Property Summary

NCBI Gene PubMed Count 65
PubMed Score 62.57
PubTator Score 46.25

Knowledge Summary


No data available


  Disease (4)

Disease Target Count Z-score Confidence
Breast cancer 3098 0.0 2.0
Disease Target Count Z-score Confidence
Cancer 2346 3.135 1.6


  Differential Expression (4)

Disease log2 FC p
malignant mesothelioma 1.600 1.7e-07
non-small cell lung cancer 1.294 1.7e-12
lung cancer 1.300 1.9e-02
subependymal giant cell astrocytoma -1.119 2.8e-02

 GWAS Trait (1)

Gene RIF (45)

26859780 Our results suggest that SIAH2 regulates multi processes in T-cell acute lymphoblastic leukemia
26654769 SIAH2 is associated with a tumor promoting role in breast cancer.
26580787 The expression of SIAH2 is increased in human lung cancer.
26512788 Overexpression of Siah2 Is Associated With Epithelial Ovarian Carcinoma
26392558 Data show that ubiquitin E3 ligase Siah2 depletion delays circadian degradation of nuclear hormone receptor RevErbalpha (Nr1d1) and lengthens period length.
26160177 A catalysis-independent role for AKR1C3 on AR activity via Siah2 has been identified.
25997740 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.
25528765 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.
25438054 the E3 ubiquitin ligase SIAH2 stimulates YAP by destabilizing LATS2, a critical component of the Hippo pathway, in response to hypoxia.
25202994 molecular basis of Siah1 and Siah2 E3 ubiquitin ligase substrate specificity
24833526 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
24244489 A common variant in the SIAH2 locus is associated with ER-positive breast cancer in the Chinese Han population.
24222137 SIAH2 overexpression is associated with oral squamous cell carcinoma.
23645672 Data suggest that Keap1 does not contribute to hypoxic Nrf2 suppression, and both HIF-1alpha and Siah2 are key regulators of hypoxic responses.
23644657 our studies demonstrate the role of Siah2 in regulation of tight junction integrity and cell polarity under hypoxia, through its regulation of ASPP2 stability.
23518348 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
23500468 USP19 interacts with the ubiquitin ligases SIAH1 and SIAH2, which promote USP19 ubiquitylation and degradation by the proteasome.
23208506 the molecular mechanisms modulating ACK1
22951594 Single Nucleotide Polymorphism in SIAH2 gene is associated with hormonal receptor-positive breast cancer.
22878263 SIAH2 knockdown increases DYRK2 stability, whereas SIAH2 expression facilitates DYRK2 polyubiquitination and degradation
22323152 SIAH-2 - as described for SIAH-1 - accumulates in nuclei of hepatocellular carcinoma cells where it supports tumor growth and tumor cell dissemination
22064479 Siah2 acts as an E3 ligase to directly ubiquitylate TIN2 in vitro.
22037769 Src kinase activity downregulates C/EBP-delta protein but not mRNA levels through a SIAH2 E3 ligase-dependent mechanism.
22037423 In sharp contrast to SIAH1/SIAH2 and UBCH8, TRIAD1 binding to PML-RARalpha has no effect on its turnover.
21659512 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
21586138 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.
21306611 SIAH2 expression is upregulated in basal-like breast cancers via copy number changes and/or transcriptional activation by p53.
21037926 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.
19744480 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.
19730683 Observational study of gene-disease association. (HuGE Navigator)
19043406 Hypoxic conditions allow a markedly increased HIPK2/Siah2 interaction and result in efficient polyubiquitylation and proteasomal degradation of the kinase.
19001609 SIAH-2 may be a viable target for novel anti-RAS and anticancer agents aimed at inhibiting EGFR and/or RAS-mediated tumorigenesis.
18850011 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.
18629630 In primary breast tumor specimens as well as in vitro low SIAH2 levels associated with resistance to endocrine therapy.
18070888 monoubiquitylation by SIAH1 and SIAH2 represents a possible trigger event for alpha-synuclein aggregation and Lewy body formation
17716627 Data show that Siah2 is an important mediator of repp86 protein degradation.
17533377 We provide evidences for hSiah2-dependent degradation of Pias as being a mechanism in the regulation of c-jun N-terminal kinase-activating pathways.
17003045 The role of Siah2 phosphorylation in the regulation of its activity toward PHD3 is reported.
16958618 Mechanism underlying the regulation of PHD3 availability and activity in hypoxia by the E3 ligase Siah2.
16899216 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.
16141343 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
15466852 2-oxoglutarate (alpha-ketoglutarate) dehydrogenase stability is regulated by the RING finger ubiquitin ligase Siah
15221006 role of interaction with AF4 and AF4.MLL fusion protein in t(4,11) pathobiology
15210114 SIAH2 regulates stability of prolyl- hydroxylases, controls HIF1alpha abundance, and modulates physiological responses to hypoxia.
14645235 SIAH2 regulates the expression of promyelocytic leukemia protein and other tripartite motif proteins

AA Sequence


Text Mined References (68)

PMID Year Title
26859780 2016 The expression and function of E3 ligase SIAH2 in acute T lymphoblastic leukemia.
26654769 2015 SIAH ubiquitin ligases regulate breast cancer cell migration and invasion independent of the oxygen status.
26580787 2015 The Expression of the Ubiquitin Ligase SIAH2 (Seven In Absentia Homolog 2) Is Increased in Human Lung Cancer.
26512788 2016 Overexpression of Siah2 Is Associated With Poor Prognosis in Patients With Epithelial Ovarian Carcinoma.
26392558 2015 Ubiquitin ligase Siah2 regulates RevErb? degradation and the mammalian circadian clock.
26160177 2015 The Steroidogenic Enzyme AKR1C3 Regulates Stability of the Ubiquitin Ligase Siah2 in Prostate Cancer Cells.
25997740 2015 miR-335 Targets SIAH2 and Confers Sensitivity to Anti-Cancer Drugs by Increasing the Expression of HDAC3.
25528765 2015 The ubiquitin ligase Siah is a novel regulator of Zeb1 in breast cancer.
25438054 2015 Hypoxia regulates Hippo signalling through the SIAH2 ubiquitin E3 ligase.
25202994 2014 Investigating the molecular basis of Siah1 and Siah2 E3 ubiquitin ligase substrate specificity.
24833526 2014 SIAH2 antagonizes TYK2-STAT3 signaling in lung carcinoma cells.
24244489 2013 A common variant in the SIAH2 locus is associated with estrogen receptor-positive breast cancer in the Chinese Han population.
24222137 2013 The E3 ubiquitin ligase SIAH2 is a prosurvival factor overexpressed in oral cancer.
23840749 2013 MOR is not enough: identification of novel mu-opioid receptor interacting proteins using traditional and modified membrane yeast two-hybrid screens.
23645672 2013 Seven in absentia homolog 2 (Siah2) protein is a regulator of NF-E2-related factor 2 (Nrf2).
23644657 2014 Siah2 regulates tight junction integrity and cell polarity through control of ASPP2 stability.
23518348 2013 The E3 ubiquitin ligase Siah2 contributes to castration-resistant prostate cancer by regulation of androgen receptor transcriptional activity.
23500468 2013 An N-terminal SIAH-interacting motif regulates the stability of the ubiquitin specific protease (USP)-19.
23208506 2013 SIAH ubiquitin ligases target the nonreceptor tyrosine kinase ACK1 for ubiquitinylation and proteasomal degradation.
23186163 2013 Toward a comprehensive characterization of a human cancer cell phosphoproteome.
22951594 2012 A genome-wide association study identifies a genetic variant in the SIAH2 locus associated with hormonal receptor-positive breast cancer in Japanese.
22878263 2012 Mutual regulation between SIAH2 and DYRK2 controls hypoxic and genotoxic signaling pathways.
22323152 2012 Nuclear accumulation of seven in absentia homologue-2 supports motility and proliferation of liver cancer cells.
22064479 2012 TIN2 stability is regulated by the E3 ligase Siah2.
22037769 2012 Identification of a Src tyrosine kinase/SIAH2 E3 ubiquitin ligase pathway that regulates C/EBP? expression and contributes to transformation of breast tumor cells.
22037423 2012 Differential regulation of PML-RAR? stability by the ubiquitin ligases SIAH1/SIAH2 and TRIAD1.
21659512 2011 USP13 enzyme regulates Siah2 ligase stability and activity via noncatalytic ubiquitin-binding domains.
21586138 2011 Possible role of death receptor-mediated apoptosis by the E3 ubiquitin ligases Siah2 and POSH.
21306611 2011 The expression of the ubiquitin ligase SIAH2 (seven in absentia homolog 2) is mediated through gene copy number in breast cancer and is associated with a basal-like phenotype and p53 expression.
21037926 2010 The Siah2-HIF-FoxA2 axis in prostate cancer – new markers and therapeutic opportunities.
19744480 2010 Regulation of MYPT1 stability by the E3 ubiquitin ligase SIAH2.
19730683 2009 The variant rs1867277 in FOXE1 gene confers thyroid cancer susceptibility through the recruitment of USF1/USF2 transcription factors.
19224863 2009 Synphilin-1A inhibits seven in absentia homolog (SIAH) and modulates alpha-synuclein monoubiquitylation and inclusion formation.
19043406 2009 An inducible autoregulatory loop between HIPK2 and Siah2 at the apex of the hypoxic response.
19028597 2009 Maturation of human dendritic cells is accompanied by functional remodelling of the ubiquitin-proteasome system.
19001609 2008 Effect of disrupting seven-in-absentia homolog 2 function on lung cancer cell growth.
18850011 2009 Inhibition of Siah ubiquitin ligase function.
18629630 2009 Downregulation of SIAH2, an ubiquitin E3 ligase, is associated with resistance to endocrine therapy in breast cancer.
18070888 2008 Monoubiquitylation of alpha-synuclein by seven in absentia homolog (SIAH) promotes its aggregation in dopaminergic cells.
17716627 2007 Regulation of repp86 stability by human Siah2.
17533377 2007 A crosstalk between hSiah2 and Pias E3-ligases modulates Pias-dependent activation.
17003045 2006 Regulation of the ring finger E3 ligase Siah2 by p38 MAPK.
16958618 2007 Hypoxia-induced assembly of prolyl hydroxylase PHD3 into complexes: implications for its activity and susceptibility for degradation by the E3 ligase Siah2.
16899216 2006 Dimerization of hSiah proteins regulates their stability.
16509823 2006 Characterization of different isoforms of the HIF prolyl hydroxylase PHD1 generated by alternative initiation.
16141343 2005 Estrogen down-regulation of the corepressor N-CoR: mechanism and implications for estrogen derepression of N-CoR-regulated genes.
15489334 2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
15466852 2004 Regulation of 2-oxoglutarate (alpha-ketoglutarate) dehydrogenase stability by the RING finger ubiquitin ligase Siah.
15221006 2004 Interaction of AF4 wild-type and AF4.MLL fusion protein with SIAH proteins: indication for t(4;11) pathobiology?
15210114 2004 Siah2 regulates stability of prolyl-hydroxylases, controls HIF1alpha abundance, and modulates physiological responses to hypoxia.
14702039 2004 Complete sequencing and characterization of 21,243 full-length human cDNAs.
14645235 2004 The coiled-coil domain is the structural determinant for mammalian homologues of Drosophila Sina-mediated degradation of promyelocytic leukemia protein and other tripartite motif proteins by the proteasome.
12952940 2003 Wnt-5a inhibits the canonical Wnt pathway by promoting GSK-3-independent beta-catenin degradation.
12810624 2003 Involvement of PEG10 in human hepatocellular carcinogenesis through interaction with SIAH1.
12477932 2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.
12411493 2002 Stress-induced decrease in TRAF2 stability is mediated by Siah2.
12136098 2002 NotI flanking sequences: a tool for gene discovery and verification of the human genome.
11786535 2002 Regulation of synaptophysin degradation by mammalian homologues of seven in absentia.
11483518 2001 Regulation of BOB.1/OBF.1 stability by SIAH.
11389839 2001 Siah-1, SIP, and Ebi collaborate in a novel pathway for beta-catenin degradation linked to p53 responses.
10704288 2000 A sequence-ready map of the Usher syndrome type III critical region on chromosome 3q.
10681424 2000 Pw1/Peg3 is a potential cell death mediator and cooperates with Siah1a in p53-mediated apoptosis.
10207103 1999 hSiah2 is a new Vav binding protein which inhibits Vav-mediated signaling pathways.
9858595 1999 Siah-1 N-terminal RING domain is required for proteolysis function, and C-terminal sequences regulate oligomerization and binding to target proteins.
9403064 1997 Characterization of human homologs of the Drosophila seven in absentia (sina) gene.
9334332 1997 Mammalian homologs of seven in absentia regulate DCC via the ubiquitin-proteasome pathway.
8889548 1996 Normalization and subtraction: two approaches to facilitate gene discovery.
8125298 1994 Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides.