Abcam offers Anti-Parkin antibody, a full-length, recombinant protein corresponding to Human Parkin.
- Product Name - Anti-Parkin antibody [PRK8]
- Description - Mouse monoclonal [PRK8] to Parkin
- Host species - Mouse
- Tested Applications - Ideal for IP, IHC-Fr, WB, and flow cytometer
- Species Reactivity - Reacts with human, rat, mouse, and Drosophila melanogaster
- Immunogen - Full-length, recombinant protein corresponding to Human Parkin
- Epitope - The epitope is the second ring domain (aa 399-465).
- Human, rat, and mouse brain tissue lysates
- WB: SH-SY5Y whole cell lysate
- Flow cytometer: SH-SY5Y cells
- Wild-type HAP1 whole cell lysate
Abpromise guarantee covers the usage of ab77924 in the below-tested applications. Recommended starting dilutions have been listed; end users should determine optimal concentrations/dilutions.
||Should be used at an assay-dependent concentration. PubMed: 20689587
||1 µg should be used for 106 cells.
ab170192—Mouse monoclonal IgG2b can be used as an isotype control with this antibody.
||A 5 µg/mL concentration should be used. Detects a band of about 55 kDa (estimated molecular weight: 52 kDa).
Abcam suggests using 1%–3% milk as the blocking agent. Optimal results may not be obtained from higher percentage blocking solutions.
||Should be used at an assay dependent concentration.
The Anti-Parkin antibody is designed to function within a multiprotein E3 ubiquitin ligase complex and catalyzes the covalent attachment of ubiquitin moieties onto substrate proteins, like SYT11, BCL2, GPR37, CCNE1, AIMP2, ZNF746, SEPT5, STUB1, and a 22 kDa O-linked glycosylated isoform of SNCAIP.
The antibody mediates monoubiquitination and also “Lys-63”-linked and “Lys-48”-linked polyubiquitination of substrates based on the context. It takes part in the removal and/or detoxification of unusually damaged or folded protein by regulating “Lys-63”-linked polyubiquitination of misfolded proteins such as PARK7: “Lys-63”-linked polyubiquitinated misfolded proteins detected by HDAC6 are recruited to aggresomes and subsequent degradation.
The Anti-Parkin antibody mediates SNCAIP’s “Lys-63”-linked polyubiquitination, potentially contributing to the formation of Lewy-body. It also mediates BCL2’s monoubiquitination, thus serving as a positive regulator of autophagy. The antibody also subjects the dysfunctional depolarized mitochondria to autophagic degradation.
The antibody mediates ZNF746’s “Lys-48”-linked polyubiquitination, followed by ZNF746 degradation by the proteasome, potentially contributing to the regulation of neuron death. It restricts the production of reactive oxygen species, or ROS. Loss of this ubiquitin ligase activity seems to be the mechanism fundamental to PARK2 pathogenesis.
The antibody may protect neurons against kainate-induced excitotoxicity, GPR37 accumulation, proteasomal dysfunction, and alpha-synuclein toxicity. It may help in regulating neurotransmitter trafficking at the presynaptic terminal and play a role in calcium-dependent exocytosis. The antibody regulates cyclin-E during neuronal apoptosis and may denote a tumor suppressor gene.
The antibody is largely expressed in the brain such as the substantia nigra. It is also expressed in skeletal muscle, testis, and heart. However, the expression is absent in the brain of PARK2 patients, and it is either absent or down-regulated in tumor biopsies. Overexpression of the Anti-Parkin antibody safeguards dopamine neurons against kainate-mediated apoptosis. It is present in serum (at protein level).
Protein ubiquitination and protein modification
Involvement in Disease
PARK2 defects lead to Parkinson disease (PARK) [MIM:168600]. This disease is a complex neurodegenerative disorder characterized by postural instability, muscular rigidity, resting tremor, and bradykinesia. Other features include dementia, dystonic cramps, dysautonomia, and characteristic postural abnormalities.
In addition, the pathology of Parkinson disease involves the presence of Lewy bodies (intraneuronal accumulations of aggregated proteins) in surviving neurons in different regions of the brain and the loss of dopaminergic neurons in the substantia nigra.
Parkinson is a progressive disease with an onset often after the age of 50 years, but early-onset cases (before 50 years) are also known. Most of the cases are random, implying a multifactorial etiology based on genetic and environmental factors. Conversely, certain patients have a positive family history for Parkinson disease. Familial forms of the disease often start at earlier ages and are linked with atypical clinical traits.
PARK2 defects lead to Parkinson disease type 2 (PARK2) [MIM:600116], also called autosomal recessive juvenile Parkinson disease (PDJ) or early-onset parkinsonism with diurnal fluctuation (EPDF). Parkinson disease type 2 is a neurodegenerative disorder that manifests typically before the age of 40. It is characterized by tremor, postural instability, rigidity, and bradykinesia.
It varies from classic Parkinson disease by hyperreflexia, early DOPA-induced dyskinesia, dystonia, sleep benefit, and diurnal fluctuation of the symptoms. However, dementia is absent. Pathologically, patients suffer from loss of dopaminergic neurons in the substantia nigra, akin to that observed in Parkinson disease, but Lewy bodies (intraneuronal accumulations of aggregated proteins) are not present.
Note—PARK2 defects are likely to be involved in the development and/or progression of ovarian cancer.
- Contains 1 ubiquitin-like domain
- Contains 2 RING-type zinc fingers
- Contains 1 IBR-type zinc finger
- Belongs to the RBR family and Parkin subfamily
The PSMD4 subunit of 26S proteasomes is bound by the ubiquitin-like domain.
The antibody auto-ubiquitinates in an E2-dependent way, causing its own degradation; it is also polyubiquitinated by RNF41 for degradation of proteasomes. The S-nitrosylation of the antibody inhibits the activity of PARK2 ubiquitin E3 ligase, potentially contributing to the degenerative process in Parkinson disease, by damaging the ubiquitination of PARK2 substrates.
Cytoplasm > cytosol; nucleus, endoplasmic reticulum, and mitochondrion. The antibody predominantly localizes in the cytosol, co-localizes with SNCAIP in brainstem Lewy bodies, co-localizes with SYT11 in neurites, and relocates to dysfunctional mitochondria that have forgone the mitochondrial membrane potential. Recruitment to mitochondria depends on PINK1.