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Validated All-in-One™ qPCR Primer for PRKN(NM_004562.2) Search again
Product ID:
HQP012193
(click here to view gene annotation page)
Powered by BiozSpecies:
Human
Symbol:
Alias:
AR-JP, LPRS2, PARK2, PDJ
Gene Description:
parkin RBR E3 ubiquitin protein ligase
Target Gene Accession:
NM_004562.2(click here to view gene page)
Estimated Delivery:
Approximately 1-3 weeks, but may vary. Please email sales@genecopoeia.com or call 301-762-0888 to confirm ETA.
Important Note:
By default, qPCR primer pairs are designed to measure the expression level of the splice variant (accession number) you selected for this gene WITHOUT consideration of other possible variants of this gene. If this gene has multiple variants, and you would like to measure the expression levels of one particular variant, multiple variants, or all variants, please contact us for a custom service project at inquiry@genecopoeia.com.
Validated result:
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| A | B |
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Each All-in-One™ qPCR Primer is experimentally validated to yield a single dissociation curve peak and to generate a single amplification of the correct size for the targeted gene. A cDNA Pool, containing reverse transcript products of 8 different human tissue total RNA(Liver, Testis,Muscle,Thyroid,Brain,Spleen,Stomach,Small Intestine)),was used as the qPCR validation template. qPCR was performed using 0.2 µM primer with 2XAll-in-One™ qPCR Mix (Catalog#: QP001,QP002,QP004,QP005). Reactions were incubated for 10min. at 95°C, followed by 40 cycles of 95°C for 10 sec.; 60°C, 20 sec. and 72°C, 15sec. using Bio-Rad iQ5™ Instrument. At the end of the last cycle, temperature was increased from 72 to 95°C to produce a melting curve. Panel A: Validated Result for Amplification Curve; Panel B: Validated Result for Melting Curve. |
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Summary
The precise function of this gene is unknown; however, the encoded protein is a component of a multiprotein E3 ubiquitin ligase complex that mediates the targeting of substrate proteins for proteasomal degradation. Mutations in this gene are known to cause Parkinson disease and autosomal recessive juvenile Parkinson disease. Alternative splicing of this gene produces multiple transcript variants encoding distinct isoforms. Additional splice variants of this gene have been described but currently lack transcript support. [provided by RefSeq].
Gene References into function
- cleavage mediated by caspase in apoptosis
- A missense mutation (Arg275Trp) and a duplication of exon 7 of parkin was discovered in a case of early-onset hemiparkinsonism and ipsilateral body hemiatrophy.
- Results suggest that functional parkin proteins may be required during LB formation.
- mutant Parkin in substantia nigra in juvenile parkinsonism may increase oxidative stress and nitric oxide production
- role in Parkinson disease [review]
- Five novel mutations at the parkin locus are reported here consisting of one missense mutation, three exon duplications, and one exon deletion.
- Data confirmed that recessive loss of Parkin is not only a risk factor for juvenile and early onset Parkinsonism but that Parkin haplo-insufficiency may be sufficient for disease in some cases.
- role in pathogenesis of juvenile autosomal dominant Parkinson disease - review
- CHIP is associated with Parkin, a gene responsible for familial Parkinson's disease, and enhances its ubiquitin ligase activity.
- Genetic variation at the PARKIN gene (including promoter polymorphisms) does not contribute to the risk of developing Parkinson's disease in the general population.
- relationship between point mutations on exon 2 of parkin gene and sporadic early-onset Parkinson's disease
- wild-type Parkin aggregates and forms inclusions, which may have implications for the pathogenesis of sporadic PD
- Functional association of the parkin gene promoter with idiopathic Parkinson's disease.
- Loss of striatal dopamine transporters was widespread and bilateral in the patient carrying the Park2 mutation, suggesting a different pattern of denervation in these individuals.
- Autosomal recessive early onset parkinsonism is linked to three loci: PARK2, PARK6, and PARK7.
- Parkin protein overexpression attenuates the accumulation of cyclin E in toxin-treated primary neurons, including midbrain dopamine neurons, and protects them from apoptosis.
- This protein binds the Rpn10 subunit of 26S proteasomes through its ubiquitin-like domain.
- coexpression of Parkin degrades Pael-R and suppresses its toxicity; study implicates Parkin as a central player in the molecular pathway of Parkinson's disease
- Point mutation in parkin gene contributes partly to the development of early-onset Parkinson's disease in Chinese population.
- role for parkin in maintaining dopaminergic neuronal integrity and strengthen the link between autosomal recessive juvenile-onset form of Parkinson's disease and the more common sporadic form of Parkinson's disease (review)
- Caspases responsible for parkin cleavage were identified by several experimental paradigms exploring the anti-Fas induced pathway and tnf-alpha pathway.
- This gene, implicated in autosomal recessive juvenile parkinsonism, is a candidate tumor suppressor gene on chromosome 6q25-q27 in breasssssst asnd ovarian cancers.
- parkinsonism due to mutations in the parkin gene is extremely rare in the US population when the disease begins over the age of 30.
- The identification of pathogenic mutations in the three genes alpha-synuclein, parkin, and UCHL1 has elucidated the ubiquitin proteasome system (UPS) and its potential role as a causal pathway in Parkinson's disease (PD).
- We report a novel heterozygous 40 base pair deletion in exon 3 of the parkin gene that increases the susceptibility of carriers to develop parkinsonism/dystonia and manifests variability in regard to age of onset and phenotype in a single family.
- patients with a single parkin mutation had significantly later and more asymmetrical onset and more frequent levodopa-induced fluctuations and dystonia than patients with two mutations
- parkin interacts with and ubiquitinates synaptotagmin XI
- brain parkin expression is age and species specific
- C-terminal truncations impede parkin folding and reveal a new mechanism for inactivation of parkin.
- RING finger 1 mutations in PARKN produce altered localization of the proteins.
- analysis of Parkin protein expression with antibodies revealed that most of the ovarian cancer cell lines and primary tumors had diminished or absent Parkin expression and it is suggested it may be a tumor suppressor gene
- Two Parkin mutations (C289G and C418R), which replace cysteine residues in the RING domains, decrease the solubility of Parkin in cells. Upon overexpression, the presumably misfolded proteins formed cytoplasmic aggregates.
- Genetics of parkin-linked disease. Review.
- Variants in the regulatory region shared by PARK2 and PACRG therefore act as common risk factors for leprosy
- Review presents evidence for the major role of parkin in vulnerable neurons, i.e., to protect against alpha synuclein toxicity.
- Pael-R is accumulated in Lewy bodies of Parkinson's disease
- Data show that a phylogenetically conserved N-myc binding site in the parkin promoter interacted with myc-family transcription factors, and N-myc bound to the parkin promoter and repressed transcription activity.
- Parkin expression suppresses alpha-synuclein induced toxicity in drosophila.
- The loss of Parkin contributes to the development of hepatocarcinoma.
- Parkin is a tumor suppressor gene whose inactivation may play an important role in non-small cell lung cancer tumorigenesis
- parkin is S-nitrosylated in vitro, as well as in vivo in brains of patients with Parkinson's disease and diffuse Lewy body disease; S-nitrosylation inhibits parkin's ubiquitin E3 ligase activity and its protective function
- ubiquitin, HSP27, parkin, and alpha-synuclein by gamma-glutamyl-epsilon-lysine bonds in Alzheimer's neurofibrillary tangles. Lys(48) is the site of the bond in parkin.
- parkin protects against dopamine toxicity by decreasing oxidative stress and ensuing activation of apoptotic programs.
- Data show both in vitro and in vivo that nitrosative stress leads to S-nitrosylation of wild-type parkin and, initially, to a dramatic increase followed by a decrease in the E3 ligase-ubiquitin-proteasome degradative pathway.
- Causative sequence variants in the parkin gene have not been identified in this cohort of Italian essential tremor patients.
- The parkin may play a role in the peripheral nervous system.
- An autosomal recessive juvenile parkinsonism patient had a homozygous exon 3 deletion in the parkin gene and [alpha]-synuclein-positive inclusions, suggesting a close relationship between ARJP and idiopathic PD.
- Extensive splicing of parkin produces regional and structural diversity and may have important implications for the pathogenetic mechanisms underlying parkinson disease.
- This study shows that Rapid eye movement sleep behavior disorder is frequent in Park2, suggesting that mechanisms other than synuclein deposition can cause Rapid eye movement sleep behavior disorder in neurodegenerative disorders.
- studies suggest that parkin increases dopamine uptake by enhancing the ubiquitination and degradation of misfolded dopamine transporter (DAT)
- complex regulation of the phosphorylation state of parkin may contribute to the unfolded protein response in stressed cells.
- Four N-terminal missense mutations, located within the ubiquitin-like domain, decrease the stability of pathogenic parkin; as a consequence, these mutants are rapidly degraded by the proteasome.
- 41 probands of two carriers had novel heterozygous exon 11 R396G substitutions. One proband had PRKN exon 2 deletion and an exon 7 G284R substitution.
- linkage to six chromosomal regions and have identified three causative genes: PARK1 (alpha-synuclein), PARK2 (parkin), and PARK7 (DJ-1) in Parkinson disease
- and parkin contribute to the assembly of ubiquitin lysine 63-linked multiubiquitin chains
- Parkin is a dual-function ubiquitin ligase. K63-linked ubiquitination of synphilin-1 by parkin may be involved in the formation of Lewy body inclusions associated with Parkinson disease.
- Parkin stabilizes microtubules through strong binding mediated by three independent domains
- Authors suggest that PARK2 functions as a ubiquitin ligase and a mutation would induce ubiquitin-proteasome dysfunction resulting in autosomal recessive juvenile parkinsonism.
- six novel mutations were found in the Parkin gene, and these included five heterozygous point mutations (C441R, Q311H, V258M, C212G, and S193I) and one homozygous deletion (exon 10-12).
- Direct sequencing of parkin did not detect mutations, but semi-quantitative analysis identified a novel exonic rearrangement of exons 2-4. Both patients were homozygous for unique genomic triplications of the parkin gene.
- We confirm that synphilin-1 and parkin are components of majority of LBs in Parkinson's disease and that both proteins are susceptible to proteasomal degradation.
- Our findings indicate that both parkin and alpha-SN share a common pathway in DA metabolism whose abnormality leads to accumulation of oxidative DA metabolites and subsequent cell death.
- Parkin interacts with the proteasome subunit alpha4
- Not all parkin mutations result in loss of parkin's E3 ligase activity, but they all appear to manifest as loss-of-function mutants due to defects in solubility.
- the parkin E4SV splice variant may have a role in sporadic sporadic Parkinson's disease
- The presence of parkin mutations in substantia nigra in Parkinson's disease may increase neuronal vulnerability to a range of toxic insults.
- The polymorphism Ser167Asn in PARKIN gene increases the risk of developing Parkinson's disease and may cause AREP when acting together with hydrargyrism.
- PRKN can be modified by dopamine, the principal transmitter lost in Parkinson disease, suggesting a mechanism for the progressive loss of its function in dopaminergic neurons during aging and sporadic Parkinson disease.
- clinical and laboratory data provide corroborative evidence that some older individuals who have the -258G variant in parkin promotor region may have a higher risk of developing Parkinson's disease
- candidate tumor suppressor genes PARK2 and PACRG are epigenetically regulated in human leukemia, suggesting that abnormal methylation and regulation of PARK2 and PACRG may play a role in the pathogenesis and development of this hematological neoplasm
- the intracellular levels of RanBP2 and its functional activity may be modulated by Parkin-mediated ubiquitination and proteasomal pathways
- pathogenic mutations of Parkin catalyze multiple monoubiquitylation in vitro
- leucine-rich repeat kinase 2 may be involved in a pathogenic pathway with other parkinson's disease (PD) -related proteins such as parkin, which may help illuminate both familial and sporadic PD
- heterozygous mutations in the Parkin gene may act as susceptibility alleles for late-onset forms of Parkinson disease in rare cases
- Parkin is expressed ubiquitously in a variety of cells, localized exclusively to mitochondria in a proliferating condition.
- PRKN suppresses the expression of monoamine oxidases.
- study suggests that complex gene-environment interactions may play a role in the pathogenesis of parkin gene early-onset parkinson's disease
- This study demonstrated corticospinal dysfunction in patient with parkinson disease and suggest that the extent of central nervous system involvement in parkin disease may be wider that hitherto supposed.
- Parkin-positive patients appear to have a greater susceptibility to the exposure to dopaminergic medication than idiopathic Parkinson's disease patients.
- These results suggest that RT-PCR using the patients' fibroblasts may be helpful for the detection of compound heterozygous abnormalities in the parkin gene.
- Overexpression of parkin and ceramide treatment both modulated gene expression
- Mutations were found in 23 families. Among the mutation-positive families, 10 contained compound heterozygotes; 3 homozygotes; and 10 heterozygotes. The onset age in patients with parkin gene mutations ranged from 20 to 76 years.
- Among eastern Indian Parkinson disease patients, mutation in Parkin was identified in 7.24% cases
- Chromosome break at PARK2 is associated with breast cancer
- Our finding provides the evidence for a relationship between parkin and a neurotransmitter receptor, suggesting that parkin may play an important role in synaptic activity.
- R42P mutant retained functional activity in contrast to the W453stop mutant. Accordingly, the functional impairment by the mutations is not simply caused by turning the proteins insoluble.
- PPI screens for parkin, a hereditary Parkinson's disease gene, elucidated the function of parkin as an E3 ubiquitin ligase, with localization regulated by contact with interaction partners, uncovering part of the pathogenesis of Parkinson's disease.
- Possesses anti-apoptotic and anti-oxidant function in neuronal or myogenic cells but not in kidney cells.
- parkin acts as a potent neuroprotective agent in vivo against 6-hydroxydopamine toxic insults
- parkin responsible for Park2 is essential for the formation of Lewy bodies--REVIEW
- Novel mutation, consisting of a deletion of the promoter and exon 1 of parkin (c.1-?_7+?del), in a family compatible with autosomal recessive early onset PD and an isolated case.
- Expression of mutant, but not wild-type human parkin in Drosophila causes age-dependent degeneration of dopaminergic neurons.
- We speculate that reduced expression of normal parkin protein may result in an early manifestation of PD symptoms.
- Study suggests that the parkin promoter -258T/G polymorphism might be a risk factor for late onset PD in Sichuan, China.
- Interacts with and promotes degradation-independent ubiquitylation of IKKgamma/NEMO and TRAF2. Direct link between neuroprotective activity of parkin and ubiquitin signaling in IKK/NF-kappaB pathway.
- analysis of sensitivity of parkin and other cysteine-containing enzymes to stress-induced solubility alterations
- Compound heterozygous mutations (EX 3_6 del and EX 5 del) in the parkin gene were identified in 2 patients with EOPD
- Lack of evidence for association of Parkin promoter polymorphism (PRKN-258) with increased risk of Parkinson's disease.
- These results indicate that induction of parkin by ER stress represents a cell type-specific response.
- These findings suggest that parkin and synphilin-1 isoform expression changes play a significant role in the pathogenesis of LB diseases.
- These findings demonstrate a cell-type dependent functional interaction between parkin and LIMK1 and provide new evidence that links parkin and LIMK1 in the pathogenesis of familial PD.
- Three point mutations were identified in 82 early-onset parkinsonism patients compared with 100 healthy controls. Mutations in intron include IVS1-39 G --> T and IVS9 +18 C --> T. The T1422C mutation was in coding region and resulted in 441 Cys --> Arg.
- Parkin Arg275Trp mutant expression mediates pathogenic outcomes and suggests the interesting possibility that select parkin mutations may directly exert neurotoxicity in vivo.
- The observed features of genotypic distribution by PARK2 marker point to the influence of the considered marker on the incidence of tuberculosis.
- Relative to controls without a mutation, Parkin and PINK1 mutation carriers displayed a bilateral increase in gray matter volume in the putamen and the internal globus pallidus.
- There were significantly more rare heterozygous parkin variants in patients (n = 10) with early-onset PD than in controls. (n = 2).
- Parkin protects against dopamine-induced cell toxicity in dopaminergic SK-N-SH cells.
- Hyperechogenicity of the SN is found in both idiopathic and Parkin-associated PD and larger aSN was associated with an increasing number of mutated alleles in this study.
- Homozygous Ser167 and Val380 are significantly associated with Parkinson's disease.
- the relative abundance of parkin enhances differentiation of noradrenergic phenotypes via a protein kinase A-dependent pathway
- Human parkin but not Parkinson's disease-associated mutants can rescue mitochondrial pathology in human cells like wild-type PTEN induced putative kinase 1 (PINK1).
- document the influence of Parkin on Pink1 subcellular distribution, providing further evidence for a common pathogenic pathway in recessive Parkinson's disease
- a GB1-Ubld fusion protein was characterized by NMR spectroscopy to show that the R42P mutation causes the complete unfolding of the parkin Ubld.
- No patients had mutations of Park2 but there was genetic association for the polymorphism Val380Leu in sporadic and familial PSP.
- data suggest that compound heterozygous mutations (EX 3 and EX 3_4 del) in the parkin gene were the cause of early-onset Parkinson disease in one of the six Caucasian families
- a novel and rare 1 bp insertion/nonsense mutation c1378_1379insG (exon 12) and the entire deletion of exon 7 in early-onset Parkinson's disease.
- accumulation of alpha-synuclein might contribute to the pathogenesis of PD and other Lewy body diseases by promoting alterations in parkin and tubulin solubility
- This study found mutations in PRKN genes. Seven of the studied patients showed pathogenic mutations, in homozygosity or compound heterozygosity for PRKN.
- Contributes to dopaminergic neuroprotection by suppression of apoptotic stress-activated protein kinase pathways.
- A multi-purpose E3 ubiquitin ligase capable of modifying proteins either via attachment of alternatively linked poly-ubiquitin chains or through multiple mono-ubiquitination to achieve alternate biological outcomes.
- analysis of folding of pathogenic Parkin mutants
- Patients with Parkin or PINK1 mutations benefit from subthalamic nucleus deep brain stimulation, but clinical response is not superior to non-mutation carriers and may be limited by more advanced axial motor symptoms at a relatively early disease stage.
- There was no evidence of association between rs9347683 and Parkinson's disease in the early-onset cohort.
- Parkin mutations were identified in 25 probands with PD (10.1%), 18 (72.0%) of whom were heterozygotes.
- PARK2 coding polymorphism Val380Leu might be interacting with environmental factors acting as a disease modifier.
- In this study found two patients carried PRKN mutations (p.G12R heterozygous and p.G430D homozygous) in early onset parkinson disease.
- This study concludes that point mutations and homozygous exon deletions in the parkin gene are not a major cause of PD in the South African population.
- Genotype-phenotype correlation revealed that parkin carriers had features similar to those of non-carrier early onset Parkinson disease patients.
- identified novel mutation in dopa-responsive dystonia is Cys253Phe in parkin gene
- parkin may counteract the alteration of tau metabolism in certain neurodegenerative diseases with tau cytopathy and parkinsonism
- a novel function for Parkin in modulating the expression of Eg5 through the Hsp70-JNK-c-Jun signaling pathway.
- No pathogenic mutations were found in PRKN protein and are not a frequent cause of Parkinson disease in Nigeria.
- Data show that Parkin immunoreactivity is observed in only a small proportion of glial cytoplasmic inclusions in multiple system atrophy inclusions.
- These results demonstrate the biochemical relationship between PINK1, Parkin, and the mitochondria and thereby suggest the possible mechanism of PINK-Parkin-associated PD pathogenesis.
- Carriers of parkin mutations are clinically indistinguishable from other patients with young-onset Parkinson disease (PD) on an individual basis.
- Parkin is recruited selectively to impaired mitochondria and promotes their autophagy.
- The results suggest that HDAC6 acts as a sensor of proteasome inhibition and directs the trafficking of parkin by using different motor proteins.
- Our study demonstrates abnormalities of mitochondrial function and morphology in parkin-mutant patients and provides proof-of-principle data for the usefulness of this new model system as a screen for disease-modifying compounds in parkinsonism.
- The parkin gene in Jordanian families with incidences of young-onset and juvenile parkinsonism shows with an exon 4 deletion segregating mutations with the recessive pattern of inheritance.
- parkin interacts with programmed cell death-2 isoform 1 (PDCD2-1)