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  4. Recombinant Human E3 ubiquitin-protein ligase SIAH2 (SIAH2)

Recombinant Human E3 ubiquitin-protein ligase SIAH2 (SIAH2)

  • 货号：
    CSB-YP021288HU
  • 规格：
  • 来源：
    Yeast
  • 其他：
  • 货号：
    CSB-EP021288HU
  • 规格：
  • 来源：
    E.coli
  • 其他：
  • 货号：
    CSB-EP021288HU-B
  • 规格：
  • 来源：
    E.coli
  • 共轭：
    Avi-tag Biotinylated

    E. coli biotin ligase (BirA) is highly specific in covalently attaching biotin to the 15 amino acid AviTag peptide. This recombinant protein was biotinylated in vivo by AviTag-BirA technology, which method is BriA catalyzes amide linkage between the biotin and the specific lysine of the AviTag.

  • 其他：
  • 货号：
    CSB-BP021288HU
  • 规格：
  • 来源：
    Baculovirus
  • 其他：
  • 货号：
    CSB-MP021288HU
  • 规格：
  • 来源：
    Mammalian cell
  • 其他：

产品详情

  • 纯度：
    >85% (SDS-PAGE)
  • 基因名：
    SIAH2
  • Uniprot No.：
  • 别名：
    E3 ubiquitin-protein ligase Siah2; hSiah2; Seven in absentia homolog 2; Siah E3 ubiquitin protein ligase 2; Siah-2; siah2; SIAH2_HUMAN; Ubiquitin Ligase Siah2
  • 种属：
    Homo sapiens (Human)
  • 蛋白长度：
    Full length protein
  • 表达区域：
    1-324
  • 氨基酸序列
    MSRPSSTGPS ANKPCSKQPP PQPQHTPSPA APPAAATISA AGPGSSAVPA AAAVISGPGG GGGAGPVSPQ HHELTSLFEC PVCFDYVLPP ILQCQAGHLV CNQCRQKLSC CPTCRGALTP SIRNLAMEKV ASAVLFPCKY ATTGCSLTLH HTEKPEHEDI CEYRPYSCPC PGASCKWQGS LEAVMSHLMH AHKSITTLQG EDIVFLATDI NLPGAVDWVM MQSCFGHHFM LVLEKQEKYE GHQQFFAIVL LIGTRKQAEN FAYRLELNGN RRRLTWEATP RSIHDGVAAA IMNSDCLVFD TAIAHLFADN GNLGINVTIS TCCP
  • 蛋白标签：
    Tag type will be determined during the manufacturing process.
    The tag type will be determined during production process. If you have specified tag type, please tell us and we will develop the specified tag preferentially.
  • 产品提供形式：
    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.
  • 复溶：
    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℃/-80℃. Our default final concentration of glycerol is 50%. Customers could use it as reference.
  • 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：
    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 ：
    Please contact us to get it.

产品评价

靶点详情

  • 功能：
    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 (GPS2, POU2AF1, PML, NCOR1), a cell surface receptor (DCC), an antiapoptotic protein (BAG1), and a protein involved in synaptic vesicle function in neurons (SYP). Mediates ubiquitination and proteasomal degradation of DYRK2 in response to hypoxia. It is thereby involved in apoptosis, tumor suppression, cell cycle, transcription and signaling processes. Has some overlapping function with SIAH1. Triggers the ubiquitin-mediated degradation of TRAF2, whereas SIAH1 does not. Promotes monoubiquitination of SNCA. Regulates cellular clock function via ubiquitination of the circadian transcriptional repressors NR1D1 and NR1D2 leading to their proteasomal degradation. Plays an important role in mediating the rhythmic degradation/clearance of NR1D1 and NR1D2 contributing to their circadian profile of protein abundance. Mediates ubiquitination and degradation of EGLN2 and EGLN3 in response to the unfolded protein response (UPR), leading to their degradation and subsequent stabilization of ATF4.
  • 基因功能参考文献：
    1. DHX15 regulates androgen receptor (AR) activity by modulating E3 ligase Siah2-mediated AR ubiquitination independent of its ATPase activity promoting prostate cancer progression. PMID: 28991234
    2. the Siah2-PHD3- HIF-1alpha-VEGF axis is an important hypoxic signaling pathway in a leukemic microenvironment. PMID: 29400343
    3. Based on the proposition that NS5 utilizes SIAH2-mediated proteasomal degradation of STAT2, an in-silico study was carried out to characterize the protein-protein interactions between NS5, SIAH2 and STAT2 proteins. PMID: 28365387
    4. SIAH2 regulates CHK2 basal turnover, with important consequences on cell-cycle control and on the ability of hypoxia to alter the DNA damage-response pathway in cancer cells. PMID: 26751770
    5. study revealed an interesting mutual regulation between Plk3 and SIAH2 and uncovered a regulatory network that functions to fine-tune the cellular hypoxic response. PMID: 28515325
    6. ETS2 and Twist1 promote invasiveness of Helicobacter pylori-infected gastric cancer cells by inducing Siah2 PMID: 27048589
    7. Manipulation of SIAH2 expression led to a 'cross-talk' of the ERK and PI3K pathway. PMID: 27459914
    8. Siah-2 expression was observed in 29.3% of oral squamous cell carcinoma. Siah-2 was located in the cytoplasm and cell membranes. PMID: 27616748
    9. SIAH2 is associated with a tumor promoting role in breast cancer. PMID: 26654769
    10. Overexpression of Siah2 Is Associated With Epithelial Ovarian Carcinoma PMID: 26512788
    11. Our results suggest that SIAH2 regulates multi processes in T-cell acute lymphoblastic leukemia PMID: 26859780
    12. The expression of SIAH2 is increased in human lung cancer. PMID: 26580787
    13. the E3 ubiquitin ligase SIAH2 stimulates YAP by destabilizing LATS2, a critical component of the Hippo pathway, in response to hypoxia. PMID: 25438054
    14. The down-regulation of SIAH2 conferred sensitivity to anti-cancer drugs. The results of the study indicated that the miR-335/SIAH2/HDAC3 axis regulates the response to anti-cancer drugs. PMID: 25997740
    15. Data show that ubiquitin E3 ligase Siah2 depletion delays circadian degradation of nuclear hormone receptor RevErbalpha (Nr1d1) and lengthens period length. PMID: 26392558
    16. A catalysis-independent role for AKR1C3 on AR activity via Siah2 has been identified. PMID: 26160177
    17. the E3 ubiquitin ligase seven-in-absentia-2 (SIAH2) accelerates the proteasomal degradation of TYK which consequently suppresses the activation of STAT3 in non-small-cell lung cancer PMID: 24833526
    18. A common variant in the SIAH2 locus is associated with ER-positive breast cancer in the Chinese Han population. PMID: 24244489
    19. our studies demonstrate the role of Siah2 in regulation of tight junction integrity and cell polarity under hypoxia, through its regulation of ASPP2 stability. PMID: 23644657
    20. SIAH2 expression is upregulated in basal-like breast cancers via copy number changes and/or transcriptional activation by p53. PMID: 21306611
    21. SIAH2 overexpression is associated with oral squamous cell carcinoma. PMID: 24222137
    22. Single Nucleotide Polymorphism in SIAH2 gene is associated with hormonal receptor-positive breast cancer. PMID: 22951594
    23. Data suggest that Keap1 does not contribute to hypoxic Nrf2 suppression, and both HIF-1alpha and Siah2 are key regulators of hypoxic responses. PMID: 23645672
    24. SIAH2 knockdown increases DYRK2 stability, whereas SIAH2 expression facilitates DYRK2 polyubiquitination and degradation PMID: 22878263
    25. study found Siah2 enhances transcriptional activity of androgen receptor (AR) by degrading transcriptionally-inactive AR on select gene promoters/enhancers; Siah2 promotes expression of select AR target genes, leading to growth of castration-resistant prostate cancer cells under androgen-deprivation conditions PMID: 23518348
    26. SIAH-2 - as described for SIAH-1 - accumulates in nuclei of hepatocellular carcinoma cells where it supports tumor growth and tumor cell dissemination PMID: 22323152
    27. Siah2 acts as an E3 ligase to directly ubiquitylate TIN2 in vitro. PMID: 22064479
    28. Src kinase activity downregulates C/EBP-delta protein but not mRNA levels through a SIAH2 E3 ligase-dependent mechanism. PMID: 22037769
    29. study identifies a new layer of Siah2 regulation mediated by USP13 binding to ubiquitinated Siah2 protein with a concomitant inhibitory effect on its activity under normoxia PMID: 21659512
    30. The data presented here define POSH and Siah2 as important mediators of death receptor mediated apoptosis and suggest targeting the interaction of these two E3 ligases is a promising novel cancer therapeutic strategy. PMID: 21586138
    31. Review: Define the regulatory axis consisting of Siah2 and HIF-1alpha/FoxA2 cooperation and suggest novel therapeutic modalities to treat these most aggressive forms of prostate cancer. PMID: 21037926
    32. The ability of myosin phosphatase to modulate myosin light chain might be regulated by the degradation of its targeting subunit MYPT1 through the SIAH2-ubiquitin-proteasomal pathway. PMID: 19744480
    33. SIAH2 regulates the expression of promyelocytic leukemia protein and other tripartite motif proteins PMID: 14645235
    34. SIAH2 regulates stability of prolyl- hydroxylases, controls HIF1alpha abundance, and modulates physiological responses to hypoxia. PMID: 15210114
    35. 2-oxoglutarate (alpha-ketoglutarate) dehydrogenase stability is regulated by the RING finger ubiquitin ligase Siah PMID: 15466852
    36. mechanism by which the estrogen-ER complex markedly reduces the level of N-CoR through a process involving the up-regulation of Siah2 and the subsequent targeting of N-CoR for proteasomal degradation PMID: 16141343
    37. Association of two isoforms Siah1 and Siah2 results in the regulation of Siah1 stability by Siah2 in the presence of a ring finger domain in HEK293 cells. PMID: 16899216
    38. Mechanism underlying the regulation of PHD3 availability and activity in hypoxia by the E3 ligase Siah2. PMID: 16958618
    39. The role of Siah2 phosphorylation in the regulation of its activity toward PHD3 is reported. PMID: 17003045
    40. We provide evidences for hSiah2-dependent degradation of Pias as being a mechanism in the regulation of c-jun N-terminal kinase-activating pathways. PMID: 17533377
    41. Data show that Siah2 is an important mediator of repp86 protein degradation. PMID: 17716627
    42. In primary breast tumor specimens as well as in vitro low SIAH2 levels associated with resistance to endocrine therapy. PMID: 18629630
    43. Siah1 (human) reduced PHD3 protein levels similar to that observed with Siah2. PHDs may not interact directly with Siah2, but that the substrate-binding groove of Siah is nevertheless important. PMID: 18850011
    44. SIAH-2 may be a viable target for novel anti-RAS and anticancer agents aimed at inhibiting EGFR and/or RAS-mediated tumorigenesis. PMID: 19001609
    45. Hypoxic conditions allow a markedly increased HIPK2/Siah2 interaction and result in efficient polyubiquitylation and proteasomal degradation of the kinase. PMID: 19043406

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  • 亚细胞定位：
    Cytoplasm. Nucleus.
  • 蛋白家族：
    SINA (Seven in absentia) family
  • 组织特异性：
    Widely expressed at low level.
  • 数据库链接：

    HGNC: 10858

    OMIM: 602213

    KEGG: hsa:6478

    STRING: 9606.ENSP00000322457

    UniGene: Hs.477959