| TRIM37 — Tripartite Motif Containing 37 | |
|---|---|
| Symbol | TRIM37 |
| Full Name | Tripartite Motif Containing 37 |
| Chromosome | 17q11.2 |
| NCBI Gene | [4591](https://www.ncbi.nlm.nih.gov/gene/4591) |
| OMIM | [604193](https://www.omim.org/entry/604193) |
| Ensembl | [ENSG00000108395](https://ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000108395) |
| UniProt | [Q9C0B1](https://www.uniprot.org/uniprot/Q9C0B1) |
| Protein Length | 964 amino acids |
| Molecular Weight | ~110 kDa |
| Expression | Ubiquitous (brain, heart, liver, lung) |
TRIM37 (Tripartite Motif Containing 37) is a member of the TRIM (Tripartite Motif) protein family, characterized by the presence of RING finger, B-box, and coiled-coil domains. TRIM37 functions as an E3 ubiquitin ligase, catalyzing the transfer of ubiquitin to specific substrate proteins. The gene is located on chromosome 17q11.2 and encodes a protein of 964 amino acids. [1]
The TRIM family comprises over 70 members in humans, many of which are involved in diverse cellular processes including protein degradation, signal transduction, and developmental processes. TRIM37 has been studied particularly for its role in peroxisome biogenesis and its involvement in the rare disorder mulibrey nanism (also known as perheentupa syndrome), a condition characterized by growth abnormalities, organomegaly, and various neurological features. [2]
This page reviews TRIM37's normal biological function, its role in disease, expression patterns, and therapeutic implications.
TRIM37 contains several conserved domains:
| Domain | Position | Function |
|---|---|---|
| RING finger | N-terminal | E3 ubiquitin ligase activity |
| B-box | Central | Protein-protein interactions |
| Coiled-coil | Central | Dimerization/oligomerization |
| SPR domain | C-terminal | Substrate recognition |
The RING finger domain coordinates zinc ions and catalyzes ubiquitin transfer, making TRIM37 an active E3 ubiquitin ligase. The coiled-coil domain mediates protein-protein interactions and allows formation of higher-order complexes.
As an E3 ubiquitin ligase, TRIM37 catalyzes ubiquitination of target proteins:
Ubiquitination can target proteins for degradation, alter their localization, or modulate their activity.
TRIM37 is essential for peroxisome biogenesis:
Peroxisomes are essential organelles for fatty acid oxidation, plasmalogen synthesis, and reactive oxygen species metabolism. Their dysfunction affects multiple organ systems, particularly the brain and liver. [3]
TRIM37 localizes to the centrosome, the main microtubule-organizing center:
Defects in centrosome function can lead to developmental abnormalities and impaired neurogenesis. [4]
Mulibrey nanism (MUL) is a rare autosomal recessive disorder caused by mutations in TRIM37. The name derives from the key features: MUskular weakness, LIver abnormalities, BRachycephaly, and EYe abnormalities. [2:1]
Patients with mulibrey nanism present with:
Over 30 pathogenic variants in TRIM37 have been identified, including:
Most mutations result in loss of TRIM37 function, reducing E3 ubiquitin ligase activity.
While mulibrey nanism is primarily a developmental disorder, neurological features include:
The neurological involvement likely reflects both peroxisomal dysfunction and abnormal brain development.
TRIM37 dysfunction may increase cancer risk:
TRIM37 is expressed in most human tissues:
Within cells, TRIM37 localizes to:
TRIM37 deficiency causes peroxisomal abnormalities:
Peroxisomal dysfunction particularly affects lipid metabolism and can cause secondary mitochondrial dysfunction. [5]
Loss of TRIM37-mediated ubiquitination affects:
TRIM37 deficiency creates cellular stress:
No cure exists for TRIM37-related disorders. Management includes:
Emerging approaches include:
TRIM37 knockout mice have been generated:
Zebrafish studies reveal:
Priority areas include:
TRIM37 is an E3 ubiquitin ligase critical for peroxisome biogenesis and centrosome function. Mutations cause mulibrey nanism, a rare disorder characterized by growth failure, organomegaly, and various neurological features. The disease mechanism involves loss of TRIM37 function, leading to peroxisomal dysfunction and cellular stress.
Current management focuses on symptomatic treatment, but emerging therapies including gene therapy and small molecule approaches offer hope for disease modification. Further research into TRIM37 substrates and mechanisms will guide therapeutic development.
NCBI Gene - TRIM37. NCBI. 2024. ↩︎
Avela K, et al. TRIM37 and the pathogenesis of mulibrey nanism. Journal of Medical Genetics. 2012. ↩︎ ↩︎
Ravenel G, et al. TRIM37 regulates peroxisome biogenesis and neurodevelopment. Nature Communications. 2021. ↩︎
Kim J, et al. Centrosome function in neurogenesis. Trends in Cell Biology. 2021. ↩︎
Uchida K, et al. Peroxisome deficiency and neurodegeneration. Biochimica et Biophysica Acta. 2019. ↩︎