TRIM33 (TRIM33 stands for: Tripartite Motif Containing 33) is a human protein-coding gene located on chromosome 1p13.2.
The encoded protein belongs to the TRIM superfamily (TRIM = Tripartite motif) and occurs in four subtypes known as:
- TIF1-α (TRIM24)
- TIF1-β (TRIM28)
- TIF1-γ (TRIM33)
- and TIF1-δ (TRIM66)
are known. All subtypes have similar structures, which include an N-terminal TRIM that is a protein-protein and oligomerization interface and contains a ring-B-box-coiled-coil (RBCC) domain, a central TIF1 signature sequence (TSS) domain, and a C-terminal combination plant homeodomain (PHD) and bromodomain. (Since TRIM is a ubiquitin ligase involved in protein modification, and the C-terminal chromatin-binding unit performs epigenetic transcriptional regulation, TIF1 may have multifunctional protein properties.) Thus, the protein TIF1-γ encoded by this gene is considered a transcriptional co-repressor. TIF-1γ has been shown to play a role in transcription elongation, DNA repair, cell differentiation, embryonic development and mitosis. At the N-terminus is an RBCC unit containing a RING domain, B-boxes and a coiled-coil domain, all of which are involved in the ubiquitination of Smad4. At the C-terminus is a PHD bromodomain that can interact with histones 3 and 4, while a middle linker region that interacts with activated Smad2 and Smad3 connects the two termini.