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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 [2] - 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

General

nuclear protein phosphoprotein tripartite motif-containing protein (trim protein) E3 ubiquitin ligase; ubiquitin-ligating enzyme E3; N end-recognizing protein

Properties

SIZE: entity length = 1127 aa MW = 123 kD COMPARTMENT: cell nucleus MOTIF: silencer element SITE: 1-147 MOTIF: glycine-rich region {13-18} glutamate-rich region {44-49} MOTIF: glutamate residue (SEVERAL) RING-finger {125-154} EFFECTOR-BOUND: Zn+2 FOR-BINDING-OF: DNA motif zinc finger B box SITE: 212-259 EFFECTOR-BOUND: Zn+2 zinc finger B box SITE: 271-312 EFFECTOR-BOUND: Zn+2 Necessary for oligomerization {299-401} MOTIF: coiled coil {299-401} Thr phosphorylation site {T505} threonine-rich region {545-550} MOTIF: threonine residue (SEVERAL) Ser phosphorylation site {S862} Zn finger PHD-type NAME: Zn finger PHD-type SITE: 887-934 EFFECTOR-BOUND: Zn+2 breakpoint {964-965} bromodomain {974-1046} Thr phosphorylation site {T1102} Ser phosphorylation site {S1105} Ser phosphorylation site {S1119}

Database Correlations

OMIM correlations UniProt Q9UPN9 PFAM correlations Entrez Gene 51592 Kegg hsa:51592

References

  1. UniProt :accession Q9UPN9
  2. PMID: 16751102