Recombinant Human E3 ubiquitin-protein ligase SIAH1(SIAH1)

Code CSB-EP818230HU
Size US$1726Purchase it in Cusabio online store
(only available for customers from the US)
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  • (Tris-Glycine gel) Discontinuous SDS-PAGE (reduced) with 5% enrichment gel and 15% separation gel.

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Product Details

Purity Greater than 90% as determined by SDS-PAGE.
Target Names SIAH1
Uniprot No. Q8IUQ4
Research Area Neuroscience
Alternative Names E3 ubiquitin-protein ligase SIAH1; FLJ08065; hSIAH1; HUMSIAH; Seven in absentia homolog 1 (Drosophila); Seven in absentia homolog 1; Siah 1; Siah 1a; Siah E3 ubiquitin protein ligase 1; Siah-1; Siah-1a; Siah1; SIAH1_HUMAN; SIAH1A; Ubiquitin ligase SIAH1
Species Homo sapiens (Human)
Source E.coli
Expression Region 1-313aa
Target Protein Sequence MTGKATPPSLYSWRGVLFTCLPAARTRKRKEMSRQTATALPTGTSKCPPSQRVPALTGTTASNNDLASLFECPVCFDYVLPPILQCQSGHLVCSNCRPKLTCCPTCRGPLGSIRNLAMEKVANSVLFPCKYASSGCEITLPHTEKADHEELCEFRPYSCPCPGASCKWQGSLDAVMPHLMHQHKSITTLQGEDIVFLATDINLPGAVDWVMMQSCFGFHFMLVLEKQEKYDGHQQFFAIVQLIGTRKQAENFAYRLELNGHRRRLTWEATPRSIHEGIATAIMNSDCLVFDTSIAQLFAENGNLGINVTISMC
Note: The complete sequence including tag sequence, target protein sequence and linker sequence could be provided upon request.
Mol. Weight 61.6kDa
Protein Length Full Length of Isoform 2
Tag Info N-terminal GST-tagged
Form 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.
Buffer If the delivery form is liquid, the default storage buffer is Tris/PBS-based buffer, 5%-50% glycerol.
Note: If you have any special requirement for the glycerol content, please remark when you place the order.
If the delivery form is lyophilized powder, the buffer before lyophilization is Tris/PBS-based buffer, 6% Trehalose, pH 8.0.
Reconstitution We recommend that this vial be briefly centrifuged prior to opening to bring the contents to the bottom. Please reconstitute protein in deionized sterile water to a concentration of 0.1-1.0 mg/mL.We recommend to add 5-50% of glycerol (final concentration) and aliquot for long-term storage at -20°C/-80°C. Our default final concentration of glycerol is 50%. Customers could use it as reference.
Troubleshooting
and FAQs
Protein FAQs
Storage Condition Store at -20°C upon receipt, aliquoting is necessary for mutiple use. Avoid repeated freeze-thaw cycles.
Shelf Life 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.
Lead Time Delivery time may differ from different purchasing way or location, please kindly consult your local distributors for specific delivery time.
Notes 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.

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Target Background

Function
(From Uniprot)
E3 ubiquitin-protein ligase that mediates ubiquitination and subsequent proteasomal degradation of target proteins. E3 ubiquitin ligases accept ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to targeted substrates. Mediates E3 ubiquitin ligase activity either through direct binding to substrates or by functioning as the essential RING domain subunit of larger E3 complexes. Triggers the ubiquitin-mediated degradation of many substrates, including proteins involved in transcription regulation (ELL2, MYB, POU2AF1, PML and RBBP8), a cell surface receptor (DCC), the cell-surface receptor-type tyrosine kinase FLT3, the cytoplasmic signal transduction molecules (KLF10/TIEG1 and NUMB), an antiapoptotic protein (BAG1), a microtubule motor protein (KIF22), a protein involved in synaptic vesicle function in neurons (SYP), a structural protein (CTNNB1) and SNCAIP. Confers constitutive instability to HIPK2 through proteasomal degradation. It is thereby involved in many cellular processes such as apoptosis, tumor suppression, cell cycle, axon guidance, transcription regulation, spermatogenesis and TNF-alpha signaling. Has some overlapping function with SIAH2. Induces apoptosis in cooperation with PEG3. Upon nitric oxid (NO) generation that follows apoptotic stimulation, interacts with S-nitrosylated GAPDH, mediating the translocation of GAPDH to the nucleus. GAPDH acts as a stabilizer of SIAH1, facilitating the degradation of nuclear proteins.
Gene References into Functions
  1. Depletion of KDM3A coincided with the loss of SIAH1 induction and the accumulation of dimethylated H3K9 surrounding the SIAH1 promoter. Interestingly, KDM3A expression was also up-regulated by nutritional stress in a HIF-1alpha dependent manner. PMID: 28843785
  2. The crystallographic models provide structural insights into the substrate binding of the SIAH family E3 ubiquitin ligases that are critically involved in regulating cancer-related pathways. PMID: 27776223
  3. Results showed that SIAH1 and PTP4A1 expression was regulated by mir-944 in breast cancer cells. miR-944 binds directly the 3 UTR of their promotor region. PMID: 27377268
  4. Study identified SIAH1/2 (SIAH) as the E3 ligase mediating Wnt-induced Axin degradation. SIAH proteins promote the ubiquitination and proteasomal degradation of Axin through interacting with a VxP motif in the GSK3-binding domain of Axin, and this function of SIAH is counteracted by GSK3 binding to Axin. PMID: 28546513
  5. results suggest that CacyBP/SIP is involved in regulation of the Hsp90 chaperone machinery PMID: 27249023
  6. PINK1 disease mutants failed to recruit synphilin-1 and did not activate mitophagy, indicating that PINK1-synphilin-1-SIAH-1 represents a new parkin-independent mitophagy pathway. Drugs that activate this pathway will provide a novel strategy to promote the clearance of damaged mitochondria in Parkinson's disease. PMID: 27334109
  7. Results suggest that activated STAT3 regulates active beta-catenin protein levels via stabilization of SIAH-1 and the subsequent ubiquitin-dependent proteasomal degradation of beta-catenin in HEK293T cells. PMID: 27871173
  8. Siah-1 expression was observed in 41.4% of oral squamous cell carcinoma. Siah-1 was expressed in the cytoplasm and cell membranes, and partially in the nucleus . PMID: 27616748
  9. SIAH1 is associated with a tumor promoting role in breast cancer. PMID: 26654769
  10. In neuroblastoma cells, siRNA silencing of SIAH1 promoted cellular proliferation and suppressed apoptosis. Protein and mRNA expression of alpha-synuclein, LC3-II and p53 decreased after SIAH1 knockdown. E1 protein and mRNA levels increased after SIAH1 siRNA. PMID: 26722480
  11. Results demonstrated that miR-107 directly down-regulated SIAH1 expression in human breast cancer cells. An inverse correlation between the expression of miR-107 and SIAH1 was found in human breast cancer tissues and cell lines. PMID: 25851994
  12. Similar to TAp73, DNp73 is stabilized by hypoxia in a HIF-1a-dependent manner, which otherwise is degraded by Siah1. PMID: 26267146
  13. findings demonstrate that dissociation of the GAPDH/Siah1 pro-apoptotic complex can block high glucose-induced pericyte apoptosis, widely considered a hallmark feature of DR PMID: 26438826
  14. Data indicate that ubiquitin ligase Siah as a regulator of to Mesenchymal Transition (EMT) by controlling the abundance of the key transcription factor Zeb1, while Siah itself is subject to regulation by EMT-inducing factors. PMID: 25528765
  15. miRNA network regulates SIAH1 in in colorectal metastasis tissues. PMID: 26069251
  16. CDK2 up-regulates the protein level of KLF10 through reducing its association with SIAH1, a KLF10 E3-ubiqutin ligase involved in proteasomal degradation. PMID: 25728284
  17. molecular basis of Siah1 and Siah2 E3 ubiquitin ligase substrate specificity PMID: 25202994
  18. Siah1 is a substrate of ASK1 for activation of the GAPDH-Siah1 oxidative stress signaling cascade. PMID: 25391652
  19. SIAH-1 plays an essential role in beta-catenin degradation in HCT116 CRC cells and that CSN5 affects beta-catenin target gene expression in these cells. PMID: 24882689
  20. miR-135a/SIAH1/beta-catenin signaling is important in the transformation and progression of cervical carcinoma. PMID: 24503442
  21. The spatial orientation of one zinc-finger subdomain in Siah1 ubiquitin ligase differs with respect to the rest of the dimeric protein. PMID: 24316825
  22. the molecular mechanisms modulating ACK1 PMID: 23208506
  23. USP19 interacts with the ubiquitin ligases SIAH1 and SIAH2, which promote USP19 ubiquitylation and degradation by the proteasome. PMID: 23500468
  24. High expression of seven-in-absentia homologue 1 is associated with nasopharyngeal carcinoma. PMID: 23228635
  25. Calmodulin-regulated Siah-1A binding to mGluR5 dynamically regulates mGluR5 trafficking PMID: 23152621
  26. Siah1 is the E3 ubiquitin ligase for ELL2 polyubiquitination and proteasomal degradation. PMID: 22483617
  27. In sharp contrast to SIAH1/SIAH2 and UBCH8, TRIAD1 binding to PML-RARalpha has no effect on its turnover. PMID: 22037423
  28. Taken together, our data suggest EFF1D functions as a novel negative regulator of SIAH-1. PMID: 21633900
  29. Siah-1 may play an important role in ubiquitin-dependent degradation of hepatitis B virus X protein and may be involved in suppressing the progression of hepatocellular carcinoma (HCC). PMID: 21878328
  30. infection of SIAH-1 knockdown cells with HSV, higher levels of ICP0 were produced, ICP0 was less ubiquitinated, and the half-life of this multifunctional viral regulatory protein was increased PMID: 21632771
  31. results suggest that hypoxia downregulates beta-catenin by increasing Siah-1 expression in a p53-dependent manner PMID: 21466614
  32. ARTS interacts with the E3 ligase Siah-1 (seven in absentia homolog 1) to induce ubiquitination and degradation of XIAP. PMID: 21185211
  33. Herp temporarily bound to E3 ligase SIAH1a during proteolytic stress but not during ER stress. PMID: 20604806
  34. Overexpression of Siah1L and Siah1 is associated with radiosensitivity of breast cancer. PMID: 20682032
  35. these results propose a novel role of SIAH-1 in regulating the expression level of HPH2 through the ubiquitin-proteasome pathway. PMID: 20471960
  36. Siah1 is a bona fide E2F1 target gene, which at least partly, mediates the suppression of beta-catenin/TCF signalling pathway PMID: 20187294
  37. Immunofluorescence microscopy shows that the intracellular distribution of SIAH-1 and Kid/KIF22 appears to be modified in human tumor tissues compared to normal controls PMID: 20144232
  38. increase of the function of SIAH1 to upregulate the expression of Bim may play an important role in the progression of breast cancer PMID: 20082325
  39. Direct ubiquitination of beta-catenin by Siah-1 and regulation by the exchange factor TBL1. PMID: 20181957
  40. JNK and ERK signaling pathways may play an important role in the SIAH1-dependent biological behavior of breast cancer. PMID: 19775288
  41. siah-1 Protein is necessary for high glucose-induced glyceraldehyde-3-phosphate dehydrogenase nuclear accumulation and cell death in Muller PMID: 19940145
  42. Siah proteins function as E3 ubiquitin-protein ligases PMID: 11786535
  43. The Siah-1 gene promoter was cloned and the basic structure of the Siah-1 gene was determined. PMID: 11852084
  44. genetic regulation in tumor reversion PMID: 12399545
  45. structural analysis and interaction with Siah-interacting protein PMID: 12421809
  46. SIAH1 has been identified as a putative tumor suppressor gene for human hepatocellular carcinomas, with a correlation between its suppressed expression and tumor size and differentiation. PMID: 12557228
  47. PEG10 protein associated with SIAH1, a mediator of apoptosis, and overexpression of PEG10 decreased the cell death mediated by SIAH1. PMID: 12810624
  48. Siah-1 was found to abrogate the inhibitory effects of synphilin-1 on dopamine release PMID: 14506261
  49. A p53-binding site was identified in the siah-1b promoter, located at nucleotides -2155/-2103 relative to the translational start site. PMID: 14985507
  50. SIAH-mediated down regulation of alternative splicing may be an important developmental difference between otherwise highly conserved T-STAR proteins. PMID: 15163637

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Subcellular Location Cytoplasm, Nucleus
Protein Families SINA (Seven in absentia) family
Tissue Specificity Widely expressed at a low level. Down-regulated in advanced hepatocellular carcinomas.
Database Links

HGNC: 10857

OMIM: 602212

KEGG: hsa:6477

STRING: 9606.ENSP00000349156

UniGene: Hs.706828

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