SIAH2 Antibody, Biotin conjugated
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Description
Definition and Structure
The SIAH2 Antibody, Biotin conjugated, is a rabbit-derived polyclonal antibody targeting the N-terminal region (amino acids 1–72) of human SIAH2 . Biotin conjugation enables high-sensitivity detection via streptavidin-based assays such as ELISA, Western blotting (WB), and immunohistochemistry (IHC) .
Key Features:
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Reactivity: Human-specific, with potential cross-reactivity in mouse and rat models under specific conditions .
Cancer Biology
SIAH2 is overexpressed in oral squamous cell carcinoma (OSCC) and promotes tumor survival by inhibiting apoptosis. The Biotin-conjugated antibody has been used to validate SIAH2 knockdown effects, showing reduced cell proliferation and increased PARP cleavage in OSCC models .
Immune Regulation
In melanoma studies, SIAH2 regulates T-regulatory (Treg) cell proliferation. Knockout mice (Siah2) exhibit reduced Treg infiltration and enhanced anti-tumor immunity, findings confirmed using SIAH2-specific antibodies .
DNA Repair Mechanisms
SIAH2 mediates CtIP ubiquitination, facilitating DNA end resection during homologous recombination (HR). Antibody-based assays identified SIAH2’s role in replication fork recovery and genomic stability .
Validation and Quality Control
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Western Blot: Detects a single band at 35–40 kDa in human, mouse, and rat lysates .
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Immunohistochemistry: Validated in formalin-fixed paraffin-embedded OSCC tissues, showing strong cytoplasmic and nuclear staining .
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Specificity: No cross-reactivity with SIAH1, confirmed via siRNA knockdown .
Role in Hypoxia and Ubiquitination
SIAH2 degrades prolyl hydroxylases (PHDs), stabilizing HIF-1α under hypoxic conditions. This mechanism was elucidated using Biotin-conjugated antibodies in co-immunoprecipitation assays .
Therapeutic Implications
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Cancer: SIAH2 depletion suppresses tumor growth in pancreatic, breast, and prostate cancers .
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Immune Modulation: Targeting SIAH2 enhances cytotoxic T-cell activity by reducing Treg-mediated immunosuppression .
Limitations and Considerations
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Species Reactivity: Primarily validated in humans; cross-reactivity with other species requires confirmation .
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Storage Sensitivity: Prolonged exposure to light or repeated freeze-thaw cycles may degrade Biotin conjugation .
Future Directions
Current efforts focus on developing small-molecule SIAH2 inhibitors for cancer therapy . The Biotin-conjugated antibody remains pivotal for target validation in preclinical models.
Product Specs
Buffer
Preservative: 0.03% Proclin 300
Constituents: 50% Glycerol, 0.01M PBS, pH 7.4
Constituents: 50% Glycerol, 0.01M PBS, pH 7.4
Form
Liquid
Lead Time
Typically, we are able to ship your order within 1-3 business days of receiving it. Delivery times may vary depending on the purchasing method or location. For specific delivery times, please consult your local distributor.
Synonyms
E3 ubiquitin-protein ligase Siah2 antibody; hSiah2 antibody; Seven in absentia homolog 2 antibody; Siah E3 ubiquitin protein ligase 2 antibody; Siah-2 antibody; siah2 antibody; SIAH2_HUMAN antibody; Ubiquitin Ligase Siah2 antibody
Target Names
SIAH2
Uniprot No.
Target Background
Function
SIAH2 is an E3 ubiquitin-protein ligase that mediates the ubiquitination and subsequent proteasomal degradation of target proteins. E3 ubiquitin ligases receive ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfer the ubiquitin to targeted substrates. SIAH2 mediates E3 ubiquitin ligase activity either through direct binding to substrates or by functioning as the essential RING domain subunit of larger E3 complexes. It triggers the ubiquitin-mediated degradation of numerous 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). SIAH2 mediates ubiquitination and proteasomal degradation of DYRK2 in response to hypoxia, thus participating in apoptosis, tumor suppression, cell cycle, transcription, and signaling processes. It shares some overlapping functionality with SIAH1 but promotes the ubiquitin-mediated degradation of TRAF2, which SIAH1 does not. SIAH2 promotes monoubiquitination of SNCA and regulates cellular clock function through the ubiquitination of the circadian transcriptional repressors NR1D1 and NR1D2, leading to their proteasomal degradation. This contributes to the rhythmic degradation/clearance of NR1D1 and NR1D2, ultimately impacting their circadian profile of protein abundance. SIAH2 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.
Gene References Into Functions
- DHX15 regulates androgen receptor (AR) activity by modulating E3 ligase Siah2-mediated AR ubiquitination independently of its ATPase activity, promoting prostate cancer progression. PMID: 28991234
- The Siah2-PHD3- HIF-1alpha-VEGF axis is a significant hypoxic signaling pathway within a leukemic microenvironment. PMID: 29400343
- Based on the proposition that NS5 utilizes Siah2-mediated proteasomal degradation of STAT2, an in-silico study was conducted to characterize the protein-protein interactions between NS5, SIAH2, and STAT2 proteins. PMID: 28365387
- SIAH2 regulates CHK2 basal turnover, with important implications for cell-cycle control and the ability of hypoxia to alter the DNA damage-response pathway in cancer cells. PMID: 26751770
- A study revealed an interesting mutual regulation between Plk3 and SIAH2, uncovering a regulatory network that fine-tunes the cellular hypoxic response. PMID: 28515325
- ETS2 and Twist1 promote invasiveness of Helicobacter pylori-infected gastric cancer cells by inducing Siah2. PMID: 27048589
- Manipulation of SIAH2 expression led to a 'cross-talk' of the ERK and PI3K pathway. PMID: 27459914
- 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
- SIAH2 is associated with a tumor-promoting role in breast cancer. PMID: 26654769
- Overexpression of Siah2 is Associated With Epithelial Ovarian Carcinoma. PMID: 26512788
- Our results suggest that SIAH2 regulates multiple processes in T-cell acute lymphoblastic leukemia. PMID: 26859780
- The expression of SIAH2 is elevated in human lung cancer. PMID: 26580787
- The E3 ubiquitin ligase SIAH2 stimulates YAP by destabilizing LATS2, a critical component of the Hippo pathway, in response to hypoxia. PMID: 25438054
- The down-regulation of SIAH2 conferred sensitivity to anti-cancer drugs. The study results indicated that the miR-335/SIAH2/HDAC3 axis regulates the response to anti-cancer drugs. PMID: 25997740
- Data show that ubiquitin E3 ligase Siah2 depletion delays circadian degradation of nuclear hormone receptor RevErbalpha (Nr1d1) and lengthens period length. PMID: 26392558
- A catalysis-independent role for AKR1C3 on AR activity via Siah2 has been identified. PMID: 26160177
- The E3 ubiquitin ligase seven-in-absentia-2 (SIAH2) accelerates the proteasomal degradation of TYK, consequently suppressing the activation of STAT3 in non-small-cell lung cancer. PMID: 24833526
- A common variant in the SIAH2 locus is associated with ER-positive breast cancer in the Chinese Han population. PMID: 24244489
- Our studies demonstrate the role of Siah2 in regulating tight junction integrity and cell polarity under hypoxia, through its regulation of ASPP2 stability. PMID: 23644657
- SIAH2 expression is upregulated in basal-like breast cancers via copy number changes and/or transcriptional activation by p53. PMID: 21306611
- SIAH2 overexpression is associated with oral squamous cell carcinoma. PMID: 24222137
- Single Nucleotide Polymorphism in the SIAH2 gene is associated with hormonal receptor-positive breast cancer. PMID: 22951594
- 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
- SIAH2 knockdown increases DYRK2 stability, whereas SIAH2 expression facilitates DYRK2 polyubiquitination and degradation. PMID: 22878263
- A study found that Siah2 enhances the transcriptional activity of the androgen receptor (AR) by degrading transcriptionally-inactive AR on select gene promoters/enhancers. Siah2 promotes the expression of select AR target genes, leading to the growth of castration-resistant prostate cancer cells under androgen-deprivation conditions. PMID: 23518348
- SIAH-2 - as described for SIAH-1 - accumulates in the nuclei of hepatocellular carcinoma cells, where it supports tumor growth and tumor cell dissemination. PMID: 22323152
- Siah2 acts as an E3 ligase to directly ubiquitylate TIN2 in vitro. PMID: 22064479
- Src kinase activity downregulates C/EBP-delta protein but not mRNA levels through a SIAH2 E3 ligase-dependent mechanism. PMID: 22037769
- A 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
- 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 as a promising novel cancer therapeutic strategy. PMID: 21586138
- A review defines the regulatory axis consisting of Siah2 and HIF-1alpha/FoxA2 cooperation and suggests novel therapeutic modalities to treat these most aggressive forms of prostate cancer. PMID: 21037926
- 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
- SIAH2 regulates the expression of promyelocytic leukemia protein and other tripartite motif proteins. PMID: 14645235
- SIAH2 regulates the stability of prolyl-hydroxylases, controls HIF1alpha abundance, and modulates physiological responses to hypoxia. PMID: 15210114
- 2-oxoglutarate (alpha-ketoglutarate) dehydrogenase stability is regulated by the RING finger ubiquitin ligase Siah. PMID: 15466852
- The mechanism by which the estrogen-ER complex markedly reduces the level of N-CoR involves the up-regulation of Siah2 and the subsequent targeting of N-CoR for proteasomal degradation. PMID: 16141343
- 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
- The mechanism underlying the regulation of PHD3 availability and activity in hypoxia by the E3 ligase Siah2. PMID: 16958618
- The role of Siah2 phosphorylation in the regulation of its activity toward PHD3 is reported. PMID: 17003045
- We provide evidence for hSiah2-dependent degradation of Pias as a mechanism in the regulation of c-jun N-terminal kinase-activating pathways. PMID: 17533377
- Data show that Siah2 is a critical mediator of repp86 protein degradation. PMID: 17716627
- In primary breast tumor specimens as well as in vitro, low SIAH2 levels were associated with resistance to endocrine therapy. PMID: 18629630
- Siah1 (human) reduced PHD3 protein levels similar to that observed with Siah2. PHDs may not interact directly with Siah2, but the substrate-binding groove of Siah is nevertheless important. PMID: 18850011
- 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
- Hypoxic conditions allow a significantly increased HIPK2/Siah2 interaction and result in efficient polyubiquitylation and proteasomal degradation of the kinase. PMID: 19043406
Database Links
Protein Families
SINA (Seven in absentia) family
Subcellular Location
Cytoplasm. Nucleus.
Tissue Specificity
Widely expressed at low level.
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