TRIM33
Function
Acts as an E3 ubiquitin-protein ligase. Promotes SMAD4 ubiquitination, nuclear exclusion and degradation via the ubiquitin proteasome pathway. According to PubMed:16751102, does not promote a decrease in the level of endogenous SMAD4. May act as a transcriptional repressor. Inhibits the transcriptional response to TGF-beta/BMP signaling cascade. Plays a role in the control of cell proliferation. Its association with SMAD2 and SMAD3 stimulates erythroid differentiation of hematopoietic stem/progenitor (By similarity). Monoubiquitinates SMAD4 and acts as an inhibitor of SMAD4-dependent TGF-beta/BMP signaling cascade (Monoubiquitination of SMAD4 hampers its ability to form a stable complex with activated SMAD2/3 resulting in inhibition of TGF-beta/BMP signaling cascade).
Involvement in disease
A chromosomal aberration involving TRIM33 is found in papillary thyroid carcinomas (PTCs). Translocation t(1;10)(p13;q11) with RET. The translocation generates the TRIM33/RET (PTC7) oncogene.
Pathway
Protein modification; protein ubiquitination.
Post-translational modifications
Sumoylated with SUMO1.
Sequence Similarities
Belongs to the TRIM/RBCC family.
Tissue Specificity
Expressed in stem cells at the bottom of the crypts of the colon (at protein level). Expressed in colon adenomas and adenocarcinomas (at protein level). Expressed in brain, lung, liver, spleen, thymus, prostate, kidney, testis, heart, placenta, pancreas, small intestine, ovary, colon, skeletal muscle and hematopoietic progenitors.
Cellular localization
- Nucleus
- In discrete nuclear dots resembling nuclear bodies (By similarity). Localizes to sites of DNA damage (PubMed:25593309).
Alternative names
KIAA1113, RFG7, TIF1G, TRIM33, E3 ubiquitin-protein ligase TRIM33, Ectodermin homolog, RET-fused gene 7 protein, RING-type E3 ubiquitin transferase TRIM33, Transcription intermediary factor 1-gamma, Tripartite motif-containing protein 33, Protein Rfg7, TIF1-gamma