Parkin Antibody (N-term) [APR32280G]

Parkin Antibody (N-term) [APR32280G] | Gentaur UK, US & Europe Distribution

Product Category: Polyclonal Antibodies

Host: Rabbit

Species Reactivity: H

Specificity: This Parkin antibody is generated from rabbits immunized with a KLH conjugated synthetic peptide between 111-140 amino acids from the N-terminal region of human Parkin.

Cellular Localisation: Cytoplasm, cytosol. Nucleus. Endoplasmic reticulum. Mitochondrion. Mitochondrion outer membrane {ECO:0000250|UniProtKB:Q9WVS6}. Cell projection, neuron projection. Cell junction, synapse, postsynaptic density {ECO:0000250|UniProtKB:Q9WVS6}. Cell junction, synapse, presynapse {ECO:0000250|UniProtKB:Q9WVS6}. Note=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) .

Molecular Weight: 51641

Clone: Polyclonal

Gene Name: PRKN (HGNC:8607)

Gene ID: 5071

Function: 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) .

Summary: Tissue Location: Highly expressed in the brain including the substantia nigra (PubMed:9560156, PubMed:19501131) . Expressed in heart, testis and skeletal muscle (PubMed:9560156) . Expression is down- regulated or absent in tumor biopsies, and absent in the brain of PARK2 patients (PubMed:14614460, PubMed:12719539) . Overexpression protects dopamine neurons from kainate-mediated apoptosis (PubMed:12628165) Found in serum (at protein level) (PubMed:19501131)

Form: Purified polyclonal antibody supplied in PBS with 0.09% (W/V) sodium azide. This antibody is purified through a protein A column, followed by peptide affinity purification.

Storage: Maintain refrigerated at 2-8°C for up to 2 weeks. For long term storage store at -20°C in small aliquots to prevent freeze-thaw cycles.

Application: WB

Dilution: WB--1:2000 FC--1:10~50 IF--1:10~50 IHC-P--1:100~500 WB--1:250-1:1000 WB--1:1000

Synonyms: E3 ubiquitin-protein ligase parkin, 632-, Parkinson juvenile disease protein 2, Parkinson disease protein 2, PARK2, PRKN