About TRIM / Tripartite Motif:
TRIM proteins are heterodimeric, with two distinct subunits; RING domain and B-box 1 or 2. TRIM was discovered in 1993 by researchers looking for proteins that interact with the vacuolar H+ ATPase (V-ATPase) and bind ubiquitin. TRIM-containing protein heterodimers are characterized by TRIM (Tripartite Motif) domains, consisting of an N-terminal RING domain, B-box 1, and B-box 2 motifs that form a contiguous structure with the RING motif in the central region.
TRIM proteins play critical roles as E3 ubiquitin-protein ligases involved in the ubiquitination and proteolysis of target proteins. TRIM was later found to mediate TRIM5α induced restriction of HIV-1, TRIM22 caused degradation of Smoothened receptor (SMO), TRIM25 mediated degradation of activated STAT1, TRIM21 mediated degradation of Cdc25C, and TRIM15 mediated degradation of MLL2.
Tripartite Motif Mechanism
TRIM5α is a retrovirus restriction factor that functions as an intracellular "spike" protein expressed in the cytosol of cells following infection by the HIV-1 virus. TRIM5α specifically targets and restricts the development of HIV-1 by inducing a post-transcriptional gene silencing (PTGS) process. TRIM5α determines the virus by targeting viral capsid (CA) protein, and TRIM22 is an essential component of TRIF-dependent signaling that plays a minor role in antiviral defense by inducing the degradation of activated STAT1. TRIM22 is essential in TRIF-dependent signaling and a not so important TRIM in antiviral defense. TRIM25, TRIM21, and TRIM15 are E3 ubiquitin ligases that promote degradation of their substrates via the ubiquitin-26S proteasome system.
TRIM21 regulates Cdc25C ubiquitination during the metaphase to anaphase transition. TRIM15 regulates MLL2 stability, which is essential in Hox gene cluster transcription regulation and leukemia treatment. TRIM proteins play critical roles as E3 ubiquitin-protein ligases involved in the ubiquitination and degradation of target proteins.