|Other Names||E3 ubiquitin-protein ligase SIAH1, 632-, Seven in absentia homolog 1, Siah-1, Siah-1a, SIAH1, HUMSIAH|
|Storage||Maintain refrigerated at 2-8°C for up to 6 months. For long term storage store at -20°C.|
|Precautions||This product is for research use only. Not for use in diagnostic or therapeutic procedures.|
|Function||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.|
|Cellular Location||Cytoplasm. Nucleus. Note=Predominantly cytoplasmic. Partially nuclear|
|Tissue Location||Widely expressed at a low level. Down- regulated in advanced hepatocellular carcinomas|
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SIAH1 is a protein that is a member of the sevenin absentia homolog (SIAH) family. The protein is an E3 ligase andis involved in ubiquitination and proteasome-mediated degradationof specific proteins. The activity of this ubiquitin ligase hasbeen implicated in the development of certain forms of Parkinson'sdisease, the regulation of the cellular response to hypoxia andinduction of apoptosis. Alternative splicing results in severaladditional transcript variants, some encoding different isoformsand others that have not been fully characterized. [provided byRefSeq].
Wu, H., et al. Biochem. Biophys. Res. Commun. 397(3):391-396(2010)Wen, Y.Y., et al. Mol. Carcinog. 49(5):440-449(2010)Dimitrova, Y.N., et al. J. Biol. Chem. 285(18):13507-13516(2010)Bruzzoni-Giovanelli, H., et al. J. Exp. Clin. Cancer Res. 29, 10 (2010) :Xie, W., et al. J. Cell. Mol. Med. 13 (8B), 1719-1727 (2009) :
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