TRIM33

TRIM33

Target · E3 ubiquitin ligase

TRIM33 Tripartite motif containing 33 · E3 ubiquitin-protein ligase TRIM33

TRIM33 (tripartite motif containing 33, also known as TIF1-gamma, TIF1G, RFG7 and PTC7) is a nuclear E3 ubiquitin-protein ligase of the TRIM/RBCC family. It acts as a transcriptional corepressor and modulates TGF-beta/BMP signalling through SMAD4. Browse Assay Genie's current range of TRIM33 research reagents below, or read on for the biology behind the target.

Nuclear proteinE3 ubiquitin ligaseRestrains TGF-beta/BMP signalling
1127 aa
Protein length
~123 kDa
Molecular weight
1p13.2
Gene locus
EC 2.3.2.27
Enzyme class
Target information

What is TRIM33 (tripartite motif containing 33)?

TRIM33 functions as an E3 ubiquitin-protein ligase and may also act as a transcriptional repressor. A well-characterised activity is its effect on SMAD4: TRIM33 monoubiquitinates SMAD4, which hampers the ability of SMAD4 to form a stable complex with activated SMAD2 and SMAD3. This inhibits the transcriptional response to the TGF-beta/BMP signalling cascade. UniProt also records that TRIM33 promotes SMAD4 ubiquitination, nuclear exclusion and degradation through the ubiquitin proteasome pathway, although a separate report (PubMed:16751102) found no decrease in endogenous SMAD4 levels.

Beyond signalling control, TRIM33 plays a role in the regulation of cell proliferation. Its association with SMAD2 and SMAD3 stimulates erythroid differentiation of haematopoietic stem and progenitor cells, so the protein can influence SMAD signalling in different directions depending on context. The TRIM33 protein is located in the nucleus.

The TRIM33 gene encodes a member of the tripartite motif family, defined by three zinc-binding domains (a RING, a B-box type 1 and a B-box type 2) and a coiled-coil region. HGNC also classifies it with PHD finger proteins and bromodomain-containing proteins. NCBI Gene describes the protein as a probable transcriptional corepressor and notes three alternatively spliced transcript variants, one of which has not been fully defined. TRIM33 is also known as TIF1-gamma (transcriptional intermediary factor 1 gamma), RFG7, PTC7, KIAA1113 and FLJ11429, and the mouse ortholog is Trim33.

TGF-beta/BMP signalling

TRIM33 monoubiquitinates SMAD4 and inhibits SMAD4-dependent TGF-beta/BMP signalling, making it a useful target for studying SMAD regulation.

Ubiquitin ligase biology

As a RING-type E3 ubiquitin-protein ligase of the TRIM family, TRIM33 is studied for substrate ubiquitination and its fate in the proteasome pathway.

Haematopoietic differentiation

Association of TRIM33 with SMAD2 and SMAD3 stimulates erythroid differentiation of haematopoietic stem and progenitor cells.

Transcriptional repression

TRIM33 is thought to act as a transcriptional corepressor, supporting research into nuclear regulation of gene expression and control of cell proliferation.

Background

TRIM33 frequently asked questions

What does TRIM33 do?

TRIM33 is an E3 ubiquitin-protein ligase that monoubiquitinates SMAD4, reducing its ability to form a stable complex with activated SMAD2/3 and so inhibiting TGF-beta/BMP signalling. It may also act as a transcriptional repressor and contributes to the control of cell proliferation.

What other names and isoforms does TRIM33 have?

TRIM33 is also called TIF1-gamma, TIF1G, TIFGAMMA, TF1G, RFG7, PTC7, KIAA1113 and FLJ11429. Its earlier name was tripartite motif-containing 33. NCBI Gene reports three alternatively spliced transcript variants, though the full-length nature of one has not been determined.

Is TRIM33 conserved across species?

Yes, TRIM33 has a mouse ortholog, Trim33, and the protein belongs to the TRIM/RBCC family defined by RING, B-box and coiled-coil domains. Check the datasheet of any product for its validated reactivity.

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Related targets

Other TRIM family E3 ubiquitin ligases, including the closely related TIF1 members, with research reagents at Assay Genie.

Gene and protein annotations from HGNC, NCBI Gene and UniProt Q9UPN9; product specifications from Assay Genie datasheets.

TRIM33 Product listing