Mouse Anti-PRKN Recombinant Antibody (1H4) (CBMAB-A6330-LY)

Mouse

Human, Rat

1H4

IgG3, κ

WB, ELISA

PARK2 (AAH22014, 288 a.a. ~ 387 a.a) partial recombinant protein with GST tag. MW of the GST tag alone is 26 KDa.

Human, Rat

IgG3, κ

Monoclonal

The COA includes recommended starting dilutions, optimal dilutions should be determined by the end user.

Liquid

> 95% Purity determined by SDS-PAGE.

Store at +4°C short term (1-2 weeks). Aliquot and store at -20°C long term. Avoid repeated freezethaw cycles.

Parkin RBR E3 ubiquitin protein ligase

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]

AR-JP; LPRS2; PDJ; PRKN

Functions within a multiprotein E3 ubiquitin ligase complex, catalyzing the covalent attachment of ubiquitin moieties onto substrate proteins (PubMed:10888878, PubMed:10973942, PubMed:11431533, PubMed:12150907, PubMed:12628165, PubMed:15105460, PubMed:16135753, PubMed:21376232, PubMed:21532592, PubMed:23754282, PubMed:23620051, PubMed:24660806, PubMed:24751536, PubMed:32047033, PubMed:29311685, PubMed:22396657).
Substrates include SYT11 and VDAC1 (PubMed:32047033, PubMed:29311685).
Other substrates are BCL2, CCNE1, GPR37, RHOT1/MIRO1, MFN1, MFN2, STUB1, SNCAIP, SEPTIN5, TOMM20, USP30, ZNF746, MIRO1 and AIMP2 (PubMed:10888878, PubMed:10973942, PubMed:11431533, PubMed:12150907, PubMed:12628165, PubMed:15105460, PubMed:16135753, PubMed:21376232, PubMed:21532592, PubMed:23754282, PubMed:23620051, PubMed:24660806, PubMed:24751536, PubMed:22396657).
Mediates monoubiquitination as well as 'Lys-6', 'Lys-11', 'Lys-48'-linked and 'Lys-63'-linked polyubiquitination of substrates depending on the context (PubMed:19229105, PubMed:20889974, PubMed:25621951, PubMed:32047033, PubMed:25474007).
Participates in the removal and/or detoxification of abnormally folded or damaged protein by mediating 'Lys-63'-linked polyubiquitination of misfolded proteins such as PARK7: 'Lys-63'-linked polyubiquitinated misfolded proteins are then recognized by HDAC6, leading to their recruitment to aggresomes, followed by degradation (PubMed:17846173, PubMed:19229105).
Mediates 'Lys-63'-linked polyubiquitination of a 22 kDa O-linked glycosylated isoform of SNCAIP, possibly playing a role in Lewy-body formation (PubMed:11431533, PubMed:11590439, PubMed:15105460, PubMed:19229105, PubMed:15728840).
Mediates monoubiquitination of BCL2, thereby acting as a positive regulator of autophagy (PubMed:20889974).
Protects against mitochondrial dysfunction during cellular stress, by acting downstream of PINK1 to coordinate mitochondrial quality control mechanisms that remove and replace dysfunctional mitochondrial components (PubMed:32047033, PubMed:19029340, PubMed:19966284, PubMed:23620051, PubMed:24896179, PubMed:25527291, PubMed:18957282, PubMed:21376232, PubMed:22396657, PubMed:24660806, PubMed:25474007, PubMed:24784582, PubMed:11439185, PubMed:22082830, PubMed:23933751).
Depending on the severity of mitochondrial damage and/or dysfunction, activity ranges from preventing apoptosis and stimulating mitochondrial biogenesis to regulating mitochondrial dynamics and eliminating severely damaged mitochondria via mitophagy (PubMed:32047033, PubMed:19029340, PubMed:19801972, PubMed:19966284, PubMed:23620051, PubMed:24896179, PubMed:25527291, PubMed:21376232, PubMed:22396657, PubMed:11439185, PubMed:22082830, PubMed:23933751, PubMed:33499712).
Activation and recruitment onto the outer membrane of damaged/dysfunctional mitochondria (OMM) requires PINK1-mediated phosphorylation of both PRKN and ubiquitin (PubMed:24660806, PubMed:25474007, PubMed:24784582, PubMed:25527291).
After mitochondrial damage, functions with PINK1 to mediate the decision between mitophagy or preventing apoptosis by inducing either the poly- or monoubiquitination of VDAC1, respectively; polyubiquitination of VDAC1 promotes mitophagy, while monoubiquitination of VDAC1 decreases mitochondrial calcium influx which ultimately inhibits apoptosis (PubMed:32047033).
When cellular stress results in irreversible mitochondrial damage, promotes the autophagic degradation of dysfunctional depolarized mitochondria (mitophagy) by promoting the ubiquitination of mitochondrial proteins such as TOMM20, RHOT1/MIRO1, MFN1 and USP30 (PubMed:19029340, PubMed:19966284, PubMed:21753002, PubMed:23620051, PubMed:24896179, PubMed:25527291, PubMed:22396657, PubMed:23933751).
Preferentially assembles 'Lys-6'-, 'Lys-11'- and 'Lys-63'-linked polyubiquitin chains, leading to mitophagy (PubMed:25621951, PubMed:32047033).
The PINK1-PRKN pathway also promotes fission of damaged mitochondria by PINK1-mediated phosphorylation which promotes the PRKN-dependent degradation of mitochondrial proteins involved in fission such as MFN2 (PubMed:23620051).
This prevents the refusion of unhealthy mitochondria with the mitochondrial network or initiates mitochondrial fragmentation facilitating their later engulfment by autophagosomes (PubMed:23620051).
Regulates motility of damaged mitochondria via the ubiquitination and subsequent degradation of MIRO1 and MIRO2; in motor neurons, this likely inhibits mitochondrial intracellular anterograde transport along the axons which probably increases the chance of the mitochondria undergoing mitophagy in the soma (PubMed:22396657).
Involved in mitochondrial biogenesis via the 'Lys-48'-linked polyubiquitination of transcriptional repressor ZNF746/PARIS which leads to its subsequent proteasomal degradation and allows activation of the transcription factor PPARGC1A (PubMed:21376232).
Limits the production of reactive oxygen species (ROS) (PubMed:18541373).
Regulates cyclin-E during neuronal apoptosis (PubMed:12628165).
In collaboration with CHPF isoform 2, may enhance cell viability and protect cells from oxidative stress (PubMed:22082830).
Independently of its ubiquitin ligase activity, protects from apoptosis by the transcriptional repression of p53/TP53 (PubMed:19801972).
May protect neurons against alpha synuclein toxicity, proteasomal dysfunction, GPR37 accumulation, and kainate-induced excitotoxicity (PubMed:11439185).
May play a role in controlling neurotransmitter trafficking at the presynaptic terminal and in calcium-dependent exocytosis. May represent a tumor suppressor gene (PubMed:12719539).

Adult locomotory behaviorISS:ParkinsonsUK-UCL
Aggresome assemblyManual Assertion Based On ExperimentIMP:BHF-UCL
Amyloid fibril formationTAS:Reactome
Autophagy of mitochondrionManual Assertion Based On ExperimentIDA:UniProtKB
Cellular response to dopamineManual Assertion Based On ExperimentTAS:ParkinsonsUK-UCL
Cellular response to manganese ionManual Assertion Based On ExperimentTAS:ParkinsonsUK-UCL
Cellular response to toxic substanceManual Assertion Based On ExperimentIMP:ParkinsonsUK-UCL
Cellular response to unfolded proteinManual Assertion Based On ExperimentTAS:ParkinsonsUK-UCL
Central nervous system developmentManual Assertion Based On ExperimentTAS:ProtInc
Dopamine metabolic processManual Assertion Based On ExperimentTAS:ParkinsonsUK-UCL
Dopamine uptake involved in synaptic transmissionIEA:Ensembl
ERAD pathway1 PublicationNAS:ParkinsonsUK-UCL
Free ubiquitin chain polymerizationManual Assertion Based On ExperimentIMP:ParkinsonsUK-UCL
LearningIEA:Ensembl
MacroautophagyTAS:Reactome
Mitochondrial fissionISS:ParkinsonsUK-UCL
Mitochondrion organizationISS:ParkinsonsUK-UCL
Mitochondrion to lysosome transportManual Assertion Based On ExperimentIDA:ParkinsonsUK-UCL
MitophagyManual Assertion Based On ExperimentIDA:UniProtKB
Negative regulation by host of viral genome replicationManual Assertion Based On ExperimentIDA:AgBase
Negative regulation of actin filament bundle assemblyManual Assertion Based On ExperimentIDA:BHF-UCL
Negative regulation of canonical Wnt signaling pathwayManual Assertion Based On ExperimentIDA:ParkinsonsUK-UCL
Negative regulation of cell deathManual Assertion Based On ExperimentIDA:BHF-UCL
Negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathwayManual Assertion Based On ExperimentIDA:ParkinsonsUK-UCL
Negative regulation of endoplasmic reticulum stress-induced neuron intrinsic apoptotic signaling pathwayIEA:Ensembl
Negative regulation of exosomal secretionManual Assertion Based On ExperimentIMP:ParkinsonsUK-UCL
Negative regulation of gene expressionManual Assertion Based On ExperimentIMP:BHF-UCL
Negative regulation of glucokinase activityManual Assertion Based On ExperimentIDA:MGI
Negative regulation of insulin secretionManual Assertion Based On ExperimentIDA:MGI
Negative regulation of intralumenal vesicle formationManual Assertion Based On ExperimentIMP:ParkinsonsUK-UCL
Negative regulation of intrinsic apoptotic signaling pathway by p53 class mediatorManual Assertion Based On ExperimentIMP:ParkinsonsUK-UCL
Negative regulation of JNK cascadeISS:ParkinsonsUK-UCL
Negative regulation of mitochondrial fusionISS:ParkinsonsUK-UCL
Negative regulation of neuron apoptotic processManual Assertion Based On ExperimentIDA:ParkinsonsUK-UCL
Negative regulation of neuron deathManual Assertion Based On ExperimentIGI:ParkinsonsUK-UCL
Negative regulation of oxidative stress-induced cell deathManual Assertion Based On ExperimentTAS:ParkinsonsUK-UCL
Negative regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathwayManual Assertion Based On ExperimentIDA:ParkinsonsUK-UCL
Negative regulation of primary amine oxidase activityManual Assertion Based On ExperimentIMP:ParkinsonsUK-UCL
Negative regulation of protein phosphorylationManual Assertion Based On ExperimentIDA:BHF-UCL
Negative regulation of reactive oxygen species metabolic processManual Assertion Based On ExperimentIGI:ParkinsonsUK-UCL
Negative regulation of release of cytochrome c from mitochondriaManual Assertion Based On ExperimentIDA:BHF-UCL
Negative regulation of spontaneous neurotransmitter secretionManual Assertion Based On ExperimentIMP:ParkinsonsUK-UCL
Negative regulation of transcription by RNA polymerase IIManual Assertion Based On ExperimentIMP:ParkinsonsUK-UCL
Neuron cellular homeostasisISS:ParkinsonsUK-UCL
Norepinephrine metabolic processIEA:Ensembl
Parkin-mediated stimulation of mitophagy in response to mitochondrial depolarizationManual Assertion Based On ExperimentIDA:ParkinsonsUK-UCL
Positive regulation of autophagy of mitochondrionManual Assertion Based On ExperimentIDA:ParkinsonsUK-UCL
Positive regulation of dendrite extensionIEA:Ensembl
Positive regulation of DNA bindingManual Assertion Based On ExperimentIDA:ParkinsonsUK-UCL
Positive regulation of gene expressionManual Assertion Based On ExperimentIMP:ParkinsonsUK-UCL
Positive regulation of I-kappaB kinase/NF-kappaB signalingManual Assertion Based On ExperimentIDA:ParkinsonsUK-UCL
Positive regulation of mitochondrial fissionISS:ParkinsonsUK-UCL
Positive regulation of mitochondrial fusionManual Assertion Based On ExperimentIMP:ParkinsonsUK-UCL
Positive regulation of mitophagy in response to mitochondrial depolarizationManual Assertion Based On ExperimentIDA:ParkinsonsUK-UCL
Positive regulation of neurotransmitter uptakeManual Assertion Based On ExperimentIMP:ParkinsonsUK-UCL
Positive regulation of proteasomal protein catabolic processManual Assertion Based On ExperimentIGI:ParkinsonsUK-UCL
Positive regulation of proteasomal ubiquitin-dependent protein catabolic processManual Assertion Based On ExperimentIBA:GO_Central
Positive regulation of protein bindingManual Assertion Based On ExperimentIMP:ParkinsonsUK-UCL
Positive regulation of protein catabolic processManual Assertion Based On ExperimentTAS:ParkinsonsUK-UCL
Positive regulation of protein linear polyubiquitinationManual Assertion Based On ExperimentIGI:ParkinsonsUK-UCL
Positive regulation of protein localization to membraneManual Assertion Based On ExperimentIMP:ParkinsonsUK-UCL
Positive regulation of retrograde transport, endosome to Golgi1 PublicationNAS:ParkinsonsUK-UCL
Positive regulation of transcription by RNA polymerase IIManual Assertion Based On ExperimentIDA:ParkinsonsUK-UCL
Positive regulation of tumor necrosis factor-mediated signaling pathwayManual Assertion Based On ExperimentIDA:ParkinsonsUK-UCL
Proteasomal protein catabolic processManual Assertion Based On ExperimentIMP:BHF-UCL
Proteasome-mediated ubiquitin-dependent protein catabolic processManual Assertion Based On ExperimentIDA:ParkinsonsUK-UCL
Protein autoubiquitinationManual Assertion Based On ExperimentIDA:UniProtKB
Protein catabolic processManual Assertion Based On ExperimentIMP:ParkinsonsUK-UCL
Protein destabilizationManual Assertion Based On ExperimentIDA:UniProtKB
Protein deubiquitinationTAS:Reactome
Protein K11-linked ubiquitinationManual Assertion Based On ExperimentIDA:UniProtKB
Protein K27-linked ubiquitinationManual Assertion Based On ExperimentTAS:ParkinsonsUK-UCL
Protein K29-linked ubiquitinationManual Assertion Based On ExperimentTAS:ParkinsonsUK-UCL
Protein K48-linked ubiquitinationManual Assertion Based On ExperimentIDA:UniProtKB
Protein K6-linked ubiquitinationManual Assertion Based On ExperimentIDA:UniProtKB
Protein K63-linked ubiquitinationManual Assertion Based On ExperimentIDA:UniProtKB
Protein localization to mitochondrionIEA:Ensembl
Protein monoubiquitinationManual Assertion Based On ExperimentIDA:UniProtKB
Protein polyubiquitinationManual Assertion Based On ExperimentIDA:UniProtKB
Protein stabilizationManual Assertion Based On ExperimentIMP:UniProtKB
Protein ubiquitinationManual Assertion Based On ExperimentIDA:ParkinsonsUK-UCL
Regulation of apoptotic processManual Assertion Based On ExperimentIBA:GO_Central
Regulation of autophagyManual Assertion Based On ExperimentIDA:UniProtKB
Regulation of canonical Wnt signaling pathwayManual Assertion Based On ExperimentTAS:ParkinsonsUK-UCL
Regulation of cellular response to oxidative stressManual Assertion Based On ExperimentIDA:ParkinsonsUK-UCL
Regulation of dopamine metabolic processManual Assertion Based On ExperimentIMP:ParkinsonsUK-UCL
Regulation of dopamine secretionManual Assertion Based On ExperimentTAS:ParkinsonsUK-UCL
Regulation of glucose metabolic processManual Assertion Based On ExperimentTAS:ParkinsonsUK-UCL
Regulation of lipid transportManual Assertion Based On ExperimentTAS:ParkinsonsUK-UCL
Regulation of mitochondrial membrane potentialIEA:Ensembl
Regulation of mitochondrion organizationManual Assertion Based On ExperimentIDA:ParkinsonsUK-UCL
Regulation of protein stabilityManual Assertion Based On ExperimentIMP:ParkinsonsUK-UCL
Regulation of protein targeting to mitochondrion1 PublicationNAS:ParkinsonsUK-UCL
Regulation of protein ubiquitinationManual Assertion Based On ExperimentIMP:ParkinsonsUK-UCL
Regulation of reactive oxygen species metabolic processManual Assertion Based On ExperimentIMP:UniProtKB
Regulation of synaptic vesicle transport1 PublicationNAS:ParkinsonsUK-UCL
Response to endoplasmic reticulum stressManual Assertion Based On ExperimentIMP:ParkinsonsUK-UCL
Response to oxidative stressISS:ParkinsonsUK-UCL
Startle responseIEA:Ensembl
Synaptic transmission, glutamatergicIEA:Ensembl
Ubiquitin-dependent protein catabolic processManual Assertion Based On ExperimentIDA:UniProtKB
Zinc ion homeostasisISS:ParkinsonsUK-UCL

Cytoplasm, cytosol
Nucleus
Endoplasmic reticulum
Mitochondrion
Mitochondrion outer membrane
Cell projection, neuron projection
Postsynaptic density
Presynapse
Mainly localizes in the cytosol (PubMed:19029340, PubMed:19229105).
Co-localizes with SYT11 in neutrites (PubMed:12925569).
Co-localizes with SNCAIP in brainstem Lewy bodies (PubMed:10319893, PubMed:11431533).
Translocates to dysfunctional mitochondria that have lost the mitochondrial membrane potential; recruitment to mitochondria is PINK1-dependent (PubMed:24898855, PubMed:18957282, PubMed:19966284, PubMed:23620051).
Mitochondrial localization also gradually increases with cellular growth (PubMed:22082830).

Parkinson disease (PARK):
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.
Parkinson disease 2 (PARK2):
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.

Auto-ubiquitinates in an E2-dependent manner leading to its own degradation (PubMed:19229105, PubMed:25474007, PubMed:23770917).
Also polyubiquitinated by RNF41 for proteasomal degradation (PubMed:19229105).
S-nitrosylated. The inhibition of PRKN ubiquitin E3 ligase activity by S-nitrosylation could contribute to the degenerative process in PD by impairing the ubiquitination of PRKN substrates.
Phosphorylated (PubMed:23754282, PubMed:24660806, PubMed:24784582, PubMed:18957282, PubMed:25474007).
Activation requires phosphorylation at Ser-65 by PINK1 and binding to PINK1 phosphorylated ubiquitin (PubMed:23754282, PubMed:24660806, PubMed:24784582, PubMed:18957282, PubMed:25474007).
Phosphorylation at Thr-175 by PINK1 and at Thr-217 is important for mitochondrial localization (PubMed:18957282).