TRIM63 Gene: Structure, Function, and Clinical Significance
A comprehensive overview of the TRIM63 gene, encoding the muscle-specific RING finger protein MuRF1, including its genomic context, expression, disease associations, and functional roles.
Gene Information Card
| Symbol | TRIM63 |
|---|---|
| Full Name | Tripartite Motif Containing 63 |
| Gene Type | Protein coding |
| Chromosomal Location | 1p36.11 |
| NCBI Gene ID | 84676 ncbi.nlm.nih.gov/gene/84676 |
| Ensembl ID | ENSG00000158022 |
| UniProt ID | Q969Q1 |
| OMIM ID | 606131 |
| HGNC ID | 23667 |
| Aliases | MuRF1, RNF28, SMRZ, IRF |
Description
The TRIM63 gene encodes the muscle-specific RING finger protein 1 (MuRF1), a member of the tripartite motif (TRIM) family. MuRF1 functions as an E3 ubiquitin ligase, playing a central role in the ubiquitin-proteasome system. It is highly expressed in skeletal and cardiac muscle, where it regulates protein degradation and is a key mediator of muscle atrophy. TRIM63 has been implicated in hypertrophic cardiomyopathy and other muscle-related conditions.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hypertrophic cardiomyopathy | Mutations in TRIM63 may impair its E3 ligase activity, leading to altered protein homeostasis and cardiac hypertrophy. | ClinVar, OMIM |
| Muscle atrophy | Upregulation of TRIM63 in catabolic conditions promotes ubiquitin-mediated degradation of muscle proteins, contributing to muscle wasting. | NCBI Gene, PubMed |
| Myopathy | Rare variants in TRIM63 have been associated with myopathic phenotypes, though the mechanism is not fully defined. | ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Skeletal muscle | High | High |
| Heart | High | High |
| Adipose tissue | Low | Low |
| Liver | Not detected | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Skeletal muscle cells (e.g., C2C12) | High | Differentiated myotubes show high expression |
| Cardiomyocytes (e.g., AC16) | High | Expression increases under stress conditions |
| HeLa | Low | Minimal expression |
| HEK293 | Low | Minimal expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.487C>T (p.Arg163Trp) | Missense | Rare | May affect protein stability or ligase activity |
| c.736G>A (p.Val246Met) | Missense | Rare | Reported in hypertrophic cardiomyopathy cases |
| c.1003C>T (p.Arg335Ter) | Nonsense | Very rare | Predicted to cause loss of function |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations in TRIM63, such as nonsense or frameshift variants, are expected to reduce E3 ubiquitin ligase activity, impairing targeted protein degradation and potentially contributing to cardiac hypertrophy.
Gain of Function (GOF)
No clear gain-of-function mutations have been documented for TRIM63. Overexpression of wild-type TRIM63 is associated with muscle atrophy, but this is not due to mutations.
Dominant Negative (DN)
Some missense mutations may exert a dominant-negative effect by interfering with dimerization or substrate binding, though evidence is limited.
View complete mutation data：
Gene Ontology (GO)
| • ubiquitin-protein transferase activity | • zinc ion binding |
| • protein binding | • ubiquitin-dependent protein catabolic process |
| • skeletal muscle tissue development | • cardiac muscle tissue development |
| • response to denervation involved in regulation of muscle atrophy |
Pathways
• Ubiquitin-proteasome system
• Muscle atrophy signaling (e.g.
• IGF-1/AKT/FOXO pathway)
• Protein ubiquitination
Protein Summary
The TRIM63 protein (MuRF1) is a 353-amino acid E3 ubiquitin ligase containing a RING finger domain, B-box, and coiled-coil domains. It interacts with structural proteins such as titin and myosin heavy chain, targeting them for proteasomal degradation. MuRF1 is a critical regulator of muscle mass, and its expression is induced by catabolic stimuli (e.g., glucocorticoids, denervation, fasting).
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| TRIM63 Knockout HEK293 Cell Line | EDJ-KQ2173 | Human | 84676 | Details Get a Quote |
| TRIM63 Knockout HeLa Cell Line | EDJ-KQ57642 | Human | 84676 | Details Get a Quote |
| TRIM63 Knockout A-549 Cell Line | EDJ-KQ66140 | Human | 84676 | Details Get a Quote |
| TRIM63 Knockout HCT 116 Cell Line | EDJ-KQ74567 | Human | 84676 | Details Get a Quote |
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