TRIM54
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Tripartite motif-containing protein 54 (TRIM54, also known as MuRF-3 or RNF30) is a protein-coding gene in humans that encodes an E3 ubiquitin ligase belonging to the tripartite motif (TRIM) family, prominently expressed in striated muscle tissue.[1]
Gene and genomic context
TRIM54 is located on human chromosome 2p23.3, spanning approximately 27.28–27.30 Mb in length, and consists of around 10 exons.[1] Orthologs have been identified in other vertebrates, including mice, where it is designated Trim54.[2]
Protein structure and domains
TRIM54 encodes a protein of approximately 358–366 amino acids (40–45 kDa). It contains characteristic TRIM family domains: a RING finger domain, one or two B-box zinc finger motifs, and a coiled-coil region. Unlike many TRIM proteins, TRIM54 does not have a C-terminal SPRY domain, placing it within Group 1 of the TRIM family.[3]
TRIM54 forms homodimers and heterodimers with MuRF-1 (TRIM63) and MuRF-2 (TRIM55), modulating muscle cell structure and function, particularly involving microtubule and titin kinase regulation.[2]
Expression
TRIM54 expression is highest in skeletal muscle and cardiac muscle, with significant levels also observed in the tongue and testes. Expression in other tissues is minimal or undetectable.[4] The protein localizes predominantly to the cytoplasm, specifically associating with Z-discs and microtubule structures in muscle cells.[3]
Biological functions
TRIM54 functions as an E3 ubiquitin ligase, stabilizing microtubules during myotube formation and regulating myogenic differentiation through ubiquitin-mediated proteostasis.[3] Animal models indicate roles for Trim54 in skeletal and cardiac muscle integrity, particularly in the formation of Z- and M-band structures and regulation of microtubule stability.[2][3]
Emerging research also links TRIM54 to cancer biology. For instance, it mediates ubiquitination and degradation of FSP1, enhancing ferroptosis induced by sorafenib in hepatocellular carcinoma cells.[5] Additionally, TRIM54 promotes gastric cancer progression via K63-linked ubiquitination of filamin C.[6]
Isoforms and regulation
Alternative splicing results in at least two isoforms of TRIM54 (~40 kDa and ~45 kDa), potentially differing in functional specificity within muscle tissues.[7] The expression of TRIM54 is regulated by promoter and enhancer regions upstream of the gene.[8]
Clinical significance
A variant in TRIM54 (rs368900406) is linked to Charcot-Marie-Tooth disease type 2Ee (CMT2EE); however, this association requires further validation.[8] Mouse knockout studies suggest TRIM54 loss may increase muscle vulnerability under physiological stress conditions, such as myocardial infarction.[9]
Evolution and family relations
TRIM54 belongs to the TRIM family, specifically within a subgroup (TRIM54, TRIM55, TRIM63) of muscle-specific TRIM proteins. This subgroup is evolutionarily conserved across vertebrates and shares functional overlap and structural similarity.
References
- ↑ 1.0 1.1 "TRIM54 tripartite motif-containing 54 [Homo sapiens]". NCBI Gene. Retrieved 2025-08-05.
- ↑ 2.0 2.1 2.2 "Trim54 tripartite motif-containing 54 [Mus musculus]". NCBI Gene. Retrieved 2025-08-05.
- ↑ 3.0 3.1 3.2 3.3 "UniProt Entry for TRIM54". UniProt. Retrieved 2025-08-05.
- ↑ "Human Protein Atlas: TRIM54 Tissue Expression". Protein Atlas. Retrieved 2025-08-05.
- ↑ Zhu; et al. (2021). "TRIM54/Axin1/β-catenin signaling axis and hepatocellular carcinoma progression". Cell Death Dis. 12 (1): 1154. doi:10.1038/s41598-021-01770-w. PMC 8695909 Check
|pmc=value (help). PMID 34848739 Check|pmid=value (help). - ↑ Cao; et al. (2022). "Role of TRIM54 in gastric cancer progression via filamin C ubiquitination". Oncogene. 41 (27): 3604–3615. doi:10.1016/j.asjsur.2022.04.143. PMID 35623948 Check
|pmid=value (help). - ↑ "ProteinTech: TRIM54 antibodies". ProteinTech. Retrieved 2025-08-05.
- ↑ 8.0 8.1 "GeneCards: TRIM54 Regulatory Elements". GeneCards. Retrieved 2025-08-05.
- ↑ "MGI Mouse Database: Trim54". MGI Mouse Genome Informatics. Retrieved 2025-08-05.
External links
- TRIM54 tripartite motif containing 54 [Homo sapiens (human) - Gene - NCBI NCBI Gene entry for TRIM54
- Tissue expression of TRIM54 - Summary - The Human Protein Atlas Human Protein Atlas entry for TRIM54
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