Muscle RING finger protein 1 (MuRF1)

Muscle RING finger protein 1 (MuRF1, encoded by the TRIM63 gene) is an **E3 ubiquitin ligase** specifically expressed in skeletal and cardiac muscle[1][2][3]. It plays a central role in **muscle protein degradation**, targeting structural (e.g., myosin heavy chain, troponin I) and regulatory proteins for ubiquitylation and subsequent **proteasomal degradation**, particularly during **muscle atrophy** in response to stimuli such as denervation, glucocorticoids, immobilization, and systemic disease[1][3]. MuRF1 interacts with major sarcomeric proteins such as **titin, troponin I/T, myosin light chain 2**, and regulatory proteins involved in mitochondrial and metabolic pathways. It is also involved in nuclear regulation via polyubiquitination and degradation of transcription factors related to muscle atrophy[2]. Post-translational SUMOylation of MuRF1 regulates its nuclear and mitochondrial localization, linking it to cellular stress and metabolic states, such as **hyperglycemia**[2]. Upregulation of MuRF1 is a key mediator of **skeletal muscle wasting**, while downregulation is implicated in **cardiac hypertrophy**[2][3]. Mutations in MuRF1 have been linked to protein aggregate myopathies, indicating its vital role in muscle homeostasis and disease[2]. At present, MuRF1 serves as a **therapeutic target** for muscle-wasting disorders, although no drugs directly targeting it are clinically available.

Other names

E3 ubiquitin-protein ligase TRIM63TRIM63Muscle Ring-Finger Protein 1

Ubiquitin ligase-mediated proteasome-dependent degradation of sarcomeric and regulatory muscle proteins (e.g., troponin I, myosin heavy chain)[1][3] Upregulated MuRF1 drives protein breakdown leading to muscle atrophy[3]