E3 ubiquitin-protein ligase TRIM63 (TRIM63)

E3 ubiquitin-protein ligase TRIM63 (commonly called MuRF1) is an enzyme predominantly expressed in striated muscle and is a key regulator of muscle protein catabolism[1][2][3]. It belongs to the RING-type E3 ubiquitin ligase subgroup within the tripartite motif (TRIM) protein family, distinguished by their zinc finger domains and coiled-coil regions that mediate protein-protein interactions[3]. TRIM63 is localized at the sarcomere Z-line and M-line where it interacts with proteins such as titin and myosin[1][2][3]. Its primary function is tagging specific muscle proteins, especially myosin, for proteasomal degradation—a process upregulated during periods of muscle atrophy, disuse, glucocorticoid treatment, or cachexia[1][2][4]. Genetically, variants in TRIM63 are associated with certain forms of hypertrophic cardiomyopathy[1]. As a central mediator of muscle protein breakdown, TRIM63 is a validated target for skeletal muscle wasting and related conditions, although no drugs are yet approved to target it directly. Upregulation of TRIM63/MuRF1 is routinely used as a molecular biomarker for muscle atrophy[1].

Other names

MuRF1Muscle RING Finger 1RING finger protein 28Tripartite motif-containing protein 63Muscle-specific RING finger protein 1MURF1RNF28SMRZIris ring finger proteinStriated muscle RING zinc finger proteinCMH31

Induction of ubiquitination and degradation of muscle proteins (e.g., myosin heavy chain, creatine kinase, actin) Regulation of sarcomere stability and muscle cell structure