SIKE1: Suppressor of IKK Epsilon and Interferon Regulatory Factor 3
A negative regulator of innate immune signaling with emerging roles in cancer and viral infection
Gene Information Card
| Symbol | SIKE1 |
|---|---|
| Full Name | Suppressor of IKK Epsilon and Interferon Regulatory Factor 3 |
| Gene Type | Protein coding |
| Chromosomal Location | 1p13.2 |
| NCBI Gene ID | 80143 ncbi.nlm.nih.gov/gene/80143 |
| Ensembl ID | ENSG00000117525 |
| UniProt ID | Q9UBC9 |
| OMIM ID | 611220 |
| HGNC ID | 29297 |
| Aliases | FLJ20637, MGC13170, SIKE |
Description
SIKE1 (Suppressor of IKK Epsilon and Interferon Regulatory Factor 3) is a protein-coding gene that encodes a negative regulator of the innate immune response. The SIKE1 protein interacts with IKK epsilon (IKBKE) and TBK1, suppressing their ability to phosphorylate and activate IRF3, thereby attenuating type I interferon production. SIKE1 is widely expressed and has been implicated in antiviral defense, cellular stress responses, and tumorigenesis.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Breast cancer | SIKE1 downregulation may enhance IKK epsilon signaling, promoting oncogenic pathways | PMID: 21317927 |
| Viral infections (e.g., influenza, hepatitis C) | SIKE1 inhibits IRF3 activation, reducing interferon response; viral proteins may target SIKE1 | PMID: 15601827 |
| Prostate cancer | Altered SIKE1 expression linked to tumor progression and immune evasion | PMID: 25636800 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Heart | 8.5 | Medium |
| Brain | 6.2 | Low |
| Liver | 10.1 | Medium |
| Lung | 7.8 | Medium |
| Kidney | 9.3 | Medium |
| Testis | 12.4 | High |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 11.2 | Embryonic kidney cells; high expression |
| HeLa | 9.8 | Cervical cancer cells; moderate expression |
| MCF7 | 7.5 | Breast cancer cells; moderate expression |
| HepG2 | 10.5 | Hepatocellular carcinoma cells; high expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G (p.Met1?) | Missense | Rare | Potential loss of start codon; functional impact unknown |
| c.214C>T (p.Arg72Cys) | Missense | 0.01% | May alter protein stability; not well characterized |
| c.487_489del (p.Lys163del) | In-frame deletion | Rare | Predicted to affect IKK epsilon binding |
Mutation functional classification
Loss of Function (LOF)
Mutations that disrupt SIKE1's ability to bind IKK epsilon or TBK1, leading to unchecked IRF3 activation and enhanced interferon signaling.
Gain of Function (GOF)
Not well documented; potential mutations that increase SIKE1 stability or binding affinity could further suppress innate immunity.
Dominant Negative (DN)
No confirmed dominant-negative mutations reported; truncating variants may interfere with wild-type function.
View complete mutation data：
Gene Ontology (GO)
| • protein binding (GO:0005515) | • innate immune response (GO:0045087) |
| • negative regulation of type I interferon production (GO:0032481) | • cytoplasm (GO:0005737) |
| • cytosol (GO:0005829) |
Pathways
• RIG-I/MDA5 mediated induction of IFN-alpha/beta pathways
• Toll-like receptor signaling pathway
• Cytosolic DNA-sensing pathway
Protein Summary
SIKE1 is a 207-amino acid protein containing a coiled-coil domain that mediates interaction with IKK epsilon and TBK1. It acts as a suppressor of IRF3 phosphorylation, thereby negatively regulating type I interferon production. The protein is predominantly cytoplasmic and is expressed in multiple tissues. SIKE1 has been implicated in antiviral responses and cancer biology, where its downregulation may contribute to tumor progression.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SIKE1 Knockout HEK293 Cell Line | EDJ-KQ2719 | Human | 80143 | Details Get a Quote |
| SIKE1 Knockout A-549 Cell Line | EDJ-KQ23570 | Human | 80143 | Details Get a Quote |
| SIKE1 Knockout HCT 116 Cell Line | EDJ-KQ23571 | Human | 80143 | Details Get a Quote |
| SIKE1 Knockout HeLa Cell Line | EDJ-KQ23572 | Human | 80143 | Details Get a Quote |
