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  4. VCP Recombinant Monoclonal Antibody

VCP Recombinant Monoclonal Antibody

  • 货号：
    CSB-RA182227A0HU
  • 规格：
    ￥1320
  • 图片：
    • Western Blot
      Positive WB detected in: Hela whole cell lysate, MCF-7 whole cell lysate, U251 whole cell lysate, Rat brain tissue, Rat liver tissue
      All lanes: VCP antibody at 1:2000
      Secondary
      Goat polyclonal to rabbit IgG at 1/50000 dilution
      Predicted band size: 90 kDa
      Observed band size: 90 kDa
    • IHC image of CSB-RA182227A0HU diluted at 1:100 and staining in paraffin-embedded human breast cancer performed on a Leica BondTM system. After dewaxing and hydration, antigen retrieval was mediated by high pressure in a citrate buffer (pH 6.0). Section was blocked with 10% normal goat serum 30min at RT. Then primary antibody (1% BSA) was incubated at 4℃ overnight. The primary is detected by a Goat anti-rabbit IgG polymer labeled by HRP and visualized using 0.05% DAB.
    • IHC image of CSB-RA182227A0HU diluted at 1:100 and staining in paraffin-embedded human glioma cancer performed on a Leica BondTM system. After dewaxing and hydration, antigen retrieval was mediated by high pressure in a citrate buffer (pH 6.0). Section was blocked with 10% normal goat serum 30min at RT. Then primary antibody (1% BSA) was incubated at 4℃ overnight. The primary is detected by a Goat anti-rabbit IgG polymer labeled by HRP and visualized using 0.05% DAB.
    • Immunofluorescence staining of SY5Y Cells with CSB-RA182227A0HU at 1:50, counter-stained with DAPI. The cells were fixed in 4% formaldehyde, permeated by 0.2% TritonX-100, and blocked in 10% normal Goat Serum. The cells were then incubated with the antibody overnight at 4℃. Nuclear DNA was labeled in blue with DAPI. The secondary antibody was FITC-conjugated AffiniPure Goat Anti-Rabbit IgG (H+L).
    • Immunoprecipitating VCP in U251 whole cell lysate
      Lane 1: Rabbit control IgG instead of CSB-RA182227A0HU in U251 whole cell lysate. For western blotting,a HRP-conjugated Protein G antibody was used as the secondary antibody (1/2000)
      Lane 2: CSB-RA182227A0HU(2µg)+ U251 whole cell lysate(500µg)
      Lane 3: U251 whole cell lysate (10µg)
  • 其他：

产品详情

  • 产品描述：

    The VCP gene genes for valosin-containing protein, which belongs to the AAA(+) ATPase family of chaperone-like proteins that govern chromatin organization, cell cycle control, membrane fusion, ubiquitin-dependent protein degradation, and autophagy, among other cellular processes. Mutations in VCP have been shown to be the cause of inclusion body myopathy, Paget’s disease and frontotemporal dementia (IBMPFD), and amyotrophic lateral sclerosis (ALS), among other degenerative diseases. VCP has also been linked to cancer. High expression of VCP has been detected in non-small cell lung carcinoma and is linked to tumor progression and prognosis.

    The generation of the recombinant VCP antibody includes obtaining the VCP antibody gene, cloning the gene into a plasma vector, introducing the recombinant vector into mammalian cell lines, and achieving expression of adequate amounts of functional antibody. The recombinant VCP antibody was purified using A synthesized peptide derived from human VCP. It is reactive with the VCP protein from Human, Rat and is suitable for the use in the ELISA, WB, IHC, IF, IP.

  • Uniprot No.：
    P55072
  • 基因名：
  • 别名：
    Transitional endoplasmic reticulum ATPase (TER ATPase) (EC 3.6.4.6) (15S Mg(2+)-ATPase p97 subunit) (Valosin-containing protein) (VCP), VCP
  • 反应种属：
    Human, Rat
  • 免疫原：
    A synthesized peptide derived from human VCP
  • 免疫原种属：
    Homo sapiens (Human)
  • 标记方式：
    Non-conjugated
  • 克隆类型：
    Monoclonal
  • 抗体亚型：
    Rabbit IgG
  • 纯化方式：
    Affinity-chromatography
  • 克隆号：
    5H12
  • 浓度：
    It differs from different batches. Please contact us to confirm it.
  • 保存缓冲液：
    Rabbit IgG in phosphate buffered saline, pH 7.4, 150mM NaCl, 0.02% sodium azide and 50% glycerol.
  • 产品提供形式：
    Liquid
  • 应用范围：
    ELISA, WB, IHC, IF, IP
  • 推荐稀释比：
    Application Recommended Dilution
    WB 1:500-1:5000
    IHC 1:50-1:200
    IF 1:20-1:200
    IP 1:200-1:1000
  • Protocols：
  • 储存条件：
    Upon receipt, store at -20°C or -80°C. Avoid repeated freeze.
  • 货期：
    Basically, we can dispatch the products out in 1-3 working days after receiving your orders. Delivery time maybe differs from different purchasing way or location, please kindly consult your local distributors for specific delivery time.

产品评价

靶点详情

  • 功能：
    Necessary for the fragmentation of Golgi stacks during mitosis and for their reassembly after mitosis. Involved in the formation of the transitional endoplasmic reticulum (tER). The transfer of membranes from the endoplasmic reticulum to the Golgi apparatus occurs via 50-70 nm transition vesicles which derive from part-rough, part-smooth transitional elements of the endoplasmic reticulum (tER). Vesicle budding from the tER is an ATP-dependent process. The ternary complex containing UFD1, VCP and NPLOC4 binds ubiquitinated proteins and is necessary for the export of misfolded proteins from the ER to the cytoplasm, where they are degraded by the proteasome. The NPLOC4-UFD1-VCP complex regulates spindle disassembly at the end of mitosis and is necessary for the formation of a closed nuclear envelope. Regulates E3 ubiquitin-protein ligase activity of RNF19A. Component of the VCP/p97-AMFR/gp78 complex that participates in the final step of the sterol-mediated ubiquitination and endoplasmic reticulum-associated degradation (ERAD) of HMGCR. Involved in endoplasmic reticulum stress-induced pre-emptive quality control, a mechanism that selectively attenuates the translocation of newly synthesized proteins into the endoplasmic reticulum and reroutes them to the cytosol for proteasomal degradation. Plays a role in the regulation of stress granules (SGs) clearance process upon arsenite-induced response. Also involved in DNA damage response: recruited to double-strand breaks (DSBs) sites in a RNF8- and RNF168-dependent manner and promotes the recruitment of TP53BP1 at DNA damage sites. Recruited to stalled replication forks by SPRTN: may act by mediating extraction of DNA polymerase eta (POLH) to prevent excessive translesion DNA synthesis and limit the incidence of mutations induced by DNA damage. Together with SPRTN metalloprotease, involved in the repair of covalent DNA-protein cross-links (DPCs) during DNA synthesis. Involved in interstrand cross-link repair in response to replication stress by mediating unloading of the ubiquitinated CMG helicase complex. Required for cytoplasmic retrotranslocation of stressed/damaged mitochondrial outer-membrane proteins and their subsequent proteasomal degradation. Essential for the maturation of ubiquitin-containing autophagosomes and the clearance of ubiquitinated protein by autophagy. Acts as a negative regulator of type I interferon production by interacting with DDX58/RIG-I: interaction takes place when DDX58/RIG-I is ubiquitinated via 'Lys-63'-linked ubiquitin on its CARD domains, leading to recruit RNF125 and promote ubiquitination and degradation of DDX58/RIG-I. May play a role in the ubiquitin-dependent sorting of membrane proteins to lysosomes where they undergo degradation. May more particularly play a role in caveolins sorting in cells. By controlling the steady-state expression of the IGF1R receptor, indirectly regulates the insulin-like growth factor receptor signaling pathway.
  • 基因功能参考文献：
    1. These results indicate that the outer membrane protein MCL1 is degraded by the VCP-UBXD1 complex and that the process is promoted by the presence of mutant Huntingtin. PMID: 27913212
    2. Study results suggest that VCP recruitment to mitochondria by mtHtt is a crucial step in the initiation of neuropathology in Huntington's disease. PMID: 27561680
    3. ASPL efficiently promotes p97 hexamer disassembly, resulting in the formation of stable p97:ASPL. Overproduction of ASPL disrupts p97 hexamer function in endoplasmic reticulum-associated protein degradation. PMID: 27762274
    4. Data indicate that approximately 9% of patients with valosin-containing protein (VCP) mutations had an amyotrophic lateral sclerosis (ALS) phenotype, 4% had been diagnosed with Parkinson's disease (PD), and 2% had been diagnosed with Alzheimer's disease (AD). PMID: 28692196
    5. CB-5083 decreases viability in multiple myeloma cell lines and patient-derived multiple myeloma cells, including those with background proteasome inhibitor (PI) resistance. CB-5083 has a unique mechanism of action that combines well with PIs, which is likely owing to the p97-dependent retro-translocation of the transcription factor, Nrf1, which transcribes proteasome subunit genes following exposure to a PI PMID: 28878026
    6. a p97 mutant that causes inclusion body myopathy, Paget's disease of bone, and frontotemporal dementia unfolds substrate faster, suggesting that excess activity may underlie pathogenesis PMID: 28512218
    7. Results report that VCP/p97 promotes the degradation of ubiquitylated GS, resulting in its accumulation in cells with compromised p97 function. Notably, p97 is also required for the degradation of all four known CRBN neo-substrates [IKZF1, IKZF3, CK1alpha, and GSPT1] whose ubiquitylation is induced by immunomodulatory drugs. PMID: 28320958
    8. non-cell-autonomous effects of VCP-mutant astrocytes on both control and mutant Motor neurons, were examined. PMID: 28564594
    9. AAA-ATPase p97 suppresses apoptotic and autophagy-associated cell death in rheumatoid arthritis synovial fibroblasts. PMID: 27623077
    10. Data suggest ATXN3 binds with low-micromolar affinity to both wild-type p97/VCP and mutants linked to proteostasis deficiency multisystem proteinopathy 1 (MSP1; also called hereditary inclusion body myopathy); stoichiometry of binding is one ATXN3 molecule per p97/VCP hexamer in presence of ATP; MSP1 mutants of p97/VCP bind ATXN3 irrespective of nucleotide state. (VCP = valosin-containing protein/ATPase; ATXN3 = ataxin-3) PMID: 28939772
    11. a substantial proportion of the beta2AR produced is non-functional and VCP plays a key role in the maturation and trafficking of the beta2AR. PMID: 27887991
    12. Its mutation is not found in a cohort of German patients with sporadic amyotrophic lateral sclerosis and frontotemporal lobar degeneration comorbidity. PMID: 28551275
    13. When HEK293T cells were co-transfected with IQGAP1 and VCP, an immunoprecipitation assay revealed that binding of IQGAP1 with disease-related mutant (R155H or A232E) VCP was markedly reduced compared to wild-type VCP. This suggests that reduction of IQGAP1 and VCP interaction may be associated with the pathophysiology of inclusion body myopathy with Paget's disease of bone and frontotemporal dementia (IBMPFD). PMID: 28970065
    14. Rare variants in VCP genes are risk for sporadic inclusion body myositis. PMID: 27594680
    15. Knockdown of the host ubiquitin-dependent segregase VCP/p97, results in loss of IE2 expression, subsequent suppression of early and late gene expression and, ultimately, failure in virus replication. NMS-873, a small molecule inhibitor of VCP, is a potent HCMV antiviral with potential as a novel host targeting therapeutic for HCMV infection. PMID: 28494016
    16. VCP removes sterically trapped Ku70/80 rings from DNA in double-strand break repair. PMID: 27716483
    17. Data suggest that AAA+ (ATPases associated with diverse cellular activities) ATPase p97 is essential to wide range of cellular functions, including endoplasmic reticulum-associated degradation, membrane fusion, NFkappaB (nuclear factor kappa-light-chain-enhancer of activated B cells) activation, and chromatin-associated processes, which are regulated by ubiquitination. [REVIEW] PMID: 28819009
    18. Upon damage, p97 translocates to lysosomes and there cooperates with a distinct set of cofactors including UBXD1, PLAA, and the deubiquitinating enzyme YOD1, which we term ELDR components for Endo-Lysosomal Damage Response. PMID: 27753622
    19. Data show that inhibition of VCP/p97, or siRNA-mediated ablation of VCP/p97 impairs ultraviolet radiation (UVR)-induced RNA polymerase II (RNAPII) degradation. PMID: 28036256
    20. p97 negatively regulates NRF2 through the canonical pathway by extracting ubiquitylated NRF2 from the KEAP1-CUL3 E3 complex. PMID: 28115426
    21. Data suggest that dimerization of UBX domain protein 7 (UBXD7) could affect the formation of the p97 ATPase-UBXD7 complex. PMID: 28274878
    22. a VCP mutation/knockdown-induced dysregulation in the adenine nucleotide translocase, which results in a slower rate of ADP or ATP translocation across the mitochondrial membranes. PMID: 28360103
    23. The functional motions of p97 using symmetric normal modes have been predicted. PMID: 27653958
    24. insights into the interactions between other SHP-containing proteins and p97N PMID: 27714797
    25. The findings of the present study indicated that VCP is very important for the proliferation and metastasis of colorectal cancer; therefore, targeting VCP and its downstream targets may represent novel therapies for the treatment of colorectal cancer. PMID: 27344168
    26. Timely and efficient degradation of ubiquitinated IkappaB[alpha], concomitant with timely and efficient liberation of RelA from ubiquitinated IkappaB[alpha] and RelA nuclear translocation, essentially depends on the presence of functional p97/VCP. PMID: 26463447
    27. Its gene mutation is correlated with occurrence of amyotrophic lateral sclerosis. PMID: 26511028
    28. results have revealed SUMOylation as a molecular signaling switch to regulate the distribution and functions of VCP during stress response, and suggest that deficiency in VCP SUMOylation caused by pathogenic mutations will render cells vulnerable to stress insults. PMID: 27226613
    29. depletion of VCP enzymatic activity triggers cancer cell death in part through inadequate regulation of protein synthesis and amino acid metabolism. PMID: 26720340
    30. new role of VCP/p97 segregase in the timely processing of ubiquitinated CSB from damaged chromatin. PMID: 26826127
    31. Ankrd13 proteins cooperate with VCP to regulate the lysosomal trafficking of ubiquitinated Cav-1. PMID: 26797118
    32. results suggest that human Cdc48 interacts functionally with the 20S proteasome. PMID: 26134898
    33. we show that loss of VCP induces endoplasmic reticulum stress and epithelial-mesenchymal transition PMID: 25970786
    34. interaction between SelK and p97(VCP) is SelS-dependent, and the resulting ERAD complex (SelS-p97(VCP)-SelK) plays an important role in ERAD and ER stress PMID: 26504085
    35. this study demonstrates significant correlation between the cytoplasmic expression of VCP and adverse prognosis in breast carcinoma, suggesting that VCP may serve as a prognostic biomarker in breast carcinoma. PMID: 26168958
    36. UBXD1-N intercalates into the p97-ND1 interface, thereby modulating interdomain communication of p97 domains and its activity with relevance for disease pathogenesis PMID: 26475856
    37. Our results provide the first structural clues of how VCP mutations may influence the activity and function of the D2 ATPase ring. PMID: 26549226
    38. Data indicate that ATPase p97 is a key mediator of several protein homeostasis processes and is a strong potential cancer target. PMID: 26555175
    39. activity of the p97-associated deubiquitinylase YOD1 is also required for substrate disposal PMID: 26463207
    40. specific silencing of Derlin-2, p97 and HRD1 by shRNAs increases steady state levels of proinsulin. these ERAD constituents are critically involved in proinsulin degradation and may therefore also play a role in subsequent antigen generation. PMID: 26107514
    41. A novel UGGT1- and p97-dependent protein quality checkpoint is shown. This checkpoint is alerted to prevent secretion of a polypeptide that passes the luminal quality control scrutiny by BiP and CNX but contains an intramembrane ionizable residue. PMID: 25694454
    42. Data show that UBXN10 localizes to cilia in a AAA-ATPase VCP-dependent manner and both VCP and UBXN10 are required for ciliogenesis. PMID: 26389662
    43. Valosin-containing protein is required for coronavirus exit from endosomes. PMID: 26311884
    44. Studies indicate that cofactor binding results in defined, productive p97 (also known as Cdc48, Ter94, and VCP) assemblies with specific cellular functions. PMID: 26320413
    45. A novel mutation, p.Arg487His Mutation in the VCP gene encoding valosin-containing protein (VCP) causes sporadic amyotrophic lateral sclerosis in Japanese. PMID: 25457024
    46. Data uncover an unexpected role for p97 in activation of transcription factor Nrf1 by relocalizing it from the endoplasmic reticulum lumen to the cytosol. PMID: 24448410
    47. Results support the idea that VCP is associated with the pathomechanism of sporadic amyotrophic lateral sclerosis and familial amyotrophic lateral sclerosis with a VCP mutation, presumably acting through a dominant-negative mechanism PMID: 25492614
    48. Data showed that VCP mutations are not a major cause of FALS in the UK population although novel rare variations in the 5' UTR of the VCP gene may be pathogenic. PMID: 25618255
    49. The level of VCP-intensity determined by immunohistochemistry could be an additional prognostic marker in HPV-negative (OSCC). PMID: 25463965
    50. targeting miR-129-5p/VCP signaling pathway may serve as a therapeutic strategy for osteosarcoma management PMID: 25566966

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  • 相关疾病：
    Inclusion body myopathy with early-onset Paget disease with or without frontotemporal dementia 1 (IBMPFD1); Amyotrophic lateral sclerosis 14, with or without frontotemporal dementia (ALS14); Charcot-Marie-Tooth disease 2Y (CMT2Y)
  • 亚细胞定位：
    Cytoplasm, cytosol. Endoplasmic reticulum. Nucleus. Cytoplasm, Stress granule.
  • 蛋白家族：
    AAA ATPase family
  • 数据库链接：

    HGNC: 12666

    OMIM: 167320

    KEGG: hsa:7415

    STRING: 9606.ENSP00000351777

    UniGene: Hs.529782