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

Gene ID: 5071, updated on 15-Apr-2019

Summary

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Official Symbol: PRKNprovided by HGNC
Official Full Name: parkin RBR E3 ubiquitin protein ligaseprovided by HGNC
Primary source: HGNC:HGNC:8607
See related: Ensembl:ENSG00000185345 MIM:602544
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; AR-JP; LPRS2; PARK2
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]
Expression: Broad expression in heart (RPKM 3.6), kidney (RPKM 3.5) and 21 other tissues See more
Orthologs: mouse all

Genomic context

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See PRKN in Genome Data Viewer

Location:: 6q26

Exon count:: 14

Annotation release	Status	Assembly	Chr	Location
109	current	GRCh38.p12 (GCF_000001405.38)	6	NC_000006.12 (161347417..162727802, complement)
105	previous assembly	GRCh37.p13 (GCF_000001405.25)	6	NC_000006.11 (161768590..163148834, complement)

Chromosome 6 - NC_000006.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

lowering parkin levels by extracellular ASN may significantly contribute to the propagation of neurodegeneration in Parkinson's disease pathology.
Title: Extracellular Alpha-Synuclein Oligomers Induce Parkin S-Nitrosylation: Relevance to Sporadic Parkinson's Disease Etiopathology.
Single nucleotide polymorphism in PARK2 gene is associated with schizophrenia.
Title: Genetic loci associated with an earlier age at onset in multiplex schizophrenia.
Parkin is an ubiquitin E3 ligase, and plays important roles in a variety of cellular processes implicated in tumorigenesis, including cell cycle, cell proliferation, apoptosis, metastasis, mitophagy and metabolic reprogramming [Review].
Title: Parkinson's disease-associated protein Parkin: an unusual player in cancer.
The results show that novel compound heterozygous mutations were identified in a Chinese pedigree that might represent a cause of familial EOPD with autosomal dominant inheritance.
Title: Novel compound heterozygous mutations in the <i>PARK2</i> gene identified in a Chinese pedigree with early-onset Parkinson's disease.
MIDN promotes the expression of parkin E3 ubiquitin ligase, and that MIDN loss can trigger Parkinson's disease-related pathogenic mechanisms.
Title: Midnolin is a novel regulator of parkin expression and is associated with Parkinson's Disease.
Define the kinetics and site specificity of PARKIN-dependent target ubiquitylation, and mechanistically define the role of PARKIN UBL phosphorylation in pathway activation in induced neurons.
Title: Dynamics of PARKIN-Dependent Mitochondrial Ubiquitylation in Induced Neurons and Model Systems Revealed by Digital Snapshot Proteomics.
The findings suggest that Parkin plays a novel role in innate immune signaling by targeting TRAF3 for degradation and maintaining the balance of innate antiviral immunity.
Title: Parkin negatively regulates the antiviral signaling pathway by targeting TRAF3 for degradation.
data show how autoinhibition in parkin is resolved, and suggest a mechanism for how parkin ubiquitinates its substrates via an untethered RING2 domain; these findings open new avenues for the design of parkin activators for clinical use
Title: Mechanism of parkin activation by PINK1.
Five different PRKN structural variations were identified in families with early onset Parkinson disease. All identified PRKN SVs might originate through retrotransposition events.
Title: Molecular characterization of PRKN structural variations identified through whole-genome sequencing.
work provides a framework for the mechanisms of parkin's loss-of-function, indicating an interplay between ARJP-associated substitutions and phosphorylation of its Ubl domain.
Title: Impact of altered phosphorylation on loss of function of juvenile Parkinsonism-associated genetic variants of the E3 ligase parkin.

Submit: New GeneRIF Correction See all GeneRIFs (546)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
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 MedGen: C1868675 OMIM: 600116 GeneReviews: Parkinson Disease Overview, Parkin Type of Early-Onset Parkinson Disease	Compare labs

NHGRI GWAS Catalog

Description
A genome-wide association study in the genetic analysis of idiopathic thrombophilia project suggests sex-specific regulation of mitochondrial DNA levels. NHGRI GWA Catalog NHGRI GWA CatalogPubMed
Genetics meets metabolomics: a genome-wide association study of metabolite profiles in human serum. NHGRI GWA Catalog NHGRI GWA CatalogPubMed
Genome-wide association study of pancreatic cancer in Japanese population. NHGRI GWA Catalog NHGRI GWA CatalogPubMed
Linkage and association of successful aging to the 6q25 region in large Amish kindreds. NHGRI GWA Catalog NHGRI GWA CatalogPubMed
Loci associated with N-glycosylation of human immunoglobulin G show pleiotropy with autoimmune diseases and haematological cancers. NHGRI GWA Catalog NHGRI GWA CatalogPubMed
Novel genetic variants associated with lumbar disc degeneration in northern Europeans: a meta-analysis of 4600 subjects. NHGRI GWA Catalog NHGRI GWA CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Pathways from BioSystems

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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
Amyloid fiber formation, organism-specific biosystem (from REACTOME)
Amyloid fiber formation, organism-specific biosystemAmyloid is a term used to describe deposits of fibrillar proteins, typically extracellular. The abnormal accumulation of amyloid, amyloidosis, is a term associated with tissue damage caused by amyloi...
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...
Deubiquitination, organism-specific biosystem (from REACTOME)
Deubiquitination, organism-specific biosystemUbiquitination, the modification of proteins by the covalent attachment of ubiquitin (Ub), is a key regulatory mechanism for many many cellular processes, including protein degradation by the 26S pro...
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...
Josephin domain DUBs, organism-specific biosystem (from REACTOME)
Josephin domain DUBs, organism-specific biosystemThe Josephin domain is present in four human DUBs: Ataxin-3 (ATXN3), ATXN3L, Josephin-1 (JOSD1) and JOSD2. All have been shown to possess DUB activity (Tzveltkov & Breuer 2007, Weeks et al. 2011). Jo...
Metabolism of proteins, organism-specific biosystem (from REACTOME)
Metabolism of proteins, organism-specific biosystemProtein metabolism comprises the pathways of translation, post-translational modification and protein folding.
Mitophagy, organism-specific biosystem (from REACTOME)
Mitophagy, organism-specific biosystemMitophagy is a specific form of autophagy where mitochondria are specifically targeted for degradation by autophagolysosomes.. In mammals there are a number of known mechanisms of mitophagy. One insu...
Mitophagy - animal, organism-specific biosystem (from KEGG)
Mitophagy - animal, organism-specific biosystemMitochondria act as the energy powerhouse of the cell, and are essential for eukaryotic cells to grow and function normally. However, deleterious byproducts of oxidative phosphorylation process calle...
Mitophagy - animal, conserved biosystem (from KEGG)
Mitophagy - animal, conserved biosystemMitochondria act as the energy powerhouse of the cell, and are essential for eukaryotic cells to grow and function normally. However, deleterious byproducts of oxidative phosphorylation process calle...
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 ...
Pink/Parkin Mediated Mitophagy, organism-specific biosystem (from REACTOME)
Pink/Parkin Mediated Mitophagy, organism-specific biosystemThis is the process of selective removal of damaged mitochondria by autophagosomes and subsequent catabolism by lysosomes. In healthy mitochondria, PINK1 is imported to the inner mitochondrial membra...
Post-translational protein modification, organism-specific biosystem (from REACTOME)
Post-translational protein modification, organism-specific biosystemAfter translation, many newly formed proteins undergo further covalent modifications that alter their functional properties and that are essentially irreversible under physiological conditions in the...
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...

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

SHGC-53410 (e-PCR)
- UniSTS:26376

G42363 (e-PCR)
- UniSTS:94222

D10S275 (e-PCR)
- UniSTS:147992

PMC156308P1 (e-PCR)
- UniSTS:271391

SHGC-8992 (e-PCR)
- UniSTS:28204

WI-11670 (e-PCR)
- UniSTS:60978

D8S2279 (e-PCR)
- UniSTS:473907

SHGC-79163 (e-PCR)
- UniSTS:102712

SHGC-106786 (e-PCR)
- UniSTS:170042

D6S1599 (e-PCR), detects polymorphism
- UniSTS:76096

D6S1404 (e-PCR)
- UniSTS:49223

RH37445 (e-PCR)
- UniSTS:22605

RH37467 (e-PCR)
- UniSTS:49230

SHGC-147718 (e-PCR)
- UniSTS:175969

D6S305 (e-PCR)
- UniSTS:26980

G10328 (e-PCR)
- UniSTS:5479

SHGC-79722 (e-PCR)
- UniSTS:101225

SHGC-149848 (e-PCR)
- UniSTS:177259

D6S955 (e-PCR), detects polymorphism
- UniSTS:18030

SHGC-146858 (e-PCR)
- UniSTS:175476

D6S411 (e-PCR), detects polymorphism
- UniSTS:74357

D11S1289 (e-PCR)
- UniSTS:15221

D1S1425 (e-PCR)
- UniSTS:149621

D6S411 (e-PCR), detects polymorphism
- UniSTS:74358

FB8B6 (e-PCR)
- UniSTS:32385

AFMa155td9 (e-PCR)
- UniSTS:50313

D6S2153 (e-PCR)
- UniSTS:1169

D16S325 (e-PCR)
- UniSTS:147089

RH76397 (e-PCR)
- UniSTS:84628

RH123443 (e-PCR)
- UniSTS:135831

D6S253 (e-PCR)
- UniSTS:45465

RH123198 (e-PCR)
- UniSTS:135579

SHGC-152656 (e-PCR)
- UniSTS:177567

G17030 (e-PCR)
- UniSTS:46242

RH45460 (e-PCR)
- UniSTS:57250

G62556 (e-PCR)
- UniSTS:139683

SHGC-141992 (e-PCR)
- UniSTS:171180

D6S305 (e-PCR)
- UniSTS:24501

AFMb281wf1 (e-PCR)
- UniSTS:26805

SHGC-80808 (e-PCR)
- UniSTS:102327

SHGC-85252 (e-PCR)
- UniSTS:104377

D6S1550 (e-PCR)
- UniSTS:64198

RH119707 (e-PCR)
- UniSTS:133076

D6S253 (e-PCR)
- UniSTS:45804

Homology

Homologs of the PRKN gene: The PRKN gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, chicken, zebrafish, fruit fly, mosquito, and C.elegans.
Orthologs from Annotation Pipeline: 224 organisms have orthologs with human gene PRKN
Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
DNA-binding transcription repressor activity, RNA polymerase II-specific	IDA Inferred from Direct Assay more info	PubMed
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
SH3 domain binding	TAS Traceable Author Statement more info	PubMed
actin binding	IPI Inferred from Physical Interaction more info	PubMed
beta-catenin binding	IDA Inferred from Direct Assay 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
enzyme binding	IPI Inferred from Physical Interaction more info	PubMed
heat shock protein binding	IPI Inferred from Physical Interaction more info	PubMed
histone deacetylase binding	IPI Inferred from Physical Interaction more info	PubMed
identical protein binding	IPI Inferred from Physical Interaction more info	PubMed
kinase binding	IPI Inferred from Physical Interaction more info	PubMed
phospholipase binding	IPI Inferred from Physical Interaction more info	PubMed
protein binding	IPI Inferred from Physical Interaction more info	PubMed
protein kinase binding	IPI Inferred from Physical Interaction more info	PubMed
transcription regulatory region sequence-specific DNA binding	IDA Inferred from Direct Assay more info	PubMed
tubulin binding	IPI Inferred from Physical Interaction more info	PubMed
ubiquitin binding	IDA Inferred from Direct Assay more info	PubMed
ubiquitin conjugating enzyme binding	IBA Inferred from Biological aspect of Ancestor more info	PubMed
ubiquitin conjugating enzyme binding	IDA Inferred from Direct Assay more info	PubMed
ubiquitin conjugating enzyme binding	IPI Inferred from Physical Interaction more info	PubMed
ubiquitin protein ligase activity	IBA Inferred from Biological aspect of Ancestor 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	PubMed
ubiquitin protein ligase activity	TAS 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-protein transferase activity	TAS Traceable Author Statement more info
ubiquitin-specific protease binding	IPI Inferred from Physical Interaction more info	PubMed
zinc ion binding	TAS Traceable Author Statement more info	PubMed

Process	Evidence Code	Pubs
ERAD pathway	NAS Non-traceable Author Statement more info	PubMed
adult locomotory behavior	ISS Inferred from Sequence or Structural Similarity more info
aggresome assembly	IMP Inferred from Mutant Phenotype more info	PubMed
autophagy of mitochondrion	IBA Inferred from Biological aspect of Ancestor more info	PubMed
autophagy of mitochondrion	IDA Inferred from Direct Assay more info	PubMed
autophagy of mitochondrion	IMP Inferred from Mutant Phenotype more info	PubMed
cellular protein catabolic process	IMP Inferred from Mutant Phenotype more info	PubMed
cellular protein metabolic process	TAS Traceable Author Statement more info
cellular response to dopamine	TAS Traceable Author Statement more info	PubMed
cellular response to manganese ion	TAS Traceable Author Statement more info	PubMed
cellular response to toxic substance	IMP Inferred from Mutant Phenotype more info	PubMed
cellular response to unfolded protein	TAS Traceable Author Statement more info	PubMed
central nervous system development	TAS Traceable Author Statement more info	PubMed
dopamine metabolic process	TAS Traceable Author Statement more info	PubMed
dopamine uptake involved in synaptic transmission	IEA Inferred from Electronic Annotation more info
free ubiquitin chain polymerization	IMP Inferred from Mutant Phenotype more info	PubMed
learning	IEA Inferred from Electronic Annotation more info
macroautophagy	TAS Traceable Author Statement more info
mitochondrial fission	ISS Inferred from Sequence or Structural Similarity more info
mitochondrion organization	ISS Inferred from Sequence or Structural Similarity more info
mitochondrion to lysosome transport	IDA Inferred from Direct Assay more info	PubMed
mitophagy	IEA Inferred from Electronic Annotation more info
negative regulation by host of viral genome replication	IDA Inferred from Direct Assay more info	PubMed
negative regulation of JNK cascade	ISS Inferred from Sequence or Structural Similarity more info
negative regulation of actin filament bundle assembly	IDA Inferred from Direct Assay more info	PubMed
negative regulation of canonical Wnt signaling pathway	IDA Inferred from Direct Assay more info	PubMed
negative regulation of canonical Wnt signaling pathway	TAS Traceable Author Statement 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	PubMed
negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
negative regulation of endoplasmic reticulum stress-induced neuron intrinsic apoptotic signaling pathway	IEA Inferred from Electronic Annotation more info
negative regulation of exosomal secretion	IMP Inferred from Mutant Phenotype more info	PubMed
negative regulation of gene expression	IMP Inferred from Mutant Phenotype more info	PubMed
negative regulation of glucokinase activity	IDA Inferred from Direct Assay more info	PubMed
negative regulation of insulin secretion	IDA Inferred from Direct Assay more info	PubMed
negative regulation of intralumenal vesicle formation	IMP Inferred from Mutant Phenotype more info	PubMed
negative regulation of intrinsic apoptotic signaling pathway by p53 class mediator	IMP Inferred from Mutant Phenotype more info	PubMed
negative regulation of mitochondrial fusion	ISS Inferred from Sequence or Structural Similarity 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	PubMed
negative regulation of oxidative stress-induced cell death	NAS Non-traceable Author Statement more info	PubMed
negative regulation of oxidative stress-induced cell death	TAS Traceable Author Statement more info	PubMed
negative regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway	IDA Inferred from Direct Assay more info	PubMed
negative regulation of primary amine oxidase activity	IMP Inferred from Mutant Phenotype more info	PubMed
negative regulation of protein phosphorylation	IBA Inferred from Biological aspect of Ancestor more info	PubMed
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
negative regulation of spontaneous neurotransmitter secretion	IMP Inferred from Mutant Phenotype more info	PubMed
negative regulation of transcription by RNA polymerase II	IMP Inferred from Mutant Phenotype more info	PubMed
neuron cellular homeostasis	ISS Inferred from Sequence or Structural Similarity more info
norepinephrine metabolic process	IEA Inferred from Electronic Annotation more info
parkin-mediated stimulation of mitophagy in response to mitochondrial depolarization	IDA Inferred from Direct Assay more info	PubMed
positive regulation of DNA binding	IDA Inferred from Direct Assay more info	PubMed
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	PubMed
positive regulation of autophagy of mitochondrion	IDA Inferred from Direct Assay more info	PubMed
positive regulation of dendrite extension	IEA Inferred from Electronic Annotation more info
positive regulation of gene expression	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of mitochondrial fission	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of mitochondrial fusion	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of mitophagy in response to mitochondrial depolarization	IDA Inferred from Direct Assay more info	PubMed
positive regulation of mitophagy in response to mitochondrial depolarization	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of neurotransmitter uptake	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of proteasomal protein catabolic process	IGI Inferred from Genetic Interaction more info	PubMed
positive regulation of proteasomal ubiquitin-dependent protein catabolic process	IBA Inferred from Biological aspect of Ancestor more info	PubMed
positive regulation of proteasomal ubiquitin-dependent protein catabolic process	TAS Traceable Author Statement more info	PubMed
positive regulation of protein binding	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of protein catabolic process	TAS Traceable Author Statement more info	PubMed
positive regulation of protein linear polyubiquitination	IGI Inferred from Genetic Interaction more info	PubMed
positive regulation of protein localization to membrane	IC Inferred by Curator more info	PubMed
positive regulation of protein localization to membrane	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of retrograde transport, endosome to Golgi	NAS Non-traceable Author Statement more info	PubMed
positive regulation of transcription by RNA polymerase II	IDA Inferred from Direct Assay more info	PubMed
positive regulation of tumor necrosis factor-mediated signaling pathway	IDA Inferred from Direct Assay more info	PubMed
proteasomal protein catabolic process	IMP Inferred from Mutant Phenotype more info	PubMed
proteasome-mediated ubiquitin-dependent protein catabolic process	IDA Inferred from Direct Assay more info	PubMed
protein K11-linked ubiquitination	IDA Inferred from Direct Assay more info	PubMed
protein K27-linked ubiquitination	TAS Traceable Author Statement more info	PubMed
protein K29-linked ubiquitination	TAS Traceable Author Statement more info	PubMed
protein K48-linked ubiquitination	IDA Inferred from Direct Assay more info	PubMed
protein K6-linked ubiquitination	IDA Inferred from Direct Assay more info	PubMed
protein K6-linked ubiquitination	TAS Traceable Author Statement more info	PubMed
protein K63-linked ubiquitination	IDA Inferred from Direct Assay more info	PubMed
protein K63-linked ubiquitination	NAS Non-traceable Author Statement more info	PubMed
protein K63-linked ubiquitination	TAS Traceable Author Statement more info	PubMed
protein autoubiquitination	IDA Inferred from Direct Assay more info	PubMed
protein destabilization	IDA Inferred from Direct Assay more info	PubMed
protein deubiquitination	TAS Traceable Author Statement more info
protein localization to mitochondrion	IEA Inferred from Electronic Annotation more info
protein monoubiquitination	IDA Inferred from Direct Assay more info	PubMed
protein monoubiquitination	IMP Inferred from Mutant Phenotype more info	PubMed
protein polyubiquitination	IBA Inferred from Biological aspect of Ancestor more info	PubMed
protein polyubiquitination	IDA Inferred from Direct Assay more info	PubMed
protein stabilization	IMP Inferred from Mutant Phenotype more info	PubMed
protein ubiquitination	IDA Inferred from Direct Assay more info	PubMed
protein ubiquitination	IMP Inferred from Mutant Phenotype more info	PubMed
regulation of apoptotic process	IBA Inferred from Biological aspect of Ancestor more info	PubMed
regulation of autophagy	IDA Inferred from Direct Assay more info	PubMed
regulation of canonical Wnt signaling pathway	TAS Traceable Author Statement more info	PubMed
regulation of cellular response to oxidative stress	IBA Inferred from Biological aspect of Ancestor more info	PubMed
regulation of cellular response to oxidative stress	IDA Inferred from Direct Assay more info	PubMed
regulation of cellular response to oxidative stress	IMP Inferred from Mutant Phenotype more info	PubMed
regulation of cellular response to oxidative stress	ISS Inferred from Sequence or Structural Similarity more info
regulation of dopamine metabolic process	IMP Inferred from Mutant Phenotype more info	PubMed
regulation of dopamine secretion	TAS Traceable Author Statement more info	PubMed
regulation of glucose metabolic process	TAS Traceable Author Statement more info	PubMed
regulation of lipid transport	TAS Traceable Author Statement more info	PubMed
regulation of mitochondrial membrane potential	IEA Inferred from Electronic Annotation more info
regulation of mitochondrion organization	IBA Inferred from Biological aspect of Ancestor more info	PubMed
regulation of mitochondrion organization	IDA Inferred from Direct Assay more info	PubMed
regulation of mitochondrion organization	IGI Inferred from Genetic Interaction more info	PubMed
regulation of mitochondrion organization	NAS Non-traceable Author Statement more info	PubMed
regulation of protein stability	IMP Inferred from Mutant Phenotype more info	PubMed
regulation of protein targeting to mitochondrion	NAS Non-traceable Author Statement more info	PubMed
regulation of protein ubiquitination	IGI Inferred from Genetic Interaction more info	PubMed
regulation of protein ubiquitination	IMP Inferred from Mutant Phenotype more info	PubMed
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	PubMed
response to endoplasmic reticulum stress	IMP Inferred from Mutant Phenotype more info	PubMed
response to oxidative stress	ISS Inferred from Sequence or Structural Similarity more info
startle response	IEA Inferred from Electronic Annotation more info
synaptic transmission, glutamatergic	IEA Inferred from Electronic Annotation more info
ubiquitin-dependent protein catabolic process	IBA Inferred from Biological aspect of Ancestor more info	PubMed
ubiquitin-dependent protein catabolic process	IC Inferred by Curator more info	PubMed
ubiquitin-dependent protein catabolic process	IDA Inferred from Direct Assay more info	PubMed
ubiquitin-dependent protein catabolic process	NAS Non-traceable Author Statement more info	PubMed
ubiquitin-dependent protein catabolic process	TAS Traceable Author Statement more info	PubMed
zinc ion homeostasis	ISS Inferred from Sequence or Structural Similarity more info

Component	Evidence Code	Pubs
Golgi apparatus	IBA Inferred from Biological aspect of Ancestor more info	PubMed
Golgi apparatus	IDA Inferred from Direct Assay more info	PubMed
colocalizes_with LUBAC complex	IPI Inferred from Physical Interaction more info	PubMed
Lewy body	TAS Traceable Author Statement more info	PubMed
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	IBA Inferred from Biological aspect of Ancestor more info	PubMed
cytoplasm	IDA Inferred from Direct Assay more info	PubMed
cytosol	IBA Inferred from Biological aspect of Ancestor more info	PubMed
cytosol	IDA Inferred from Direct Assay more info	PubMed
cytosol	IMP Inferred from Mutant Phenotype more info	PubMed
cytosol	TAS Traceable Author Statement more info
endoplasmic reticulum	IBA Inferred from Biological aspect of Ancestor more info	PubMed
endoplasmic reticulum	IDA Inferred from Direct Assay more info	PubMed
mitochondrion	IBA Inferred from Biological aspect of Ancestor more info	PubMed
mitochondrion	IDA Inferred from Direct Assay more info	PubMed
mitochondrion	IMP Inferred from Mutant Phenotype more info	PubMed
colocalizes_with mitochondrion	IMP Inferred from Mutant Phenotype more info	PubMed
colocalizes_with mitochondrion-derived vesicle	IDA Inferred from Direct Assay more info	PubMed
neuron projection	IDA Inferred from Direct Assay more info	PubMed
nuclear speck	IDA Inferred from Direct Assay more info
nucleus	IDA Inferred from Direct Assay more info	PubMed
perinuclear region of cytoplasm	IDA Inferred from Direct Assay more info	PubMed
presynapse	IEA Inferred from Electronic Annotation more info
ubiquitin ligase complex	IBA Inferred from Biological aspect of Ancestor more info	PubMed
ubiquitin ligase complex	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: E3 ubiquitin-protein ligase parkin

Names: Parkinson disease (autosomal recessive, juvenile) 2, parkin; parkinson juvenile disease protein 2; parkinson protein 2 E3 ubiquitin protein ligase; parkinson protein 2, E3 ubiquitin protein ligase (parkin)

NP_004553.2

EC 2.3.2.31

NP_054642.2

EC 2.3.2.31

NP_054643.2

EC 2.3.2.31

XP_011534165.1

EC 2.3.2.31

XP_016866397.1

EC 2.3.2.31

XP_016866398.1

EC 2.3.2.31

XP_024302217.1

EC 2.3.2.31

NCBI Reference Sequences (RefSeq)

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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

NG_008289.2 RefSeqGene

Range

5001..1385245

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_004562.3 → NP_004553.2 E3 ubiquitin-protein ligase parkin isoform 1

See identical proteins and their annotated locations for 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

ENSP00000355865.1, ENST00000366898.6

Conserved Domains (4) summary

cd01798
Location:3 → 72

parkin_N; amino-terminal ubiquitin-like of parkin protein

smart00213
Location:1 → 72

UBQ; Ubiquitin homologues

smart00647
Location:313 → 375

IBR; In Between Ring fingers

pfam01485
Location:413 → 453

IBR; IBR domain, a half RING-finger domain
NM_013987.2 → NP_054642.2 E3 ubiquitin-protein ligase parkin isoform 2

See identical proteins and their annotated locations for 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

Related

ENSP00000355863.1, ENST00000366897.5

Conserved Domains (4) summary

cd01798
Location:3 → 72

parkin_N; amino-terminal ubiquitin-like of parkin protein

smart00213
Location:1 → 72

UBQ; Ubiquitin homologues

smart00647
Location:285 → 347

IBR; In Between Ring fingers

pfam01485
Location:385 → 425

IBR; IBR domain, a half RING-finger domain
NM_013988.2 → NP_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

Related

ENSP00000355862.1, ENST00000366896.5

Conserved Domains (4) summary

cd01798
Location:3 → 82

parkin_N; amino-terminal ubiquitin-like of parkin protein

smart00213
Location:1 → 58

UBQ; Ubiquitin homologues

smart00647
Location:164 → 226

IBR; In Between Ring fingers

pfam01485
Location:264 → 304

IBR; IBR domain, a half RING-finger domain

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 109

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

Reference GRCh38.p12 Primary Assembly

Genomic

NC_000006.12 Reference GRCh38.p12 Primary Assembly

Range

161347417..162727802 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_011535863.1 → XP_011534165.1 E3 ubiquitin-protein ligase parkin isoform X2

Conserved Domains (4) summary

cd01798
Location:3 → 72

parkin_N; amino-terminal ubiquitin-like of parkin protein

smart00213
Location:1 → 72

UBQ; Ubiquitin homologues

smart00647
Location:312 → 374

IBR; In Between Ring fingers

pfam01485
Location:412 → 452

IBR; IBR domain, a half RING-finger domain
XM_024446449.1 → XP_024302217.1 E3 ubiquitin-protein ligase parkin isoform X3

Conserved Domains (2) summary

pfam01485
Location:234 → 296

IBR; IBR domain, a half RING-finger domain

cd16627
Location:157 → 215

RING-HC_RBR_parkin; RING finger, HC subclass, found in parkin and similar proteins
XM_017010909.2 → XP_016866398.1 E3 ubiquitin-protein ligase parkin isoform X4
XM_017010908.1 → XP_016866397.1 E3 ubiquitin-protein ligase parkin isoform X1