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O60260 (PRKN2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 146. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (8) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
E3 ubiquitin-protein ligase parkin

EC=6.3.2.-
Alternative name(s):
Parkinson juvenile disease protein 2
Short name=Parkinson disease protein 2
Gene names
Name:PARK2
Synonyms:PRKN
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length465 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Functions within a multiprotein E3 ubiquitin ligase complex, catalyzing the covalent attachment of ubiquitin moieties onto substrate proteins, such as BCL2, SYT11, CCNE1, GPR37, STUB1, a 22 kDa O-linked glycosylated isoform ofSNCAIP, SEPT5, ZNF746 and AIMP2. Mediates monoubiquitination as well as 'Lys-48'-linked and 'Lys-63'-linked polyubiquitination of substrates depending on the context. Participates in the removal and/or detoxification of abnormally folded or damaged protein by mediating 'Lys-63'-linked polyubiquitination of misfolded proteins such as PARK7: 'Lys-63'-linked polyubiquitinated misfolded proteins are then recognized by HDAC6, leading to their recruitment to aggresomes, followed by degradation. Mediates 'Lys-63'-linked polyubiquitination of SNCAIP, possibly playing a role in Lewy-body formation. Mediates monoubiquitination of BCL2, thereby acting as a positive regulator of autophagy. Promotes the autophagic degradation of dysfunctional depolarized mitochondria (mitophagy), potentially by the ubiquitination of mitochondrial proteins. Mediates 'Lys-48'-linked polyubiquitination of ZNF746, followed by degradation of ZNF746 by the proteasome; possibly playing a role in the regulation of neuron death. Limits the production of reactive oxygen species (ROS). Regulates cyclin-E during neuronal apoptosis. In collaboration with CHPF isoform 2, may enhance cell viability and protect cells from oxidative stress. Independently of its ubiquitin ligase activity, protects from apoptosis by the transcriptional repression of p53/TP53. May protect neurons against alpha synuclein toxicity, proteasomal dysfunction, GPR37 accumulation, and kainate-induced excitotoxicity. May play a role in controlling neurotransmitter trafficking at the presynaptic terminal and in calcium-dependent exocytosis. May represent a tumor suppressor gene. Ref.11 Ref.12 Ref.21 Ref.23 Ref.25 Ref.27 Ref.28 Ref.32 Ref.33 Ref.34 Ref.35 Ref.37 Ref.38 Ref.39 Ref.40 Ref.41 Ref.42 Ref.44

Enzyme regulation

In the autoinhibited state the side chain of Phe-463 inserts into a hydrophobic groove in RING-0, occluding the ubiquitin acceptor site Cys-431, whereas the REP repressor element binds RING-1 and blocks its E2-binding site By similarity.

Pathway

Protein modification; protein ubiquitination.

Subunit structure

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 PARK2, 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 PARK2 and GPR37, thus facilitating PARK2-mediated GPR37 ubiquitination. HSP70 transiently associates with unfolded GPR37 and inhibits the E3 activity of PARK2, whereas, STUB1 enhances the E3 activity of PARK2 through promotion of dissociation of HSP70 from PARK2-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 PARK2 transport into the mitochondria. Interacts with MFN2 (phosphorylated), promotes PARK2 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. Ref.13 Ref.15 Ref.18 Ref.19 Ref.20 Ref.21 Ref.26 Ref.27 Ref.28 Ref.29 Ref.30 Ref.31 Ref.34 Ref.36 Ref.37 Ref.38 Ref.39 Ref.40 Ref.41 Ref.42 Ref.43 Ref.44 Ref.45

Subcellular location

Cytoplasmcytosol. Nucleus. Endoplasmic reticulum. Mitochondrion. Note: Mainly localizes in the cytosol. Co-localizes with SYT11 in neutrites. Co-localizes with SNCAIP in brainstem Lewy bodies. Mitochondrial localization gradually increases with cellular growth. Also relocates to dysfunctional mitochondria that have lost the mitochondrial membrane potential; recruitment to mitochondria is PINK1-dependent. Ref.2 Ref.10 Ref.16 Ref.31 Ref.32 Ref.33 Ref.37 Ref.38 Ref.41 Ref.42 Ref.44

Tissue specificity

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). Ref.2

Domain

The ubiquitin-like domain binds the PSMD4 subunit of 26S proteasomes. Ref.17 Ref.35

The RING-type 1 zinc finger domain is required to repress p53/TP53 transcription (Ref.35). Ref.17 Ref.35

Post-translational modification

Auto-ubiquitinates in an E2-dependent manner leading to its own degradation. Also polyubiquitinated by RNF41 for proteasomal degradation.

S-nitrosylated. The inhibition of PARK2 ubiquitin E3 ligase activity by S-nitrosylation could contribute to the degenerative process in PD by impairing the ubiquitination of PARK2 substrates.

Involvement in disease

Parkinson disease (PARK) [MIM:168600]: A 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.
Note: 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 (Ref.66 and Ref.67). Ref.1 Ref.12 Ref.15 Ref.16 Ref.19 Ref.35 Ref.37 Ref.38 Ref.39 Ref.46 Ref.48 Ref.50 Ref.52 Ref.54 Ref.55 Ref.56 Ref.57 Ref.58 Ref.60 Ref.61 Ref.62 Ref.63 Ref.64 Ref.65 Ref.66 Ref.67 Ref.69 Ref.70 Ref.71

Parkinson disease 2 (PARK2) [MIM:600116]: A 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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.1 Ref.12 Ref.15 Ref.16 Ref.19 Ref.35 Ref.37 Ref.39 Ref.46 Ref.48 Ref.50 Ref.52 Ref.54 Ref.55 Ref.56 Ref.57 Ref.58 Ref.60 Ref.61 Ref.62 Ref.63 Ref.64 Ref.65 Ref.66 Ref.67 Ref.69 Ref.70 Ref.71

Defects in PARK2 may be involved in the development and/or progression of ovarian cancer.

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.

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 (Ref.40).

Sequence similarities

Belongs to the RBR family. Parkin subfamily.

Contains 1 IBR-type zinc finger.

Contains 3 RING-type zinc fingers.

Contains 1 ubiquitin-like domain.

Ontologies

Keywords
   Biological processAutophagy
Transcription
Transcription regulation
Ubl conjugation pathway
   Cellular componentCytoplasm
Endoplasmic reticulum
Mitochondrion
Nucleus
   Coding sequence diversityAlternative splicing
Polymorphism
   DiseaseDisease mutation
Neurodegeneration
Parkinson disease
Parkinsonism
   DomainRepeat
Zinc-finger
   LigandMetal-binding
Zinc
   Molecular functionLigase
   PTMS-nitrosylation
Ubl conjugation
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processaggresome assembly

Inferred from mutant phenotype PubMed 14645198. Source: BHF-UCL

cell death

Inferred from direct assay Ref.39. Source: UniProtKB

central nervous system development

Traceable author statement Ref.1. Source: ProtInc

mitochondrion degradation

Inferred from mutant phenotype Ref.33Ref.42. Source: UniProtKB

negative regulation of actin filament bundle assembly

Inferred from direct assay PubMed 17512523. Source: BHF-UCL

negative regulation of cell death

Inferred from direct assay PubMed 15603737. Source: BHF-UCL

negative regulation of glucokinase activity

Inferred from direct assay PubMed 24187134. Source: MGI

negative regulation of insulin secretion

Inferred from direct assay PubMed 24187134. Source: MGI

negative regulation of neuron apoptotic process

Inferred from direct assay PubMed 22511790. Source: BHF-UCL

negative regulation of protein phosphorylation

Inferred from direct assay PubMed 17512523. Source: BHF-UCL

negative regulation of release of cytochrome c from mitochondria

Inferred from direct assay PubMed 19880420. Source: BHF-UCL

neuron death

Inferred from direct assay Ref.39. Source: UniProtKB

positive regulation of I-kappaB kinase/NF-kappaB signaling

Inferred from direct assay PubMed 19880420. Source: BHF-UCL

protein K48-linked ubiquitination

Inferred from direct assay Ref.39. Source: UniProtKB

protein K63-linked ubiquitination

Inferred from direct assay Ref.27. Source: UniProtKB

protein autoubiquitination

Inferred from direct assay Ref.27. Source: UniProtKB

protein monoubiquitination

Inferred from direct assay Ref.37. Source: UniProtKB

protein polyubiquitination

Inferred from direct assay Ref.34. Source: UniProtKB

protein ubiquitination

Inferred from mutant phenotype Ref.42. Source: UniProtKB

protein ubiquitination involved in ubiquitin-dependent protein catabolic process

Inferred from direct assay PubMed 17097639. Source: UniProtKB

regulation of autophagy

Inferred from direct assay Ref.37. Source: UniProtKB

regulation of reactive oxygen species metabolic process

Inferred from mutant phenotype Ref.34. Source: UniProtKB

regulation of transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

ubiquitin-dependent protein catabolic process

Inferred from direct assay Ref.39. Source: UniProtKB

   Cellular_componentGolgi apparatus

Inferred from direct assay PubMed 17097639. Source: UniProtKB

aggresome

Inferred from direct assay PubMed 14645198. Source: BHF-UCL

cytoplasm

Inferred from direct assay Ref.39. Source: UniProtKB

cytosol

Inferred from direct assay Ref.33Ref.37Ref.42. Source: UniProtKB

endoplasmic reticulum

Inferred from electronic annotation. Source: UniProtKB-SubCell

mitochondrion

Inferred from direct assay Ref.37Ref.42. Source: UniProtKB

nucleus

Inferred from electronic annotation. Source: UniProtKB-SubCell

perinuclear region of cytoplasm

Inferred from direct assay PubMed 17097639. Source: UniProtKB

ubiquitin ligase complex

Inferred from direct assay Ref.42. Source: UniProtKB

   Molecular_functionPDZ domain binding

Inferred from physical interaction PubMed 17512523. Source: BHF-UCL

chaperone binding

Inferred from physical interaction PubMed 15603737. Source: BHF-UCL

enzyme binding

Inferred from physical interaction. Source: ParkinsonsUK-UCL

identical protein binding

Inferred from physical interaction PubMed 21694720. Source: IntAct

kinase binding

Inferred from physical interaction PubMed 17512523PubMed 19880420. Source: BHF-UCL

protein binding

Inferred from physical interaction Ref.12Ref.15PubMed 12364339Ref.27Ref.29PubMed 17097639Ref.37Ref.39. Source: UniProtKB

protein kinase binding

Inferred from physical interaction Ref.36. Source: UniProtKB

ubiquitin protein ligase binding

Inferred from physical interaction Ref.40. Source: UniProtKB

ubiquitin-protein transferase activity

Inferred from direct assay Ref.27PubMed 17097639Ref.34Ref.37Ref.39. Source: UniProtKB

zinc ion binding

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Alternative products

This entry describes 8 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: O60260-1)

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.
Isoform 2 (identifier: O60260-2)

Also known as: SV5DEL;

The sequence of this isoform differs from the canonical sequence as follows:
     179-206: Missing.
Isoform 3 (identifier: O60260-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-79: Missing.
     291-297: AGCPNSL → VCLLPGM
     298-465: Missing.
Isoform 4 (identifier: O60260-4)

The sequence of this isoform differs from the canonical sequence as follows:
     1-191: Missing.
Isoform 5 (identifier: O60260-5)

The sequence of this isoform differs from the canonical sequence as follows:
     290-290: V → VGTGDTVVLRGALGGFRRGV
     362-368: FAFCREC → YGQRRTK
     369-465: Missing.
Isoform 6 (identifier: O60260-6)

The sequence of this isoform differs from the canonical sequence as follows:
     58-206: Missing.
Isoform 7 (identifier: O60260-7)

Also known as: SV5,9DEL;

The sequence of this isoform differs from the canonical sequence as follows:
     179-206: Missing.
     312-361: Missing.
Isoform 8 (identifier: O60260-8)

Also known as: SV9DEL;

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 465465E3 ubiquitin-protein ligase parkin
PRO_0000058576

Regions

Domain1 – 7676Ubiquitin-like
Zinc finger141 – 22585RING-type 0; atypical
Zinc finger238 – 29356RING-type 1; atypical
Zinc finger313 – 37765IBR-type
Zinc finger418 – 44932RING-type 2
Region204 – 23835SYT11 binding 1
Region257 – 29337SYT11 binding 2
Region378 – 41033REP By similarity

Sites

Active site4311 By similarity

Natural variations

Alternative sequence1 – 191191Missing in isoform 4.
VSP_011705
Alternative sequence1 – 7979Missing in isoform 3.
VSP_011706
Alternative sequence58 – 206149Missing in isoform 6.
VSP_041563
Alternative sequence179 – 20628Missing in isoform 2 and isoform 7.
VSP_011707
Alternative sequence2901V → VGTGDTVVLRGALGGFRRGV in isoform 5.
VSP_011708
Alternative sequence291 – 2977AGCPNSL → VCLLPGM in isoform 3.
VSP_011709
Alternative sequence298 – 465168Missing in isoform 3.
VSP_011710
Alternative sequence312 – 36150Missing in isoform 7 and isoform 8.
VSP_053651
Alternative sequence362 – 3687FAFCREC → YGQRRTK in isoform 5.
VSP_011711
Alternative sequence369 – 46597Missing in isoform 5.
VSP_011712
Natural variant151V → M in PARK2. Ref.63
VAR_019733
Natural variant331R → Q in PARK2. Ref.66
VAR_019734
Natural variant371P → L in PARK2. Ref.60
Corresponds to variant rs148990138 [ dbSNP | Ensembl ].
VAR_019735
Natural variant421R → P in PARK2; induces a conformational change in the PSMD4-binding site of Ubl resulting in impaired proteasomal binding. Ref.12 Ref.16 Ref.64 Ref.69
VAR_019736
Natural variant461A → P in PARK2. Ref.65
VAR_019737
Natural variant561V → E in PARK2. Ref.61
VAR_070078
Natural variant821A → E in PARK2. Ref.56 Ref.58 Ref.66
Corresponds to variant rs55774500 [ dbSNP | Ensembl ].
VAR_019738
Natural variant921A → V in PARK2.
VAR_019739
Natural variant1001Q → H. Ref.68
VAR_019740
Natural variant1611K → N in PARK2; severely compromises the mitochondrial localization; fails to stabilize BCL2; decreased binding to the TP53 promoter; abolishes TP53 transcriptional repression. Ref.35 Ref.37 Ref.50 Ref.54 Ref.70
VAR_019741
Natural variant1671S → N. Ref.50 Ref.51 Ref.53 Ref.67
Corresponds to variant rs1801474 [ dbSNP | Ensembl ].
VAR_019742
Natural variant1921M → L in PARK2; unknown pathological significance. Ref.64
Corresponds to variant rs9456735 [ dbSNP | Ensembl ].
VAR_054107
Natural variant1921M → V in PARK2; unknown pathological significance. Ref.67
Corresponds to variant rs9456735 [ dbSNP | Ensembl ].
VAR_019743
Natural variant2111K → N in PARK2; severely compromises the mitochondrial localization; fails to stabilize BCL2. Ref.54 Ref.62 Ref.67 Ref.70
VAR_019744
Natural variant2111K → R in PARK2. Ref.55
VAR_019745
Natural variant2121C → Y in PARK2. Ref.57 Ref.61
VAR_019746
Natural variant2401T → M in PARK2. Ref.67
VAR_019747
Natural variant2401T → R in PARK2; impairs the ability to ubiquitinate SNCAIP and BCL2; loss of UBE2L3 binding; severely compromises the mitochondrial localization. Ref.12 Ref.15 Ref.16 Ref.37 Ref.48 Ref.70
VAR_019748
Natural variant2531C → Y in PARK; late onset. Ref.66
VAR_019749
Natural variant2561R → 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. Ref.15 Ref.35 Ref.50 Ref.54 Ref.58 Ref.64 Ref.66
Corresponds to variant rs150562946 [ dbSNP | Ensembl ].
VAR_019750
Natural variant2711R → S. Ref.68
VAR_019751
Natural variant2751R → 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. Ref.15 Ref.35 Ref.39 Ref.50 Ref.54 Ref.55 Ref.58 Ref.62 Ref.64 Ref.66 Ref.71
Corresponds to variant rs34424986 [ dbSNP | Ensembl ].
VAR_019752
Natural variant2801D → N in PARK; does not affect PINK-1 dependent localization to depolarized mitochondria. Ref.54 Ref.66 Ref.70
VAR_019753
Natural variant2841G → R in PARK2.
VAR_019754
Natural variant2891C → G in PARK2; fails to ubiquitinate SYT11; loses ability to bind SYT11. Ref.19 Ref.54
Corresponds to variant rs55961220 [ dbSNP | Ensembl ].
VAR_019755
Natural variant3111Q → R in a patient with Parkinson disease; unknown pathological significance. Ref.2
VAR_062672
Natural variant3281G → E in PARK2; does not affect PINK-1 dependent localization to depolarized mitochondria. Ref.54 Ref.58 Ref.70
VAR_019756
Natural variant3341R → C in PARK2. Ref.54
VAR_019757
Natural variant3391A → S. Ref.68
VAR_019758
Natural variant3511T → P in PARK2; impairs folding of IBR domain. Ref.46 Ref.60
VAR_019759
Natural variant3661R → W. Ref.53
Corresponds to variant rs56092260 [ dbSNP | Ensembl ].
VAR_019760
Natural variant3711A → T in a patient with Parkinson disease; unknown pathological significance. Ref.2
VAR_062673
Natural variant3801V → L. Ref.50 Ref.53 Ref.63 Ref.66
Corresponds to variant rs1801582 [ dbSNP | Ensembl ].
VAR_019761
Natural variant3941D → N. Ref.50 Ref.63 Ref.66
Corresponds to variant rs1801334 [ dbSNP | Ensembl ].
VAR_019762
Natural variant4021R → C in PARK2. Ref.69
VAR_070079
Natural variant4151T → N in PARK2; impairs the ability to ubiquitinate SNCAIP; does not affect turnover of CDCRE1; impairs PINK1-dependent localization to dysfunctional depolarized mitochondria. Ref.15 Ref.38 Ref.50 Ref.54 Ref.69
VAR_019763
Natural variant4181C → 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. Ref.19 Ref.35 Ref.69
VAR_070080
Natural variant4301G → D in PARK2; impairs PINK1-dependent localization to dysfunctional depolarized mitochondria; impaired E3 ubiquitin-protein ligase toward ZNF746. Ref.38 Ref.39 Ref.54 Ref.55 Ref.62 Ref.64 Ref.66
VAR_019764
Natural variant4311C → F in PARK2; impaired E3 ubiquitin-protein ligase toward ZNF746 and BCL2. Ref.37 Ref.39 Ref.52
VAR_019765
Natural variant4371P → L in PARK2; impaired E3 ubiquitin-protein ligase toward BCL2. Ref.37 Ref.62 Ref.64 Ref.66 Ref.67
Corresponds to variant rs149953814 [ dbSNP | Ensembl ].
VAR_019766
Natural variant4411C → R in PARK2; decreased binding to the TP53 promoter; abolishes TP53 transcriptional repression. Ref.35 Ref.58
VAR_019767

Experimental info

Mutagenesis3321C → S: Impairs folding of IBR domain. Ref.46
Mutagenesis3371C → A: Impairs the ability to ubiquitinate SNCAIP. Ref.15
Mutagenesis3651C → S: Impairs protein folding. Ref.46
Mutagenesis4211C → A: Impairs the ability of self-ubiquitination and to ubiquitinate SNCAIP. Ref.15 Ref.34
Mutagenesis4311C → A: Impairs the ability to ubiquitinate SNCAIP. Ref.15
Sequence conflict2231S → P in BAA25751. Ref.1
Sequence conflict2231S → P in AAM21458. Ref.3
Sequence conflict2231S → P in AAM21457. Ref.3
Sequence conflict289 – 2902CV → MI in AAM21461. Ref.2
Sequence conflict3391A → V in AAS88422. Ref.9

Secondary structure

................................................................................... 465
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified October 17, 2006. Version 2.
Checksum: 9A8BB802A3FC84C3

FASTA46551,641
        10         20         30         40         50         60 
MIVFVRFNSS HGFPVEVDSD TSIFQLKEVV AKRQGVPADQ LRVIFAGKEL RNDWTVQNCD 

        70         80         90        100        110        120 
LDQQSIVHIV QRPWRKGQEM NATGGDDPRN AAGGCEREPQ SLTRVDLSSS VLPGDSVGLA 

       130        140        150        160        170        180 
VILHTDSRKD SPPAGSPAGR SIYNSFYVYC KGPCQRVQPG KLRVQCSTCR QATLTLTQGP 

       190        200        210        220        230        240 
SCWDDVLIPN RMSGECQSPH CPGTSAEFFF KCGAHPTSDK ETSVALHLIA TNSRNITCIT 

       250        260        270        280        290        300 
CTDVRSPVLV FQCNSRHVIC LDCFHLYCVT RLNDRQFVHD PQLGYSLPCV AGCPNSLIKE 

       310        320        330        340        350        360 
LHHFRILGEE QYNRYQQYGA EECVLQMGGV LCPRPGCGAG LLPEPDQRKV TCEGGNGLGC 

       370        380        390        400        410        420 
GFAFCRECKE AYHEGECSAV FEASGTTTQA YRVDERAAEQ ARWEAASKET IKKTTKPCPR 

       430        440        450        460 
CHVPVEKNGG CMHMKCPQPQ CRLEWCWNCG CEWNRVCMGD HWFDV 

« Hide

Isoform 2 (SV5DEL) [UniParc].

Checksum: A435AF6495DED559
Show »

FASTA43748,713
Isoform 3 [UniParc].

Checksum: 4CB1B7EBD8A25F4B
Show »

FASTA21823,639
Isoform 4 [UniParc].

Checksum: CAE5D2F530395FA1
Show »

FASTA27430,616
Isoform 5 [UniParc].

Checksum: 48C0F41C86226606
Show »

FASTA38742,407
Isoform 6 [UniParc].

Checksum: 4AE7F62C46499A24
Show »

FASTA31635,631
Isoform 7 (SV5,9DEL) [UniParc].

Checksum: 0521F623B06DDDE6
Show »

FASTA38743,485
Isoform 8 (SV9DEL) [UniParc].

Checksum: 0EF24F73366A6454
Show »

FASTA41546,413

References

« Hide 'large scale' references
[1]"Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism."
Kitada T., Asakawa S., Hattori N., Matsumine H., Yamamura Y., Minoshima S., Yokochi M., Mizuno Y., Shimizu N.
Nature 392:605-608(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), INVOLVEMENT IN PARK2.
Tissue: Fetal brain and Skeletal muscle.
[2]"Evidence for the presence of full-length PARK2 mRNA and Parkin protein in human blood."
Kasap M., Akpinar G., Sazci A., Idrisoglu H.A., Vahaboglu H.
Neurosci. Lett. 460:196-200(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION, TISSUE SPECIFICITY, VARIANTS ARG-311 AND THR-371, IDENTIFICATION BY MASS SPECTROMETRY.
[3]"Functional and molecular diversity of parkin."
D'Agata V., Scapagnini G., Cavallaro S.
Submitted (MAY-2001) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 3 AND 4).
[4]"Homo sapiens PARK2 transcript variants."
Campello L., Esteve-Rudd J., Cuenca N., Martin-Nieto J.
Submitted (DEC-2009) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2; 7 AND 8).
Tissue: Retina.
[5]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Testis.
[6]"The DNA sequence and analysis of human chromosome 6."
Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., Andrews T.D. expand/collapse author list , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S.
Nature 425:805-811(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 5).
Tissue: Testis.
[9]Zou H.Q., Chan P.
Submitted (MAR-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 312-361.
[10]"Immunohistochemical and subcellular localization of Parkin protein: absence of protein in autosomal recessive juvenile parkinsonism patients."
Shimura H., Hattori N., Kubo S., Yoshikawa M., Kitada T., Matsumine H., Asakawa S., Minoshima S., Yamamura Y., Shimizu N., Mizuno Y.
Ann. Neurol. 45:668-672(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION.
[11]"Parkin suppresses unfolded protein stress-induced cell death through its E3 ubiquitin-protein ligase activity."
Imai Y., Soda M., Takahashi R.
J. Biol. Chem. 275:35661-35664(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN UBIQUITINATION.
[12]"Familial Parkinson disease gene product, parkin, is a ubiquitin-protein ligase."
Shimura H., Hattori N., Kubo S., Mizuno Y., Asakawa S., Minoshima S., Shimizu N., Iwai K., Chiba T., Tanaka K., Suzuki T.
Nat. Genet. 25:302-305(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, CHARACTERIZATION OF VARIANTS PARK2 PRO-42 AND ARG-240.
[13]"Parkin functions as an E2-dependent ubiquitin-protein ligase and promotes the degradation of the synaptic vesicle-associated protein, CDCrel-1."
Zhang Y., Gao J., Chung K.K.K., Huang H., Dawson V.L., Dawson T.M.
Proc. Natl. Acad. Sci. U.S.A. 97:13354-13359(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH UBE2L6 AND SEPT5, UBIQUITINATION OF SEPT5.
[14]"An unfolded putative transmembrane polypeptide, which can lead to endoplasmic reticulum stress, is a substrate of Parkin."
Imai Y., Soda M., Inoue H., Hattori N., Mizuno Y., Takahashi R.
Cell 105:891-902(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: UBIQUITINATION OF GPR37.
[15]"Parkin ubiquitinates the alpha-synuclein-interacting protein, synphilin-1: implications for Lewy-body formation in Parkinson disease."
Chung K.K.K., Zhang Y., Lim K.L., Tanaka Y., Huang H., Gao J., Ross C.A., Dawson V.L., Dawson T.M.
Nat. Med. 7:1144-1150(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION, UBIQUITINATION OF SNCAIP, CHARACTERIZATION OF VARIANTS PARK2 ARG-240; CYS-256; TRP-275 AND ASN-415, MUTAGENESIS OF CYS-337; CYS-421 AND CYS-431.
[16]"Ubiquitination of a new form of alpha-synuclein by parkin from human brain: implications for Parkinson's disease."
Shimura H., Schlossmacher M.G., Hattori N., Frosch M.P., Trockenbacher A., Schneider R., Mizuno Y., Kosik K.S., Selkoe D.J.
Science 293:263-269(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: UBIQUITINATION OF AN O-GLYCOSYLATED ISOFORM OF SNCAIP, SUBCELLULAR LOCATION, CHARACTERIZATION OF VARIANTS PARK2 PRO-42 AND ARG-240.
[17]"Comparative genomics of the RBR family, including the Parkinson's disease-related gene parkin and the genes of the ariadne subfamily."
Marin I., Ferrus A.
Mol. Biol. Evol. 19:2039-2050(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: PRESENCE OF ATYPICAL RING FINGER DOMAINS.
[18]"CHIP is associated with Parkin, a gene responsible for familial Parkinson's disease, and enhances its ubiquitin ligase activity."
Imai Y., Soda M., Hatakeyama S., Akagi T., Hashikawa T., Nakayama K., Takahashi R.
Mol. Cell 10:55-67(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH STUB1 AND HSP70, UBIQUITINATION OF STUB1.
[19]"The autosomal recessive juvenile Parkinson disease gene product, parkin, interacts with and ubiquitinates synaptotagmin XI."
Huynh D.P., Scoles D.R., Nguyen D., Pulst S.M.
Hum. Mol. Genet. 12:2587-2597(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH SYT11, CHARACTERIZATION OF VARIANTS PARK2 GLY-289 AND ARG-418.
[20]"A product of the human gene adjacent to parkin is a component of Lewy bodies and suppresses Pael receptor-induced cell death."
Imai Y., Soda M., Murakami T., Shoji M., Abe K., Takahashi R.
J. Biol. Chem. 278:51901-51910(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH PACRG.
[21]"Parkin is a component of an SCF-like ubiquitin ligase complex and protects postmitotic neurons from kainate excitotoxicity."
Staropoli J.F., McDermott C., Martinat C., Schulman B., Demireva E., Abeliovich A.
Neuron 37:735-749(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH FBXW7 AND CUL1, UBIQUITINATION OF CYCLIN E.
[22]"Alterations in the common fragile site gene Parkin in ovarian and other cancers."
Denison S.R., Wang F., Becker N.A., Schuele B., Kock N., Phillips L.A., Klein C., Smith D.I.
Oncogene 22:8370-8378(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN CANCER.
[23]"Parkin, a gene implicated in autosomal recessive juvenile parkinsonism, is a candidate tumor suppressor gene on chromosome 6q25-q27."
Cesari R., Martin E.S., Calin G.A., Pentimalli F., Bichi R., McAdams H., Trapasso F., Drusco A., Shimizu M., Masciullo V., D'Andrilli G., Scambia G., Picchio M.C., Alder H., Godwin A.K., Croce C.M.
Proc. Natl. Acad. Sci. U.S.A. 100:5956-5961(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INVOLVEMENT IN CANCER.
[24]"How does parkin ligate ubiquitin to Parkinson's disease?"
Kahle P.J., Haass C.
EMBO Rep. 5:681-685(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
[25]"S-nitrosylation of parkin regulates ubiquitination and compromises parkin's protective function."
Chung K.K.K., Thomas B., Li X., Pletnikova O., Troncoso J.C., Marsh L., Dawson V.L., Dawson T.M.
Science 304:1328-1331(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, UBIQUITINATION, S-NITROSYLATION.
[26]"Parkin interacts with the proteasome subunit alpha4."
Dachsel J.C., Lucking C.B., Deeg S., Schultz E., Lalowski M., Casademunt E., Corti O., Hampe C., Patenge N., Vaupel K., Yamamoto A., Dichgans M., Brice A., Wanker E.E., Kahle P.J., Gasser T.
FEBS Lett. 579:3913-3919(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH PSMA7.
[27]"Parkin mediates nonclassical, proteasomal-independent ubiquitination of synphilin-1: implications for Lewy body formation."
Lim K.L., Chew K.C., Tan J.M., Wang C., Chung K.K., Zhang Y., Tanaka Y., Smith W., Engelender S., Ross C.A., Dawson V.L., Dawson T.M.
J. Neurosci. 25:2002-2009(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH SNCAIP.
[28]"Accumulation of the authentic parkin substrate aminoacyl-tRNA synthetase cofactor, p38/JTV-1, leads to catecholaminergic cell death."
Ko H.S., von Coelln R., Sriram S.R., Kim S.W., Chung K.K.K., Pletnikova O., Troncoso J., Johnson B., Saffary R., Goh E.L., Song H., Park B.-J., Kim M.J., Kim S., Dawson V.L., Dawson T.M.
J. Neurosci. 25:7968-7978(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH AIMP2.
[29]"Leucine-rich repeat kinase 2 (LRRK2) interacts with parkin and mutant LRRK2 induces neuronal degeneration."
Smith W.W., Pei Z., Jiang H., Moore D.J., Liang Y., West A.B., Dawson V.L., Dawson T.M., Ross C.A.
Proc. Natl. Acad. Sci. U.S.A. 102:18676-18681(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH LRRK2.
[30]"Parkin ubiquitinates and promotes the degradation of RanBP2."
Um J.W., Min D.S., Rhim H., Kim J., Paik S.R., Chung K.C.
J. Biol. Chem. 281:3595-3603(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH RANBP2.
[31]"Functional modulation of parkin through physical interaction with SUMO-1."
Um J.W., Chung K.C.
J. Neurosci. Res. 84:1543-1554(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH SUMO1, SUBCELLULAR LOCATION.
[32]"Parkin-mediated K63-linked polyubiquitination targets misfolded DJ-1 to aggresomes via binding to HDAC6."
Olzmann J.A., Li L., Chudaev M.V., Chen J., Perez F.A., Palmiter R.D., Chin L.S.
J. Cell Biol. 178:1025-1038(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION.
[33]"Parkin is recruited selectively to impaired mitochondria and promotes their autophagy."
Narendra D., Tanaka A., Suen D.F., Youle R.J.
J. Cell Biol. 183:795-803(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN MITOCHONDRIAL AUTOPHAGY, SUBCELLULAR LOCATION.
[34]"Parkin is ubiquitinated by Nrdp1 and abrogates Nrdp1-induced oxidative stress."
Yu F., Zhou J.
Neurosci. Lett. 440:4-8(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH RNF41, UBIQUITINATION, MUTAGENESIS OF CYS-421, FUNCTION.
[35]"Transcriptional repression of p53 by parkin and impairment by mutations associated with autosomal recessive juvenile Parkinson's disease."
da Costa C.A., Sunyach C., Giaime E., West A., Corti O., Brice A., Safe S., Abou-Sleiman P.M., Wood N.W., Takahashi H., Goldberg M.S., Shen J., Checler F.
Nat. Cell Biol. 11:1370-1375(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PROTECTION OF APOPTOSIS, CHARACTERIZATION OF VARIANTS PARK2 ASN-161; CYS-256; TRP-275; ARG-418 AND ARG-441, DOMAIN.
[36]"The PINK1/Parkin-mediated mitophagy is compromised by PD-associated mutations."
Geisler S., Holmstrom K.M., Treis A., Skujat D., Weber S.S., Fiesel F.C., Kahle P.J., Springer W.
Autophagy 6:871-878(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH PINK1.
[37]"Parkin mono-ubiquitinates Bcl-2 and regulates autophagy."
Chen D., Gao F., Li B., Wang H., Xu Y., Zhu C., Wang G.
J. Biol. Chem. 285:38214-38223(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH BCL2, SUBCELLULAR LOCATION, CHARACTERIZATION OF VARIANTS PARK2 ASN-161; ARG-240; PHE-431 AND LEU-437.
[38]"PINK1-dependent recruitment of Parkin to mitochondria in mitophagy."
Vives-Bauza C., Zhou C., Huang Y., Cui M., de Vries R.L., Kim J., May J., Tocilescu M.A., Liu W., Ko H.S., Magrane J., Moore D.J., Dawson V.L., Grailhe R., Dawson T.M., Li C., Tieu K., Przedborski S.
Proc. Natl. Acad. Sci. U.S.A. 107:378-383(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN MITOCHONDRIAL AUTOPHAGY, SUBCELLULAR LOCATION, INTERACTION WITH PINK1, CHARACTERIZATION OF VARIANTS PARK ASN-415 AND ASP-430.
[39]"PARIS (ZNF746) repression of PGC-1alpha contributes to neurodegeneration in Parkinson's disease."
Shin J.H., Ko H.S., Kang H., Lee Y., Lee Y.I., Pletinkova O., Troconso J.C., Dawson V.L., Dawson T.M.
Cell 144:689-702(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH ZNF746, CHARACTERIZATION OF VARIANTS PARK2 TRP-275; ASP-430 AND PHE-431.
[40]"UBCH7 reactivity profile reveals parkin and HHARI to be RING/HECT hybrids."
Wenzel D.M., Lissounov A., Brzovic P.S., Klevit R.E.
Nature 474:105-108(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, REACTION MECHANISM, INTERACTION WITH UBE2L3.
[41]"Parkin interacts with Klokin1 for mitochondrial import and maintenance of membrane potential."
Kuroda Y., Sako W., Goto S., Sawada T., Uchida D., Izumi Y., Takahashi T., Kagawa N., Matsumoto M., Matsumoto M., Takahashi R., Kaji R., Mitsui T.
Hum. Mol. Genet. 21:991-1003(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH CHPF, SUBCELLULAR LOCATION.
[42]"The Parkinson's disease-linked proteins Fbxo7 and Parkin interact to mediate mitophagy."
Burchell V.S., Nelson D.E., Sanchez-Martinez A., Delgado-Camprubi M., Ivatt R.M., Pogson J.H., Randle S.J., Wray S., Lewis P.A., Houlden H., Abramov A.Y., Hardy J., Wood N.W., Whitworth A.J., Laman H., Plun-Favreau H.
Nat. Neurosci. 16:1257-1265(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH FBXO7.
[43]"High-content genome-wide RNAi screens identify regulators of parkin upstream of mitophagy."
Hasson S.A., Kane L.A., Yamano K., Huang C.H., Sliter D.A., Buehler E., Wang C., Heman-Ackah S.M., Hessa T., Guha R., Martin S.E., Youle R.J.
Nature 504:291-295(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH BAG4; BAG5; HSPA1L; HSPA1A AND HSPA8.
[44]"PINK1-phosphorylated mitofusin 2 is a Parkin receptor for culling damaged mitochondria."
Chen Y., Dorn G.W. II
Science 340:471-475(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN MITOPHAGY, INTERACTION WITH MFN2, SUBCELLULAR LOCATION.
[45]"Parkin binds the Rpn10 subunit of 26S proteasomes through its ubiquitin-like domain."
Sakata E., Yamaguchi Y., Kurimoto E., Kikuchi J., Yokoyama S., Yamada S., Kawahara H., Yokosawa H., Hattori N., Mizuno Y., Tanaka K., Kato K.
EMBO Rep. 4:301-306(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF 1-76, INTERACTION WITH PSMD4.
[46]"Structure of the Parkin in-between-ring domain provides insights for E3-ligase dysfunction in autosomal recessive Parkinson's disease."
Beasley S.A., Hristova V.A., Shaw G.S.
Proc. Natl. Acad. Sci. U.S.A. 104:3095-3100(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF 307-384 IN COMPLEX WITH ZINC IONS, CHARACTERIZATION OF VARIANT PARK2 PRO-351, MUTAGENESIS OF CYS-332 AND CYS-365, IDENTIFICATION BY MASS SPECTROMETRY.
[47]"Parkin genetics: one model for Parkinson's disease."
Mata I.F., Lockhart P.J., Farrer M.J.
Hum. Mol. Genet. 13:R127-R133(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON VARIANTS.
[48]"Point mutations (Thr240Arg and Gln311Stop) in the Parkin gene."
Hattori N., Matsumine H., Asakawa S., Kitada T., Yoshino H., Elibol B., Brookes A.J., Yamamura Y., Kobayashi T., Wang M., Yoritaka A., Minoshima S., Shimizu N., Mizuno Y.
Biochem. Biophys. Res. Commun. 249:754-758(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PARK2 ARG-240.
[49]Erratum
Hattori N., Matsumine H., Asakawa S., Kitada T., Yoshino H., Elibol B., Brookes A.J., Yamamura Y., Kobayashi T., Wang M., Yoritaka A., Minoshima S., Shimizu N., Mizuno Y.
Biochem. Biophys. Res. Commun. 251:666-666(1998)
[50]"A wide variety of mutations in the parkin gene are responsible for autosomal recessive parkinsonism in Europe."
Abbas N., Luecking C.B., Ricard S., Duerr A., Bonifati V., De Michele G., Bouley S., Vaughan J.R., Gasser T., Marconi R., Broussolle E., Brefel-Courbon C., Harhangi B.S., Oostra B.A., Fabrizio E., Bohme G.A., Pradier L., Wood N.W. expand/collapse author list , Filla A., Meco G., Denefle P., Agid Y., Brice A.
Hum. Mol. Genet. 8:567-574(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS PARK2 ASN-161; CYS-256; TRP-275 AND ASN-415, VARIANTS ASN-167; LEU-380 AND ASN-394.
[51]"Association of codon 167 Ser/Asn heterozygosity in the parkin gene with sporadic Parkinson's disease."
Satoh J., Kuroda Y.
NeuroReport 10:2735-2739(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT ASN-167.
[52]"Novel mutations, pseudo-dominant inheritance, and possible familial affects in patients with autosomal recessive juvenile parkinsonism."
Maruyama M., Ikeuchi T., Saito M., Ishikawa A., Yuasa T., Tanaka H., Hayashi S., Wakabayashi K., Takahashi H., Tsuji S.
Ann. Neurol. 48:245-250(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PARK2 PHE-431.
[53]"Polymorphisms of the parkin gene in sporadic Parkinson's disease among Chinese in Taiwan."
Hu C.-J., Sung S.-M., Liu H.-C., Lee C.-C., Tsai C.-H., Chang J.-G.
Eur. Neurol. 44:90-93(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS ASN-167; TRP-366 AND LEU-380.
[54]"Association between early-onset Parkinson's disease and mutations in the parkin gene."
Luecking C.B., Duerr A., Bonifati V., Vaughan J.R., De Michele G., Gasser T., Harhangi B.S., Meco G., Denefle P., Wood N.W., Agid Y., Brice A.
N. Engl. J. Med. 342:1560-1567(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS PARK2 ASN-161; ASN-211; CYS-256; TRP-275; ASN-280; GLY-289; GLU-328; CYS-334; ASN-415 AND ASP-430.
[55]"Origin of the mutations in the parkin gene in Europe: exon rearrangements are independent recurrent events, whereas point mutations may result from founder effects."
Periquet M., Luecking C.B., Vaughan J.R., Bonifati V., Duerr A., De Michele G., Horstink M., Farrer M., Illarioshkin S.N., Pollak P., Borg M., Brefel-Courbon C., Denefle P., Meco G., Gasser T., Breteler M.M., Wood N.W., Agid Y., Brice A.
Am. J. Hum. Genet. 68:617-626(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS PARK2 ARG-211; TRP-275 AND ASP-430.
[56]"The importance of gene dosage studies: mutational analysis of the parkin gene in early-onset parkinsonism."
Hedrich K., Kann M., Lanthaler A.J., Dalski A., Eskelson C., Landt O., Schwinger E., Vieregge P., Lang A.E., Breakefield X.O., Ozelius L.J., Pramstaller P.P., Klein C.
Hum. Mol. Genet. 10:1649-1656(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PARK2 GLU-82.
[57]"A novel Cys212Tyr founder mutation in parkin and allelic heterogeneity of juvenile parkinsonism in a population from North West Colombia."
Pineda-Trujillo N., Carvajal-Carmona L.G., Buritica O., Moreno S., Uribe C., Pineda D., Toro M., Garcia F., Arias W., Bedoya G., Lopera F., Ruiz-Linares A.
Neurosci. Lett. 298:87-90(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PARK2 TYR-212.
[58]"Complex relationship between parkin mutations and Parkinson disease."
French Parkinson's disease genetics study group, European consortium on genetic susceptibility on Parkinson's disease
West A., Periquet M., Lincoln S., Luecking C.B., Nicholl D., Bonifati V., Rawal N., Gasser T., Lohmann E., Deleuze J.-F., Maraganore D., Levey A., Wood N.W., Duerr A., Hardy J., Brice A., Farrer M.
Am. J. Med. Genet. 114:584-591(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS PARK2 GLU-82; CYS-256; TRP-275; GLU-328 AND ARG-441.
[59]Erratum
French Parkinson's disease genetics study group, European consortium on genetic susceptibility on Parkinson's disease
West A., Periquet M., Lincoln S., Luecking C.B., Nicholl D., Bonifati V., Rawal N., Gasser T., Lohmann E., Deleuze J.-F., Maraganore D., Levey A., Wood N.W., Duerr A., Hardy J., Brice A., Farrer M.J.
Am. J. Med. Genet. 114:992-992(2002)
[60]"Role of parkin mutations in 111 community-based patients with early-onset parkinsonism."
Kann M., Jacobs H., Mohrmann K., Schumacher K., Hedrich K., Garrels J., Wiegers K., Schwinger E., Pramstaller P.P., Breakefield X.O., Ozelius L.J., Vieregge P., Klein C.
Ann. Neurol. 51:621-625(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS PARK2 LEU-37 AND PRO-351.
[61]"Molecular findings in familial Parkinson disease in Spain."
Hoenicka J., Vidal L., Morales B., Ampuero I., Jimenez-Jimenez F.J., Berciano J., del Ser T., Jimenez A., Ruiz P.G., de Yebenes J.G.
Arch. Neurol. 59:966-970(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS PARK2 GLU-56 AND TYR-212.
[62]"Linkage stratification and mutation analysis at the parkin locus identifies mutation positive Parkinson's disease families."
Nichols W.C., Pankratz N., Uniacke S.K., Pauciulo M.W., Halter C., Rudolph A., Conneally P.M., Foroud T.
J. Med. Genet. 39:489-492(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS PARK2 ASN-211; TRP-275; ASP-430 AND LEU-437.
[63]"Relative high frequency of the c.255delA parkin gene mutation in Spanish patients with autosomal recessive parkinsonism."
Munoz E., Tolosa E., Pastor P., Marti M.J., Valldeoriola F., Campdelacreu J., Oliva R.
J. Neurol. Neurosurg. Psych. 73:582-584(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PARK2 MET-15, VARIANTS LEU-380 AND ASN-394.
[64]"Evaluation of 50 probands with early-onset Parkinson's disease for parkin mutations."
Hedrich K., Marder K., Harris J., Kann M., Lynch T., Meija-Santana H., Pramstaller P.P., Schwinger E., Bressman S.B., Fahn S., Klein C.
Neurology 58:1239-1246(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS PARK2 PRO-42; LEU-192; CYS-256; TRP-275; ASP-430 AND LEU-437.
[65]"A new point mutation on exon 2 of parkin gene in Parkinson's disease."
Xu Y., Liu Z., Wang Y., Tao E., Chen G., Chen B.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi 19:409-411(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PARK2 PRO-46.
[66]"Parkin mutations and susceptibility alleles in late-onset Parkinson's disease."
Oliveira S.A., Scott W.K., Martin E.R., Nance M.A., Watts R.L., Hubble J.P., Koller W.C., Pahwa R., Stern M.B., Hiner B.C., Ondo W.G., Allen F.H. Jr., Scott B.L., Goetz C.G., Small G.W., Mastaglia F., Stajich J.M., Zhang F. expand/collapse author list , Booze M.W., Winn M.P., Middleton L.T., Haines J.L., Pericak-Vance M.A., Vance J.M.
Ann. Neurol. 53:624-629(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS PARK2 GLN-33; GLU-82; ASP-430 AND LEU-437, VARIANTS PARK TYR-253; CYS-256; TRP-275 AND ASN-280, VARIANTS LEU-380 AND ASN-394.
[67]"Heterozygosity for a mutation in the parkin gene leads to later onset Parkinson disease."
Foroud T., Uniacke S.K., Liu L., Pankratz N., Rudolph A., Halter C., Shults C., Marder K., Conneally P.M., Nichols W.C.
Neurology 60:796-801(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS PARK2 VAL-192; ASN-211; MET-240 AND LEU-437, VARIANT ASN-167, INVOLVEMENT IN LATE-ONSET PARK.
[68]"Parkin mutations are rare in patients with young-onset parkinsonism in a US population."
Chen R., Gosavi N.S., Langston J.W., Chan P.
Parkinsonism Relat. Disord. 9:309-312(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS HIS-100; SER-271 AND SER-339.
[69]"Novel parkin mutations detected in patients with early-onset Parkinson's disease."
Italian Parkinson Genetics Network
Bertoli-Avella A.M., Giroud-Benitez J.L., Akyol A., Barbosa E., Schaap O., van der Linde H.C., Martignoni E., Lopiano L., Lamberti P., Fincati E., Antonini A., Stocchi F., Montagna P., Squitieri F., Marini P., Abbruzzese G., Fabbrini G., Marconi R. expand/collapse author list , Dalla Libera A., Trianni G., Guidi M., De Gaetano A., Boff Maegawa G., De Leo A., Gallai V., de Rosa G., Vanacore N., Meco G., van Duijn C.M., Oostra B.A., Heutink P., Bonifati V.
Mov. Disord. 20:424-431(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS PARK2 PRO-42; CYS-402; ASN-415 AND ARG-418.
[70]"PINK1 stabilized by mitochondrial depolarization recruits Parkin to damaged mitochondria and activates latent Parkin for mitophagy."
Matsuda N., Sato S., Shiba K., Okatsu K., Saisho K., Gautier C.A., Sou Y.S., Saiki S., Kawajiri S., Sato F., Kimura M., Komatsu M., Hattori N., Tanaka K.
J. Cell Biol. 189:211-221(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION OF VARIANTS PARK2 ASN-161; ASN-211; ARG-240; ASN-280 AND GLU-328.
[71]"Systematic review and UK-based study of PARK2 (parkin), PINK1, PARK7 (DJ-1) and LRRK2 in early-onset Parkinson's disease."
Kilarski L.L., Pearson J.P., Newsway V., Majounie E., Knipe M.D., Misbahuddin A., Chinnery P.F., Burn D.J., Clarke C.E., Marion M.H., Lewthwaite A.J., Nicholl D.J., Wood N.W., Morrison K.E., Williams-Gray C.H., Evans J.R., Sawcer S.J., Barker R.A. expand/collapse author list , Wickremaratchi M.M., Ben-Shlomo Y., Williams N.M., Morris H.R.
Mov. Disord. 27:1522-1529(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PARK2 TRP-275.
+Additional computationally mapped references.

Web resources

Protein Spotlight

Life's tremors - Issue 131 of September 2011

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AB009973 mRNA. Translation: BAA25751.1.
EF375726 mRNA. Translation: ABN46990.1.
AF381282 mRNA. Translation: AAM21457.1.
AF381283 mRNA. Translation: AAM21458.1.
AF381286 mRNA. Translation: AAM21461.1.
GU345839 mRNA. Translation: ADB90270.1.
GU345840 mRNA. Translation: ADB90271.1.
GU361467 mRNA. Translation: ADB91979.1.
AK292590 mRNA. Translation: BAF85279.1.
AL445215 expand/collapse EMBL AC list , AL035697, AL132982, AP000886, AP000887, AP001576, AP001577, AP001578, AP003699 Genomic DNA. Translation: CAH73681.1.
AL035697 expand/collapse EMBL AC list , AL132982, AL445215, AP000886, AP000887, AP001576, AP001577, AP001578, AP003699 Genomic DNA. Translation: CAI21385.1.
AL132982 expand/collapse EMBL AC list , AL035697, AL445215, AP000886, AP000887, AP001576, AP001577, AP001578, AP003699 Genomic DNA. Translation: CAI23601.1.
CH471051 Genomic DNA. Translation: EAW47573.1.
CH471051 Genomic DNA. Translation: EAW47574.1.
BC022014 mRNA. Translation: AAH22014.1.
AY564225 Genomic DNA. Translation: AAS88422.1.
CCDSCCDS5281.1. [O60260-1]
CCDS5282.1. [O60260-2]
CCDS5283.1. [O60260-6]
RefSeqNP_004553.2. NM_004562.2. [O60260-1]
NP_054642.2. NM_013987.2. [O60260-2]
NP_054643.2. NM_013988.2. [O60260-6]
UniGeneHs.132954.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1IYFNMR-A1-76[»]
2JMONMR-A308-384[»]
4BM9X-ray2.25A137-465[»]
4I1FX-ray1.58A141-465[»]
4I1HX-ray2.00A141-465[»]
ProteinModelPortalO60260.
SMRO60260. Positions 1-76, 141-465.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid111105. 381 interactions.
DIPDIP-37655N.
IntActO60260. 21 interactions.
MINTMINT-1351124.
STRING9606.ENSP00000355865.

PTM databases

PhosphoSiteO60260.

Proteomic databases

PaxDbO60260.
PRIDEO60260.

Protocols and materials databases

DNASU5071.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000338468; ENSP00000343589; ENSG00000185345. [O60260-4]
ENST00000366894; ENSP00000355860; ENSG00000185345. [O60260-4]
ENST00000366896; ENSP00000355862; ENSG00000185345. [O60260-6]
ENST00000366897; ENSP00000355863; ENSG00000185345. [O60260-2]
ENST00000366898; ENSP00000355865; ENSG00000185345. [O60260-1]
ENST00000479615; ENSP00000434414; ENSG00000185345. [O60260-3]
GeneID5071.
KEGGhsa:5071.
UCSCuc003qtx.4. human. [O60260-1]
uc010kke.1. human. [O60260-5]

Organism-specific databases

CTD5071.
GeneCardsGC06M161740.
GeneReviewsPARK2.
HGNCHGNC:8607. PARK2.
HPACAB016257.
MIM168600. phenotype.
600116. phenotype.
602544. gene.
neXtProtNX_O60260.
Orphanet2828. Young adult-onset Parkinsonism.
PharmGKBPA32942.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG278133.
HOVERGENHBG053682.
InParanoidO60260.
KOK04556.
OMASTKPCPK.
OrthoDBEOG738054.
PhylomeDBO60260.
TreeFamTF314529.

Enzyme and pathway databases

ReactomeREACT_6900. Immune System.
SignaLinkO60260.
UniPathwayUPA00143.

Gene expression databases

ArrayExpressO60260.
BgeeO60260.
CleanExHS_PARK2.
GenevestigatorO60260.

Family and domain databases

InterProIPR003977. Parkin.
IPR000626. Ubiquitin-like.
IPR029071. Ubiquitin-rel_dom.
IPR002867. Znf_C6HC.
[Graphical view]
PfamPF01485. IBR. 2 hits.
PF00240. ubiquitin. 1 hit.
[Graphical view]
PIRSFPIRSF037880. Parkin. 1 hit.
PRINTSPR01475. PARKIN.
SMARTSM00647. IBR. 2 hits.
SM00213. UBQ. 1 hit.
[Graphical view]
SUPFAMSSF54236. SSF54236. 1 hit.
PROSITEPS50053. UBIQUITIN_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceO60260.
GeneWikiParkin_(ligase).
GenomeRNAi5071.
NextBio19538.
PROO60260.
SOURCESearch...

Entry information

Entry namePRKN2_HUMAN
AccessionPrimary (citable) accession number: O60260
Secondary accession number(s): A3FG77 expand/collapse secondary AC list , A8K975, D3JZW7, D3K2X0, Q5TFV8, Q5VVX4, Q6Q2I6, Q8NI41, Q8NI43, Q8NI44, Q8WW07
Entry history
Integrated into UniProtKB/Swiss-Prot: October 11, 2004
Last sequence update: October 17, 2006
Last modified: July 9, 2014
This is version 146 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Protein Spotlight

Protein Spotlight articles and cited UniProtKB/Swiss-Prot entries

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

PATHWAY comments

Index of metabolic and biosynthesis pathways

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 6

Human chromosome 6: entries, gene names and cross-references to MIM