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PARK2 parkin RBR E3 ubiquitin protein ligase [ Homo sapiens (human) ]

Gene ID: 5071, updated on 15-Sep-2014
Official Symbol
PARK2provided by HGNC
Official Full Name
parkin RBR E3 ubiquitin protein ligaseprovided by HGNC
Primary source
HGNC:HGNC:8607
Locus tag
KB-152G3.1
See related
Ensembl:ENSG00000185345; HPRD:03967; MIM:602544; Vega:OTTHUMG00000015970
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
PDJ; PRKN; AR-JP; LPRS2
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]
See PARK2 in Epigenomics, MapViewer
Location:
6q25.2-q27
Exon count:
12
Annotation release Status Assembly Chr Location
106 current GRCh38 (GCF_000001405.26) 6 NC_000006.12 (161347558..162727802, complement)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 6 NC_000006.11 (161768590..163148834, complement)

Chromosome 6 - NC_000006.12Genomic Context describing neighboring genes Neighboring gene mitogen-activated protein kinase kinase kinase 4 Neighboring gene AGPAT4 intronic transcript 1 (non-protein coding) Neighboring gene 1-acylglycerol-3-phosphate O-acyltransferase 4 Neighboring gene keratin 8 pseudogene 44 Neighboring gene transfer RNA-Glu (TTC) 15-1 Neighboring gene PARK2 co-regulated Neighboring gene ribosomal protein L34 pseudogene 15

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

Associated conditions

Description Tests
Leprosy 2
MedGen: C1843632 OMIM: 607572 GeneReviews: Not available
Compare labs
Lung cancer
MedGen: C0684249 OMIM: 211980 GeneReviews: Not available
Compare labs
Neoplasm of ovary
MedGen: C0919267 OMIM: 167000 GeneReviews: Not available
Compare labs
Parkinson disease 2 Compare labs

NHGRI GWAS Catalog

Description
Genetics meets metabolomics: a genome-wide association study of metabolite profiles in human serum.
NHGRI GWA Catalog
Genome-wide association study of pancreatic cancer in Japanese population.
NHGRI GWA Catalog
Linkage and association of successful aging to the 6q25 region in large Amish kindreds.
NHGRI GWA Catalog
Loci associated with N-glycosylation of human immunoglobulin G show pleiotropy with autoimmune diseases and haematological cancers.
NHGRI GWA Catalog
Novel genetic variants associated with lumbar disc degeneration in northern Europeans: a meta-analysis of 4600 subjects.
NHGRI GWA Catalog
  • Adaptive Immune System, organism-specific biosystem (from REACTOME)
    Adaptive Immune System, organism-specific biosystemAdaptive immunity refers to antigen-specific immune response efficiently involved in clearing the pathogens. The adaptive immune system is comprised of B and T lymphocytes that express receptors with...
  • Alpha-synuclein signaling, organism-specific biosystem (from Pathway Interaction Database)
    Alpha-synuclein signaling, organism-specific biosystem
    Alpha-synuclein signaling
  • Antigen processing: Ubiquitination & Proteasome degradation, organism-specific biosystem (from REACTOME)
    Antigen processing: Ubiquitination & Proteasome degradation, organism-specific biosystemIntracellular foreign or aberrant host proteins are cleaved into peptide fragments of a precise size, such that they can be loaded on to class I MHC molecules and presented externally to cytotoxic T ...
  • Class I MHC mediated antigen processing & presentation, organism-specific biosystem (from REACTOME)
    Class I MHC mediated antigen processing & presentation, organism-specific biosystemMajor histocompatibility complex (MHC) class I molecules play an important role in cell mediated immunity by reporting on intracellular events such as viral infection, the presence of intracellular b...
  • Immune System, organism-specific biosystem (from REACTOME)
    Immune System, organism-specific biosystemHumans are exposed to millions of potential pathogens daily, through contact, ingestion, and inhalation. Our ability to avoid infection depends on the adaptive immune system and during the first crit...
  • Parkin-Ubiquitin Proteasomal System pathway, organism-specific biosystem (from WikiPathways)
    Parkin-Ubiquitin Proteasomal System pathway, organism-specific biosystemThis pathway describes the Parkin-Ubiquitin proteasome degradation system.
  • Parkinson's disease, organism-specific biosystem (from KEGG)
    Parkinson's disease, organism-specific biosystemParkinson's disease (PD) is a progressive neurodegenerative movement disorder that results primarily from the death of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNc). Mutations...
  • Parkinsons Disease Pathway, organism-specific biosystem (from WikiPathways)
    Parkinsons Disease Pathway, organism-specific biosystemMost people with Parkinson's disease have idiopathic Parkinson's disease (having no specific known cause). A small proportion of cases, however, can be attributed to known genetic factors. Mutations ...
  • Protein processing in endoplasmic reticulum, organism-specific biosystem (from KEGG)
    Protein processing in endoplasmic reticulum, organism-specific biosystemThe endoplasmic reticulum (ER) is a subcellular organelle where proteins are folded with the help of lumenal chaperones. Newly synthesized peptides enter the ER via the sec61 pore and are glycosylate...
  • Protein processing in endoplasmic reticulum, conserved biosystem (from KEGG)
    Protein processing in endoplasmic reticulum, conserved biosystemThe endoplasmic reticulum (ER) is a subcellular organelle where proteins are folded with the help of lumenal chaperones. Newly synthesized peptides enter the ER via the sec61 pore and are glycosylate...
  • Ubiquitin mediated proteolysis, organism-specific biosystem (from KEGG)
    Ubiquitin mediated proteolysis, organism-specific biosystemProtein ubiquitination plays an important role in eukaryotic cellular processes. It mainly functions as a signal for 26S proteasome dependent protein degradation. The addition of ubiquitin to protein...
  • Ubiquitin mediated proteolysis, conserved biosystem (from KEGG)
    Ubiquitin mediated proteolysis, conserved biosystemProtein ubiquitination plays an important role in eukaryotic cellular processes. It mainly functions as a signal for 26S proteasome dependent protein degradation. The addition of ubiquitin to protein...
Products Interactant Other Gene Complex Source Pubs Description

Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
F-box domain binding IPI
Inferred from Physical Interaction
more info
PubMed 
G-protein coupled receptor binding IPI
Inferred from Physical Interaction
more info
PubMed 
Hsp70 protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
PDZ domain binding IPI
Inferred from Physical Interaction
more info
PubMed 
chaperone binding IPI
Inferred from Physical Interaction
more info
PubMed 
cullin family protein binding IDA
Inferred from Direct Assay
more info
PubMed 
heat shock protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
identical protein binding IPI
Inferred from Physical Interaction
more info
 
kinase binding IPI
Inferred from Physical Interaction
more info
PubMed 
ligase activity IEA
Inferred from Electronic Annotation
more info
 
protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
protein kinase binding IPI
Inferred from Physical Interaction
more info
 
ubiquitin binding IDA
Inferred from Direct Assay
more info
 
ubiquitin conjugating enzyme binding IPI
Inferred from Physical Interaction
more info
PubMed 
ubiquitin protein ligase activity IDA
Inferred from Direct Assay
more info
PubMed 
ubiquitin protein ligase activity NAS
Non-traceable Author Statement
more info
 
ubiquitin protein ligase binding IPI
Inferred from Physical Interaction
more info
PubMed 
ubiquitin-protein transferase activity IDA
Inferred from Direct Assay
more info
PubMed 
ubiquitin-specific protease binding IPI
Inferred from Physical Interaction
more info
 
zinc ion binding IEA
Inferred from Electronic Annotation
more info
 
Process Evidence Code Pubs
adult locomotory behavior IEA
Inferred from Electronic Annotation
more info
 
aggresome assembly IMP
Inferred from Mutant Phenotype
more info
PubMed 
cell death IEA
Inferred from Electronic Annotation
more info
 
cellular protein catabolic process IMP
Inferred from Mutant Phenotype
more info
 
cellular response to manganese ion TAS
Traceable Author Statement
more info
 
cellular response to toxic substance IMP
Inferred from Mutant Phenotype
more info
PubMed 
central nervous system development TAS
Traceable Author Statement
more info
PubMed 
dopamine metabolic process IEA
Inferred from Electronic Annotation
more info
 
dopamine uptake involved in synaptic transmission IEA
Inferred from Electronic Annotation
more info
 
learning IEA
Inferred from Electronic Annotation
more info
 
mitochondrion degradation IMP
Inferred from Mutant Phenotype
more info
PubMed 
negative regulation of actin filament bundle assembly IDA
Inferred from Direct Assay
more info
PubMed 
negative regulation of cell death IDA
Inferred from Direct Assay
more info
PubMed 
negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway IDA
Inferred from Direct Assay
more info
 
negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway IMP
Inferred from Mutant Phenotype
more info
 
negative regulation of glucokinase activity IDA
Inferred from Direct Assay
more info
 
negative regulation of insulin secretion IDA
Inferred from Direct Assay
more info
 
negative regulation of neuron apoptotic process IDA
Inferred from Direct Assay
more info
PubMed 
negative regulation of neuron death IGI
Inferred from Genetic Interaction
more info
 
negative regulation of oxidative stress-induced cell death NAS
Non-traceable Author Statement
more info
 
negative regulation of protein phosphorylation IDA
Inferred from Direct Assay
more info
PubMed 
negative regulation of reactive oxygen species metabolic process IGI
Inferred from Genetic Interaction
more info
PubMed 
negative regulation of release of cytochrome c from mitochondria IDA
Inferred from Direct Assay
more info
PubMed 
norepinephrine metabolic process IEA
Inferred from Electronic Annotation
more info
 
positive regulation of I-kappaB kinase/NF-kappaB signaling IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of I-kappaB kinase/NF-kappaB signaling IMP
Inferred from Mutant Phenotype
more info
 
positive regulation of mitochondrial fusion IMP
Inferred from Mutant Phenotype
more info
 
positive regulation of proteasomal protein catabolic process IGI
Inferred from Genetic Interaction
more info
 
positive regulation of protein linear polyubiquitination IGI
Inferred from Genetic Interaction
more info
 
positive regulation of transcription from RNA polymerase II promoter IDA
Inferred from Direct Assay
more info
 
positive regulation of tumor necrosis factor-mediated signaling pathway IDA
Inferred from Direct Assay
more info
 
proteasome-mediated ubiquitin-dependent protein catabolic process IDA
Inferred from Direct Assay
more info
 
protein K48-linked ubiquitination IDA
Inferred from Direct Assay
more info
 
protein K63-linked ubiquitination IDA
Inferred from Direct Assay
more info
PubMed 
protein autoubiquitination IDA
Inferred from Direct Assay
more info
PubMed 
protein monoubiquitination IDA
Inferred from Direct Assay
more info
 
protein polyubiquitination IDA
Inferred from Direct Assay
more info
PubMed 
protein ubiquitination IDA
Inferred from Direct Assay
more info
PubMed 
protein ubiquitination IMP
Inferred from Mutant Phenotype
more info
 
protein ubiquitination TAS
Traceable Author Statement
more info
 
protein ubiquitination involved in ubiquitin-dependent protein catabolic process IC
Inferred by Curator
more info
 
protein ubiquitination involved in ubiquitin-dependent protein catabolic process IDA
Inferred from Direct Assay
more info
PubMed 
protein ubiquitination involved in ubiquitin-dependent protein catabolic process NAS
Non-traceable Author Statement
more info
PubMed 
protein ubiquitination involved in ubiquitin-dependent protein catabolic process TAS
Traceable Author Statement
more info
PubMed 
regulation of autophagy IDA
Inferred from Direct Assay
more info
 
regulation of dopamine secretion TAS
Traceable Author Statement
more info
 
regulation of mitochondrion degradation TAS
Traceable Author Statement
more info
 
regulation of mitochondrion organization IDA
Inferred from Direct Assay
more info
 
regulation of neurotransmitter secretion IEA
Inferred from Electronic Annotation
more info
 
regulation of reactive oxygen species metabolic process IMP
Inferred from Mutant Phenotype
more info
PubMed 
regulation of synaptic vesicle transport NAS
Non-traceable Author Statement
more info
 
response to endoplasmic reticulum stress IMP
Inferred from Mutant Phenotype
more info
 
startle response IEA
Inferred from Electronic Annotation
more info
 
synaptic transmission, glutamatergic IEA
Inferred from Electronic Annotation
more info
 
transcription, DNA-templated IEA
Inferred from Electronic Annotation
more info
 
Component Evidence Code Pubs
Golgi apparatus IDA
Inferred from Direct Assay
more info
PubMed 
colocalizes_with LUBAC complex IPI
Inferred from Physical Interaction
more info
 
Lewy body TAS
Traceable Author Statement
more info
 
Parkin-FBXW7-Cul1 ubiquitin ligase complex IPI
Inferred from Physical Interaction
more info
PubMed 
NOT SCF ubiquitin ligase complex IDA
Inferred from Direct Assay
more info
PubMed 
aggresome IDA
Inferred from Direct Assay
more info
PubMed 
cytoplasm IDA
Inferred from Direct Assay
more info
PubMed 
cytosol IDA
Inferred from Direct Assay
more info
PubMed 
endoplasmic reticulum IDA
Inferred from Direct Assay
more info
PubMed 
mitochondrion IDA
Inferred from Direct Assay
more info
 
mitochondrion IMP
Inferred from Mutant Phenotype
more info
PubMed 
neuron projection IEA
Inferred from Electronic Annotation
more info
 
nucleus IC
Inferred by Curator
more info
 
perinuclear region of cytoplasm IDA
Inferred from Direct Assay
more info
PubMed 
ubiquitin ligase complex IDA
Inferred from Direct Assay
more info
PubMed 
Preferred Names
E3 ubiquitin-protein ligase parkin
Names
E3 ubiquitin-protein ligase parkin
parkinson juvenile disease protein 2
parkinson protein 2, E3 ubiquitin protein ligase (parkin)
Parkinson disease (autosomal recessive, juvenile) 2, parkin

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

  1. NG_008289.1 

    Range
    5001..1385245
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_004562.2NP_004553.2  E3 ubiquitin-protein ligase parkin isoform 1

    See proteins identical to NP_004553.2

    Status: REVIEWED

    Description
    Transcript Variant: Transcript variant 1 represents the predominant and full-length form of this gene.
    Source sequence(s)
    AK292590, AL132982, DB023187
    Consensus CDS
    CCDS5281.1
    UniProtKB/Swiss-Prot
    O60260
    UniProtKB/TrEMBL
    X5DR79
    Related
    ENSP00000355865, OTTHUMP00000017565, ENST00000366898, OTTHUMT00000042995
    Conserved Domains (3) summary
    cd01798
    Location:372
    Blast Score: 361
    parkin_N; amino-terminal ubiquitin-like of parkin protein
    smart00647
    Location:313375
    Blast Score: 116
    IBR; In Between Ring fingers
    pfam01485
    Location:412453
    Blast Score: 80
    IBR; IBR domain
  2. NM_013987.2NP_054642.2  E3 ubiquitin-protein ligase parkin isoform 2

    See proteins identical to NP_054642.2

    Status: REVIEWED

    Description
    Transcript Variant: Transcript variant 2 lacks exons 5 which is present in the full-length variant 1.
    Source sequence(s)
    AK292590, AL132982, DB023187
    Consensus CDS
    CCDS5282.1
    UniProtKB/Swiss-Prot
    O60260
    Conserved Domains (3) summary
    cd01798
    Location:372
    Blast Score: 361
    parkin_N; amino-terminal ubiquitin-like of parkin protein
    smart00647
    Location:285347
    Blast Score: 117
    IBR; In Between Ring fingers
    pfam01485
    Location:384425
    Blast Score: 81
    IBR; IBR domain
  3. NM_013988.2NP_054643.2  E3 ubiquitin-protein ligase parkin isoform 3

    Status: REVIEWED

    Description
    Transcript Variant: Transcript variant 3 lacks exons 3 to 5 present in the full-length transcript variant 1.
    Source sequence(s)
    AK292590, AL132982, DB023187
    Consensus CDS
    CCDS5283.1
    UniProtKB/Swiss-Prot
    O60260
    Conserved Domains (3) summary
    cd01798
    Location:382
    Blast Score: 311
    parkin_N; amino-terminal ubiquitin-like of parkin protein
    smart00647
    Location:164226
    Blast Score: 112
    IBR; In Between Ring fingers
    pfam01485
    Location:263304
    Blast Score: 77
    IBR; IBR domain

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 106

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38 Primary Assembly

Genomic

  1. NC_000006.12 

    Range
    161347558..162727802
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

  1. AC_000138.1 

    Range
    159224034..160600983
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate CHM1_1.1

Genomic

  1. NC_018917.2 

    Range
    162031091..163411071
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)