产品: Parkin 抗体
货号: AF0235
描述: Rabbit polyclonal antibody to Parkin
应用: WB IHC
反应: Human, Mouse, Rat
分子量: 52kDa; 52kD(Calculated).
蛋白号: O60260
RRID: AB_2833410

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产品描述

来源:
Rabbit
应用:
WB 1:500-1:3000, IHC 1:50-1:200
*The optimal dilutions should be determined by the end user.
*Tips:

WB: 适用于变性蛋白样本的免疫印迹检测. IHC: 适用于组织样本的石蜡(IHC-p)或冰冻(IHC-f)切片样本的免疫组化/荧光检测. IF/ICC: 适用于细胞样本的荧光检测. ELISA(peptide): 适用于抗原肽的ELISA检测.

反应:
Human,Mouse,Rat
克隆:
Polyclonal
特异性:
Parkin Antibody detects endogenous levels of total Parkin.
RRID:
AB_2833410
引用格式: Affinity Biosciences Cat# AF0235, RRID:AB_2833410.
偶联:
Unconjugated.
纯化:
The antiserum was purified by peptide affinity chromatography using SulfoLink™ Coupling Resin (Thermo Fisher Scientific).
保存:
Rabbit IgG in phosphate buffered saline , pH 7.4, 150mM NaCl, 0.02% sodium azide and 50% glycerol. Store at -20 °C. Stable for 12 months from date of receipt.
别名:

展开/折叠

AR JP; E3 ubiquitin ligase; E3 ubiquitin protein ligase parkin; E3 ubiquitin-protein ligase parkin; FRA6E; LPRS 2; LPRS2; PARK 2; Park2; Parkin 2; Parkinson disease (autosomal recessive juvenile) 2; Parkinson disease (autosomal recessive, juvenile) 2, parkin; Parkinson disease protein 2; Parkinson juvenile disease protein 2; Parkinson protein 2 E3 ubiquitin protein ligase; Parkinson protein 2, E3 ubiquitin protein ligase (parkin); PDJ; PRKN 2; PRKN; PRKN2; PRKN2_HUMAN; Ubiquitin E3 ligase PRKN;

抗原和靶标

免疫原:
Uniprot:
基因/基因ID:
表达:
O60260 PRKN_HUMAN:

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).

描述:
PARK2 Functions within a multiprotein E3 ubiquitin ligase complex, catalyzing the covalent attachment of ubiquitin moieties onto substrate proteins. These substrates include SYT11, CCNE1, GPR37, STUB1, a 22 kDa O-linked glycosylated isoform of SNCAIP, SEPT5 and AIMP2. May play a more general role in the ubiquitin proteasomal pathway by participating in the removal and/or detoxification of abnormally folded or damaged protein. Loss of this ubiquitin ligase activity appears to be the mechanism underlying pathogenesis of PARK2.
序列:
MIVFVRFNSSHGFPVEVDSDTSIFQLKEVVAKRQGVPADQLRVIFAGKELRNDWTVQNCDLDQQSIVHIVQRPWRKGQEMNATGGDDPRNAAGGCEREPQSLTRVDLSSSVLPGDSVGLAVILHTDSRKDSPPAGSPAGRSIYNSFYVYCKGPCQRVQPGKLRVQCSTCRQATLTLTQGPSCWDDVLIPNRMSGECQSPHCPGTSAEFFFKCGAHPTSDKETSVALHLIATNSRNITCITCTDVRSPVLVFQCNSRHVICLDCFHLYCVTRLNDRQFVHDPQLGYSLPCVAGCPNSLIKELHHFRILGEEQYNRYQQYGAEECVLQMGGVLCPRPGCGAGLLPEPDQRKVTCEGGNGLGCGFAFCRECKEAYHEGECSAVFEASGTTTQAYRVDERAAEQARWEAASKETIKKTTKPCPRCHVPVEKNGGCMHMKCPQPQCRLEWCWNCGCEWNRVCMGDHWFDV

翻译修饰 - O60260 作为底物

Site PTM Type Enzyme
Ubiquitination
S9 Phosphorylation
S19 Phosphorylation
K27 Ubiquitination
K48 Ubiquitination
S65 Phosphorylation Q9BXM7 (PINK1)
K76 Ubiquitination
S101 Phosphorylation P48729 (CSNK1A1)
S108 Phosphorylation
S116 Phosphorylation
S131 Phosphorylation Q00535 (CDK5)
S136 Phosphorylation
Y143 Phosphorylation P00519 (ABL1)
S193 Phosphorylation
S198 Phosphorylation
T204 Phosphorylation
S296 Phosphorylation
Y372 Phosphorylation
S378 Phosphorylation P48729 (CSNK1A1) , P53350 (PLK1)
T388 Phosphorylation
Y391 Phosphorylation

研究背景

功能:

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, SEPTIN5, TOMM20, USP30, ZNF746 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. Promotes the autophagic degradation of dysfunctional depolarized mitochondria (mitophagy) by promoting the ubiquitination of mitochondrial proteins such as TOMM20, RHOT1/MIRO1 and USP30. Preferentially assembles 'Lys-6'-, 'Lys-11'- and 'Lys-63'-linked polyubiquitin chains following mitochondrial damage, leading to mitophagy. 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.

翻译修饰:

Auto-ubiquitinates in an E2-dependent manner leading to its own degradation. Also polyubiquitinated by RNF41 for proteasomal degradation.

S-nitrosylated. The inhibition of PRKN ubiquitin E3 ligase activity by S-nitrosylation could contribute to the degenerative process in PD by impairing the ubiquitination of PRKN substrates.

Phosphorylation at Ser-65 by PINK1 contributes to activate PRKN activity. It is however not sufficient and requires binding to phosphorylated ubiquitin as well.

细胞定位:

Cytoplasm>Cytosol. Nucleus. Endoplasmic reticulum. Mitochondrion.
Note: 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.

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionSubcellular location
组织特异性:

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).

亚基结构:

Forms an E3 ubiquitin ligase complex with UBE2L3 or UBE2L6. Mediates 'Lys-63'-linked polyubiquitination by associating with UBE2V1. Part of a SCF-like complex, consisting of PRKN, CUL1 and FBXW7. Interacts with SNCAIP. Binds to the C2A and C2B domains of SYT11. Interacts and regulates the turnover of SEPTIN5. Part of a complex, including STUB1, HSP70 and GPR37. The amount of STUB1 in the complex increases during ER stress. STUB1 promotes the dissociation of HSP70 from PRKN and GPR37, thus facilitating PRKN-mediated GPR37 ubiquitination. HSP70 transiently associates with unfolded GPR37 and inhibits the E3 activity of PRKN, whereas, STUB1 enhances the E3 activity of PRKN through promotion of dissociation of HSP70 from PRKN-GPR37 complexes. Interacts with PSMD4 and PACRG. Interacts with LRRK2. Interacts with RANBP2. Interacts with SUMO1 but not SUMO2, which promotes nuclear localization and autoubiquitination. Interacts (via first RING-type domain) with AIMP2 (via N-terminus). Interacts with PSMA7 and RNF41. Interacts with PINK1. Interacts with CHPF, the interaction with isoform 2 may facilitate PRKN transport into the mitochondria. Interacts with MFN2 (phosphorylated), promotes PRKN localization in dysfunctional depolarized mitochondria. Interacts with FBXO7; this promotes translocation to dysfunctional depolarized mitochondria. Interacts with heat shock protein 70 family members, including HSPA1L, HSPA1A and HSPA8; interaction HSPA1L promotes translocation to damaged mitochondria. Interacts with BAG4 and, to a lesser extent, BAG5; interaction with BAG4 inhibits translocation to damaged mitochondria. Forms a complex with PINK1 and PARK7.

蛋白家族:

The ubiquitin-like domain binds the PSMD4 subunit of 26S proteasomes.

The RING-type 1 zinc finger domain is required to repress p53/TP53 transcription.

Members of the RBR family are atypical E3 ligases. They interact with the E2 conjugating enzyme UBE2L3 and function like HECT-type E3 enzymes: they bind E2s via the first RING domain, but require an obligate trans-thiolation step during the ubiquitin transfer, requiring a conserved cysteine residue in the second RING domain (PubMed:21532592).

Belongs to the RBR family. Parkin subfamily.

研究领域

· Genetic Information Processing > Folding, sorting and degradation > Ubiquitin mediated proteolysis.   (View pathway)

· Genetic Information Processing > Folding, sorting and degradation > Protein processing in endoplasmic reticulum.   (View pathway)

· Human Diseases > Neurodegenerative diseases > Parkinson's disease.

文献引用

1). Sirt3-mediated mitophagy regulates AGEs-induced BMSCs senescence and senile osteoporosis. Redox Biology, 2021 (PubMed: 33662874) [IF=11.4]

Application: WB    Species: mice    Sample: bone marrow mesenchymal stem (BMSCs)

Fig. 2. Effects of different concentrations of AGEs on mitochondrial function and mitophagy of BMSCs. The BMSCs were treated with AGEs (50–200 μg/mL) or BSA for 24–72 h. (A) Representative fluorescence images with DCF (green) staining in BMSCs stimulated with AGEs. Scale bar: 50 μm. (B) Representative fluorescence images with Mito-SOX (red) and Mito-Tracker (green) double-staining in BMSCs stimulated with AGEs. Scale bar: 50 μm. (C) The MMP was detected through JC-1 staining in BMSCs stimulated with AGEs. Scale bar: 50 μm. (D) Representative fluorescence images with Mtphagy Dye (red) and Mito-Tracker (green) double-staining in BMSCs stimulated with AGEs. Scale bar: 50 μm. (E) Representative fluorescence images with LC3B (red) and Mito-Tracker (green) double-staining in BMSCs stimulated with AGEs. Scale bar: 50 μm. (F) Representative Western blotting assay and quantitation of the level of LC3B, P62, Parkin, Sirt3. **p < 0.01 versus BSA. (For interpretation of the references to colour in this figure legend, the reader is referred to the Web version of this article.)

2). Integrating network analysis and experimental validation to reveal the mitophagy-associated mechanism of Yiqi Huoxue (YQHX) prescription in the treatment of myocardial ischemia/reperfusion injury. PHARMACOLOGICAL RESEARCH, 2023 (PubMed: 36736970) [IF=9.3]

3). Betulinic Acid Inhibits ROS-Mediated Pyroptosis in Spinal Cord Injury by Augmenting Autophagy via the AMPK-mTOR-TFEB Signaling Pathway. International Journal of Biological Sciences, 2020 (PubMed: 33867836) [IF=9.2]

Application: WB    Species: Mice    Sample: spinal cords

Figure 6 BA attenuates mitophagy and reduces ROS accumulation after SCI. (A) ELISA of 8-OHdG, AOPP, and MDA in spinal cord lesions from Sham, SCI, BA and BA+3MA groups as indicated. (B) Immunofluorescence staining for Nix and NeuN co-localization in the spinal cords of the Sham, SCI, BA and BA+3MA groups (scale bar = 25 µm). (C) The quantitative mean optical density of the Nix in motor neurons of spinal cord lesion in each group. (D) Western blotting for Bnip3, Nix and Parkin expression levels in the Sham, SCI and BA groups. The gels were run under the same experimental conditions, and the cropped blots are shown here. (E) The optical density values of the Bnip3, Nix and Parkin expression levels were quantified and analyzed in the three groups. (F) Western blotting for Bnip3, Nix and Parkin expression levels in the BA and BA+3MA groups. The gels were run under the same experimental conditions, and the cropped blots are shown here. (G) The optical density values of the Bnip3, Nix and Parkin expression levels were quantified and analyzed in the both groups. The values are expressed as the means ± SEM, n=5 per group. *p< 0.05 and **p< 0.01, vs. Sham group. #p< 0.05 and ##p< 0.01, vs. SCI group. &p< 0.05 and &&p< 0.01, vs. BA group.

Application: WB    Species: Mice    Sample: spinal cords

Figure 6 BA attenuates mitophagy and reduces ROS accumulation after SCI. (A) ELISA of 8-OHdG, AOPP, and MDA in spinal cord lesions from Sham, SCI, BA and BA+3MA groups as indicated. (B) Immunofluorescence staining for Nix and NeuN co-localization in the spinal cords of the Sham, SCI, BA and BA+3MA groups (scale bar = 25 µm). (C) The quantitative mean optical density of the Nix in motor neurons of spinal cord lesion in each group. (D) Western blotting for Bnip3, Nix and Parkin expression levels in the Sham, SCI and BA groups. The gels were run under the same experimental conditions, and the cropped blots are shown here. (E) The optical density values of the Bnip3, Nix and Parkin expression levels were quantified and analyzed in the three groups. (F) Western blotting for Bnip3, Nix and Parkin expression levels in the BA and BA+3MA groups. The gels were run under the same experimental conditions, and the cropped blots are shown here. (G) The optical density values of the Bnip3, Nix and Parkin expression levels were quantified and analyzed in the both groups. The values are expressed as the means ± SEM, n=5 per group. *p< 0.05 and **p< 0.01, vs. Sham group. #p< 0.05 and ##p< 0.01, vs. SCI group. &p< 0.05 and &&p< 0.01, vs. BA group.

4). Downregulation of VEGFA accelerates AGEs-mediated nucleus pulposus degeneration through inhibiting protective mitophagy in high glucose environments. International journal of biological macromolecules, 2024 (PubMed: 38320636) [IF=8.2]

5). Dietary disodium fumarate supplementation alleviates subacute ruminal acidosis (SARA)-induced liver damage by inhibiting pyroptosis via mitophagy-NLRP3 inflammasome pathway in lactating Hu sheep. Frontiers in Immunology, 2023 (PubMed: 37275885) [IF=7.3]

Application: WB    Species: Hu Sheep    Sample: liver tissue

Figure 8 Effect of DF supplementation on mitophagy. (A) Expression of autophagy-related genes. (B, C) Expression of autophagy-related proteins in the whole cell lysate. (D, E) Expression of mitophagy-related proteins in the mitochondria protein extract. n=6 per group and the values are the mean ± SEM. ** P

6). Activation of aldehyde dehydrogenase-2 improves ischemic random skin flap survival in rats. Frontiers in Immunology, 2023 (PubMed: 37441072) [IF=7.3]

Application: IHC    Species: Mouse    Sample:

Figure 9 (A) Immunohistochemistry images of ALDH2, PINK1 and Parkin. All images were obtained at identical magnification, ×200, scale bar = 50 μm. (B) Quantitative analysis of ALDH2, PINK1 and Parkin content (n = 3). Data are represented as mean ± SEM. **P

7). Polystyrene microplastics induce mitochondrial damage in mouse GC-2 cells. ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY, 2022 (PubMed: 35489138) [IF=6.8]

Application: WB    Species: mouse    Sample: GC-2 cells

Fig. 2.| Effects of PS-MPS on mitochondrial membrane protein and membrane potential in control group and PS-MPS group after 24 h. (D) Relative protein expression of Parkin. The grey value was analyzed by Image J software.

8). Bexarotene improves motor function after spinal cord injury in mice. Neural Regeneration Research, 2023 (PubMed: 37449638) [IF=6.1]

Application: WB    Species: Mouse    Sample: spinal cord

Figure 6 Bexarotene promotes mitophagy and decreases ROS levels after SCI. (A) Immunofluorescence staining for GSDMD (pyroptosis-related marker, green), C-CASP1 (pyroptosis-related marker, red), NIX (mitophagy-related marker, red) and DHE (indicating ROS-positive cells, red) in neurons in the spinal cord (original magnification 30×). Scale bar: 25 μm. (B–E) Quantitative analysis of levels of GSDMD (B), C-CASP1 (C), NIX (D) and DHE (E) in A. (F–H) The levels of 8-OHdG and AOPP in the spinal cord were detected by ELISA, and the levels of MDA were detected by the thiobarbituric acid assay. (I, L) Western blot assay for pyroptosis-related and mitophagy-related proteins. Data were normalized to GAPDH. (M) The levels of mitophagy-related genes in the spinal cord were detected by qPCR and normalized to β-actin. Data are expressed as the mean ± SEM (n = 6 mice per group). *P < 0.05 and **P < 0.01, vs. SCI group; #P < 0.05 and ##P < 0.01, vs. SCI + Bex group (one-way analysis of variance with the least significance difference post hoc test). ASC: Apoptosis-associated speck-like protein containing a CARD; Bex: bexarotene; BNIP3: BCL2/adenovirus E1B 19 kDa interacting protein 3; C-CASP-1: cleaved Caspase 1; DAPI: 4′,6-diamidino-2-phenylindole; DHE: dihydroethidium; ELISA: enzyme-linked immunosorbent assay; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; GSDMD-N: gasdermin D-N; IOD: integrated optical density; MDA: malondialdehyde; NIX/BNIP3L: BCL2/adenovirus E1B 19 kDa interacting protein 3 like; NLRP3: NOD-like receptor thermal protein domain associated protein 3; SCI: spinal cord injury.

9). 贝沙罗汀改善脊髓损伤后运动功能的机制. 中国神经再生研究(英文版), 2023 (PubMed: 37449638) [IF=6.1]

Application: WB    Species: Mouse    Sample:

Figure 6 Bexarotene promotes mitophagy and decreases ROS levels after SCI. (A) Immunofluorescence staining for GSDMD (pyroptosis-related marker, green), C-CASP1 (pyroptosis-related marker, red), NIX (mitophagy-related marker, red) and DHE (indicating ROS-positive cells, red) in neurons in the spinal cord (original magnification 30×). Scale bar: 25 μm. (B–E) Quantitative analysis of levels of GSDMD (B), C-CASP1 (C), NIX (D) and DHE (E) in A. (F–H) The levels of 8-OHdG and AOPP in the spinal cord were detected by ELISA, and the levels of MDA were detected by the thiobarbituric acid assay. (I, L) Western blot assay for pyroptosis-related and mitophagy-related proteins. Data were normalized to GAPDH. (M) The levels of mitophagy-related genes in the spinal cord were detected by qPCR and normalized to β-actin. Data are expressed as the mean ± SEM (n = 6 mice per group). *P < 0.05 and **P < 0.01, vs. SCI group; #P < 0.05 and ##P < 0.01, vs. SCI + Bex group (one-way analysis of variance with the least significance difference post hoc test). ASC: Apoptosis-associated speck-like protein containing a CARD; Bex: bexarotene; BNIP3: BCL2/adenovirus E1B 19 kDa interacting protein 3; C-CASP-1: cleaved Caspase 1; DAPI: 4′,6-diamidino-2-phenylindole; DHE: dihydroethidium; ELISA: enzyme-linked immunosorbent assay; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; GSDMD-N: gasdermin D-N; IOD: integrated optical density; MDA: malondialdehyde; NIX/BNIP3L: BCL2/adenovirus E1B 19 kDa interacting protein 3 like; NLRP3: NOD-like receptor thermal protein domain associated protein 3; SCI: spinal cord injury.

10). Investigation of He's Yang Chao recipe against oxidative stress-related mitophagy and pyroptosis to improve ovarian function. Frontiers in Endocrinology, 2023 (PubMed: 36777359) [IF=5.2]

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