ID:TRI33_HUMAN DESCRIPTION: RecName: Full=E3 ubiquitin-protein ligase TRIM33; EC=6.3.2.-; AltName: Full=Ectodermin homolog; AltName: Full=RET-fused gene 7 protein; Short=Protein Rfg7; AltName: Full=Transcription intermediary factor 1-gamma; Short=TIF1-gamma; AltName: Full=Tripartite motif-containing protein 33; 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). PATHWAY: Protein modification; protein ubiquitination. SUBUNIT: Homooligomer and heterooligomer with TRIM24 and TRIM28 family members. Interacts with SMAD4 in unstimulated cells. Found in a complex with SMAD2 and SMAD3 upon addition of TGF-beta. Interacts with SMAD2 and SMAD3. Interacts with SMAD4 under basal and induced conditions and, upon TGF-beta signaling, with activated SMAD2. Forms a ternary complex with SMAD4 and SMAD2 upon TGF-beta signaling. INTERACTION: Q15796:SMAD2; NbExp=6; IntAct=EBI-2214398, EBI-1040141; Q13485:SMAD4; NbExp=5; IntAct=EBI-2214398, EBI-347263; SUBCELLULAR LOCATION: Nucleus. Note=In discrete nuclear dots resembling nuclear bodies (By similarity). 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. DISEASE: Defects in TRIM33 are a cause of thyroid papillary carcinoma (TPC) [MIM:188550]. TPC is a common tumor of the thyroid that typically arises as an irregular, solid or cystic mass from otherwise normal thyroid tissue. Papillary carcinomas are malignant neoplasm characterized by the formation of numerous, irregular, finger-like projections of fibrous stroma that is covered with a surface layer of neoplastic epithelial cells. Note=A chromosomal aberration involving TRIM33 is found in thyroid papillary carcinomas. Translocation t(1;10)(p13;q11) with RET. The translocation generates the TRIM33/RET (PTC7) oncogene. SIMILARITY: Belongs to the TRIM/RBCC family. SIMILARITY: Contains 2 B box-type zinc fingers. SIMILARITY: Contains 1 bromo domain. SIMILARITY: Contains 1 PHD-type zinc finger. SIMILARITY: Contains 1 RING-type zinc finger. SEQUENCE CAUTION: Sequence=AAD17259.1; Type=Frameshift; Positions=1114; Sequence=BAA83065.1; Type=Erroneous initiation; Note=Translation N-terminally shortened; Sequence=CAI13548.1; Type=Erroneous gene model prediction; Sequence=CAI21895.1; Type=Erroneous gene model prediction;
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on Q9UPN9
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
US Server
Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
