SIKE1 Gene

Name	suppressor of IKBKE 1
Description	SIKE interacts with IKK-epsilon (IKBKE; MIM 605048) and TBK1 (MIM 604834) and acts as a suppressor of TLR3 (MIM 603029) and virus-triggered interferon activation pathways (Huang et al., 2005 [PubMed 16281057]).[supplied by OMIM, Mar 2008]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nSIKE1, originally described as the “Suppressor of IKKε,” functions as a key negative regulator of innate immune signaling. In viral‐infected or TLR3-stimulated cells, SIKE1 interacts with the IKK-related kinases IKKε and TBK1 to interrupt their normal association with essential adaptor proteins and IRF3, thereby specifically dampening the IRF3-mediated induction of type I interferons without affecting NF-κB activation. Biochemical studies further reveal that SIKE1 is a high-affinity substrate of TBK1, and its phosphorylation (notably at Ser-185) modulates TBK1 binding, effectively redirecting TBK1’s catalytic activity away from IRF3 phosphorylation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its role in antiviral signaling, SIKE1 exerts protective effects in cardiac tissue. Experimental models have demonstrated that SIKE1 attenuates pathological cardiac hypertrophy by directly inhibiting the TBK1-AKT signaling axis. Mice deficient in SIKE1 develop hypertrophy and progress to heart failure, whereas transgenic overexpression of SIKE1 confers resistance to hypertrophic stimuli, and these findings have been consistently validated in rodent and non-human primate studies."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nMoreover, the expression levels of SIKE1 have prognostic implications in cancer. In gastric cancer, higher SIKE1 mRNA expression is generally associated with unfavorable overall survival outcomes, although its impact appears to vary with disease stage, histological subtype, and treatment regimen. Thus, SIKE1 may also represent a potential biomarker and therapeutic target in oncological settings."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Jun Huang, Ting Liu, Liang-Guo Xu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "SIKE is an IKK epsilon/TBK1-associated suppressor of TLR3- and virus-triggered IRF-3 activation pathways."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "EMBO J (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/sj.emboj.7600863"}], "href": "https://doi.org/10.1038/sj.emboj.7600863"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16281057"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16281057"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "James D Marion, Charlotte F Roberts, R Jason Call, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mechanism of endogenous regulation of the type I interferon response by suppressor of IκB kinase epsilon (SIKE), a novel substrate of TANK-binding kinase 1 (TBK1)."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M112.440859"}], "href": "https://doi.org/10.1074/jbc.M112.440859"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23649622"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23649622"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Ke-Qiong Deng, Aibing Wang, Yan-Xiao Ji, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Suppressor of IKKɛ is an essential negative regulator of pathological cardiac hypertrophy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ncomms11432"}], "href": "https://doi.org/10.1038/ncomms11432"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27249321"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27249321"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "David Timothy Gayed, Jayant Wodeyar, Zi-Xiang Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Prognostic values of inhibitory κB kinases mRNA expression in human gastric cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biosci Rep (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1042/BSR20180617"}], "href": "https://doi.org/10.1042/BSR20180617"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30487159"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30487159"}]}]}]}
Synonyms	SIKE
Proteins	SIKE1_HUMAN
NCBI Gene ID	80143
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

SIKE1 has 5,537 functional associations with biological entities spanning 8 categories (molecular profile, organism, chemical, functional term, phrase or reference, disease, phenotype or trait, structural feature, cell line, cell type or tissue, gene, protein or microRNA) extracted from 109 datasets.

Click the + buttons to view associations for SIKE1 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

SIKE1 Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of SIKE1 gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles	tissues with high or low expression of SIKE1 gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles	tissue samples with high or low expression of SIKE1 gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of SIKE1 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq	tissue samples with high or low expression of SIKE1 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq dataset.
	Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of SIKE1 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of SIKE1 gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of SIKE1 gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	BioGPS Mouse Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of SIKE1 gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	Carcinogenome Chemical Perturbation Carcinogenicity Signatures	small molecule perturbations changing expression of SIKE1 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of SIKE1 gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
	CCLE Cell Line Gene Expression Profiles	cell lines with high or low expression of SIKE1 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with SIKE1 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with SIKE1 gene from the CellMarker Gene-Cell Type Associations dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of SIKE1 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of SIKE1 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
	ChEA Transcription Factor Targets 2022	transcription factors binding the promoter of SIKE1 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	CM4AI KOLF21J CRISPRi Gene Perturbation Atlas	gene perturbations changing expression of SIKE1 gene from the CM4AI KOLF21J CRISPRi Gene Perturbation Atlas dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of SIKE1 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing SIKE1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing SIKE1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing SIKE1 protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores 2025	cellular components containing SIKE1 protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with SIKE1 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025	cellular components co-occuring with SIKE1 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	CORUM Protein Complexes	protein complexs containing SIKE1 protein from the CORUM Protein Complexes dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of SIKE1 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with SIKE1 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Disease Associations	diseases associated with SIKE1 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of SIKE1 protein relative to other small molecule perturbations from the DeepCoverMOA Drug Mechanisms of Action dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by SIKE1 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with SIKE1 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with SIKE1 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores 2025	diseases co-occuring with SIKE1 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
	DisGeNET Gene-Disease Associations	diseases associated with SIKE1 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at SIKE1 gene from the ENCODE Histone Modification Site Profiles dataset.
	ENCODE Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of SIKE1 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of SIKE1 gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.
	ESCAPE Omics Signatures of Genes and Proteins for Stem Cells	PubMedIDs of publications reporting gene signatures containing SIKE1 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GDSC Cell Line Gene Expression Profiles	cell lines with high or low expression of SIKE1 gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.