TRIM55

TRIM55 Full Name

tripartite motif containing 55

TRIM55 Introduction

Tripartite motif containing 55 (TRIM55), also known as muscle-specific RING finger protein 2 (MURF-2), is a member of the TRIM (tripartite motif) family of E3 ubiquitin ligases that is specifically expressed in cardiac and skeletal muscle. Encoded by the TRIM55 gene on chromosome 8q21.13, TRIM55/MURF-2 has the canonical TRIM/RBCC architecture consisting of an N-terminal RING finger domain (conferring E3 ubiquitin ligase activity), one or two B-box zinc-finger domains, and a coiled-coil region that mediates homo- and heterodimerization. Together with the related proteins TRIM54/MURF-1 and TRIM63/MURF-3, TRIM55 constitutes the MURF (muscle RING finger) subfamily of TRIM proteins that regulate sarcomere assembly, protein quality control, and muscle mass homeostasis.

Figure 1. Strcuture of TRIM55.

Sarcomeric Localization and Microtubule Regulation
A defining characteristic of TRIM55/MURF-2 is its dual localization within striated muscle cells: it associates transiently with microtubules and also stably integrates into the sarcomeric M-line, the central transverse structure of the sarcomere. During myofibrillogenesis, TRIM55 is initially bound to microtubules, where it functions as a ubiquitin ligase and is proposed to mediate the delivery of sarcomeric components to nascent myofibrils. As sarcomeres mature, TRIM55 translocates to the M-line, where it interacts with the giant scaffold protein titin through its C-terminal domain. At the M-line, TRIM55 contributes to the structural organization of the thick filament lattice and participates in the mechanosensitive signaling pathways that couple sarcomere stretch to changes in gene expression. TRIM55 also associates with glucocorticoid modulatory element-binding protein 1 (GMEB-1) and serum response factor (SRF), linking sarcomere status to transcriptional regulation of muscle gene programs.

TRIM55 in Cardiac Hypertrophy, Atrophy, and Muscle Disease
The MURF family plays a central role in muscle mass regulation, with MURF-1 (TRIM63) primarily mediating skeletal muscle atrophy and MURF-2 (TRIM55) and MURF-3 (TRIM54) implicated more prominently in cardiac muscle remodeling. TRIM55 is upregulated in response to cardiac hypertrophic stimuli, and its forced overexpression in cardiomyocytes induces hypertrophy, in part through stabilization of SRF-dependent transcription. Conversely, TRIM55 knockout mice are viable but exhibit altered cardiac responses to pressure overload, implicating TRIM55 as a modulator rather than an obligate initiator of cardiac hypertrophy. TRIM55 also functions in the quality control of sarcomeric proteins: as an E3 ubiquitin ligase, it catalyzes the ubiquitination of specific sarcomere-associated substrates, targeting them for proteasomal degradation. This activity is particularly important during cardiac stress, when damaged sarcomeric proteins must be efficiently removed and replaced to maintain contractile function. Mutations or dysregulation of TRIM55 have been investigated in the context of cardiomyopathies, including hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM), although definitive human disease associations await larger genetic studies.

Alternate Names for TRIM55

TRIM55; tripartite motif containing 55; RNF29; muRF2; MURF-2; tripartite motif-containing protein 55; ring finger protein 29; muscle specific ring finger 2; tripartite motif-containing 55; muscle-specific RING finger protein 2;