TRIM63 Gene

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TRIM63 Gene

Overview

TRIM63 (Tripartite Motif Containing 63), also known as MURF-1 (Muscle-Specific RING Finger Protein 1), is a muscle-specific E3 ubiquitin ligase that plays a critical role in protein degradation pathways [1](https://pubmed.ncbi.nlm.nih.gov/11679637/). While primarily studied in the context of skeletal and cardiac muscle biology, TRIM63 has emerging connections to neurodegenerative diseases through pathways involving protein homeostasis, [autophagy](/entities/autophagy), and muscle-brain interactions. [@bodine2001]

Gene Information

<div class="infobox infobox-gene"> [@glass2010]

| Property | Value | [@cohen2009]
|----------|-------| [@milan2009]
| Gene Symbol | TRIM63 | [@sartori2023]
| Gene Name | Tripartite Motif Containing 63 (MURF-1) | [@pradat2020]
| Aliases | MURF-1, IRF, RNF28 | [@gomes2011]
| Chromosomal Location | 1p36.22 |
| NCBI Gene ID | [55177](https://www.ncbi.nlm.nih.gov/gene/55177) |
| OMIM | [606471](https://www.omim.org/entry/606471) |
| UniProt | [Q9C0B1](https://www.uniprot.org/uniprot/Q9C0B1) |
| Ensembl | ENSG00000146070 |

</div>

Function

Ubiquitin Ligase Activity

TRIM63 functions as an E3 ubiquitin ligase, specifically targeting proteins for degradation via the [ubiquitin-proteasome system](/mechanisms/ubiquitin-proteasome-system) (UPS). Key substrates include:

...

TRIM63 Gene

Overview

Gene Information

<div class="infobox infobox-gene"> [@glass2010]

</div>

Function

Ubiquitin Ligase Activity

Myosin heavy chain (MyHC): Structural protein in muscle fibers [2](https://pubmed.ncbi.nlm.nih.gov/20160128/)
Troponin I: Regulatory protein in muscle contraction
Titin: Large protein responsible for muscle elasticity
Nuclear proteins: Involved in gene regulation

Role in Muscle Atrophy

TRIM63 is a key mediator of muscle atrophy pathways:

FoxO transcription factors: Activated during atrophy, upregulate TRIM63 expression [3](https://pubmed.ncbi.nlm.nih.gov/19470920/)

Akt/mTOR signaling: Inhibits TRIM63 when active; loss of Akt signaling promotes expression

Inflammatory cytokines: TNF-α and IL-6 can induce TRIM63 transcription

Oxidative stress: Increases TRIM63 levels in muscle tissue

Autophagy Regulation

TRIM63 interacts with autophagy pathways:

LC3 interaction: Can bind to autophagy-related proteins [4](https://pubmed.ncbi.nlm.nih.gov/19801663/)
Selective autophagy: Targets damaged proteins for autophagic degradation
Mitophagy: May influence mitochondrial quality control in muscle

Expression Pattern

Tissue Distribution

TRIM63 shows highly restricted expression:

Skeletal muscle: Highest expression in fast-twitch (type II) fibers
Cardiac muscle: Moderate expression in heart tissue
Brain: Very low to undetectable under normal conditions
Other tissues: Minimal expression

Regulation

TRIM63 expression is tightly regulated by:

Transcriptional control: FoxO1, FoxO3, and [NF-κB](/entities/nf-kb) response elements
Hormonal signaling: Glucocorticoids, thyroid hormone
Activity-dependent: Disuse and unloading increase expression
Circadian regulation: Shows diurnal variation in muscle

Disease Associations

Sarcopenia

TRIM63 plays a significant role in age-related muscle loss (sarcopenia):

Upregulation in aging: TRIM63 expression increases with age in skeletal muscle
Protein degradation: Enhanced ubiquitin-proteasome activity contributes to muscle fiber loss
Therapeutic targeting: Inhibition of TRIM63 may preserve muscle mass in elderly [5](https://pubmed.ncbi.nlm.nih.gov/25498203/)

Amyotrophic Lateral Sclerosis (ALS)

Connections between TRIM63 and ALS include:

Muscle involvement: ALS patients show elevated TRIM63 in muscle biopsies [6](https://pubmed.ncbi.nlm.nih.gov/32654211/)
Denervation atrophy: Motor neuron degeneration leads to muscle TRIM63 upregulation
Biomarker potential: TRIM63 as a marker of muscle involvement in ALS
Preclinical studies: Murf1 knockout mice show improved muscle function in ALS models

Muscular Dystrophies

TRIM63 dysregulation in muscular dystrophies:

Duchenne Muscular Dystrophy (DMD): Elevated TRIM63 in muscle biopsies
Limb-Girdle Muscular Dystrophies: Variable TRIM63 expression patterns
Myotonic Dystrophy: TRIM63 upregulation correlates with disease severity

Cardiomyopathy

In cardiac muscle:

Heart failure: TRIM63 expression increases in failing hearts [7](https://pubmed.ncbi.nlm.nih.gov/21368165/)
Cardiac atrophy: Associated with pathological cardiac remodeling
Pressure overload: Mechanical stress induces TRIM63 in cardiac tissue

Neurodegenerative Disease Context

Muscle-Brain Axis

The muscle-brain axis provides connections between peripheral muscle function and neurodegenerative diseases:

Exercise effects: Physical activity reduces TRIM63 in muscle and may have neuroprotective effects

Myokines: Muscle-secreted factors influence brain function

Metabolic health: Muscle metabolism affects systemic inflammation

Inflammatory Connections

Chronic inflammation in neurodegeneration affects muscle:

Cytokine signaling: Peripheral IL-6, TNF-α cross the [blood-brain barrier](/entities/blood-brain-barrier)
Muscle inflammation: Neurodegeneration can cause muscle inflammatory responses
TRIM63 regulation: Inflammatory cytokines upregulate muscle TRIM63

Therapeutic Implications

TRIM63 as a therapeutic target:

Small molecule inhibitors: Under development for muscle wasting disorders
Antisense oligonucleotides: ASO-based approaches to reduce TRIM63 expression
Natural compounds: Some flavonoids and polyphenols inhibit TRIM63 transcription
Combination therapies: TRIM63 inhibition with exercise and nutrition

Research Methods

Experimental Models

Knockout mice: Murf1-/- mice show resistance to muscle atrophy
Cell culture: C2C12 myotubes for in vitro studies
Tissue samples: Human muscle biopsies from patients

Detection Methods

qPCR: mRNA expression analysis
Western blot: Protein level detection
Immunohistochemistry: Tissue localization
Enzyme activity: Ubiquitin ligase activity assays

Interactions and Pathways

Protein Interactions

TRIM63 interacts with:

Ubiquitin-conjugating enzymes: UBE2D2, UBE2L3
Muscle structural proteins: Myosin, troponin, titin
Transcription factors: FoxO1, FoxO3
Autophagy proteins: LC3, p62

Signaling Pathways

Akt/mTOR: Negative regulation when active
FoxO transcription factors: Direct transcriptional activation
NF-κB signaling: Inflammatory cytokine-mediated induction
MAPK pathways: Stress-activated signaling

Clinical Significance

Biomarker Potential

TRIM63 as a biomarker:

Blood levels: Detectable in serum; correlates with muscle mass
Disease progression: Levels track with disease severity in some conditions
Therapeutic monitoring: May predict response to atrophy treatments

Therapeutic Targeting

Current approaches:

Pharmacological inhibitors: Preclinical development
Gene therapy: AAV-mediated knockdown approaches
Repurposing: Existing drugs that modulate TRIM63

External Links

[NCBI Gene - TRIM63](https://www.ncbi.nlm.nih.gov/gene/55177)
[OMIM - TRIM63](https://www.omim.org/entry/606471)
[UniProt - TRIM63](https://www.uniprot.org/uniprot/Q9C0B1)
[Ensembl - TRIM63](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000146070)
[PubMed - TRIM63 Research](https://pubmed.ncbi.nlm.nih.gov/?term=TRIM63+MURF1+muscle)

References

[Bodine et al., Identification of ubiquitin ligases required for skeletal muscle atrophy (2001) (2001)](https://pubmed.ncbi.nlm.nih.gov/11679637/))

[Unknown, Glass, Molecular mechanisms of muscle cachexia (2010) (2010)](https://pubmed.ncbi.nlm.nih.gov/20160128/))

[Cohen et al., FoxO3 transcription factor in muscle atrophy (2009) (2009)](https://pubmed.ncbi.nlm.nih.gov/19470920/))

[Milan et al., FoxO3 controls autophagy in skeletal muscle (2009) (2009)](https://pubmed.ncbi.nlm.nih.gov/19801663/))

[Sartori et al., Muscle atrophy: causes and therapeutic targets (2023) (2023)](https://pubmed.ncbi.nlm.nih.gov/37252145/))

[Pradat et al., Muscle biomarkers in ALS (2020) (2020)](https://pubmed.ncbi.nlm.nih.gov/32654211/))

[Gomes et al., Role of muRF1 in cardiac atrophy (2011) (2011)](https://pubmed.ncbi.nlm.nih.gov/21368165/))

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TRIM63 Gene

TRIM63 Gene

Overview

Gene Information

Function

Ubiquitin Ligase Activity

TRIM63 Gene

Overview

Gene Information

Function

Ubiquitin Ligase Activity

Role in Muscle Atrophy

Autophagy Regulation

Expression Pattern

Tissue Distribution

Regulation

Disease Associations

Sarcopenia

Amyotrophic Lateral Sclerosis (ALS)

Muscular Dystrophies

Cardiomyopathy

Neurodegenerative Disease Context

Muscle-Brain Axis

Inflammatory Connections

Therapeutic Implications

Research Methods

Experimental Models

Detection Methods

Interactions and Pathways

Protein Interactions

Signaling Pathways

Clinical Significance

Biomarker Potential

Therapeutic Targeting

See Also

External Links

References