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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, SEPT5, 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 ‘Function’ 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 ‘Function’ 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 ‘Function’ 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 ‘Function’ 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

Eukaryotic Pathogen Database Resources

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EuPathDBi
HostDB:ENSG00000185345.18

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; 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.
See also OMIM:168600
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:rs150562946EnsemblClinVar.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:rs72480422EnsemblClinVar.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.
See also OMIM:600116
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:rs147757966EnsemblClinVar.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:rs150562946EnsemblClinVar.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:rs778125254EnsemblClinVar.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

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
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

CleanEx database of gene expression profiles

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CleanExi
HS_PARK2

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 SEPT5. 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, 461 interactors

CORUM comprehensive resource of mammalian protein complexes

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CORUMi
O60260

Database of interacting proteins

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DIPi
DIP-37655N

Protein interaction database and analysis system

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IntActi
O60260, 37 interactors

Molecular INTeraction database

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MINTi
O60260

STRING: functional protein association networks

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STRINGi
9606.ENSP00000355865

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

Secondary structure

1465
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

Select the link destinations:

Protein Data Bank Europe

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PDBei

Protein Data Bank RCSB

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RCSB PDBi

Protein Data Bank Japan

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PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1IYFNMR-A1-76[»]
2JMONMR-A308-384[»]
4BM9X-ray2.25A137-465[»]
4I1FX-ray1.58A141-465[»]
4I1HX-ray2.00A141-465[»]
5C1ZX-ray1.79A/B1-465[»]
5C23X-ray2.37A/B1-465[»]
5C9VX-ray2.35A137-465[»]
5N2WX-ray2.68A1-465[»]
5N38X-ray2.60A1-465[»]
5TR5NMR-A1-76[»]
6GLCX-ray1.80A1-382[»]
6HUEX-ray2.85A/B1-465[»]

Protein Model Portal of the PSI-Nature Structural Biology Knowledgebase

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ProteinModelPortali
O60260

SWISS-MODEL Repository - a database of annotated 3D protein structure models

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SMRi
O60260

Database of comparative protein structure models

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ModBasei
Search...

MobiDB: a database of protein disorder and mobility annotations

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MobiDBi
Search...

Miscellaneous databases

Relative evolutionary importance of amino acids within a protein sequence

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EvolutionaryTracei
O60260

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/family_and_domains_section">Family and Domains</a> section describes the position and type of a domain, which is defined as a specific combination of secondary structures organized into a characteristic three-dimensional structure or fold.<p><a href='/help/domain' target='_top'>More...</a></p>Domaini1 – 76Ubiquitin-likePROSITE-ProRule annotationAdd BLAST76

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Family and Domains’ section describes a region of interest that cannot be described in other subsections.<p><a href='/help/region' target='_top'>More...</a></p>Regioni204 – 238SYT11 binding 11 PublicationAdd BLAST35
Regioni234 – 465TRIAD supradomainPROSITE-ProRule annotationAdd BLAST232
Regioni257 – 293SYT11 binding 21 PublicationAdd BLAST37
Regioni378 – 410REPBy similarityAdd BLAST33

<p>This subsection of the ‘Family and domains’ section provides general information on the biological role of a domain. The term ‘domain’ is intended here in its wide acceptation, it may be a structural domain, a transmembrane region or a functional domain. Several domains are described in this subsection.<p><a href='/help/domain_cc' target='_top'>More...</a></p>Domaini

The ubiquitin-like domain binds the PSMD4 subunit of 26S proteasomes.1 Publication
The RING-type 1 zinc finger domain is required to repress p53/TP53 transcription.1 Publication
Members of the RBR family are atypical E3 ligases. They interact with the E2 conjugating enzyme UBE2L3 and function like HECT-type E3 enzymes: they bind E2s via the first RING domain, but require an obligate trans-thiolation step during the ubiquitin transfer, requiring a conserved cysteine residue in the second RING domain (PubMed:21532592).1 Publication

<p>This subsection of the ‘Family and domains’ section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesi

Belongs to the RBR family. Parkin subfamily.Curated

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
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

Keywords - Domaini

Repeat, Zinc-finger

Phylogenomic databases

evolutionary genealogy of genes: Non-supervised Orthologous Groups

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eggNOGi
KOG0006 Eukaryota
ENOG410YG4B LUCA

Ensembl GeneTree

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GeneTreei
ENSGT00390000011034

The HOGENOM Database of Homologous Genes from Fully Sequenced Organisms

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HOGENOMi
HOG000013184

The HOVERGEN Database of Homologous Vertebrate Genes

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HOVERGENi
HBG053682

InParanoid: Eukaryotic Ortholog Groups

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InParanoidi
O60260

KEGG Orthology (KO)

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KOi
K04556

Identification of Orthologs from Complete Genome Data

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OMAi
CGYVFCR

Database of Orthologous Groups

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OrthoDBi
716326at2759

Database for complete collections of gene phylogenies

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PhylomeDBi
O60260

TreeFam database of animal gene trees

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TreeFami
TF314529

Family and domain databases

Integrated resource of protein families, domains and functional sites

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InterProi
View protein in InterPro
IPR031127 E3_UB_ligase_RBR
IPR002867 IBR_dom
IPR003977 Parkin
IPR029071 Ubiquitin-like_domsf
IPR000626 Ubiquitin_dom

The PANTHER Classification System

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PANTHERi
PTHR11685 PTHR11685, 1 hit

Pfam protein domain database

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Pfami
View protein in Pfam
PF01485 IBR, 1 hit
PF00240 ubiquitin, 1 hit

PIRSF; a whole-protein classification database

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PIRSFi
PIRSF037880 Parkin, 1 hit

Protein Motif fingerprint database; a protein domain database

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PRINTSi
PR01475 PARKIN

Simple Modular Architecture Research Tool; a protein domain database

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SMARTi
View protein in SMART
SM00647 IBR, 2 hits
SM00213 UBQ, 1 hit

Superfamily database of structural and functional annotation

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SUPFAMi
SSF54236 SSF54236, 1 hit

PROSITE; a protein domain and family database

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PROSITEi
View protein in PROSITE
PS51873 TRIAD, 1 hit
PS50053 UBIQUITIN_2, 1 hit

<p>This section displays by default the canonical protein sequence and upon request all isoforms described in the entry. It also includes information pertinent to the sequence(s), including <a href="http://www.uniprot.org/help/sequence_length">length</a> and <a href="http://www.uniprot.org/help/sequences">molecular weight</a>.<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequences (8+)i

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences_section">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical_and_isoforms">canonical sequence</a> displayed by default in the entry is complete or not.<p><a href='/help/sequence_status' target='_top'>More...</a></p>Sequence statusi: Complete.

This entry describes 8 <p>This subsection of the ‘Sequence’ section lists the alternative protein sequences (isoforms) that can be generated from the same gene by a single or by the combination of up to four biological events (alternative promoter usage, alternative splicing, alternative initiation and ribosomal frameshifting). Additionally, this section gives relevant information on each alternative protein isoform.<p><a href='/help/alternative_products' target='_top'>More...</a></p> isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 8 described isoforms and 5 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: O60260-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        10         20         30         40         50
MIVFVRFNSS HGFPVEVDSD TSIFQLKEVV AKRQGVPADQ LRVIFAGKEL
60 70 80 90 100
RNDWTVQNCD LDQQSIVHIV QRPWRKGQEM NATGGDDPRN AAGGCEREPQ
110 120 130 140 150
SLTRVDLSSS VLPGDSVGLA VILHTDSRKD SPPAGSPAGR SIYNSFYVYC
160 170 180 190 200
KGPCQRVQPG KLRVQCSTCR QATLTLTQGP SCWDDVLIPN RMSGECQSPH
210 220 230 240 250
CPGTSAEFFF KCGAHPTSDK ETSVALHLIA TNSRNITCIT CTDVRSPVLV
260 270 280 290 300
FQCNSRHVIC LDCFHLYCVT RLNDRQFVHD PQLGYSLPCV AGCPNSLIKE
310 320 330 340 350
LHHFRILGEE QYNRYQQYGA EECVLQMGGV LCPRPGCGAG LLPEPDQRKV
360 370 380 390 400
TCEGGNGLGC GFAFCRECKE AYHEGECSAV FEASGTTTQA YRVDERAAEQ
410 420 430 440 450
ARWEAASKET IKKTTKPCPR CHVPVEKNGG CMHMKCPQPQ CRLEWCWNCG
460
CEWNRVCMGD HWFDV
Length:465
Mass (Da):51,641
Last modified:October 17, 2006 - v2
<p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.</p> <p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.</p> <p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).</p> <p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x<sup>64</sup> + x<sup>4</sup> + x<sup>3</sup> + x + 1. The algorithm is described in the ISO 3309 standard. </p> <p class="publication">Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.<br /> <strong>Cyclic redundancy and other checksums</strong><br /> <a href="http://www.nrbook.com/b/bookcpdf.php">Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993)</a>)</p> Checksum:i9A8BB802A3FC84C3
GO
Isoform 2 (identifier: O60260-2) [UniParc]FASTAAdd to basket
Also known as: SV5DEL

The sequence of this isoform differs from the canonical sequence as follows:
     179-206: Missing.

Show »
Length:437
Mass (Da):48,713
Checksum:iA435AF6495DED559
GO
Isoform 3 (identifier: O60260-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-79: Missing.
     291-297: AGCPNSL → VCLLPGM
     298-465: Missing.

Show »
Length:218
Mass (Da):23,639
Checksum:i4CB1B7EBD8A25F4B
GO
Isoform 4 (identifier: O60260-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-191: Missing.

Show »
Length:274
Mass (Da):30,616
Checksum:iCAE5D2F530395FA1
GO
Isoform 5 (identifier: O60260-5) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     290-290: V → VGTGDTVVLRGALGGFRRGV
     362-368: FAFCREC → YGQRRTK
     369-465: Missing.

Show »
Length:387
Mass (Da):42,407
Checksum:i48C0F41C86226606
GO
Isoform 6 (identifier: O60260-6) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     58-206: Missing.

Show »
Length:316
Mass (Da):35,631
Checksum:i4AE7F62C46499A24
GO
Isoform 7 (identifier: O60260-7) [UniParc]FASTAAdd to basket
Also known as: SV5,9DEL

The sequence of this isoform differs from the canonical sequence as follows:
     179-206: Missing.
     312-361: Missing.

Show »
Length:387
Mass (Da):43,485
Checksum:i0521F623B06DDDE6
GO
Isoform 8 (identifier: O60260-8) [UniParc]FASTAAdd to basket
Also known as: SV9DEL

The sequence of this isoform differs from the canonical sequence as follows:
     312-361: Missing.

Show »
Length:415
Mass (Da):46,413
Checksum:i0EF24F73366A6454
GO

<p>In eukaryotic reference proteomes, unreviewed entries that are likely to belong to the same gene are computationally mapped, based on gene identifiers from Ensembl, EnsemblGenomes and model organism databases.<p><a href='/help/gene_centric_isoform_mapping' target='_top'>More...</a></p>Computationally mapped potential isoform sequencesi

There are 5 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A0A087X0Z9A0A087X0Z9_HUMAN
RBR-type E3 ubiquitin transferase
PRKN
176Annotation score:

Annotation score:2 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>
A0A087WX46A0A087WX46_HUMAN
E3 ubiquitin-protein ligase parkin
PRKN
74Annotation score:

Annotation score:1 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>
B1AKC3B1AKC3_HUMAN
E3 ubiquitin-protein ligase parkin
PRKN PARK2
368Annotation score:

Annotation score:1 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>
A0A087WU39A0A087WU39_HUMAN
E3 ubiquitin-protein ligase parkin
PRKN
201Annotation score:

Annotation score:1 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>
A0A087X1E2A0A087X1E2_HUMAN
E3 ubiquitin-protein ligase parkin
PRKN
87Annotation score:

Annotation score:1 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 Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Sequence’ section reports difference(s) between the canonical sequence (displayed by default in the entry) and the different sequence submissions merged in the entry. These various submissions may originate from different sequencing projects, different types of experiments, or different biological samples. Sequence conflicts are usually of unknown origin.<p><a href='/help/conflict' target='_top'>More...</a></p>Sequence conflicti223S → P in BAA25751 (PubMed:9560156).Curated1
Sequence conflicti223S → P in AAM21458 (Ref. 3) Curated1
Sequence conflicti223S → P in AAM21457 (Ref. 3) Curated1
Sequence conflicti289 – 290CV → MI in AAM21461 (PubMed:19501131).Curated2
Sequence conflicti339A → V in AAS88422 (Ref. 9) Curated1

Natural variant

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:rs147757966EnsemblClinVar.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_019740100Q → H1 PublicationCorresponds to variant dbSNP:rs1256316516Ensembl.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_019742167S → N4 PublicationsCorresponds to variant dbSNP:rs1801474EnsemblClinVar.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_019749253C → Y in PARK; late onset. 1 Publication