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  4. Recombinant Rat E3 ubiquitin-protein ligase parkin (Park2)

Recombinant Rat E3 ubiquitin-protein ligase parkin (Park2)

  • 货号：
    CSB-EP864348RAb1
  • 规格：
    ￥2328
  • 图片：
    • (Tris-Glycine gel) Discontinuous SDS-PAGE (reduced) with 5% enrichment gel and 15% separation gel.
  • 其他：

产品详情

  • 纯度：
    Greater than 90% as determined by SDS-PAGE.
  • 基因名：
  • Uniprot No.：
  • 别名：
    Prkn; Park2; E3 ubiquitin-protein ligase parkin; EC 2.3.2.31; Parkin RBR E3 ubiquitin-protein ligase
  • 种属：
    Rattus norvegicus (Rat)
  • 蛋白长度：
    Full Length
  • 来源：
    E.coli
  • 分子量：
    56.7 kDa
  • 表达区域：
    1-465aa
  • 氨基酸序列
    MIVFVRFNSSYGFPVEVDSDTSIFQLKEVVAKRQGVPADQLRVIFAGKELQNHLTVQNCDLEQQSIVHIVQRPQRKSHETNASGGDKPQSTPEGSIWEPRSLTRVDLSSHILPADSVGLAVILDTDSKSDSEAARGPEAKPTYHSFFVYCKGPCHKVQPGKLRVQCGTCRQATLTLAQGPSCWDDVLIPNRMSGECQSPDCPGTRAEFFFKCGAHPTSDKDTSVALNLITNNSRSIPCIACTDVRNPVLVFQCNHRHVICLDCFHLYCVTRLNDRQFVHDAQLGYSLPCVAGCPNSLIKELHHFRILGEEQYNRYQQYGAEECVLQMGGVLCPRPGCGAGLLPEQGQKKVTCEGGNGLGCGFVFCRDCKEAYHEGECDSMFEASGATSQAYRVDQRAAEQARWEEASKETIKKTTKPCPRCNVPIEKNGGCMHMKCPQPQCKLEWCWNCGCEWNRACMGDHWFDV
    Note: The complete sequence including tag sequence, target protein sequence and linker sequence could be provided upon request.
  • 蛋白标签：
    N-terminal 10xHis-tagged and C-terminal Myc-tagged
  • 产品提供形式：
    Liquid or Lyophilized powder
    Note: We will preferentially ship the format that we have in stock, however, if you have any special requirement for the format, please remark your requirement when placing the order, we will prepare according to your demand.
  • 缓冲液：
    Tris-based buffer，50% glycerol
  • 储存条件：
    Store at -20°C/-80°C upon receipt, aliquoting is necessary for mutiple use. Avoid repeated freeze-thaw cycles.
  • 保质期：
    The shelf life is related to many factors, storage state, buffer ingredients, storage temperature and the stability of the protein itself.
    Generally, the shelf life of liquid form is 6 months at -20°C/-80°C. The shelf life of lyophilized form is 12 months at -20°C/-80°C.
  • 货期：
    Basically, we can dispatch the products out in 1-3 working days after receiving your orders. Delivery time may differ from different purchasing way or location, please kindly consult your local distributors for specific delivery time.
    Note: All of our proteins are default shipped with normal blue ice packs, if you request to ship with dry ice, please communicate with us in advance and extra fees will be charged.
  • 注意事项：
    Repeated freezing and thawing is not recommended. Store working aliquots at 4°C for up to one week.
  • Datasheet & COA：
    Please contact us to get it.

产品评价

靶点详情

  • 功能：
    Functions within a multiprotein E3 ubiquitin ligase complex, catalyzing the covalent attachment of ubiquitin moieties onto substrate proteins. Substrates include SYT11 and VDAC1. Other substrates are BCL2, CCNE1, GPR37, RHOT1/MIRO1, MFN1, MFN2, STUB1, SNCAIP, SEPTIN5, TOMM20, USP30, ZNF746, MIRO1 and AIMP2. Mediates monoubiquitination as well as 'Lys-6', 'Lys-11', '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 a 22 kDa O-linked glycosylated isoform of SNCAIP, possibly playing a role in Lewy-body formation. Mediates monoubiquitination of BCL2, thereby acting as a positive regulator of autophagy. 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. 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. Activation and recruitment onto the outer membrane of damaged/dysfunctional mitochondria (OMM) requires PINK1-mediated phosphorylation of both PRKN and ubiquitin. 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. 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. Preferentially assembles 'Lys-6'-, 'Lys-11'- and 'Lys-63'-linked polyubiquitin chains, leading to mitophagy. 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. This prevents the refusion of unhealthy mitochondria with the mitochondrial network or initiates mitochondrial fragmentation facilitating their later engulfment by autophagosomes. 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. 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. 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.
  • 基因功能参考文献：
    1. Altogether, these findings suggest that 2 month-old Park2 knockout male rats have altered dopaminergic and trace aminergic signaling. PMID: 29367643
    2. Overexpression of parkin exerted a significant protective effect on cultured retinal ganglion cells (RGCs) against glutamate excitotoxicity. Interventions to alter the parkin-mediated mitochondria pathway may be useful in protecting RGCs against excitotoxic RGC damage. PMID: 28761318
    3. These findings demonstrate a novel role for Parkin in synaptic AMPA receptor internalization and suggest a Parkin-dependent mechanism for hippocampal dysfunction that may explain cognitive deficits associated with some forms of PD. PMID: 27903732
    4. Tissue-specific parkin isoforms expression in the prefrontal cortex, hippocampus, substantia nigra and cerebellum has been documented. PMID: 27601173
    5. ubiquitin plays a dual role in parkin activation by competing with the inhibitory UBL domain and stabilizing the active form of parkin. PMID: 27284007
    6. These data are the first direct morphological evidence linking PINK1-Parkin pathway activation to the enhanced mitophagic response of hepatocytes to ethanol toxicity PMID: 26935412
    7. Data suggest that expression of atrogin-1/Fbxo32 and E3 ubiquitin ligase/parkin protein can be down-regulated by dietary factors; here, L-carnitine dietary supplementation represses expression of these two ligases in skeletal muscle in a model of disuse muscle atrophy due to weightlessness (hindlimb suspension). PMID: 27841025
    8. After Parkin is translocated at mitochondria, WDR26 can increase mitochondrial protein ubiquitination in hypoxia of H9c2 cells. WDR26 is a mediator of response to hypoxia, and WDR26 plays an important role in hypoxia-mediated autophagy and mitophagy PMID: 27797717
    9. Parkin protects PC12 cells against 6-hydroxydopamine - induced apoptosis via ubiquitinating and stabilizing scaffold protein p62, and repressing ERK1/2 activation. PMID: 26364802
    10. ACetylcholine promoted mitochondrial translocation of PINK1/Parkin to stimulate cytoprotective mitophagy via M2 receptor PMID: 26465230
    11. Parkin regulates RTP801 protein in neuronal PC12 cells. PMID: 25101677
    12. BECN1 interacts with PARK2 and regulates PARK2 translocation to mitochondria as well as PARK2-induced mitophagy prior to autophagosome formation. PMID: 24879156
    13. a fundamental role of the PARK2 gene in the maintenance of beta-cell function, is reported. PMID: 24096089
    14. crystal structure of full-length parkin; structure shows parkin in an autoinhibited state and provides insight into how it is activated PMID: 23661642
    15. Parkin ubiquitinates TDP-43 and facilitates its cytosolic accumulation through a multiprotein complex with HDAC6. PMID: 23258539
    16. results suggest that Parkin plays a critical role in adapting to stress in the myocardium by promoting removal of damaged mitochondria PMID: 23152496
    17. ARTS is a novel substrate of Parkin. These observations link Parkin directly to a pro-apoptotic protein and reveal a novel connection between Parkin, apoptosis, and Parkinson's disease (PD). PMID: 22792159
    18. Suggest that induction of mitochondrial autophagy in response to Bnip3 is a protective response activated by the cardiac myocytes that involves Drp1-mediated mitochondrial fission and recruitment of Parkin. PMID: 21890690
    19. The PINK1/Parkin pathway plays conserved roles in regulating neuronal mitochondrial dynamics and function. PMID: 21613270
    20. Immunohistochemistry of adult rat brain sections shows widespread distribution of parkin in cell bodies, nuclei as well as processes in the hippocampus, cerebral cortex, cerebellum, and several nuclei in the brainstem. PMID: 11999903
    21. expression of parkin genes in the nigro-striatal pathway may have significant implication for pathophysiology and treatment of parkinson disease PMID: 12618056
    22. Parkin is a novel tubulin-binding protein, as well as a microtubule-associated protein; alpha-tubulin and beta-tubulin were strongly coimmunoprecipitated with parkin PMID: 12716939
    23. Parkin functions as a ubiquitin protein ligase in the degradation of several proteins, including the neuron-specific septin CDCrel-1. PMID: 14530399
    24. Data show both in vitro and in vivo that nitrosative stress leads to S-nitrosylation of wild-type parkin and, initially, to a dramatic increase followed by a decrease in the E3 ligase-ubiquitin-proteasome degradative pathway. PMID: 15252205
    25. Extensive splicing of parkin produces regional and structural diversity and may have important implications for the pathogenetic mechanisms underlying parkinson disease. PMID: 15453267
    26. parkin-mediated neuroprotection was associated with an increase in hyperphosphorylated alpha-synuclein inclusions, suggesting a key role for parkin in the genesis of Lewy bodies PMID: 15576511
    27. Parkin therefore protects dopamine neurons against tau as it does against alpha-synuclein, which further supports parkin as a therapeutic target for diseases involving loss of dopamine neurons. PMID: 16554120
    28. Possesses anti-apoptotic and anti-oxidant function in neuronal or myogenic cells but not in kidney cells. PMID: 16905117
    29. This work provides a mechanism explaining how defects in parkin-mediated PICK1 monoubiquitination could enhance ASIC activity and thereby promote neurodegeneration in Parkinson's disease. PMID: 17553932
    30. We show the sensitivity of parkin to DA-induced modifications, and show the ability of parkin to become insoluble in part through self-association and oligomer formation. PMID: 17883392
    31. parkin negatively regulates the number and strength of excitatory synapses so increased excitatory drive produced by disruption of parkin may contribute to the pathophysiology of Parkinson disease PMID: 19033459
    32. The identification of the RING0 domain in parkin provides a new overall domain structure for the protein. PMID: 19339245

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  • 亚细胞定位：
    Cytoplasm, cytosol. Nucleus. Endoplasmic reticulum. Mitochondrion. Mitochondrion outer membrane. Cell projection, neuron projection. Cell junction, synapse, postsynaptic density. Cell junction, synapse, presynapse.
  • 蛋白家族：
    RBR family, Parkin subfamily
  • 组织特异性：
    Largely confined to neuronal elements, including fibers and neuropil. Highly expressed at the forebrain level, in pyramidal cells of layer V, in various cortical regions and cerebellum. Expressed in the nucleus of diagonal band of Broca, nucleus basalis,
  • 数据库链接：

    KEGG: rno:56816

    STRING: 10116.ENSRNOP00000040511

    UniGene: Rn.207194