E3 ubiquitin-protein ligase TRIM63 is an enzyme that in humans is encoded by the TRIM63gene.
This gene encodes a member of the RING zinc finger protein family found in striated muscle and iris. The product of this gene is localized to the Z-line and M-line lattices of myofibrils, where titin's N-terminal and C-terminal regions respectively bind to the sarcomere. In vitro binding studies have shown that this protein also binds directly to titin near the region of titin containing kinase activity. Another member of this protein family binds to microtubules. Since these family members can form heterodimers, this suggests that these proteins may serve as a link between titin kinase and microtubule-dependent signal pathways in muscle.
The protein encoded by the Trim63 gene is also called MuRF1. MuRF1 is the name most commonly used in the literature, and it stands for "Muscle RING Finger 1." Structurally, there are two closely related MuRFs, MuRF2 and MuRF3. These also have TRIM codes: MuRF2 is TRIM55; MuRF3 is TRIM54.
Trim63/MuRF1 has been shown to be an E3 ubiquitin ligase. It's major substrate is Myosin Heavy Chain. MuRF1 is upregulated during skeletal muscle atrophy - and thus the degradation of myosin heavy chain, which is a major component of the sarcomere, is an important mechanism in the breakdown of skeletal muscle under atrophy conditions. MuRF1 has been shown to be upregulated during denervation, administration of glucocorticods, immobilization, and casting. All of these treatments cause skeletal muscle atrophy.
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