PRKN Antibody

1. work provides a framework for the mechanisms of parkin's loss-of-function, indicating an interplay between ARJP-associated substitutions and phosphorylation of its Ubl domain. PMID: 29530980
2. Data show that E3 ubiquitin-protein ligase parkin (Parkin) undergoes a conformational change upon phosphorylation. PMID: 28276439
3. carnosic acid induces parkin by enhancing the ubiquitination of ARTS, leading to induction of XIAP. PMID: 28224479
4. PARK2 promoter SNP's rs2276201 and rs9347683 are shown to be significantly associated with the risk of colorectal cancer development PMID: 30296568
5. Increased levels of Parkin are detected in lens epithelial cells exposed to H2O2-oxidative stress. Parkin translocates to mitochondria of lens epithelial cells upon H2O2-oxidative stress exposure. Parkin ubiquitin ligase activity is required for clearance of damaged mitochondria in lens epithelial cells exposed to H2O2-oxidative stress. PMID: 27702626
6. Examined the enzymatic activity of Parkin with M458L mutation. We show that the M458L mutant retains its autoubiquitination potential in vitro but not in cells. M458L mutant fails to protect the mitochondria against hydrogen peroxide, leading to cell death. PMID: 29223129
7. The results demonstrate that Nix can serve as an alternative mediator of mitophagy to maintain mitochondrial turnover, identifying Nix as a promising target for neuroprotective treatment in PINK1/Parkin-related Parkinson's disease. PMID: 28281653
8. Female patients with PARK2 polymorphism had significantly higher risk of VTE recurrence PMID: 29671165
9. Studies indicate a functional PTEN-induced putative kinase 1)(PINK1)/E3 ubiquitin protein ligase (parkin) mitophagy pathway in neurons [Review]. PMID: 29085955
10. indings indicate that PRKN mutations are associated with large global gene expression changes as observed in fibroblasts from PRKN-Parkinson's disease patients PMID: 29501959
11. parkin deficiency induces synaptotagmin-11 accumulation and PD-like neurotoxicity in mouse models, which is reversed by SYT11 knockdown in the SNpc or knockout of SYT11 restricted to dopaminergic neuron PMID: 29311685
12. Parkin expression is inversely correlated with HIF-1alpha expression and metastasis in breast cancer. Results reveal an important mechanism for Parkin in tumor suppression and HIF-1alpha regulation. PMID: 29180628
13. mitochondrial dysfunction activates the PINK1/Parkin signaling and mitophagy in renal tubular epithelial cells under albumin overload condition. PMID: 29494565
14. The authors demonstrate that RABGEF1, the upstream factor of the endosomal Rab GTPase cascade, is recruited to damaged mitochondria via ubiquitin binding downstream of Parkin. RABGEF1 directs the downstream Rab proteins, RAB5 and RAB7A, to damaged mitochondria, whose associations are further regulated by mitochondrial Rab-GAPs. PMID: 29360040
15. DNAJ proteins keep Parkin C289G mutant protein in a soluble, degradation-competent form. PMID: 27713507
16. S-nitrosylated PINK1 decreases Parkin translocation to mitochondrial membranes PMID: 29166608
17. Parkinsonism associated with Parkin gene mutation is one of the most common familial forms of Parkinson Disease, which is characterized by early onset of symptoms, slow progression, elective dopaminergic neuronal loss and the absence of Lewy bodies. PMID: 28523222
18. A transcriptional repressor network including THAP domain containing 11 protein (THAP11) was identified and negatively regulates endogenous PARKIN abundance. PMID: 29269392
19. Study explored the role of parkin proteins in Parkinson's disease (PD) neurodegeneration by analyzing their expression profile in an in vitro model exposed to divers neurotoxins. Results showed that up- or down-regulation of specific splice isoforms may be a direct effect of toxin exposure. Moreover, the isoforms may exert different actions in neurodegeneration via modulation of different molecular pathways. PMID: 28688199
20. Mutations in the PARK2 gene were detected in four of the six tested families with a history of early-onset Parkinson disease. PMID: 28913705
21. This study showed that the heterozygous Parkin mutation carriers show subtle motor abnormalities when a detailed, specialized motor examination is applied and compared to mutation-negative matched control subjects. PMID: 28716427
22. The methylation of SNCA and PARK2 promoter regions were significantly lower in early-onset Parkinson's disease patients compared to control group. Methylation status of the SNCA might be associated with positive family history of Parkinson's disease. PMID: 28830306
23. Show that the C-terminal GTPase of the Parkin primary substrates Miro1 and Miro2 are necessary and sufficient for efficient ubiquitination. We present several new X-ray crystal structures of both Miro1 and Miro2 that reveal substrate recognition and ubiquitin transfer to be specific to particular protein domains and lysine residues. PMID: 27605430
24. This study showed that the manganese exposure among smelters may lead to a reduced expression of PARK2. PMID: 28826884
25. parkin-dependent targeting of misregulated BAX on the mitochondria provides substantial protection against BAX apoptotic activity. PMID: 28760928
26. This study indicated that heterozygous deletions and duplications can play an important role in the pathogenesis of Parkinson's disease and can be considered as dominant mutations with low penetrance. PMID: 27798970
27. Parkin was found to interact with p53; however, this was abolished in Parkin KO mice model, which prevented p53 degradation reducing inflammatory arthritis. PMID: 28395174
28. These findings unveil an important role of Parkin in protecting genome stability through positively regulating translesion DNA synthesis (TLS) upon UV damage, providing a novel mechanistic link between Parkin deficiency and predisposition to skin cancers in PD patients. PMID: 28430587
29. Thus, the present study indicated that parkin knockout inhibits neural stem cell differentiation by JNK-dependent proteasomal degradation of p21. PMID: 28656059
30. Parkin hyper-activation by pUb(S57) demonstrates the first PINK1-independent route to active parkin, revealing the roles of multiple ubiquitin phosphorylation sites in governing parkin stimulation and catalytic activity. PMID: 28689991
31. the results of this study suggest that mutations on specific genes (PARK2 and LRRK2) compromising basal ganglia functioning may be subtly related to language-processing mechanisms. PMID: 28205494
32. This study identified five microRNAs that play a role in the etiology of Parkinson's disease likely by modifying expression of PRKN and additional genes required for normal cellular function. PMID: 27717584
33. MicroRNA-181a has a role in suppressing parkin-mediated mitophagy and sensitizing neuroblastoma cells to mitochondrial uncoupler-induced apoptosis PMID: 27281615
34. Findings suggest that PARK2 might have a tumor suppressor role in the development of chronic obstructive pulmonary disease (COPD) and lung cancer. PMID: 27329585
35. Here we review the evidence supporting PINK1/Parkin mitophagy in vivo and its causative role in neurodegeneration, and outline outstanding questions for future investigations. PMID: 28213158
36. Although PARK2 may be a pathological factor for neurodevelopmental disorders , likely not all variants are pathogenic, and a conclusive assessment of PARK2 variant pathogenicity requires an accurate analysis of their location within the coding region and encoded functional domains. PMID: 27824727
37. VPS35 regulates parkin substrate AIMP2 toxicity by facilitating lysosomal clearance of AIMP2. PMID: 28383562
38. Results show that HERC5 mediates covalent ISG15 conjugation to parkin in mammalian cells and that ISG15 is conjugated to the Lys349 and Lys369 residues of parkin. This ISGylation increases the ubiquitin E3 ligase activity of parkin. Also, some familial Parkinson's disease-associated missense mutations of parkin display defective ISGylation. PMID: 27534820
39. an impaired PINK1-PARK2-mediated neuroimmunology pathway contributes to septic death. PMID: 27754761
40. This work provided strong new evidence that PARK2 participates to the regulatory networks associated with oxidative phosphorylation and suggested that PARK2 genetic variations could act as a trans regulator of OXPHOS gene macrophage expression in humans. PMID: 27558669
41. REVIEW: role of parkin in modulating excitatory and dopaminergic synapse functions PMID: 28335015
42. The effects of variants in the Parkin, PINK1, and DJ-1 genes along with evidence for their pathogenicity have been summarized. (Review) PMID: 26965687
43. Parkin is a potential link between melanoma and Parkinson's disease PMID: 27297116
44. these results unveil a novel functional coupling between Parkin and the CaV2.2 channels. PMID: 28957379
45. These results demonstrate the feasibility of using UbFluor for quantitative studies of the biochemistry of RBR E3s and for high-throughput screening of small-molecule activators or inhibitors of PARKIN and other RBR E3 ligases. PMID: 28710279
46. data suggest that ROS may act as a trigger for the induction of Parkin/PINK1-dependent mitophagy. PMID: 28848050
47. The proportions of some phospholipids and glycosphingolipids were altered in the lipid profiles of parkin-mutant skin fibroblasts obtained from Parkinson disease patients. PMID: 28109117
48. Adipogenic process can be dissected into 3 stages according to the participation of PARL-PINK1-Parkin system. Findings reveal the sequential adipogenic events directed by PARL-PINK1-Parkin system, add more evidence supporting the convergence of pathogenesis leading to neurodegenerative and metabolic disease PMID: 28641777
49. These results highlight the combined effects of Parkin and PGC-1alpha in the maintenance of mitochondrial homeostasis in dopaminergic neurons. These two factors synergistically control the quality and function of mitochondria, which is important for the survival of neurons in Parkinson's disease. PMID: 28053050
50. Data suggest that inactivation of cytosolic parkin in dopaminergic neurons of the substantia nigra contributes to neurodegeneration in sporadic Parkinson disease. [REVIEW] PMID: 28860335
51. we identified a genome-wide significant association involving measures of midface height at 6q26 within an intron of PARK2 PMID: 28441456
52. PARK2 inactivation connects energy and oxidative stress to Akt activation via redox-mediated inactivation of PTEN by S-nitrosylation to support cell survival under conditions of energy deprivation. PMID: 28306514
53. These results suggest that degradation of endogenous APE1 by Parkin occur when cells are stressed to activate Parkin, and imply a role of Parkin in maintaining the quality of APE1, and loss of Parkin may contribute to elevated APE1 levels in glioblastoma. PMID: 27148961
54. Neurodegeneration in Parkinson's patients harboring homozygous loss-of-function mutations in the PARK2 gene may result from unbalanced levels of ROS, which are mostly produced in mitochondria and can irreparably damage macromolecules and trigger apoptosis. PMID: 27374431
55. These findings suggest that insufficient mitophagy-mediated PDGFR/PI3K/AKT activation, which is mainly attributed to reduced PARK2 expression, is a potent underlying mechanism for myofibroblast differentiation and proliferation in fibroblastic foci formation during idiopathic pulmonary fibrosis pathogenesis PMID: 27279371
56. PKA-mediated phosphorylation of MIC60 negatively regulates mitochondrial clearance that is initiated by PINK1 and Parkin. PMID: 27153535
57. Mfn2 downregulation or the exogenous expression of normal Parkin restored cytosolic Ca(2+) transients in fibroblasts from patients with PARK2 mutations, a catalytically inactive Parkinson's disease (PD)-related Parkin variant had no effect. Parkin is directly involved in regulating ER-mitochondria contacts and provide new insight into the role of the loss of Parkin function in PD development PMID: 27206984
58. This study found that Parkin-deficient animals do not accumulate senescent mitochondria in their motor axons or neuromuscular junctions. PMID: 27413149
59. Our study provided sufficient information and insight for investigation of PARK-2 and highlighted its role as a tumor suppressor gene in cervical cancer in North Indian population PMID: 28631565
60. The authors now report the crystal structure of a human Parkin-phosphoubiquitin complex, which shows that phosphoubiquitin binding induces movement in the 'in-between RING' (IBR) domain to reveal a cryptic ubiquitin-binding site. PMID: 28414322
61. These results suggest a previously unidentified role of parkin in mediating endotoxin-induced endothelial proinflammatory signaling and indicate that it may play a critical role in acute inflammation. PMID: 27693468
62. Dopa-responsive dystonia phenotype may have heterogeneous genetic background and may be caused by point mutations or rearrangements in the GCH1 gene as well as in the PARK2 gene. PMID: 27667361
63. study highlights the novel role of parkin in antiviral signaling PMID: 27348524
64. using the mt-mKeima reporter system to monitor mitophagy, we determined that mitophagy is impaired in PARK2 induced pluripotent stem cell (iPSC)-derived dopaminergic neurons in an in vitro model of Parkinson's disease PMID: 28057485
65. Findings may provide new insights into the cause and diagnosis of autosomal recessive juvenile parkinsonism and have implications for genetic counseling. PMID: 27177722
66. Although neither GABARAPs nor LC3s are required for autophagosome biogenesis, loss of all Atg8s yields smaller autophagosomes and a slowed initial rate of autophagosome formation. PMID: 27864321
67. Multicenter, case-control study investigated the prevalence and severity of impulsive-compulsive behaviors (ICBs) in a cohort of patients with parkin-associated Parkinson disease, expanded the parkin-associated phenotypic spectrum demonstrating higher frequency and severity of specific ICBs, and suggesting an association between the parkin genotype, smoking status, and ICB severity PMID: 27590295
68. we discovered that deletions involving the PARK2 gene are significantly anti-correlated with focal amplifications of the gene encoding BCL-XL. PMID: 28038320
69. findings underscore the importance of a mitophagy regulatory network of ATM and PINK1/Parkin and elucidate a novel mechanism by which ATM influences spermidine-induced mitophagy PMID: 27089984
70. miR-17 regulates proliferation and apoptosis in human pulmonary artery smooth muscle cells through MFN2 modulation. PMID: 27640178
71. Parkin is frequently inactivated by promoter methylation, and its mRNA and protein expression correlate with lymph node metastasis and genomic instability. Parkin deficiency probably promotes tumorigenesis in nasopharyngeal carcinoma. PMID: 28351314
72. Study analysed mis-sense mutations spanning the Parkin RING2 and adjoining REP domain to study the structure-function relationship of human Parkin. The mutations except P437L and A379V resulted in protein structure deformation and functional loss of Parkin. PMID: 28189762
73. Association of early onset Parkinson' and severe clinical signs with multiple alterations in PRKN in Turkish patients. PMID: 27455133
74. Parkin is downregulated under hypoxia and that it interferes with HIF expression based on cellular oxygen tension. PMID: 26742768
75. SNP rs10945859 in the PARK2 gene could prove useful in predicting the clinical outcome in HCV-infected patients. PMID: 27740515
76. Patients with Parkin compound heterozygous mutations have relatively preserved olfaction compared to Parkin single heterozygotes and non-carriers PMID: 26626018
77. This study showed that LRRK2, PARK2 and ATP13A2 are under copy number variations influence in patient with Parkinson disease. PMID: 27399248
78. Our results using the multivariate analysis between the additive and dominant model demonstrated that tag SNP rs2803073 of PARK2 is associated with susceptibility to epithelial ovarian cancer (p = 0.018, OR = 0.42). PMID: 27286703
79. Exonic duplication might result in a more severe interference of PARK2 expression and the clinical feature than deletion at the A region (exons 2-4) of the PARK2 locus. PMID: 27042285
80. parkin influences the spatial organization of actin filaments, the shape of human fibroblasts, and their elastic response to an external applied force PMID: 25399302
81. this study results may reveal a unique genetic-environmental interactions contributing to the disease mechanism of a PD patient carrying Ex5del in PARK2 PMID: 26797011
82. Pedigree of Parkinson's disease family indicating consanguineous marriages as well as two sequence variants identified in the Parkin gene PMID: 26860075
83. assessed two sisters with PARK2 early-onset Parkinson's disease confirmed on genetic testing. Both sisters demonstrated a compound heterozygous missense mutation on exon 7 PMID: 26855076
84. Impairment in mitophagy has been proven to be due to diminished PARK2 and insufficient vesicle induction, accumulating depolarized mitochondria and PINK1. PMID: 26721933
85. Ubiquitylation of PKM2 by parkin does not affect its stability but decreases its enzymatic activity. PMID: 26975375
86. Fibroblasts isolated from skin biopsy specimens from patients with genetic forms of Parkinson's disease, carriers of mutations in LRRK2 and PARK2 genes, and from a healthy volunteer were reprogrammed into induced pluripotent stem cells. PMID: 26519280
87. PARK2 mutant neuroprogenitors show increased cytotoxicity with copper (Cu) and cadmium (Cd) exposure, and a substantial increase in mitochondrial fragmentation, initial ROS generation, and loss of mitochondrial membrane potential following Cu exposure. PMID: 25315681
88. These studies provide valuable insight into the roles, and cellular hierarchy, of distinct phosphorylation events in parkin activation, and profiles mutations in Parkinson's patients. PMID: 26928937
89. UBL domain specifically interacts with the R1 domain and negatively regulates Parkin E3 ligase activity. PMID: 26631732
90. A recent report, solving the structure of a Parkin-phosphoubiquitin complex, greatly advances the understanding of the Parkin activation mechanism. PMID: 26259832
91. Study shows that heterozygous carriers of copy number variants affecting exons of PARK2 have greater risk of Parkinson's disease than non-carriers. PMID: 26188007
92. A role was established for Parkin in regulating the endo-lysomal pathway. PMID: 26911690
93. pathogenic PINK1 mutants which are not cleaved by PARL affect PINK1 kinase activity and the ability to induce PARK2-mediated mitophagy. PMID: 26101826
94. Maintenance of appropriate mitochondrial HSD17B10 levels is one of mechanisms by which PARK2 preserves mitochondrial quality. The loss of this protective mechanism may contribute to mitochondrial dysfunction and neuronal degeneration in Parkinson Disease PMID: 25591737
95. Epistatic SNP-SNP interactions involving PARK2 and cytokine genes provide an additive risk towards leprosy susceptibility. PMID: 24578538
96. study reports that ubiquitinPhospho-Ser65 can prime Parkin to be efficiently phosphorylated by PINK1 at Ser65 of its Ubl domain, which in turn leads to maximal activation of Parkin E3 ligase activity PMID: 26116755
97. results are consistent with increased iron load in LRRK2- and Parkin-mutation carriers. The increased R2* in asymptomatic PD-mutation carriers suggests that iron deposition occurs early during the preclinical phase of the disease PMID: 26011561
98. Differential expression of parkin in multiple system atrophy brains was found compared to control and Parkinson's disease brains. PMID: 26465922
99. A comprehensive structural and functional analysis of 21 PARK2 missense mutations distributed across the individual protein domains. The combined approach helped to pinpoint some of the pathogenic mechanisms of individual sequence variants. PMID: 25939424
100. Total of 366 cases were collected from 39 ethnic origins and 96 pathogenic mutations were found. PARK2 gene mutations were found also in some general Parkinson disease patients. The majority (63%) of mutations in PARK2 were restricted to two particular domains (UBL and RING1) of the Parkin protein. PMID: 25907632

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HGNC: 8607

OMIM: 168600

KEGG: hsa:5071

STRING: 9606.ENSP00000355865

UniGene: Hs.132954