PARK2 - E3 ubiquitin-protein ligase parkin - human protein (Function)
 
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PARK2 »  E3 ubiquitin-protein ligase parkin   [ EC 6.3.2.- ]
 
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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1 361 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, STUB1, a 22 kDa O-linked glycosylated isoform of SNCAIP, SEPT5, ZNF746 and AIMP2. Mediates monoubiquitination as well as '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 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), potentially by the ubiquitination of mitochondrial proteins. 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.  
18
  • CuratedUniProtKB
GO molecular function 
Chaperone bindingdefinition[GO:0051087]  
1
  • IPIBHF-UCL
Identical protein bindingdefinition[GO:0042802]  
1
  • IPIIntAct
Kinase bindingdefinition[GO:0019900]  
2
  • IPIBHF-UCL
PDZ domain bindingdefinition[GO:0030165]  
1
  • IPIBHF-UCL
Protein bindingdefinition[GO:0005515]  
18
  • IPIIntAct
  • IPIUniProtKB
  • IPIBHF-UCL
Protein kinase bindingdefinition[GO:0019901]  
1
  • IPIUniProtKB
Ubiquitin protein ligase bindingdefinition[GO:0031625]  
1
  • IPIUniProtKB
Ubiquitin-protein ligase activitydefinition[GO:0004842]  
7
  • IDAUniProtKB
  • IDABHF-UCL
Zinc ion bindingdefinition[GO:0008270] silver  
  • IEAInterPro 2 GO
GO biological process 
Aggresome assemblydefinition[GO:0070842]  
1
  • IMPBHF-UCL
Cell deathdefinition[GO:0008219]  
1
  • IDAUniProtKB
Central nervous system developmentdefinition[GO:0007417]  
1
  • TASPINC
Mitochondrion degradationdefinition[GO:0000422]  
2
  • IMPUniProtKB
Negative regulation of actin filament bundle assemblydefinition[GO:0032232]  
1
  • IDABHF-UCL
Negative regulation of cell deathdefinition[GO:0060548]  
1
  • IDABHF-UCL
Negative regulation of glucokinase activitydefinition[GO:0033132]  
1
  • IDAMGI
Negative regulation of insulin secretiondefinition[GO:0046676]  
1
  • IDAMGI
Negative regulation of neuron apoptotic processdefinition[GO:0043524]  
1
  • IDABHF-UCL
Negative regulation of protein phosphorylationdefinition[GO:0001933]  
1
  • IDABHF-UCL
Negative regulation of release of cytochrome c from mitochondriadefinition[GO:0090201]  
1
  • IDABHF-UCL
Neuron deathdefinition[GO:0070997]  
1
  • IDAUniProtKB
Positive regulation of I-kappaB kinase/NF-kappaB signalingdefinition[GO:0043123]  
1
  • IDABHF-UCL
Protein autoubiquitinationdefinition[GO:0051865]  
2
  • IDABHF-UCL
  • IDAUniProtKB
Protein K48-linked ubiquitinationdefinition[GO:0070936]  
1
  • IDAUniProtKB
Protein K63-linked ubiquitinationdefinition[GO:0070534]  
2
  • IDABHF-UCL
  • IDAUniProtKB
Protein monoubiquitinationdefinition[GO:0006513]  
1
  • IDAUniProtKB
Protein polyubiquitinationdefinition[GO:0000209]  
3
  • IDABHF-UCL
  • IDAUniProtKB
Protein ubiquitinationdefinition[GO:0016567]  
1
  • IMPUniProtKB
Protein ubiquitination involved in ubiquitin-dependent protein catabolic processdefinition[GO:0042787]  
1
  • IDAUniProtKB
Regulation of autophagydefinition[GO:0010506]  
1
  • IDAUniProtKB
Regulation of reactive oxygen species metabolic processdefinition[GO:2000377]  
1
  • IMPUniProtKB
Regulation of transcription, DNA-templateddefinition[GO:0006355]  
  • IEAUniProtKB KW
Transcription, DNA-templateddefinition[GO:0006351]  
  • IEAUniProtKB KW
Ubiquitin-dependent protein catabolic processdefinition[GO:0006511]  
1
  • IDAUniProtKB
Enzymatic activity 
It is regulated in the following manner
In the autoinhibited state the side chain of Phe-463 inserts into a hydrophobic groove in RING-0, occluding the ubiquitin acceptor site Cys-431, whereas the REP repressor element binds RING-1 and blocks its E2-binding site (By similarity).  
  • CuratedUniProtKB
Pathways 
This protein is involved in the following pathway
According to KEGG, this protein belongs to the following pathways:
Parkinson's disease  hsa05012+5071  
Protein processing in endoplasmic reticulum  hsa04141+5071  
Ubiquitin mediated proteolysis  hsa04120+5071  
According to Reactome, this protein belongs to the following pathway:
Immune System  REACT_6900  
Note 
The parkin locus (PRKN), adjacent to the 6q telomere is hyper-recombinable and lies within FRA6E, the third most common fragile site in tumor tissue.  
  • CuratedUniProtKB
 

Keywords

Biological process 
Autophagy  definition   [KW-0072]
Transcription  definition   [KW-0804]
Transcription regulation  definition   [KW-0805]
Ubl conjugation pathway  definition   [KW-0833]
Molecular function 
Ligase  definition   [KW-0436]
Technical term 
Reference proteome  definition   [KW-1185]
 

Further external links

GeneWiki: Parkin_(ligase)
GenomeRNAi: 5071
PRO: PR:O60260