PARK2 - E3 ubiquitin-protein ligase parkin - human protein (Function)
 
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PARK2 »  E3 ubiquitin-protein ligase parkin   [ EC 6.3.2.- ]  (Parkin)
 
Protein also known as:  Parkinson juvenile disease protein 2 (Parkinson disease protein 2).
Gene name:  PARK2
Family name: RBR » Parkin
Entry whose protein(s) existence is based on evidence at protein level
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1 416 8
GENE REF ISO

Function

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Overview 
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, SEPT5, TOMM20, USP30, ZNF746 and AIMP2 (PubMed10973942, PubMed10888878, PubMed11431533, PubMed:12150907, PubMed12628165, PubMed16135753, PubMed21376232, PubMed23754282, PubMed23620051, PubMed24660806, PubMed24751536). Mediates monoubiquitination as well as 'Lys-6', 'Lys-11', 'Lys-48'-linked and 'Lys-63'-linked polyubiquitination of substrates depending on the context (PubMed19229105, PubMed20889974, PubMed25621951). 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 (PubMed17846173, PubMed19229105). Mediates 'Lys-63'-linked polyubiquitination of a 22 kDa O-linked glycosylated isoform of SNCAIP, possibly playing a role in Lewy-body formation (PubMed11590439, PubMed11431533, PubMed19229105, PubMed11590439, PubMed15728840). Mediates monoubiquitination of BCL2, thereby acting as a positive regulator of autophagy (PubMed20889974). Promotes the autophagic degradation of dysfunctional depolarized mitochondria (mitophagy) by promoting the ubiquitination of mitochondrial proteins such as TOMM20, RHOT1/MIRO1 and USP30 (PubMed19029340, PubMed19966284, PubMed23620051, PubMed24896179, PubMed25527291). Preferentially assembles 'Lys-6'-, 'Lys-11'- and 'Lys-63'-linked polyubiquitin chains following mitochondrial damage, leading to mitophagy (PubMed25621951). 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 (PubMed21376232). 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 (PubMed22082830). Independently of its ubiquitin ligase activity, protects from apoptosis by the transcriptional repression of p53/TP53 (PubMed19801972). May protect neurons against alpha synuclein toxicity, proteasomal dysfunction, GPR37 accumulation, and kainate-induced excitotoxicity (PubMed:11439185). May play a role in controlling neurotransmitter trafficking at the presynaptic terminal and in calcium-dependent exocytosis. May represent a tumor suppressor gene.  
29
  • UniProtKB
GO molecular function 
Actin bindingdefinition[GO:0003779]  
1
  • ParkinsonsUK-UCL
Chaperone bindingdefinition[GO:0051087]  
3
  • ParkinsonsUK-UCL
  • BHF-UCL
Cullin family protein bindingdefinition[GO:0097602]  
1
  • ParkinsonsUK-UCL
Enzyme bindingdefinition[GO:0019899]  
1
  • ParkinsonsUK-UCL
F-box domain bindingdefinition[GO:1990444]  
1
  • ParkinsonsUK-UCL
G-protein coupled receptor bindingdefinition[GO:0001664]  
1
  • ParkinsonsUK-UCL
Heat shock protein bindingdefinition[GO:0031072]  
1
  • ParkinsonsUK-UCL
Histone deacetylase bindingdefinition[GO:0042826]  
1
  • ParkinsonsUK-UCL
Hsp70 protein bindingdefinition[GO:0030544]  
2
  • ParkinsonsUK-UCL
Identical protein bindingdefinition[GO:0042802]  
1
  • IntAct
Kinase bindingdefinition[GO:0019900]  
4
  • MGI
  • BHF-UCL
  • UniProtKB
Ligase activitydefinition[GO:0016874]  
1
  • UniProtKB KW
PDZ domain bindingdefinition[GO:0030165]  
1
  • BHF-UCL
Phospholipase bindingdefinition[GO:0043274]  
1
  • ParkinsonsUK-UCL
Protein bindingdefinition[GO:0005515]  
29
  • IntAct
  • ParkinsonsUK-UCL
  • UniProtKB
  • BHF-UCL
Protein kinase bindingdefinition[GO:0019901]  
1
  • UniProtKB
SH3 domain bindingdefinition[GO:0017124]  
1
  • ParkinsonsUK-UCL
Tubulin bindingdefinition[GO:0015631]  
1
  • ParkinsonsUK-UCL
Ubiquitin bindingdefinition[GO:0043130]  
1
  • UniProtKB
Ubiquitin conjugating enzyme bindingdefinition[GO:0031624]  
2
  • ParkinsonsUK-UCL
Ubiquitin protein ligase activitydefinition[GO:0061630]  
11
  • UniProtKB
  • ParkinsonsUK-UCL
  • MGI
  • BHF-UCL
Ubiquitin protein ligase bindingdefinition[GO:0031625]  
3
  • ParkinsonsUK-UCL
  • UniProtKB
Ubiquitin-protein transferase activitydefinition[GO:0004842]  
8
  • UniProtKB
  • CACAO
Ubiquitin-specific protease bindingdefinition[GO:1990381]  
1
  • ParkinsonsUK-UCL
Zinc ion bindingdefinition[GO:0008270]  
1
  • ParkinsonsUK-UCL
GO biological process 
Activation of mitophagy in response to mitochondrial depolarizationdefinition[GO:0098779]  
4
  • ParkinsonsUK-UCL
Adult locomotory behaviordefinition[GO:0008344]  
1
  • Ortholog Curator
Aggresome assemblydefinition[GO:0070842]  
1
  • BHF-UCL
Cellular protein catabolic processdefinition[GO:0044257]  
1
  • ParkinsonsUK-UCL
Cellular response to dopaminedefinition[GO:1903351]  
1
  • ParkinsonsUK-UCL
Cellular response to manganese iondefinition[GO:0071287]  
1
  • ParkinsonsUK-UCL
Cellular response to toxic substancedefinition[GO:0097237]  
1
  • ParkinsonsUK-UCL
Cellular response to unfolded proteindefinition[GO:0034620]  
1
  • ParkinsonsUK-UCL
Central nervous system developmentdefinition[GO:0007417]  
1
  • PINC
Dopamine metabolic processdefinition[GO:0042417]  
1
  • ParkinsonsUK-UCL
Dopamine uptake involved in synaptic transmissiondefinition[GO:0051583] silver  
1
  • Ortholog Compara
Learningdefinition[GO:0007612] silver  
1
  • Ortholog Compara
Mitochondrial fissiondefinition[GO:0000266]  
1
  • Ortholog Curator
Mitochondrion degradationdefinition[GO:0000422]  
5
  • UniProtKB
  • Ortholog Curator
Mitochondrion organizationdefinition[GO:0007005]  
1
  • Ortholog Curator
Negative regulation by host of viral genome replicationdefinition[GO:0044828]  
1
  • AgBase
Negative regulation of actin filament bundle assemblydefinition[GO:0032232]  
1
  • BHF-UCL
Negative regulation of cell deathdefinition[GO:0060548]  
2
  • BHF-UCL
  • ParkinsonsUK-UCL
Negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathwaydefinition[GO:1902236]  
3
  • ParkinsonsUK-UCL
Negative regulation of endoplasmic reticulum stress-induced neuron intrinsic apoptotic signaling pathwaydefinition[GO:1903382] silver  
1
  • Ortholog Compara
Negative regulation of gene expressiondefinition[GO:0010629]  
2
  • ParkinsonsUK-UCL
Negative regulation of glucokinase activitydefinition[GO:0033132]  
1
  • MGI
Negative regulation of insulin secretiondefinition[GO:0046676]  
1
  • MGI
Negative regulation of JNK cascadedefinition[GO:0046329]  
1
  • Ortholog Curator
Negative regulation of mitochondrial fusiondefinition[GO:0010637]  
1
  • Ortholog Curator
Negative regulation of neuron apoptotic processdefinition[GO:0043524]  
2
  • BHF-UCL
  • ParkinsonsUK-UCL
Negative regulation of neuron deathdefinition[GO:1901215]  
1
  • ParkinsonsUK-UCL
Negative regulation of oxidative stress-induced cell deathdefinition[GO:1903202]  
2
  • ParkinsonsUK-UCL
Negative regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathwaydefinition[GO:1903377]  
1
  • ParkinsonsUK-UCL
Negative regulation of primary amine oxidase activitydefinition[GO:1902283]  
1
  • ParkinsonsUK-UCL
Negative regulation of protein phosphorylationdefinition[GO:0001933]  
1
  • BHF-UCL
Negative regulation of reactive oxygen species metabolic processdefinition[GO:2000378]  
1
  • ParkinsonsUK-UCL
Negative regulation of release of cytochrome c from mitochondriadefinition[GO:0090201]  
2
  • ParkinsonsUK-UCL
  • BHF-UCL
Negative regulation of spontaneous neurotransmitter secretiondefinition[GO:1904049]  
1
  • ParkinsonsUK-UCL
Neuron cellular homeostasisdefinition[GO:0070050]  
1
  • Ortholog Curator
Norepinephrine metabolic processdefinition[GO:0042415] silver  
1
  • Ortholog Compara
Positive regulation of DNA bindingdefinition[GO:0043388]  
1
  • ParkinsonsUK-UCL
Positive regulation of gene expressiondefinition[GO:0010628]