SIAH2 Antibody, FITC conjugated
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Description
Research Applications of SIAH2 Antibody, FITC Conjugated
The FITC conjugate is pivotal for studying SIAH2’s subcellular localization and interactions in dynamic processes:
Role in DNA Repair and Replication Fork Recovery
SIAH2 regulates homologous recombination (HR) repair by ubiquitinating CtIP, a key endonuclease for DNA end resection. Using the FITC-conjugated antibody, researchers can visualize CtIP-SIAH2 colocalization at double-strand break (DSB) sites, as shown in studies where SIAH2 depletion impaired CtIP recruitment and HR efficiency .
Modulation of Hypoxia-Responsive Proteins
SIAH2 targets hypoxia-inducible factors (e.g., DBC1, HO-1) for degradation under stress. FITC-based IF allows tracking SIAH2’s interaction with these substrates:
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HO-1 Degradation: SIAH2-mediated HO-1 ubiquitination reduces its levels, as shown by co-immunoprecipitation and fluorescence colocalization studies .
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DBC1 Regulation: Hypoxia-induced SIAH2-DBC1 interactions can be visualized via FITC-labeled antibodies, confirming their role in proteasomal degradation under low-oxygen conditions .
Hippo-YAP Signaling Pathway
In breast cancer cells, SIAH2 interacts with Zyxin and Lats2, forming a ternary complex that downregulates Hippo signaling. FITC-conjugated antibodies enable imaging of SIAH2’s membrane localization and its impact on YAP/TAZ activity .
Comparative Analysis of SIAH2 Antibody Conjugates
The FITC conjugate is one of several formats available for SIAH2 detection. Below is a comparison with other conjugates:
Key Advantages of FITC:
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Fluorescence Sensitivity: Enables high-resolution imaging of SIAH2 localization.
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Compatibility with Multiplexing: FITC’s emission spectrum (≈520 nm) allows combination with other fluorophores (e.g., Alexa Fluor® 594) for multi-target studies .
Experimental Considerations
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 can ship the products within 1-3 business days after receiving your order. The delivery time may vary depending on the purchasing method or location. Please consult your local distributors for specific delivery timelines.
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, also known as Seven in Absentia Homolog 2, is an E3 ubiquitin-protein ligase. It plays a crucial role in mediating the ubiquitination and subsequent proteasomal degradation of various target proteins. E3 ubiquitin ligases function by accepting ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transferring the ubiquitin to targeted substrates. SIAH2 can mediate E3 ubiquitin ligase activity either through direct binding to substrates or by acting as the essential RING domain subunit of larger E3 complexes. It regulates the degradation of a wide array of 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). Notably, SIAH2 mediates the ubiquitination and proteasomal degradation of DYRK2 in response to hypoxia. This process is involved in apoptosis, tumor suppression, cell cycle regulation, transcription, and signaling processes. SIAH2 shares some overlapping functions with SIAH1 but also displays distinct activities. For instance, SIAH2 triggers the ubiquitin-mediated degradation of TRAF2, which is not observed with SIAH1. Additionally, SIAH2 promotes the monoubiquitination of SNCA. In the context of cellular clock function, SIAH2 regulates the rhythmic degradation/clearance of the circadian transcriptional repressors NR1D1 and NR1D2 through ubiquitination, contributing to their circadian protein abundance profile. Furthermore, SIAH2 mediates the 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 independent of its ATPase activity, promoting prostate cancer progression. PMID: 28991234
- The Siah2-PHD3- HIF-1alpha-VEGF axis is an important hypoxic signaling pathway in 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 significant consequences for cell-cycle control and the ability of hypoxia to alter the DNA damage-response pathway in cancer cells. PMID: 26751770
- A study revealed a notable 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 localized to the cytoplasm and cell membranes. PMID: 27616748
- SIAH2 is associated with a tumor-promoting role in breast cancer. PMID: 26654769
- Overexpression of Siah2 is linked to Epithelial Ovarian Carcinoma. PMID: 26512788
- Our findings 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 indicated that the miR-335/SIAH2/HDAC3 axis regulates the response to anti-cancer drugs. PMID: 25997740
- Data demonstrate that ubiquitin E3 ligase Siah2 depletion delays circadian degradation of nuclear hormone receptor RevErbalpha (Nr1d1) and extends 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, which consequently suppresses 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 linked to 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 transcriptional activity of the androgen receptor (AR) by degrading transcriptionally-inactive AR on select gene promoters/enhancers; Siah2 promotes expression of select AR target genes, leading to the growth of castration-resistant prostate cancer cells under androgen-deprivation conditions. PMID: 23518348
- Similar to SIAH1, SIAH-2 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 identified 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 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
- This review defines the regulatory axis consisting of Siah2 and HIF-1alpha/FoxA2 cooperation and suggests novel therapeutic modalities to treat the 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 has been studied. PMID: 16958618
- The role of Siah2 phosphorylation in the regulation of its activity toward PHD3 has been reported. PMID: 17003045
- Evidence for hSiah2-dependent degradation of Pias as a mechanism in the regulation of c-jun N-terminal kinase-activating pathways has been provided. PMID: 17533377
- Data show that Siah2 is a crucial mediator of repp86 protein degradation. PMID: 17716627
- In primary breast tumor specimens and in vitro studies, low SIAH2 levels have been associated with resistance to endocrine therapy. PMID: 18629630
- Siah1 (human) reduced PHD3 protein levels similar to that observed with Siah2. While PHDs may not interact directly with Siah2, the substrate-binding groove of Siah is nevertheless important. PMID: 18850011
- SIAH-2 could be a viable target for novel anti-RAS and anticancer agents aimed at inhibiting EGFR and/or RAS-mediated tumorigenesis. PMID: 19001609
- Hypoxic conditions facilitate 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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