E3 ubiquitin-protein ligase TRIM33; tripartite motif-containing protein 33; transcription intermediary factor 1-gamma; TIF1-gamma; ectodermin homolog; RET-fused gene 7 protein; protein Rfg7 (TRIM33, KIAA1113, RFG7, TIF1G)

Function

• acts as an E3 ubiquitin-protein ligase
• promotes SMAD4 ubiquitination, nuclear exclusion & degradation via the ubiquitin proteasome pathway
  • may 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
• role in control of cell proliferation
• association with SMAD2 & SMAD3 stimulates erythroid differentiation of hematopoietic stem/progenitor (putative)
• monoubiquitinates SMAD4 & 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
• protein modification; protein ubiquitination
• homooligomer & heterooligomer with TRIM24 & TRIM28 family members
• interacts with SMAD4 in unstimulated cells
• found in a complex with SMAD2 & SMAD3 upon addition of TGF-beta
• interacts with SMAD2 & SMAD3
• interacts with SMAD4 under basal & induced conditions &, upon TGF-beta signaling, with activated SMAD2
• forms a ternary complex with SMAD4 & SMAD2 upon TGF-beta signaling

Structure

• belongs to the TRIM/RBCC family
• contains 2 B box-type Zn+2 fingers
• contains 1 bromo domain
• contains 1 PHD-type Zn+2 finger
• contains 1 RING-type Zn+2 finger

Compartment

• nucleus
• in discrete nuclear dots resembling nuclear bodies (putative)

Alternative splicing

named isoforms=2; alpha, beta

Expression

• expressed in stem cells at the bottom of the crypts of the colon (at protein level)
• expressed in colon adenomas & adenocarcinomas (at protein level)
• expressed in brain, lung, liver, spleen, thymus, prostate, kidney, testis, heart, placenta, pancreas, small intestine, ovary, colon, skeletal muscle & hematopoietic progenitors

Pathology

• chromosomal translocation t(1;10)(p13;q11) involving TRIM33 with RET is a cause of thyroid papillary carcinoma
  • the translocation generates the TRIM33/RET (PTC7) oncogene

Laboratory

• TIF1-gamma Ab in serum
  • TIF1-gamma IgG in serum

More general terms

• tripartite motif-containing protein (trim protein)
• E3 ubiquitin ligase
• nuclear protein
• phosphoprotein

Database

• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=51592
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:51592
• OMIM: https://mirror.omim.org/entry/188550
• OMIM: https://mirror.omim.org/entry/605769
• UniProt: http://www.uniprot.org/uniprot/Q9UPN9.html