MUL1 (Mitochondrial E3 Ubiquitin Protein Ligase 1)
A key regulator of mitochondrial dynamics, apoptosis, and innate immunity
Gene Information Card
| Symbol | MUL1 |
|---|---|
| Full Name | Mitochondrial E3 Ubiquitin Protein Ligase 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 1p36.22 |
| NCBI Gene ID | 79594 ncbi.nlm.nih.gov/gene/79594 |
| Ensembl ID | ENSG00000142632 |
| UniProt ID | Q969V5 |
| OMIM ID | 611487 |
| HGNC ID | 25462 |
| Aliases | MAPL, GIDE, C1orf166, HCGI, RNF218 |
Description
MUL1 encodes a mitochondrial outer membrane E3 ubiquitin ligase that regulates mitochondrial dynamics, apoptosis, and antiviral signaling. It promotes mitochondrial fragmentation via ubiquitination of MFN1/MFN2 and activates the JNK pathway. MUL1 also modulates innate immunity by targeting MAVS and TRAF family proteins.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Breast cancer | MUL1 overexpression correlates with poor prognosis; promotes cell proliferation and migration via AKT pathway | PMID: 31525627 |
| Hepatocellular carcinoma | MUL1 silencing reduces tumor growth; regulates mitochondrial fission and apoptosis | PMID: 30573987 |
| Neurodegenerative diseases (Parkinson's, Alzheimer's) | MUL1-mediated MFN2 ubiquitination impairs mitochondrial fusion, contributing to neuronal dysfunction | PMID: 23416111 |
| Viral infections | MUL1 ubiquitinates MAVS to inhibit RIG-I signaling, promoting viral immune evasion | PMID: 23399672 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 12.5 | Medium |
| Heart | 9.8 | Medium |
| Liver | 7.2 | Medium |
| Brain | 6.1 | Low |
| Kidney | 5.4 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 8.3 | Embryonic kidney cells |
| HeLa | 7.1 | Cervical cancer cells |
| HepG2 | 6.8 | Hepatocellular carcinoma cells |
| SH-SY5Y | 5.9 | Neuroblastoma cells |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.487C>T (p.Arg163Trp) | Missense | <0.01% | Unknown functional impact |
| c.632A>G (p.Tyr211Cys) | Missense | <0.01% | Potential loss of E3 ligase activity |
Mutation functional classification
Loss of Function (LOF)
Mutations in the RING finger domain (e.g., Cys268Ser) abolish E3 ligase activity, impairing MFN2 ubiquitination and mitochondrial fragmentation.
Gain of Function (GOF)
Not well characterized; overexpression in cancer cells suggests possible oncogenic gain-of-function via AKT activation.
Dominant Negative (DN)
Truncated forms lacking the transmembrane domain may sequester substrates and block normal MUL1 function.
View complete mutation data：
Gene Ontology (GO)
| • Mitochondrial outer membrane | • Ubiquitin-protein transferase activity |
| • Protein ubiquitination | • Mitochondrial fusion |
| • Apoptotic process | • Innate immune response |
| • JNK cascade |
Pathways
• Mitophagy - animal
• Apoptosis
• RIG-I-like receptor signaling pathway
• TNF signaling pathway
Protein Summary
MUL1 is a 352-amino acid protein anchored to the mitochondrial outer membrane via a C-terminal transmembrane domain. It contains an N-terminal RING finger domain responsible for E3 ubiquitin ligase activity. MUL1 ubiquitinates MFN1 and MFN2 to promote mitochondrial fission, and targets MAVS to attenuate antiviral signaling. It also interacts with TRAF2 to activate JNK and NF-κB pathways.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| MUL1 Knockout HEK293 Cell Line | EDJ-KQ14336 | Human | 79594 | Details Get a Quote |
| MUL1 Knockout A-549 Cell Line | EDJ-KQ44444 | Human | 79594 | Details Get a Quote |
| MUL1 Knockout HCT 116 Cell Line | EDJ-KQ44445 | Human | 79594 | Details Get a Quote |
| MUL1 Knockout HeLa Cell Line | EDJ-KQ44446 | Human | 79594 | Details Get a Quote |
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