Parkin

Summary

Gene Symbol: Parkin
Description: parkin RBR E3 ubiquitin protein ligase
Alias: AR-JP, LPRS2, PARK2, PDJ, E3 ubiquitin-protein ligase parkin, Parkinson disease (autosomal recessive, juvenile) 2, parkin, parkinson juvenile disease protein 2, parkinson protein 2 E3 ubiquitin protein ligase, parkinson protein 2, E3 ubiquitin protein ligase (parkin)
Species: human
Products:     Parkin

Top Publications

  1. Poulogiannis G, McIntyre R, Dimitriadi M, Apps J, Wilson C, Ichimura K, et al. PARK2 deletions occur frequently in sporadic colorectal cancer and accelerate adenoma development in Apc mutant mice. Proc Natl Acad Sci U S A. 2010;107:15145-50 pubmed publisher
    ..genomic hybridization (aCGH) that 33% show DNA copy number (DCN) loss involving PARK2, the gene encoding PARKIN, the E3 ubiquitin ligase whose deficiency is responsible for a form of autosomal recessive juvenile parkinsonism...
  2. Kemeny S, Dery D, Loboda Y, Rovner M, Lev T, Zuri D, et al. Parkin promotes degradation of the mitochondrial pro-apoptotic ARTS protein. PLoS ONE. 2012;7:e38837 pubmed publisher
    ..Dysfunction of the Ubiquitin Proteasome System (UPS) is associated with the pathophysiology of PD. Mutations in Parkin which impair its E3-ligase activity play a major role in the pathogenesis of inherited PD...
  3. Chan N, Salazar A, Pham A, Sweredoski M, Kolawa N, Graham R, et al. Broad activation of the ubiquitin-proteasome system by Parkin is critical for mitophagy. Hum Mol Genet. 2011;20:1726-37 pubmed publisher
    b>Parkin, an E3 ubiquitin ligase implicated in Parkinson's disease, promotes degradation of dysfunctional mitochondria by autophagy...
  4. Lee M, Mata I, Lin C, Tzen K, Lincoln S, Bounds R, et al. Genotype-phenotype correlates in Taiwanese patients with early-onset recessive Parkinsonism. Mov Disord. 2009;24:104-8 pubmed publisher
    We screened for mutations in the PARKIN, DJ-1, and PINK1 genes in a Taiwanese cohort (68 probands; 58 sporadic and 10 familial) with early-onset parkinsonism (EOP, onset <50 years of age)...
  5. Durcan T, Kontogiannea M, Bedard N, Wing S, Fon E. Ataxin-3 deubiquitination is coupled to Parkin ubiquitination via E2 ubiquitin-conjugating enzyme. J Biol Chem. 2012;287:531-41 pubmed publisher
    We reported previously that parkin, a Parkinson disease-associated E3 ubiquitin-ligase interacts with ataxin-3, a deubiquitinating enzyme associated with Machado-Joseph disease...
  6. Wenzel D, Lissounov A, Brzovic P, Klevit R. UBCH7 reactivity profile reveals parkin and HHARI to be RING/HECT hybrids. Nature. 2011;474:105-8 pubmed publisher
    ..lacking lysine reactivity, UBCH7 exhibits activity with the RING-in-between-RING (RBR) family of E3s that includes parkin (also known as PARK2) and human homologue of ariadne (HHARI; also known as ARIH1)...
  7. Müller Rischart A, Pilsl A, Beaudette P, Patra M, Hadian K, Funke M, et al. The E3 ligase parkin maintains mitochondrial integrity by increasing linear ubiquitination of NEMO. Mol Cell. 2013;49:908-21 pubmed publisher
    b>Parkin, a RING-between-RING-type E3 ubiquitin ligase associated with Parkinson's disease, has a wide neuroprotective activity, preventing cell death in various stress paradigms...
  8. Scheuerle A, Wilson K. PARK2 copy number aberrations in two children presenting with autism spectrum disorder: further support of an association and possible evidence for a new microdeletion/microduplication syndrome. Am J Med Genet B Neuropsychiatr Genet. 2011;156B:413-20 pubmed publisher
    Microdeletions of PARK2 have been reported previously in seven patients with autism spectrum disorder. There are no reports of PARK2 microduplications in this population...
  9. Lee J, Nagano Y, Taylor J, Lim K, Yao T. Disease-causing mutations in parkin impair mitochondrial ubiquitination, aggregation, and HDAC6-dependent mitophagy. J Cell Biol. 2010;189:671-9 pubmed publisher
    Mutations in parkin, a ubiquitin ligase, cause early-onset familial Parkinson's disease (AR-JP). How parkin suppresses parkinsonism remains unknown...

More Information

Publications165 found, 100 shown here

  1. Gaweda Walerych K, Safranow K, Jasinska Myga B, Bialecka M, Klodowska Duda G, Rudzinska M, et al. PARK2 variability in Polish Parkinson's disease patients--interaction with mitochondrial haplogroups. Parkinsonism Relat Disord. 2012;18:520-4 pubmed publisher
    ..b>Parkin complexed with mitochondrial transcription factor A (TFAM) binds mtDNA and promotes mitochondrial biogenesis, ..
  2. Liu M, Aneja R, Sun X, Xie S, Wang H, Wu X, et al. Parkin regulates Eg5 expression by Hsp70 ubiquitination-dependent inactivation of c-Jun NH2-terminal kinase. J Biol Chem. 2008;283:35783-8 pubmed publisher
    ..In this study, we present the first evidence that the cellular Eg5 level is down-regulated by Parkin, an E3 ubiquitin ligase well known for its role in the development of Parkinson disease...
  3. Chaugule V, Burchell L, Barber K, Sidhu A, Leslie S, Shaw G, et al. Autoregulation of Parkin activity through its ubiquitin-like domain. EMBO J. 2011;30:2853-67 pubmed publisher
    b>Parkin is an E3-ubiquitin ligase belonging to the RBR (RING-InBetweenRING-RING family), and is involved in the neurodegenerative disorder Parkinson's disease...
  4. Fiesel F, Moussaud Lamodière E, Ando M, Springer W. A specific subset of E2 ubiquitin-conjugating enzymes regulate Parkin activation and mitophagy differently. J Cell Sci. 2014;127:3488-504 pubmed publisher
    Loss-of-function mutations in the genes encoding PINK1 and Parkin (also known as PARK2) are the most common causes of recessive Parkinson's disease...
  5. Geisler S, Vollmer S, Golombek S, Kahle P. The ubiquitin-conjugating enzymes UBE2N, UBE2L3 and UBE2D2/3 are essential for Parkin-dependent mitophagy. J Cell Sci. 2014;127:3280-93 pubmed publisher
    ..are degraded by mitophagy in a process that depends on the Parkinson's disease gene products PINK1 and Parkin. This is accompanied by ubiquitylation of several mitochondrial substrates...
  6. Trempe J, Fon E. Structure and Function of Parkin, PINK1, and DJ-1, the Three Musketeers of Neuroprotection. Front Neurol. 2013;4:38 pubmed publisher
    Autosomal recessive forms of Parkinson's disease are caused by mutations in three genes: Parkin, PINK1, and DJ-1. These genes encode for proteins with distinct enzymatic activities that may work together to confer neuroprotection...
  7. Safadi S, Shaw G. Differential interaction of the E3 ligase parkin with the proteasomal subunit S5a and the endocytic protein Eps15. J Biol Chem. 2010;285:1424-34 pubmed publisher
    b>Parkin is a multidomain E3 ligase associated with autosomal recessive Parkinson disease. The N-terminal ubiquitin-like domain (Ubld) of parkin functions with the S5a proteasomal subunit, positioning substrate proteins for degradation...
  8. Zhang Y, Wang Z, Sun H. Lack of association between p.Ser167Asn variant of Parkin and Parkinson's disease: a meta-analysis of 15 studies involving 2,280 cases and 2,459 controls. Am J Med Genet B Neuropsychiatr Genet. 2012;159B:38-47 pubmed publisher
    Previous clinical trials have evaluated the association between Parkin p.Ser167Asn (c.601G>A) variant and Parkinson's disease (PD) risk. However, the results remain conflicting rather than conclusive...
  9. da Costa C, Sunyach C, Giaime E, West A, Corti O, Brice A, et al. Transcriptional repression of p53 by parkin and impairment by mutations associated with autosomal recessive juvenile Parkinson's disease. Nat Cell Biol. 2009;11:1370-5 pubmed publisher
    Mutations of the ubiquitin ligase parkin account for most autosomal recessive forms of juvenile Parkinson's disease (AR-JP). Several studies have suggested that parkin possesses DNA-binding and transcriptional activity...
  10. Rakovic A, Grünewald A, Seibler P, Ramirez A, Kock N, Orolicki S, et al. Effect of endogenous mutant and wild-type PINK1 on Parkin in fibroblasts from Parkinson disease patients. Hum Mol Genet. 2010;19:3124-37 pubmed publisher
    Mutations in the PTEN-induced putative kinase 1 (PINK1), a mitochondrial serine-threonine kinase, and Parkin, an E3 ubiquitin ligase, are associated with autosomal-recessive forms of Parkinson disease (PD)...
  11. Safadi S, Barber K, Shaw G. Impact of autosomal recessive juvenile Parkinson's disease mutations on the structure and interactions of the parkin ubiquitin-like domain. Biochemistry. 2011;50:2603-10 pubmed publisher
    ..Approximately 50% of all ARJP cases are attributed to mutations in the gene park2, coding for the protein parkin. Parkin is a multidomain E3 ubiquitin ligase with six distinct domains including an N-terminal ubiquitin-like (Ubl)..
  12. McLelland G, Soubannier V, Chen C, McBride H, Fon E. Parkin and PINK1 function in a vesicular trafficking pathway regulating mitochondrial quality control. EMBO J. 2014;33:282-95 pubmed publisher
    Mitochondrial dysfunction has long been associated with Parkinson's disease (PD). Parkin and PINK1, two genes associated with familial PD, have been implicated in the degradation of depolarized mitochondria via autophagy (mitophagy)...
  13. Lonskaya I, Hebron M, Algarzae N, Desforges N, Moussa C. Decreased parkin solubility is associated with impairment of autophagy in the nigrostriatum of sporadic Parkinson's disease. Neuroscience. 2013;232:90-105 pubmed publisher
    ..b>Parkin is an autosomal recessive gene that is mutated in early onset PD...
  14. Mills R, Sim C, Mok S, Mulhern T, Culvenor J, Cheng H. Biochemical aspects of the neuroprotective mechanism of PTEN-induced kinase-1 (PINK1). J Neurochem. 2008;105:18-33 pubmed publisher
    ..The most prominent examples are the E3 ubiquitin ligase Parkin, the mitochondrial protease high temperature requirement serine protease 2 and the mitochondrial chaperone tumor ..
  15. Moro E, Volkmann J, Konig I, Winkler S, Hiller A, Hassin Baer S, et al. Bilateral subthalamic stimulation in Parkin and PINK1 parkinsonism. Neurology. 2008;70:1186-91 pubmed publisher
    ..patients with disease onset at age <or= 45 years and bilateral STN-DBS were screened for mutations in the Parkin gene and PINK1 gene and for the recurrent p.G2019S mutation in the LRRK2 gene...
  16. Joch M, Ase A, Chen C, MacDonald P, Kontogiannea M, Corera A, et al. Parkin-mediated monoubiquitination of the PDZ protein PICK1 regulates the activity of acid-sensing ion channels. Mol Biol Cell. 2007;18:3105-18 pubmed
    Mutations in the parkin gene result in an autosomal recessive juvenile-onset form of Parkinson's disease. As an E3 ubiquitin-ligase, parkin promotes the attachment of ubiquitin onto specific substrate proteins...
  17. Bertolin G, Ferrando Miguel R, Jacoupy M, Traver S, Grenier K, Greene A, et al. The TOMM machinery is a molecular switch in PINK1 and PARK2/PARKIN-dependent mitochondrial clearance. Autophagy. 2013;9:1801-17 pubmed publisher
    Loss-of-function mutations in PARK2/PARKIN and PINK1 cause early-onset autosomal recessive Parkinson disease (PD)...
  18. Choi J, Woo M, Ma H, Kang S, Sung Y, Yong S, et al. Analysis of PARK genes in a Korean cohort of early-onset Parkinson disease. Neurogenetics. 2008;9:263-9 pubmed publisher
    Mutations in five PARK genes (SNCA, PARKIN, DJ-1, PINK1, and LRRK2) are well-established genetic causes of Parkinson disease (PD). Recently, G2385R substitution in LRRK2 has been determined as a susceptibility allele in Asian PD...
  19. Narendra D, Tanaka A, Suen D, Youle R. Parkin-induced mitophagy in the pathogenesis of Parkinson disease. Autophagy. 2009;5:706-8 pubmed
    Knockout of the ubiquitin ligase Parkin, the gene product of the Parkinson associated Park2, leads to loss of mitochondrial integrity and function in Drosophila melanogaster...
  20. Kondapalli C, Kazlauskaite A, Zhang N, Woodroof H, Campbell D, Gourlay R, et al. PINK1 is activated by mitochondrial membrane potential depolarization and stimulates Parkin E3 ligase activity by phosphorylating Serine 65. Open Biol. 2012;2:120080 pubmed publisher
    ..We have discovered that insect PINK1 efficiently phosphorylates only one of these proteins, namely the E3 ligase Parkin. We have mapped the phosphorylation site to a highly conserved residue within the Ubl domain of Parkin at Ser(65)...
  21. Monroy Jaramillo N, Guerrero Camacho J, Rodríguez Violante M, Boll Woehrlen M, Yescas Gomez P, Alonso Vilatela M, et al. Genetic mutations in early-onset Parkinson's disease Mexican patients: molecular testing implications. Am J Med Genet B Neuropsychiatr Genet. 2014;165B:235-44 pubmed publisher
    Mutations in PARK2, PINK1, and DJ-1 have been associated with autosomal recessive early-onset Parkinson's disease...
  22. Vives Bauza C, Zhou C, Huang Y, Cui M, de Vries R, Kim J, et al. PINK1-dependent recruitment of Parkin to mitochondria in mitophagy. Proc Natl Acad Sci U S A. 2010;107:378-83 pubmed publisher
    Phosphatase and tensin homolog (PTEN)-induced putative kinase 1 (PINK1) and PARK2/Parkin mutations cause autosomal recessive forms of Parkinson's disease...
  23. Kim K, Stevens M, Akter M, Rusk S, Huang R, Cohen A, et al. Parkin is a lipid-responsive regulator of fat uptake in mice and mutant human cells. J Clin Invest. 2011;121:3701-12 pubmed publisher
    ..We therefore investigated whether Parkin, an E3 ubiquitin ligase found to be defective in patients with early onset PD, regulates systemic lipid metabolism...
  24. Lonskaya I, Shekoyan A, Hebron M, Desforges N, Algarzae N, Moussa C. Diminished parkin solubility and co-localization with intraneuronal amyloid-? are associated with autophagic defects in Alzheimer's disease. J Alzheimers Dis. 2013;33:231-47 pubmed publisher
    ..Autophagic defects, leading to accumulation of autophagosomes, are recognized in AD. Parkin is an E3 ubiquitin ligase involved in degradation of proteins via autophagy and the proteasome...
  25. Marder K, Tang M, Mejia Santana H, Rosado L, Louis E, Comella C, et al. Predictors of parkin mutations in early-onset Parkinson disease: the consortium on risk for early-onset Parkinson disease study. Arch Neurol. 2010;67:731-8 pubmed publisher
    Mutations in the parkin gene are the most common genetic cause of early-onset Parkinson disease (PD). Results from a multicenter study of patients with PD systematically sampled by age at onset have not been reported to date...
  26. Wong E, Tan J, Wang C, Zhang Z, Tay S, Zaiden N, et al. Relative sensitivity of parkin and other cysteine-containing enzymes to stress-induced solubility alterations. J Biol Chem. 2007;282:12310-8 pubmed
    Loss of parkin function is a predominant cause of familial Parkinsonism. Emerging evidence also suggests that parkin expression variability may confer a risk for sporadic Parkinson disease...
  27. Ros R, Ampuero I, Garcia de Yebenes J. Parkin polymorphisms in progressive supranuclear palsy. J Neurol Sci. 2008;268:176-8 pubmed
    ..Mutations of the Park2 gene cause autosomal recessive parkinsonism with neuropathological findings consistent with neurofibrillary ..
  28. Geisler S, Holmström K, Skujat D, Fiesel F, Rothfuss O, Kahle P, et al. PINK1/Parkin-mediated mitophagy is dependent on VDAC1 and p62/SQSTM1. Nat Cell Biol. 2010;12:119-31 pubmed publisher
    Parkinson's disease is the most common neurodegenerative movement disorder. Mutations in PINK1 and PARKIN are the most frequent causes of recessive Parkinson's disease. However, their molecular contribution to pathogenesis remains unclear...
  29. Van Humbeeck C, Cornelissen T, Hofkens H, Mandemakers W, Gevaert K, De Strooper B, et al. Parkin interacts with Ambra1 to induce mitophagy. J Neurosci. 2011;31:10249-61 pubmed publisher
    Mutations in the gene encoding Parkin are a major cause of recessive Parkinson's disease. Recent work has shown that Parkin translocates from the cytosol to depolarized mitochondria and induces their autophagic removal (mitophagy)...
  30. Bouman L, Schlierf A, Lutz A, Shan J, Deinlein A, Kast J, et al. Parkin is transcriptionally regulated by ATF4: evidence for an interconnection between mitochondrial stress and ER stress. Cell Death Differ. 2011;18:769-82 pubmed publisher
    Loss of parkin function is responsible for the majority of autosomal recessive parkinsonism. Here, we show that parkin is not only a stress-protective, but also a stress-inducible protein...
  31. Okatsu K, Oka T, Iguchi M, Imamura K, Kosako H, Tani N, et al. PINK1 autophosphorylation upon membrane potential dissipation is essential for Parkin recruitment to damaged mitochondria. Nat Commun. 2012;3:1016 pubmed publisher
    ..on the membrane potential (??m)-deficient mitochondria, where it recruits another familial PD gene product, Parkin, to ubiquitylate the damaged mitochondria...
  32. Kamp F, Exner N, Lutz A, Wender N, Hegermann J, Brunner B, et al. Inhibition of mitochondrial fusion by ?-synuclein is rescued by PINK1, Parkin and DJ-1. EMBO J. 2010;29:3571-89 pubmed publisher
    ..Finally, mitochondrial fragmentation induced by expression of ?S is rescued by coexpression of PINK1, parkin or DJ-1 but not the PD-associated mutations PINK1 G309D and parkin ?1-79 or by DJ-1 C106A.
  33. Xiong H, Wang D, Chen L, Choo Y, Ma H, Tang C, et al. Parkin, PINK1, and DJ-1 form a ubiquitin E3 ligase complex promoting unfolded protein degradation. J Clin Invest. 2009;119:650-60 pubmed publisher
    Mutations in PARKIN, pten-induced putative kinase 1 (PINK1), and DJ-1 are individually linked to autosomal recessive early-onset familial forms of Parkinson disease (PD)...
  34. Nuytemans K, Meeus B, Crosiers D, Brouwers N, Goossens D, Engelborghs S, et al. Relative contribution of simple mutations vs. copy number variations in five Parkinson disease genes in the Belgian population. Hum Mutat. 2009;30:1054-61 pubmed publisher
    The relative contribution of simple mutations and copy number variations (CNVs) in SNCA, PARK2, PINK1, PARK7, and LRRK2 to the genetic etiology of Parkinson disease (PD) is still unclear because most studies did not completely analyze ..
  35. Narendra D, Kane L, Hauser D, Fearnley I, Youle R. p62/SQSTM1 is required for Parkin-induced mitochondrial clustering but not mitophagy; VDAC1 is dispensable for both. Autophagy. 2010;6:1090-106 pubmed
    ..We recently demonstrated that the E3 ubiquitin ligase Parkin, which is linked to recessive forms of parkinsonism, causes a dramatic increase in mitophagy and a change in ..
  36. Schlehe J, Lutz A, Pilsl A, Lämmermann K, Grgur K, Henn I, et al. Aberrant folding of pathogenic Parkin mutants: aggregation versus degradation. J Biol Chem. 2008;283:13771-9 pubmed publisher
    Loss-of-function mutations in the Parkin gene (PARK2) are responsible for the majority of autosomal recessive Parkinson disease...
  37. Sha D, Chin L, Li L. Phosphorylation of parkin by Parkinson disease-linked kinase PINK1 activates parkin E3 ligase function and NF-kappaB signaling. Hum Mol Genet. 2010;19:352-63 pubmed publisher
    Mutations in PTEN-induced putative kinase 1 (PINK1) or parkin cause autosomal recessive forms of Parkinson disease (PD), but how these mutations trigger neurodegeneration is poorly understood and the exact functional relationship between ..
  38. Greene A, Grenier K, Aguileta M, Muise S, Farazifard R, Haque M, et al. Mitochondrial processing peptidase regulates PINK1 processing, import and Parkin recruitment. EMBO Rep. 2012;13:378-85 pubmed publisher
    ..depolarization, PINK1 accumulates on the mitochondrial surface where it recruits the PD-linked E3 ubiquitin ligase Parkin from the cytosol, which in turn mediates the autophagic destruction of the dysfunctional organelles...
  39. Sun X, Liu J, Crary J, Malagelada C, Sulzer D, Greene L, et al. ATF4 protects against neuronal death in cellular Parkinson's disease models by maintaining levels of parkin. J Neurosci. 2013;33:2398-407 pubmed publisher
    ..We further show that parkin, a gene associated with autosomal recessive PD, plays a critical role in ATF4-mediated protection...
  40. Fiala O, Pospisilova L, Prochazkova J, Matejckova M, Martasek P, Novakova L, et al. Parkin mutations and phenotypic features in Czech patients with early-onset Parkinson's disease. Neuro Endocrinol Lett. 2010;31:187-92 pubmed
    Mutations in several genes such as parkin can be detected in up to 20% of patients with early-onset Parkinson's disease (EOPD)...
  41. Zhang C, Lin M, Wu R, Wang X, Yang B, Levine A, et al. Parkin, a p53 target gene, mediates the role of p53 in glucose metabolism and the Warburg effect. Proc Natl Acad Sci U S A. 2011;108:16259-64 pubmed publisher
    Regulation of energy metabolism is a novel function of p53 in tumor suppression. Parkin (PARK2), a Parkinson disease-associated gene, is a potential tumor suppressor whose expression is frequently diminished in tumors...
  42. Berwick D, Harvey K. The importance of Wnt signalling for neurodegeneration in Parkinson's disease. Biochem Soc Trans. 2012;40:1123-8 pubmed
    ..This suggests the prospect of targeting Wnt signalling pathways to modify PD progression. ..
  43. Vandiver M, Paul B, Xu R, Karuppagounder S, Rao F, Snowman A, et al. Sulfhydration mediates neuroprotective actions of parkin. Nat Commun. 2013;4:1626 pubmed publisher
    Increases in S-nitrosylation and inactivation of the neuroprotective ubiquitin E3 ligase, parkin, in the brains of patients with Parkinson's disease are thought to be pathogenic and suggest a possible mechanism linking parkin to sporadic ..
  44. Matsuda N, Sato S, Shiba K, Okatsu K, Saisho K, Gautier C, et al. PINK1 stabilized by mitochondrial depolarization recruits Parkin to damaged mitochondria and activates latent Parkin for mitophagy. J Cell Biol. 2010;189:211-21 pubmed publisher
    ..Recent identification of genes linked to familial forms of PD such as Parkin and PINK1 (PTEN-induced putative kinase 1) has revealed that ubiquitylation and mitochondrial integrity are key ..
  45. Sironi F, Primignani P, Zini M, Tunesi S, Ruffmann C, Ricca S, et al. Parkin analysis in early onset Parkinson's disease. Parkinsonism Relat Disord. 2008;14:326-33 pubmed publisher
    We analysed the parkin gene in a large consecutive series (146) of unrelated early onset Parkinson's disease (onset ?40 years of age) patients. Twelve cases (8...
  46. Zhang B, Hu Z, Yin X, Cai M, Zhao G, Liu Z, et al. Mutation analysis of parkin and PINK1 genes in early-onset Parkinson's disease in China. Neurosci Lett. 2010;477:19-22 pubmed publisher
    ..index cases and 3 relatives) with early-onset Parkinson's disease (EOPD) were studied to assess the frequency of parkin and PINK1 gene mutations...
  47. Spratt D, Martinez Torres R, Noh Y, Mercier P, Manczyk N, Barber K, et al. A molecular explanation for the recessive nature of parkin-linked Parkinson's disease. Nat Commun. 2013;4:1983 pubmed publisher
    Mutations in the park2 gene, encoding the RING-inBetweenRING-RING E3 ubiquitin ligase parkin, cause 50% of autosomal recessive juvenile Parkinsonism cases...
  48. Humbert J, Beyer K, Carrato C, Mate J, Ferrer I, Ariza A. Parkin and synphilin-1 isoform expression changes in Lewy body diseases. Neurobiol Dis. 2007;26:681-7 pubmed
    Alternative splicing gives rise to at least seven parkin and eight synphilin-1 isoforms...
  49. Shiba Fukushima K, Imai Y, Yoshida S, Ishihama Y, Kanao T, Sato S, et al. PINK1-mediated phosphorylation of the Parkin ubiquitin-like domain primes mitochondrial translocation of Parkin and regulates mitophagy. Sci Rep. 2012;2:1002 pubmed publisher
    Parkinson's disease genes PINK1 and parkin encode kinase and ubiquitin ligase, respectively. The gene products PINK1 and Parkin are implicated in mitochondrial autophagy, or mitophagy...
  50. Glauser L, Sonnay S, Stafa K, Moore D. Parkin promotes the ubiquitination and degradation of the mitochondrial fusion factor mitofusin 1. J Neurochem. 2011;118:636-45 pubmed publisher
    Mutations in the parkin gene cause early-onset, autosomal recessive Parkinson's disease. Parkin functions as an E3 ubiquitin ligase to mediate the covalent attachment of ubiquitin monomers or linked chains to protein substrates...
  51. Marras C, Klein C, Lang A, Wakutani Y, Moreno D, Sato C, et al. LRRK2 and Parkin mutations in a family with parkinsonism-Lack of genotype-phenotype correlation. Neurobiol Aging. 2010;31:721-2 pubmed publisher
    ..the relationship between age at onset, clinical course and genotype in a family with combined LRRK2 G2019S and Parkin exon 2 deletions...
  52. Witte M, Bol J, Gerritsen W, van der Valk P, Drukarch B, van Horssen J, et al. Parkinson's disease-associated parkin colocalizes with Alzheimer's disease and multiple sclerosis brain lesions. Neurobiol Dis. 2009;36:445-52 pubmed publisher
    b>Parkin is implicated in the pathogenesis of Parkinson's disease. Furthermore, parkin targets misfolded proteins for degradation and protects cells against various forms of cellular stress, including unfolded-protein and oxidative stress...
  53. Tanaka A. Parkin-mediated selective mitochondrial autophagy, mitophagy: Parkin purges damaged organelles from the vital mitochondrial network. FEBS Lett. 2010;584:1386-92 pubmed publisher
    ..Mitochondrial dysfunction is one of the key aspects of the pathobiology of neurodegenerative disease. Parkin, an E3 ligase located in the cytosol and originally discovered as mutated in monogenic forms of Parkinson's ..
  54. Rakovic A, Shurkewitsch K, Seibler P, Grünewald A, Zanon A, Hagenah J, et al. Phosphatase and tensin homolog (PTEN)-induced putative kinase 1 (PINK1)-dependent ubiquitination of endogenous Parkin attenuates mitophagy: study in human primary fibroblasts and induced pluripotent stem cell-derived neurons. J Biol Chem. 2013;288:2223-37 pubmed publisher
    Mutations in the E3 ubiquitin ligase Parkin and the mitochondrial PTEN-induced putative kinase 1 (PINK1) have been identified to cause autosomal recessive forms of familial Parkinson disease, with PINK1 functioning upstream of Parkin in a ..
  55. Koyano F, Okatsu K, Kosako H, Tamura Y, Go E, Kimura M, et al. Ubiquitin is phosphorylated by PINK1 to activate parkin. Nature. 2014;510:162-6 pubmed publisher
    PINK1 (PTEN induced putative kinase 1) and PARKIN (also known as PARK2) have been identified as the causal genes responsible for hereditary recessive early-onset Parkinsonism...
  56. Wang X, Winter D, Ashrafi G, Schlehe J, Wong Y, Selkoe D, et al. PINK1 and Parkin target Miro for phosphorylation and degradation to arrest mitochondrial motility. Cell. 2011;147:893-906 pubmed publisher
    ..We report here that two Parkinson's disease proteins, the Ser/Thr kinase PINK1 and ubiquitin ligase Parkin, participate in this regulation by arresting mitochondrial movement...
  57. Kazlauskaite A, Kelly V, Johnson C, Baillie C, Hastie C, Peggie M, et al. Phosphorylation of Parkin at Serine65 is essential for activation: elaboration of a Miro1 substrate-based assay of Parkin E3 ligase activity. Open Biol. 2014;4:130213 pubmed publisher
    Mutations in PINK1 and Parkin are associated with early-onset Parkinson's disease...
  58. Deng H, Le W, Shahed J, Xie W, Jankovic J. Mutation analysis of the parkin and PINK1 genes in American Caucasian early-onset Parkinson disease families. Neurosci Lett. 2008;430:18-22 pubmed
    Mutations in the parkin gene and the PTEN-induced putative kinase 1 gene (PINK1) have been identified as the most common causes of autosomal recessive early-onset Parkinson disease (EOPD)...
  59. Guo J, Xiao B, Liao B, Zhang X, Nie L, Zhang Y, et al. Mutation analysis of Parkin, PINK1, DJ-1 and ATP13A2 genes in Chinese patients with autosomal recessive early-onset Parkinsonism. Mov Disord. 2008;23:2074-9 pubmed publisher
    Autosomal recessive early-onset Parkinsonism (AREP) has been associated with mutations in the Parkin, PINK1, DJ-1, and ATP13A2 genes...
  60. Kuroda Y, Sako W, Goto S, Sawada T, Uchida D, Izumi Y, et al. Parkin interacts with Klokin1 for mitochondrial import and maintenance of membrane potential. Hum Mol Genet. 2012;21:991-1003 pubmed publisher
    b>Parkin is a multifunctional protein, including maintaining mitochondrial homeostasis. Recent evidence suggests that Parkin is recruited from the cytoplasm to damaged mitochondria with low membrane potential...
  61. Moura K, Junior M, de Rosso A, Nicaretta D, Pereira J, José Silva D, et al. Exon dosage variations in Brazilian patients with Parkinson's disease: analysis of SNCA, PARKIN, PINK1 and DJ-1 genes. Dis Markers. 2012;32:173-8 pubmed publisher
    ..Exon dosage variations account for a high proportion of Parkinson's disease mutations, mainly for PARKIN gene...
  62. Scuderi S, La Cognata V, Drago F, Cavallaro S, D Agata V. Alternative splicing generates different parkin protein isoforms: evidences in human, rat, and mouse brain. Biomed Res Int. 2014;2014:690796 pubmed publisher
    ..b>Parkin deficiency has also been linked to other human pathologies, for example, sporadic Parkinson disease, Alzheimer ..
  63. Hagenah J, Konig I, Becker B, Hilker R, Kasten M, Hedrich K, et al. Substantia nigra hyperechogenicity correlates with clinical status and number of Parkin mutated alleles. J Neurol. 2007;254:1407-13 pubmed
    ..TCS) for (pre)clinical diagnosis of Parkinson's disease (PD) and (2) to examine asymptomatic carriers of Parkin mutations we investigated substantia nigra (SN) hyperechogenicity in PD patients and unaffected subjects with and ..
  64. Kim Y, Park J, Kim S, Song S, Kwon S, Lee S, et al. PINK1 controls mitochondrial localization of Parkin through direct phosphorylation. Biochem Biophys Res Commun. 2008;377:975-80 pubmed publisher
    PTEN-induced putative kinase 1 (PINK1) and Parkin, encoded by their respective genes associated with Parkinson's disease (PD), are linked in a common pathway involved in the protection of mitochondrial integrity and function...
  65. Suen D, Narendra D, Tanaka A, Manfredi G, Youle R. Parkin overexpression selects against a deleterious mtDNA mutation in heteroplasmic cybrid cells. Proc Natl Acad Sci U S A. 2010;107:11835-40 pubmed publisher
    ..The cytosolic E3 ligase, Parkin, commonly mutated in recessive familial parkinsonism, translocates to depolarized mitochondria and induces their ..
  66. Lazarou M, Narendra D, Jin S, Tekle E, Banerjee S, Youle R. PINK1 drives Parkin self-association and HECT-like E3 activity upstream of mitochondrial binding. J Cell Biol. 2013;200:163-72 pubmed publisher
    Genetic studies indicate that the mitochondrial kinase PINK1 and the RING-between-RING E3 ubiquitin ligase Parkin function in the same pathway...
  67. Wauer T, Komander D. Structure of the human Parkin ligase domain in an autoinhibited state. EMBO J. 2013;32:2099-112 pubmed publisher
    Mutations in the protein Parkin are associated with Parkinson's disease (PD), the second most common neurodegenerative disease in men...
  68. Dagda R, Cherra S, Kulich S, Tandon A, Park D, Chu C. Loss of PINK1 function promotes mitophagy through effects on oxidative stress and mitochondrial fission. J Biol Chem. 2009;284:13843-55 pubmed publisher
    ..Autophagy/mitophagy served a protective role in limiting cell death, and overexpressing Parkin further enhanced this protective mitophagic response...
  69. Berger A, Cortese G, Amodeo K, Weihofen A, Letai A, LaVoie M. Parkin selectively alters the intrinsic threshold for mitochondrial cytochrome c release. Hum Mol Genet. 2009;18:4317-28 pubmed publisher
    Autosomal-recessive mutations in the Parkin gene are the second most common cause of familial Parkinson's disease (PD)...
  70. Ding W, Ni H, Li M, Liao Y, Chen X, Stolz D, et al. Nix is critical to two distinct phases of mitophagy, reactive oxygen species-mediated autophagy induction and Parkin-ubiquitin-p62-mediated mitochondrial priming. J Biol Chem. 2010;285:27879-90 pubmed publisher
    ..b>Parkin is a ubiquitin-protein isopeptide ligase able to translocate to the mitochondria that are to be removed...
  71. Okatsu K, Saisho K, Shimanuki M, Nakada K, Shitara H, Sou Y, et al. p62/SQSTM1 cooperates with Parkin for perinuclear clustering of depolarized mitochondria. Genes Cells. 2010;15:887-900 pubmed publisher
    PINK1 and Parkin were first identified as the causal genes responsible for familial forms of early-onset Parkinson's disease (PD), a prevalent neurodegenerative disorder...
  72. Narendra D, Tanaka A, Suen D, Youle R. Parkin is recruited selectively to impaired mitochondria and promotes their autophagy. J Cell Biol. 2008;183:795-803 pubmed publisher
    Loss-of-function mutations in Park2, the gene coding for the ubiquitin ligase Parkin, are a significant cause of early onset Parkinson's disease...
  73. Kao S. Regulation of DNA repair by parkin. Biochem Biophys Res Commun. 2009;382:321-5 pubmed publisher
    Mutation of parkin is one of the most prevalent causes of autosomal recessive Parkinson's disease (PD)...
  74. Chopra R, Ali S, Srivastava A, Aggarwal S, Kumar B, Manvati S, et al. Mapping of PARK2 and PACRG overlapping regulatory region reveals LD structure and functional variants in association with leprosy in unrelated indian population groups. PLoS Genet. 2013;9:e1003578 pubmed publisher
    ..Mapping of the PARK2 and PACRG gene regulatory region with 96 SNPs, with a resolution of 1 SNP per 1 Kb for PARK2 gene regulatory ..
  75. Kane L, Lazarou M, Fogel A, Li Y, Yamano K, Sarraf S, et al. PINK1 phosphorylates ubiquitin to activate Parkin E3 ubiquitin ligase activity. J Cell Biol. 2014;205:143-53 pubmed publisher
    PINK1 kinase activates the E3 ubiquitin ligase Parkin to induce selective autophagy of damaged mitochondria. However, it has been unclear how PINK1 activates and recruits Parkin to mitochondria...
  76. Moszczynska A, Saleh J, Zhang H, Vukusic B, Lee F, Liu F. Parkin disrupts the alpha-synuclein/dopamine transporter interaction: consequences toward dopamine-induced toxicity. J Mol Neurosci. 2007;32:217-27 pubmed
    ..In the present study, we report that parkin, an E2-dependent E3 protein ubiquitin ligase associated with recessive early onset Parkinson's disease, exerts a ..
  77. Exner N, Treske B, Paquet D, Holmström K, Schiesling C, Gispert S, et al. Loss-of-function of human PINK1 results in mitochondrial pathology and can be rescued by parkin. J Neurosci. 2007;27:12413-8 pubmed
    ..Human parkin but not PD-associated mutants could rescue mitochondrial pathology in human cells like wild-type PINK1...
  78. Macedo M, Verbaan D, Fang Y, van Rooden S, Visser M, Anar B, et al. Genotypic and phenotypic characteristics of Dutch patients with early onset Parkinson's disease. Mov Disord. 2009;24:196-203 pubmed publisher
    Early onset Parkinson's disease (EOPD) has been associated with mutations in the Parkin, DJ-1, PINK1, LRRK2, and SNCA genes...
  79. Um J, Stichel Gunkel C, Lübbert H, Lee G, Chung K. Molecular interaction between parkin and PINK1 in mammalian neuronal cells. Mol Cell Neurosci. 2009;40:421-32 pubmed publisher
    ..Mutations in PTEN-induced putative kinase 1 (PINK1) and parkin are linked to early-onset autosomal recessive forms of familial PD...
  80. Limousin N, Konofal E, Karroum E, Lohmann E, Theodorou I, Durr A, et al. Restless legs syndrome, rapid eye movement sleep behavior disorder, and hypersomnia in patients with two parkin mutations. Mov Disord. 2009;24:1970-6 pubmed publisher
    b>Parkin gene mutations cause a juvenile parkinsonism. Patients with these mutations may commonly exhibit REM sleep behaviour disorders, but other sleep problems (insomnia, sleepiness, restless legs syndrome) have not been studied...
  81. Ko H, Lee Y, Shin J, Karuppagounder S, Gadad B, Koleske A, et al. Phosphorylation by the c-Abl protein tyrosine kinase inhibits parkin's ubiquitination and protective function. Proc Natl Acad Sci U S A. 2010;107:16691-6 pubmed publisher
    Mutations in PARK2/Parkin, which encodes a ubiquitin E3 ligase, cause autosomal recessive Parkinson disease (PD)...
  82. Lonskaya I, Hebron M, Desforges N, Franjie A, Moussa C. Tyrosine kinase inhibition increases functional parkin-Beclin-1 interaction and enhances amyloid clearance and cognitive performance. EMBO Mol Med. 2013;5:1247-62 pubmed publisher
    ..Here we show that AD animals have high levels of insoluble parkin and decreased parkin-Beclin-1 interaction, while peripheral administration of TKIs, including Nilotinib and ..
  83. Wang H, Imai Y, Kataoka A, Takahashi R. Cell type-specific upregulation of Parkin in response to ER stress. Antioxid Redox Signal. 2007;9:533-42 pubmed
    b>Parkin is the gene responsible for a familial form of Parkinson's disease (PD) termed autosomal recessive juvenile parkinsonism (AR-JP)/PARK2...
  84. Lu X, Fleming S, Meurers B, Ackerson L, Mortazavi F, Lo V, et al. Bacterial artificial chromosome transgenic mice expressing a truncated mutant parkin exhibit age-dependent hypokinetic motor deficits, dopaminergic neuron degeneration, and accumulation of proteinase K-resistant alpha-synuclein. J Neurosci. 2009;29:1962-76 pubmed publisher
    Recessive mutations in parkin are the most common cause of familial early-onset Parkinson's disease (PD)...
  85. Pankratz N, Kissell D, Pauciulo M, Halter C, Rudolph A, Pfeiffer R, et al. Parkin dosage mutations have greater pathogenicity in familial PD than simple sequence mutations. Neurology. 2009;73:279-86 pubmed publisher
    Mutations in both alleles of parkin have been shown to result in Parkinson disease (PD). However, it is unclear whether haploinsufficiency (presence of a mutation in only 1 of the 2 parkin alleles) increases the risk for PD...
  86. Rakovic A, Grünewald A, Kottwitz J, Brüggemann N, Pramstaller P, Lohmann K, et al. Mutations in PINK1 and Parkin impair ubiquitination of Mitofusins in human fibroblasts. PLoS ONE. 2011;6:e16746 pubmed publisher
    PINK1 and Parkin mutations cause recessive Parkinson's disease (PD)...
  87. Padmaja M, Jayaraman M, Srinivasan A, Srisailapathy C, Ramesh A. PARK2 gene mutations in early onset Parkinson's disease patients of South India. Neurosci Lett. 2012;523:145-7 pubmed publisher
    ..Mutations in PARK2 gene have been implicated to cause autosomal recessive early onset PD...
  88. Zhang Y, Wang Z, Sun H. Meta-analysis of the influence of Parkin p.Asp394Asn variant on the susceptibility of Parkinson's disease. Neurosci Lett. 2012;524:60-4 pubmed publisher
    Parkinson's disease (PD) is one of the most common neurodegenerative disorders. The Parkin p.Asp394Asn variant (c...
  89. Um J, Im E, Lee H, Min B, Yoo L, Yoo J, et al. Parkin directly modulates 26S proteasome activity. J Neurosci. 2010;30:11805-14 pubmed publisher
    ..While proteasome dysfunction is observed in PD, diverse mutations in the parkin gene are linked to early-onset autosomal-recessive forms of familial PD...
  90. Jiang H, Ren Y, Yuen E, Zhong P, Ghaedi M, Hu Z, et al. Parkin controls dopamine utilization in human midbrain dopaminergic neurons derived from induced pluripotent stem cells. Nat Commun. 2012;3:668 pubmed publisher
    ..by the degeneration of nigral dopaminergic (DA) neurons and can be caused by monogenic mutations of genes such as parkin. The lack of phenotype in parkin knockout mice suggests that human nigral DA neurons have unique vulnerabilities...
  91. Moura K, Campos Junior M, de Rosso A, Nicaretta D, Pereira J, Silva D, et al. Genetic analysis of PARK2 and PINK1 genes in Brazilian patients with early-onset Parkinson's disease. Dis Markers. 2013;35:181-5 pubmed publisher
    ..In the present study, we screened mutations in coding regions of PARK2 and PINK1 genes in 136 unrelated Brazilian patients with early-onset Parkinson's disease through automatic ..
  92. Kawajiri S, Saiki S, Sato S, Sato F, Hatano T, Eguchi H, et al. PINK1 is recruited to mitochondria with parkin and associates with LC3 in mitophagy. FEBS Lett. 2010;584:1073-9 pubmed publisher
    ..PINK1 acts upstream of parkin, regulating mitochondrial integrity and functions...