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Entry version 203 (18 Sep 2019)
Sequence version 2 (17 Oct 2006)
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Protein

E3 ubiquitin-protein ligase parkin

Gene

PRKN

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score:

Annotation score:5 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
-Experimental evidence at protein leveli <p>This indicates the type of evidence that supports the existence of the protein. Note that the ‘protein existence’ evidence does not give information on the accuracy or correctness of the sequence(s) displayed.<p><a href='/help/protein_existence' target='_top'>More...</a></p>

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

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, SEPTIN5, TOMM20, USP30, ZNF746 and AIMP2 (PubMed:10973942, PubMed:10888878, PubMed:11431533, PubMed:12150907, PubMed:12628165, PubMed:16135753, PubMed:21376232, PubMed:23754282, PubMed:23620051, PubMed:24660806, PubMed:24751536). Mediates monoubiquitination as well as 'Lys-6', 'Lys-11', 'Lys-48'-linked and 'Lys-63'-linked polyubiquitination of substrates depending on the context (PubMed:19229105, PubMed:20889974, PubMed:25621951). 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 (PubMed:17846173, PubMed:19229105). Mediates 'Lys-63'-linked polyubiquitination of a 22 kDa O-linked glycosylated isoform of SNCAIP, possibly playing a role in Lewy-body formation (PubMed:11590439, PubMed:11431533, PubMed:19229105, PubMed:11590439, PubMed:15728840). Mediates monoubiquitination of BCL2, thereby acting as a positive regulator of autophagy (PubMed:20889974). Promotes the autophagic degradation of dysfunctional depolarized mitochondria (mitophagy) by promoting the ubiquitination of mitochondrial proteins such as TOMM20, RHOT1/MIRO1 and USP30 (PubMed:19029340, PubMed:19966284, PubMed:23620051, PubMed:24896179, PubMed:25527291). Preferentially assembles 'Lys-6'-, 'Lys-11'- and 'Lys-63'-linked polyubiquitin chains following mitochondrial damage, leading to mitophagy (PubMed:25621951). 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 (PubMed:21376232). 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 (PubMed:22082830). Independently of its ubiquitin ligase activity, protects from apoptosis by the transcriptional repression of p53/TP53 (PubMed:19801972). 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.28 Publications

Miscellaneous

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.

<p>This subsection of the <a href="http://www.uniprot.org/help/function_section">Function</a> section describes the catalytic activity of an enzyme, i.e. a chemical reaction that the enzyme catalyzes.<p><a href='/help/catalytic_activity' target='_top'>More...</a></p>Catalytic activityi

<p>This subsection of the <a href="http://www.uniprot.org/help/function_section">Function</a> section describes regulatory mechanisms for enzymes, transporters or microbial transcription factors, and reports the components which regulate (by activation or inhibition) the reaction.<p><a href='/help/activity_regulation' target='_top'>More...</a></p>Activity regulationi

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 (PubMed:23727886, PubMed:23770887). Activation of PRKN requires 2 steps: (1) phosphorylation at Ser-65 by PINK1 and (2) binding to phosphorylated ubiquitin, leading to unlock repression of the catalytic Cys-431 by the RING-0 region via an allosteric mechanism and converting PRKN to its fully-active form (PubMed:24660806, PubMed:24784582, PubMed:25527291). According to another report, phosphorylation at Ser-65 by PINK1 is not essential for activation and only binding to phosphorylated ubiquitin is essential to unlock repression (PubMed:24751536).6 Publications

<p>This subsection of the <a href="http://www.uniprot.org/help/function_section">'Function'</a> section describes the metabolic pathway(s) associated with a protein.<p><a href='/help/pathway' target='_top'>More...</a></p>Pathwayi: protein ubiquitination

This protein is involved in the pathway protein ubiquitination, which is part of Protein modification.
View all proteins of this organism that are known to be involved in the pathway protein ubiquitination and in Protein modification.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/function_section">Function</a> section indicates at which position the protein binds a given metal ion. The nature of the metal is indicated in the ‘Description’ field.<p><a href='/help/metal' target='_top'>More...</a></p>Metal bindingi238Zinc 1PROSITE-ProRule annotation1
Metal bindingi241Zinc 1PROSITE-ProRule annotation1
Metal bindingi253Zinc 2PROSITE-ProRule annotation1
Metal bindingi257Zinc 2; via pros nitrogenPROSITE-ProRule annotation1
Metal bindingi260Zinc 1PROSITE-ProRule annotation1
Metal bindingi263Zinc 1PROSITE-ProRule annotation1
Metal bindingi289Zinc 2PROSITE-ProRule annotation1
Metal bindingi293Zinc 2PROSITE-ProRule annotation1
Metal bindingi332Zinc 3PROSITE-ProRule annotation1
Metal bindingi337Zinc 3PROSITE-ProRule annotation1
Metal bindingi352Zinc 3PROSITE-ProRule annotation1
Metal bindingi360Zinc 3PROSITE-ProRule annotation1
Metal bindingi365Zinc 4PROSITE-ProRule annotation1
Metal bindingi368Zinc 4PROSITE-ProRule annotation1
Metal bindingi373Zinc 4; via tele nitrogenPROSITE-ProRule annotation1
Metal bindingi377Zinc 4PROSITE-ProRule annotation1
Metal bindingi418Zinc 5PROSITE-ProRule annotation1
Metal bindingi421Zinc 5PROSITE-ProRule annotation1
<p>This subsection of the <a href="http://www.uniprot.org/help/function_section">Function</a> section is used for enzymes and indicates the residues directly involved in catalysis.<p><a href='/help/act_site' target='_top'>More...</a></p>Active sitei431PROSITE-ProRule annotation1
Metal bindingi436Zinc 5PROSITE-ProRule annotation1
Metal bindingi441Zinc 5PROSITE-ProRule annotation1
Metal bindingi446Zinc 6PROSITE-ProRule annotation1
Metal bindingi449Zinc 6PROSITE-ProRule annotation1
Metal bindingi457Zinc 6PROSITE-ProRule annotation1
Metal bindingi461Zinc 6; via tele nitrogenPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/function_section">Function</a> section specifies the position(s) and type(s) of zinc fingers within the protein.<p><a href='/help/zn_fing' target='_top'>More...</a></p>Zinc fingeri141 – 225RING-type 0; atypicalAdd BLAST85
Zinc fingeri238 – 293RING-type 1PROSITE-ProRule annotationAdd BLAST56
Zinc fingeri313 – 377IBR-typePROSITE-ProRule annotationAdd BLAST65
Zinc fingeri418 – 449RING-type 2; atypicalPROSITE-ProRule annotationAdd BLAST32

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

GO - Biological processi

<p>UniProtKB Keywords constitute a <a href="http://www.uniprot.org/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>Keywordsi

Molecular functionTransferase
Biological processAutophagy, Transcription, Transcription regulation, Ubl conjugation pathway
LigandMetal-binding, Zinc

Enzyme and pathway databases

BRENDA Comprehensive Enzyme Information System

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BRENDAi
2.3.2.B10 2681

Reactome - a knowledgebase of biological pathways and processes

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Reactomei
R-HSA-5205685 Pink/Parkin Mediated Mitophagy
R-HSA-5689877 Josephin domain DUBs
R-HSA-977225 Amyloid fiber formation
R-HSA-983168 Antigen processing: Ubiquitination & Proteasome degradation

SignaLink: a signaling pathway resource with multi-layered regulatory networks

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SignaLinki
O60260

SIGNOR Signaling Network Open Resource

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SIGNORi
O60260

UniPathway: a resource for the exploration and annotation of metabolic pathways

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UniPathwayi
UPA00143

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section provides an exhaustive list of all names of the protein, from commonly used to obsolete, to allow unambiguous identification of a protein.<p><a href='/help/protein_names' target='_top'>More...</a></p>Protein namesi
Recommended name:
E3 ubiquitin-protein ligase parkinCurated (EC:2.3.2.311 Publication)
Short name:
Parkin
Alternative name(s):
Parkin RBR E3 ubiquitin-protein ligaseImported
Parkinson juvenile disease protein 2
Short name:
Parkinson disease protein 2
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section indicates the name(s) of the gene(s) that code for the protein sequence(s) described in the entry. Four distinct tokens exist: ‘Name’, ‘Synonyms’, ‘Ordered locus names’ and ‘ORF names’.<p><a href='/help/gene_name' target='_top'>More...</a></p>Gene namesi
Name:PRKNImported
Synonyms:PARK2
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section provides information on the name(s) of the organism that is the source of the protein sequence.<p><a href='/help/organism-name' target='_top'>More...</a></p>OrganismiHomo sapiens (Human)
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section shows the unique identifier assigned by the NCBI to the source organism of the protein. This is known as the ‘taxonomic identifier’ or ‘taxid’.<p><a href='/help/taxonomic_identifier' target='_top'>More...</a></p>Taxonomic identifieri9606 [NCBI]
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section contains the taxonomic hierarchical classification lineage of the source organism. It lists the nodes as they appear top-down in the taxonomic tree, with the more general grouping listed first.<p><a href='/help/taxonomic_lineage' target='_top'>More...</a></p>Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section is present for entries that are part of a <a href="http://www.uniprot.org/proteomes">proteome</a>, i.e. of a set of proteins thought to be expressed by organisms whose genomes have been completely sequenced.<p><a href='/help/proteomes_manual' target='_top'>More...</a></p>Proteomesi
  • UP000005640 <p>A UniProt <a href="http://www.uniprot.org/manual/proteomes_manual">proteome</a> can consist of several components. <br></br>The component name refers to the genomic component encoding a set of proteins.<p><a href='/help/proteome_component' target='_top'>More...</a></p> Componenti: Chromosome 6

Organism-specific databases

Human Gene Nomenclature Database

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HGNCi
HGNC:8607 PRKN

Online Mendelian Inheritance in Man (OMIM)

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MIMi
602544 gene

neXtProt; the human protein knowledge platform

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neXtProti
NX_O60260

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte & Seán O’Donoghue; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Endoplasmic reticulum, Mitochondrion, Nucleus

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

<p>This subsection of the ‘Pathology and Biotech’ section provides information on the disease(s) associated with genetic variations in a given protein. The information is extracted from the scientific literature and diseases that are also described in the <a href="http://www.ncbi.nlm.nih.gov/sites/entrez?db=omim">OMIM</a> database are represented with a <a href="http://www.uniprot.org/diseases">controlled vocabulary</a> in the following way:<p><a href='/help/involvement_in_disease' target='_top'>More...</a></p>Involvement in diseasei

Parkinson disease (PARK)3 Publications
Disease susceptibility may be associated with variations affecting the gene represented in this entry. Heterozygous mutations act as susceptibility alleles for late-onset Parkinson disease (PubMed:12730996 and PubMed:12629236).
Disease descriptionA complex neurodegenerative disorder characterized by bradykinesia, resting tremor, muscular rigidity and postural instability. Additional features are characteristic postural abnormalities, dysautonomia, dystonic cramps, and dementia. The pathology of Parkinson disease involves the loss of dopaminergic neurons in the substantia nigra and the presence of Lewy bodies (intraneuronal accumulations of aggregated proteins), in surviving neurons in various areas of the brain. The disease is progressive and usually manifests after the age of 50 years, although early-onset cases (before 50 years) are known. The majority of the cases are sporadic suggesting a multifactorial etiology based on environmental and genetic factors. However, some patients present with a positive family history for the disease. Familial forms of the disease usually begin at earlier ages and are associated with atypical clinical features.
Related information in OMIM
Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Sequence’ section describes natural variant(s) of the protein sequence.<p><a href='/help/variant' target='_top'>More...</a></p>Natural variantiVAR_019749253C → Y in PARK; late onset. 1 PublicationCorresponds to variant dbSNP:rs747427602Ensembl.1
Natural variantiVAR_019750256R → C in PARK2 and PARK; at heterozygosity it is associated with late onset Parkinson disease; impairs the ability to ubiquitinate SNCAIP and ZNF746; decreased binding to the TP53 promoter; abolishes TP53 transcriptional repression. 7 PublicationsCorresponds to variant dbSNP:rs150562946Ensembl.1
Natural variantiVAR_019752275R → W in PARK2 and PARK; at heterozygosity it is associated with late onset Parkinson disease; impairs the ability to ubiquitinate SNCAIP; abolishes p53/TP53 transcriptional repression. 11 PublicationsCorresponds to variant dbSNP:rs34424986EnsemblClinVar.1
Natural variantiVAR_019753280D → N in PARK; does not affect PINK-1 dependent localization to depolarized mitochondria. 3 PublicationsCorresponds to variant dbSNP:rs72480422Ensembl.1
Parkinson disease 2 (PARK2)30 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA neurodegenerative disorder characterized by bradykinesia, rigidity, postural instability, tremor, and onset usually before 40. It differs from classic Parkinson disease by early DOPA-induced dyskinesia, diurnal fluctuation of the symptoms, sleep benefit, dystonia and hyper-reflexia. Dementia is absent. Pathologically, patients show loss of dopaminergic neurons in the substantia nigra, similar to that seen in Parkinson disease; however, Lewy bodies (intraneuronal accumulations of aggregated proteins) are absent.
Related information in OMIM
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01973315V → M in PARK2. 1 PublicationCorresponds to variant dbSNP:rs532703934Ensembl.1
Natural variantiVAR_01973433R → Q in PARK2. 1 PublicationCorresponds to variant dbSNP:rs147757966Ensembl.1
Natural variantiVAR_01973537P → L in PARK2. 1 PublicationCorresponds to variant dbSNP:rs148990138Ensembl.1
Natural variantiVAR_01973642R → P in PARK2; induces a conformational change in the PSMD4-binding site of Ubl resulting in impaired proteasomal binding; decreases ubiquitination and degradation; increased aggregation. 6 PublicationsCorresponds to variant dbSNP:rs368134308Ensembl.1
Natural variantiVAR_01973746A → P in PARK2. 1 Publication1
Natural variantiVAR_07007856V → E in PARK2. 1 PublicationCorresponds to variant dbSNP:rs137853059EnsemblClinVar.1
Natural variantiVAR_01973882A → E in PARK2. 3 PublicationsCorresponds to variant dbSNP:rs55774500EnsemblClinVar.1
Natural variantiVAR_01973992A → V in PARK2. Corresponds to variant dbSNP:rs566229879Ensembl.1
Natural variantiVAR_019741161K → N in PARK2; severely compromises the mitochondrial localization; fails to stabilize BCL2; decreased binding to the TP53 promoter; abolishes TP53 transcriptional repression. 5 PublicationsCorresponds to variant dbSNP:rs137853057EnsemblClinVar.1
Natural variantiVAR_054107192M → L in PARK2; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs9456735EnsemblClinVar.1
Natural variantiVAR_019743192M → V in PARK2; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs9456735EnsemblClinVar.1
Natural variantiVAR_019744211K → N in PARK2; severely compromises the mitochondrial localization; fails to stabilize BCL2. 5 PublicationsCorresponds to variant dbSNP:rs137853060EnsemblClinVar.1
Natural variantiVAR_019746212C → Y in PARK2. 2 PublicationsCorresponds to variant dbSNP:rs137853058EnsemblClinVar.1
Natural variantiVAR_019747240T → M in PARK2. 1 PublicationCorresponds to variant dbSNP:rs137853054EnsemblClinVar.1
Natural variantiVAR_019748240T → R in PARK2; impairs the ability to ubiquitinate SNCAIP and BCL2; loss of UBE2L3 binding; severely compromises the mitochondrial localization. 6 PublicationsCorresponds to variant dbSNP:rs137853054EnsemblClinVar.1
Natural variantiVAR_019750256R → C in PARK2 and PARK; at heterozygosity it is associated with late onset Parkinson disease; impairs the ability to ubiquitinate SNCAIP and ZNF746; decreased binding to the TP53 promoter; abolishes TP53 transcriptional repression. 7 PublicationsCorresponds to variant dbSNP:rs150562946Ensembl.1
Natural variantiVAR_019752275R → W in PARK2 and PARK; at heterozygosity it is associated with late onset Parkinson disease; impairs the ability to ubiquitinate SNCAIP; abolishes p53/TP53 transcriptional repression. 11 PublicationsCorresponds to variant dbSNP:rs34424986EnsemblClinVar.1
Natural variantiVAR_019754284G → R in PARK2. Corresponds to variant dbSNP:rs751037529EnsemblClinVar.1
Natural variantiVAR_019755289C → G in PARK2; increased aggregation; fails to ubiquitinate SYT11; loses ability to bind SYT11; impaired relocalization to damaged mitochondria; loss of function in mitophagy. 3 PublicationsCorresponds to variant dbSNP:rs55961220Ensembl.1
Natural variantiVAR_019756328G → E in PARK2; does not affect PINK-1 dependent localization to depolarized mitochondria. 3 Publications1
Natural variantiVAR_019759351T → P in PARK2; impairs folding of IBR domain. 2 Publications1
Natural variantiVAR_070079402R → C in PARK2. 1 PublicationCorresponds to variant dbSNP:rs55830907EnsemblClinVar.1
Natural variantiVAR_019763415T → N in PARK2; impairs the ability to ubiquitinate SNCAIP; does not affect turnover of CDCRE1; impairs PINK1-dependent localization to dysfunctional depolarized mitochondria. 5 PublicationsCorresponds to variant dbSNP:rs778125254Ensembl.1
Natural variantiVAR_070080418C → R in PARK2; decreased binding to the TP53 promoter; abolishes TP53 transcriptional repression; fails to ubiquitinate SYT11 but does not loose ability to bind SYT11. 3 Publications1
Natural variantiVAR_019764430G → D in PARK2; impairs PINK1-dependent localization to dysfunctional depolarized mitochondria; impaired E3 ubiquitin-protein ligase toward ZNF746. 7 PublicationsCorresponds to variant dbSNP:rs191486604EnsemblClinVar.1
Natural variantiVAR_019765431C → F in PARK2; impaired E3 ubiquitin-protein ligase toward ZNF746 and BCL2. 3 PublicationsCorresponds to variant dbSNP:rs397514694EnsemblClinVar.1
Natural variantiVAR_019766437P → L in PARK2; impaired E3 ubiquitin-protein ligase toward BCL2. 5 PublicationsCorresponds to variant dbSNP:rs149953814EnsemblClinVar.1
Natural variantiVAR_019767441C → R in PARK2; decreased binding to the TP53 promoter; abolishes TP53 transcriptional repression. 2 PublicationsCorresponds to variant dbSNP:rs778305273Ensembl.1
Defects in PRKN may be involved in the development and/or progression of ovarian cancer.

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/manual/pathology_and_biotech_section">'Pathology and Biotech'</a> section describes the effect of the experimental mutation of one or more amino acid(s) on the biological properties of the protein.<p><a href='/help/mutagen' target='_top'>More...</a></p>Mutagenesisi65S → E: Phosphomimetic mutant; still requires PINK1 for activation. PRKN is activated in presence of phosphorylated ubiquitin. 2 Publications1
Mutagenesisi332C → S: Impairs folding of IBR domain. 1 Publication1
Mutagenesisi337C → A: Impairs the ability to ubiquitinate SNCAIP. 1 Publication1
Mutagenesisi365C → S: Impairs protein folding. 1 Publication1
Mutagenesisi403W → A: Decreased autoinhibition and increased E3 activity. 1 Publication1
Mutagenesisi421C → A: Impairs the ability of self-ubiquitination and to ubiquitinate SNCAIP. 2 Publications1
Mutagenesisi431C → S: Impairs the ability to ubiquitinate target proteins. 3 Publications1
Mutagenesisi433H → N or A: Impaired activity. 2 Publications1
Mutagenesisi444E → Q or A: Impaired activity. 2 Publications1

Keywords - Diseasei

Disease mutation, Neurodegeneration, Parkinson disease, Parkinsonism

Organism-specific databases

DisGeNET

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DisGeNETi
5071

GeneReviews a resource of expert-authored, peer-reviewed disease descriptions.

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GeneReviewsi
PRKN

MalaCards human disease database

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MalaCardsi
PRKN
MIMi168600 phenotype
600116 phenotype

Open Targets

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OpenTargetsi
ENSG00000185345

Orphanet; a database dedicated to information on rare diseases and orphan drugs

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Orphaneti
2828 Young-onset Parkinson disease

The Pharmacogenetics and Pharmacogenomics Knowledge Base

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PharmGKBi
PA32942

Polymorphism and mutation databases

BioMuta curated single-nucleotide variation and disease association database

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BioMutai
PRKN

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘PTM / Processing’ section describes the extent of a polypeptide chain in the mature protein following processing.<p><a href='/help/chain' target='_top'>More...</a></p>ChainiPRO_00000585761 – 465E3 ubiquitin-protein ligase parkinAdd BLAST465

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘PTM / Processing’ section specifies the position and type of each modified residue excluding <a href="http://www.uniprot.org/manual/lipid">lipids</a>, <a href="http://www.uniprot.org/manual/carbohyd">glycans</a> and <a href="http://www.uniprot.org/manual/crosslnk">protein cross-links</a>.<p><a href='/help/mod_res' target='_top'>More...</a></p>Modified residuei65Phosphoserine; by PINK13 Publications1

<p>This subsection of the <a href="http://www.uniprot.org/help/ptm_processing_section">PTM/processing</a> section describes post-translational modifications (PTMs). This subsection <strong>complements</strong> the information provided at the sequence level or describes modifications for which <strong>position-specific data is not yet available</strong>.<p><a href='/help/post-translational_modification' target='_top'>More...</a></p>Post-translational modificationi

Auto-ubiquitinates in an E2-dependent manner leading to its own degradation (PubMed:19229105). Also polyubiquitinated by RNF41 for proteasomal degradation.1 Publication
S-nitrosylated. The inhibition of PRKN ubiquitin E3 ligase activity by S-nitrosylation could contribute to the degenerative process in PD by impairing the ubiquitination of PRKN substrates.1 Publication
Phosphorylation at Ser-65 by PINK1 contributes to activate PRKN activity. It is however not sufficient and requires binding to phosphorylated ubiquitin as well.3 Publications

Keywords - PTMi

Phosphoprotein, S-nitrosylation, Ubl conjugation

Proteomic databases

MassIVE - Mass Spectrometry Interactive Virtual Environment

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MassIVEi
O60260

PaxDb, a database of protein abundance averages across all three domains of life

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PaxDbi
O60260

PeptideAtlas

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PeptideAtlasi
O60260

PRoteomics IDEntifications database

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PRIDEi
O60260

ProteomicsDB human proteome resource

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ProteomicsDBi
49290 [O60260-1]
49291 [O60260-2]
49292 [O60260-3]
49293 [O60260-4]
49294 [O60260-5]
49295 [O60260-6]

PTM databases

iPTMnet integrated resource for PTMs in systems biology context

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iPTMneti
O60260

Comprehensive resource for the study of protein post-translational modifications (PTMs) in human, mouse and rat.

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PhosphoSitePlusi
O60260

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

<p>This subsection of the ‘Expression’ section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms. By default, the information is derived from experiments at the mRNA level, unless specified ‘at protein level’. <br></br>Examples: <a href="http://www.uniprot.org/uniprot/P92958#expression">P92958</a>, <a href="http://www.uniprot.org/uniprot/Q8TDN4#expression">Q8TDN4</a>, <a href="http://www.uniprot.org/uniprot/O14734#expression">O14734</a><p><a href='/help/tissue_specificity' target='_top'>More...</a></p>Tissue specificityi

Highly expressed in the brain including the substantia nigra. Expressed in heart, testis and skeletal muscle. Expression is down-regulated or absent in tumor biopsies, and absent in the brain of PARK2 patients. Overexpression protects dopamine neurons from kainate-mediated apoptosis. Found in serum (at protein level).1 Publication

Gene expression databases

Bgee dataBase for Gene Expression Evolution

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Bgeei
ENSG00000185345 Expressed in 111 organ(s), highest expression level in frontal cortex

ExpressionAtlas, Differential and Baseline Expression

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ExpressionAtlasi
O60260 baseline and differential

Genevisible search portal to normalized and curated expression data from Genevestigator

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Genevisiblei
O60260 HS

Organism-specific databases

Human Protein Atlas

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HPAi
CAB016257
HPA036012

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

<p>This subsection of the <a href="http://www.uniprot.org/help/interaction_section">'Interaction'</a> section provides information about the protein quaternary structure and interaction(s) with other proteins or protein complexes (with the exception of physiological receptor-ligand interactions which are annotated in the <a href="http://www.uniprot.org/help/function_section">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>Subunit structurei

Forms an E3 ubiquitin ligase complex with UBE2L3 or UBE2L6. Mediates 'Lys-63'-linked polyubiquitination by associating with UBE2V1.

Part of a SCF-like complex, consisting of PRKN, CUL1 and FBXW7.

Interacts with SNCAIP. Binds to the C2A and C2B domains of SYT11.

Interacts and regulates the turnover of SEPTIN5. Part of a complex, including STUB1, HSP70 and GPR37. The amount of STUB1 in the complex increases during ER stress. STUB1 promotes the dissociation of HSP70 from PRKN and GPR37, thus facilitating PRKN-mediated GPR37 ubiquitination. HSP70 transiently associates with unfolded GPR37 and inhibits the E3 activity of PRKN, whereas, STUB1 enhances the E3 activity of PRKN through promotion of dissociation of HSP70 from PRKN-GPR37 complexes.

Interacts with PSMD4 and PACRG.

Interacts with LRRK2.

Interacts with RANBP2.

Interacts with SUMO1 but not SUMO2, which promotes nuclear localization and autoubiquitination.

Interacts (via first RING-type domain) with AIMP2 (via N-terminus).

Interacts with PSMA7 and RNF41.

Interacts with PINK1.

Interacts with CHPF, the interaction with isoform 2 may facilitate PRKN transport into the mitochondria.

Interacts with MFN2 (phosphorylated), promotes PRKN localization in dysfunctional depolarized mitochondria.

Interacts with FBXO7; this promotes translocation to dysfunctional depolarized mitochondria.

Interacts with heat shock protein 70 family members, including HSPA1L, HSPA1A and HSPA8; interaction HSPA1L promotes translocation to damaged mitochondria.

Interacts with BAG4 and, to a lesser extent, BAG5; interaction with BAG4 inhibits translocation to damaged mitochondria.

Forms a complex with PINK1 and PARK7 (PubMed:19229105).

25 Publications

<p>This subsection of the '<a href="http://www.uniprot.org/help/interaction_section%27">Interaction</a> section provides information about binary protein-protein interactions. The data presented in this section are a quality-filtered subset of binary interactions automatically derived from the <a href="http://www.ebi.ac.uk/intact/">IntAct database</a>. It is updated on a monthly basis. Each binary interaction is displayed on a separate line.<p><a href='/help/binary_interactions' target='_top'>More...</a></p>Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

The Biological General Repository for Interaction Datasets (BioGrid)

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BioGridi
111105, 471 interactors

CORUM comprehensive resource of mammalian protein complexes

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