Phospho-Parkin (S131) Polyclonal Antibody, 100µg, (ATB-P0962)

Description

Background:

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, Jul 2008]

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, a 22 kDa O-linked glycosylated isoform of SNCAIP, SEPT5, TOMM20, USP30, ZNF746 and AIMP2. Mediates monoubiquitination as well as ‘Lys-48’-linked and ‘Lys-63’-linked polyubiquitination of substrates depending on the context. 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. Mediates ‘Lys-63’-linked polyubiquitination of SNCAIP, possibly playing a role in Lewy-body formation. Mediates monoubiquitination of BCL2, thereby acting as a positive regulator of autophagy. Promotes the autophagic degradation of dysfunctional depolarized mitochondria (mitophagy) by promoting the ubiquitination of mitochondrial proteins such as TOMM20, RHOT1/MIRO1 and USP30 (PubMed:24896179). 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. 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. Independently of its ubiquitin ligase activity, protects from apoptosis by the transcriptional repression of p53/TP53. May protect neurons against alpha synuclein toxicity, proteasomal dysfunction, GPR37 accumulation, and kainate-induced excitotoxicity. May play a role in controlling neurotransmitter trafficking at the presynaptic terminal and in calcium-dependent exocytosis. May represent a tumor suppressor gene.

Product datasheet:

References:

1. Quantitative proteomics reveal a feedforward mechanism for mitochondrial PARKIN translocation and ubiquitin chain synthesis. Ordureau A, et al. Mol Cell, 2014 Nov 6. PMID 25284222
2. HSPA1A-independent suppression of PARK2 C289G protein aggregation by human small heat shock proteins. Minoia M, et al. Mol Cell Biol, 2014 Oct 1. PMID 25022755
3. Parkin-mediated ubiquitination of mutant glucocerebrosidase leads to competition with its substrates PARIS and ARTS. Bendikov-Bar I, et al. Orphanet J Rare Dis, 2014 Jun 16. PMID 24935484 Free PMC Article
4. Pan-cancer genetic analysis identifies PARK2 as a master regulator of G1/S cyclins. Gong Y, et al. Nat Genet, 2014 Jun. PMID 24793136 Free PMC Article
5. Mitochondrial impairment observed in fibroblasts from South African Parkinson’s disease patients with parkin mutations. van der Merwe C, et al. Biochem Biophys Res Commun, 2014 May 2. PMID 24721425
6. Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism.
   Kitada T., Asakawa S., Hattori N., Matsumine H., Yamamura Y., Minoshima S., Yokochi M., Mizuno Y., Shimizu N.
   Nature 392:605-608(1998) [PubMed] [Europe PMC] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), INVOLVEMENT IN PARK2. Tissue: Fetal brain and Skeletal muscle.
7. Evidence for the presence of full-length PARK2 mRNA and Parkin protein in human blood.
   Kasap M., Akpinar G., Sazci A., Idrisoglu H.A., Vahaboglu H.
   Neurosci. Lett. 460:196-200(2009) [PubMed] [Europe PMC] Cited for: NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION, TISSUE SPECIFICITY, VARIANTS ARG-311 AND THR-371, IDENTIFICATION BY MASS SPECTROMETRY.
8. Functional and molecular diversity of parkin.
   D’Agata V., Scapagnini G., Cavallaro S.
   Submitted (MAY-2001) to the EMBL/GenBank/DDBJ databasesCited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 3 AND 4).
9. Homo sapiens PARK2 transcript variants.
   Campello L., Esteve-Rudd J., Cuenca N., Martin-Nieto J.
   Submitted (DEC-2009) to the EMBL/GenBank/DDBJ databasesCited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2; 7 AND 8). Tissue: Retina.
10. Complete sequencing and characterization of 21,243 full-length human cDNAs.
    Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
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    Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC]

    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Testis.