Anti-Parkin/PRKN Antibody Picoband® Fluoro647 Conjugated

Parkin is a RING domain-containing E3 ubiquitin ligase involved in proteasome-dependent degradation of proteins. It is mapped to 6q26. This gene is important for mitochondrial quality control by lysosome-dependent degradation of damaged mitochondria through autophagy, or mitophagy. Parkin is expressed in neuronal processes and cell bodies of neurons, but not glial cells, in the midbrain, basal ganglia, cerebral cortex, and cerebellum. Parkin assimilated with actin filaments, suggesting that it is a cytoskeletal-associated protein. Parkin is identified as a transcriptional repressor of p53 independent of its ubiquitin ligase function. It also has been found that parkin was associated physically with mitochondrial DNA (mtDNA) in proliferating as well as in differentiated SH-SY5Y neuroblastoma cells.

E.coli-derived human Parkin recombinant protein (Position: I23-K416) . Human Parkin shares 82% and 84% amino acid (aa) sequence identity with mouse and rat Parkin, respectively.

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

Functions within a multiprotein E3 ubiquitin ligase complex, catalyzing the covalent attachment of ubiquitin moieties onto substrate proteins, such as BCL2, SYT11, CCNE1, GPR37, RHOT1/MIRO1, MFN1, MFN2, STUB1, SNCAIP, SEPT5, TOMM20, USP30, ZNF746 and AIMP2 (PubMed:10973942, PubMed:10888878, PubMed:11431533, PubMed:12150907, PubMed:12628165, PubMed:16135753, PubMed:21376232, PubMed:23754282, PubMed:23620051, PubMed:24660806, PubMed:24751536) . 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) . 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:11590439, PubMed:11431533, PubMed:19229105, PubMed:11590439, PubMed:15728840) . Mediates monoubiquitination of BCL2, thereby acting as a positive regulator of autophagy (PubMed:20889974) . Promotes the autophagic degradation of dysfunctional depolarized mitochondria (mitophagy) by promoting the ubiquitination of mitochondrial proteins such as TOMM20, RHOT1/MIRO1 and USP30 (PubMed:19029340, PubMed:19966284, PubMed:23620051, PubMed:24896179, PubMed:25527291) . Preferentially assembles 'Lys-6'-, 'Lys-11'- and 'Lys-63'-linked polyubiquitin chains following mitochondrial damage, leading to mitophagy (PubMed:25621951) . Mediates 'Lys-48'-linked polyubiquitination of ZNF746, followed by degradation of ZNF746 by the proteasome; possibly playing a role in the regulation of neuron death (PubMed:21376232) . Limits the production of reactive oxygen species (ROS) . Regulates cyclin-E during neuronal apoptosis. 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. .

1. Huynh, D. P., Scoles, D. R., Ho, T. H., Del Bigio, M. R., Pulst, S.-M. Parkin is associated with actin filaments in neuronal and nonneural cells. Ann. Neurol. 48: 737-744, 2000. 2. Kitada T, Asakawa S, Hattori N, Matsumine H, Yamamura Y, Minoshima S et al. (Apr 1998) . Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism. Nature 392 (6676) : 605–608. 3. Rothfuss, O., Fischer, H., Hasegawa, T., Maisel, M., Leitner, P., Miesel, F., Sharma, M., Bornemann, A., Berg, D., Gasser, T., Patenge, N. Parkin promotes mitochondrial genome integrity and supports mitochondrial DNA repair. Hum. Molec. Genet. 18: 3832-3850, 2009.

Cytoplasm, cytosol . Nucleus. Endoplasmic reticulum. Mitochondrion . Mainly localizes in the cytosol. Co-localizes with SYT11 in neutrites. Co-localizes with SNCAIP in brainstem Lewy bodies. Mitochondrial localization gradually increases with cellular growth. Also relocates to dysfunctional mitochondria that have lost the mitochondrial membrane potential; recruitment to mitochondria is PINK1- dependent.