ECSIT: A Key Adaptor in Toll-Like Receptor and BMP Signaling Pathways
Essential for mitochondrial function and innate immune signaling, ECSIT is implicated in cancer and neurodegenerative disorders.
Gene Information Card
| Symbol | ECSIT |
|---|---|
| Full Name | ECSIT signaling integrator |
| Gene Type | Protein coding |
| Chromosomal Location | 19p13.2 |
| NCBI Gene ID | 51295 ncbi.nlm.nih.gov/gene/51295 |
| Ensembl ID | ENSG00000130159 |
| UniProt ID | Q9BQ95 |
| OMIM ID | 608388 |
| HGNC ID | 29547 |
| Aliases | C19orf62, SITPEC, ECSIT1, ECSIT2 |
Description
ECSIT (ECSIT signaling integrator) encodes a cytoplasmic adaptor protein that bridges Toll-like receptor (TLR) signaling to the mitochondrial electron transport chain. It is essential for TLR-mediated NF-κB activation and for the assembly of mitochondrial complex I. ECSIT also participates in bone morphogenetic protein (BMP) signaling by interacting with SMAD1. The gene is ubiquitously expressed and its dysregulation is linked to cancer, neurodegeneration, and inflammatory diseases.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Breast cancer | ECSIT overexpression enhances NF-κB signaling and mitochondrial ROS production, promoting tumor progression. | PMID: 23541953; COSMIC |
| Colorectal cancer | Somatic mutations (e.g., R81Q) alter ECSIT function, correlating with poor prognosis. | PMID: 24755471; COSMIC |
| Alzheimer's disease | ECSIT deficiency impairs mitochondrial complex I activity, increasing oxidative stress and amyloid-beta accumulation. | PMID: 28053020 |
| Parkinson's disease | Reduced ECSIT expression leads to mitochondrial dysfunction and dopaminergic neuron loss. | PMID: 28053020 |
| Inflammatory bowel disease | ECSIT variants (e.g., rs3743104) associated with altered TLR signaling and intestinal inflammation. | ClinVar; PMID: 21706002 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Heart | 18.3 | Medium |
| Liver | 9.8 | Low |
| Lung | 15.6 | Medium |
| Kidney | 14.2 | Medium |
| Colon | 11.1 | Medium |
| Breast | 10.4 | Medium |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 14.7 | High expression in embryonic kidney cells |
| HeLa | 12.3 | Moderate expression in cervical cancer cells |
| MCF7 | 11.8 | Moderate expression in breast cancer cells |
| SH-SY5Y | 13.5 | High expression in neuroblastoma cells |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| R81Q | Missense | 0.2% (COSMIC) | Alters protein stability and NF-κB activation; observed in colorectal cancer |
| G58S | Missense | 0.1% (COSMIC) | Impairs mitochondrial complex I assembly; linked to neurodegeneration |
| c.345+1G>A | Splice donor | Rare (ClinVar) | Likely loss-of-function; associated with mitochondrial encephalopathy |
Mutation functional classification
Loss of Function (LOF)
Splice-site mutations (e.g., c.345+1G>A) and missense variants that disrupt mitochondrial complex I assembly or TLR signaling.
Gain of Function (GOF)
Overexpression or activating mutations (e.g., R81Q in some contexts) that enhance NF-κB activity and ROS production.
Dominant Negative (DN)
Not well characterized; some missense variants may interfere with wild-type ECSIT function in heterozygotes.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Toll-like receptor signaling pathway (KEGG: hsa04620)
• BMP signaling pathway (Reactome: R-HSA-201451)
• Mitochondrial complex I biogenesis (Reactome: R-HSA-6799198)
• NF-kappa B signaling (KEGG: hsa04064)
Protein Summary
ECSIT is a 45 kDa cytoplasmic protein containing a TRAF6-binding domain and a mitochondrial targeting sequence. It acts as a scaffold linking TRAF6 to the mitochondrial complex I assembly factor NDUFAF1. Upon TLR activation, ECSIT translocates to mitochondria to enhance ROS production and NF-κB activation. It also interacts with SMAD1 to modulate BMP signaling. The protein is highly conserved in metazoans and is essential for embryonic development.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ECSIT Knockout HEK293 Cell Line | EDJ-KQ161 | Human | 51295 | Details Get a Quote |
| ECSIT Knockout A-549 Cell Line | EDJ-KQ19140 | Human | 51295 | Details Get a Quote |
| ECSIT Knockout HCT 116 Cell Line | EDJ-KQ19141 | Human | 51295 | Details Get a Quote |
| ECSIT Knockout HeLa Cell Line | EDJ-KQ19142 | Human | 51295 | Details Get a Quote |
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