |
| positive regulation of catabolic process |
| trans-synaptic signaling |
| mitochondrion organization |
| modulation of chemical synaptic transmission |
| regulation of trans-synaptic signaling |
| negative regulation of phosphorylation |
| organic hydroxy compound metabolic process |
| synaptic signaling |
| protein kinase binding |
| regulation of protein secretion |
| positive regulation of neurogenesis |
| negative regulation of transport |
| divalent inorganic cation homeostasis |
| regulation of cell morphogenesis |
| regulation of peptide secretion |
| regulation of neuron projection development |
| drug metabolic process |
| negative regulation of intracellular signal transduction |
| response to toxic substance |
| ubiquitin-dependent protein catabolic process |
| modification-dependent protein catabolic process |
| regulation of hormone levels |
| response to inorganic substance |
| positive regulation of nervous system development |
| regulation of cellular protein localization |
| regulation of cytoskeleton organization |
| cellular response to organic cyclic compound |
| positive regulation of cell development |
| modification-dependent macromolecule catabolic process |
| regulation of vesicle-mediated transport |
| negative regulation of phosphate metabolic process |
| negative regulation of phosphorus metabolic process |
| behavior |
| proteolysis involved in cellular protein catabolic process |
| negative regulation of protein modification process |
| cellular response to organonitrogen compound |
| cellular protein catabolic process |
| positive regulation of organelle organization |
| metal ion homeostasis |
| regulation of neuron differentiation |
| cellular response to nitrogen compound |
| regulation of growth |
| import into cell |
| protein catabolic process |
| protein ubiquitination |
| regulation of plasma membrane bounded cell projection organization |
| perinuclear region of cytoplasm |
| regulation of ion transport |
| negative regulation of cellular component organization |
| cation homeostasis |
| regulation of protein transport |
| regulation of cell projection organization |
| inorganic ion homeostasis |
| regulation of proteolysis |
| regulation of cellular response to stress |
| protein localization to organelle |
| regulation of peptide transport |
| regulation of establishment of protein localization |
| regulation of secretion by cell |
| regulation of MAPK cascade |
| protein modification by small protein conjugation |
| regulation of multi-organism process |
| symbiotic process |
| ion homeostasis |
| negative regulation of catalytic activity |
| regulation of secretion |
| regulation of neurogenesis |
| interspecies interaction between organisms |
| cation transport |
| regulation of cellular catabolic process |
| zinc ion binding |
| cellular protein-containing complex assembly |
| negative regulation of transcription by RNA polymerase II |
| regulation of kinase activity |
| negative regulation of apoptotic process |
| cellular homeostasis |
| negative regulation of programmed cell death |
| cellular macromolecule catabolic process |
| regulation of cellular localization |
| response to organic cyclic compound |
| regulation of nervous system development |
| regulation of cell development |
| negative regulation of developmental process |
| regulation of cellular component biogenesis |
| positive regulation of cell differentiation |
| regulation of transferase activity |
| central nervous system development |
| Golgi apparatus |
| protein modification by small protein conjugation or removal |
| positive regulation of transport |
| negative regulation of cell death |
| regulation of catabolic process |
| response to organonitrogen compound |
| endoplasmic reticulum |
| response to drug |
| positive regulation of intracellular signal transduction |
| regulation of protein localization |
| negative regulation of cellular protein metabolic process |
| macromolecule catabolic process |
| cellular response to oxygen-containing compound |
| regulation of anatomical structure morphogenesis |
| organonitrogen compound catabolic process |
| identical protein binding |
| response to nitrogen compound |
| negative regulation of protein metabolic process |
| chemical homeostasis |
| cell-cell signaling |
| negative regulation of molecular function |
| negative regulation of transcription, DNA-templated |
| positive regulation of cellular component organization |
| positive regulation of transcription by RNA polymerase II |
| cellular response to endogenous stimulus |
| positive regulation of protein modification process |
| negative regulation of nucleic acid-templated transcription |
| negative regulation of RNA biosynthetic process |
| mitochondrion |
| negative regulation of signal transduction |
| proteolysis |
| regulation of organelle organization |
| negative regulation of RNA metabolic process |
| negative regulation of cell communication |
| negative regulation of signaling |
| positive regulation of developmental process |
| ion transport |
| nervous system process |
| negative regulation of cellular macromolecule biosynthetic process |
| negative regulation of nucleobase-containing compound metabolic process |
| regulation of protein phosphorylation |
| negative regulation of macromolecule biosynthetic process |
| response to endogenous stimulus |
| regulation of response to stress |
| negative regulation of cellular biosynthetic process |
| generation of neurons |
| positive regulation of transcription, DNA-templated |
| regulation of apoptotic process |
| negative regulation of biosynthetic process |
| response to oxygen-containing compound |
| protein-containing complex assembly |
| regulation of programmed cell death |
| cellular protein localization |
| regulation of phosphorylation |
| cellular macromolecule localization |
| positive regulation of cellular protein metabolic process |
| negative regulation of response to stimulus |
| neurogenesis |
| positive regulation of nucleic acid-templated transcription |
| positive regulation of RNA biosynthetic process |
| homeostatic process |
| positive regulation of signal transduction |
| regulation of cell death |
| cellular response to stress |
| positive regulation of protein metabolic process |
| negative regulation of gene expression |
| positive regulation of RNA metabolic process |
| positive regulation of multicellular organismal process |
| organic substance catabolic process |
| positive regulation of molecular function |
| regulation of phosphate metabolic process |
| regulation of phosphorus metabolic process |
| cellular catabolic process |
| regulation of cell differentiation |
| positive regulation of cell communication |
| positive regulation of signaling |
| regulation of intracellular signal transduction |
| establishment of localization in cell |
| nitrogen compound transport |
| regulation of protein modification process |
| protein-containing complex subunit organization |
| regulation of transport |
| positive regulation of nucleobase-containing compound metabolic process |
| positive regulation of macromolecule biosynthetic process |
| vesicle-mediated transport |
| system process |
| positive regulation of cellular biosynthetic process |
| positive regulation of gene expression |
| positive regulation of biosynthetic process |
CRISPR Data
Compound Hit Most Correlated Genes in Chemogenomics Tissues where Essential in the Avana Dataset (DepMap 20Q1)
Compound Hit
| Screen | Score |
|---|---|
| Temozolomide 200μM R04 exp189 | -2.37 |
| Pyronaridine 1μM R06 exp295 | -2.15 |
| MLN-4924 2μM R00 exp22 | -1.75 |
| Ibrutinib 1μM R07 exp372 | -1.72 |
| CFI-400945 25μM R08 exp469 | 2.35 |
Most Correlated Genes in Chemogenomics
No correlation found to any other genes in chemogenomics.
Tissues where Essential in the Avana Dataset (DepMap 20Q1)
Global Fraction of Cell Lines Where Essential: 0/739
| Tissue | Fraction Of Cell Lines Where Essential |
|---|---|
| 1290807.0 | 0/1 |
| 909776.0 | 0/1 |
| bile duct | 0/28 |
| blood | 0/28 |
| bone | 0/26 |
| breast | 0/33 |
| central nervous system | 0/56 |
| cervix | 0/4 |
| colorectal | 0/17 |
| esophagus | 0/13 |
| fibroblast | 0/1 |
| gastric | 0/16 |
| kidney | 0/21 |
| liver | 0/20 |
| lung | 0/75 |
| lymphocyte | 0/16 |
| ovary | 0/26 |
| pancreas | 0/24 |
| peripheral nervous system | 0/16 |
| plasma cell | 0/15 |
| prostate | 0/1 |
| skin | 0/24 |
| soft tissue | 0/9 |
| thyroid | 0/2 |
| upper aerodigestive | 0/22 |
| urinary tract | 0/29 |
| uterus | 0/5 |
Essentiality in NALM6
- Essentiality Rank: 18320
- Expression level (log2 read counts): 2.55
Expression Distribution
PARK2 Expression in NALM6 Cells: 2.55
