Disease relevance of TRIM32

• Limb-girdle muscular dystrophy type 2H associated with mutation in TRIM32, a putative E3-ubiquitin-ligase gene [1].
• Commonality of TRIM32 mutation in causing sarcotubular myopathy and LGMD2H [2].
• Overall, these data suggest that HT2A may play a significant role in mediating the biological activity of the HIV-1 Tat protein in vivo [3].

High impact information on TRIM32

• Homozygosity mapping with SNP arrays identifies TRIM32, an E3 ubiquitin ligase, as a Bardet-Biedl syndrome gene (BBS11) [4].
• Functional analysis of this gene in zebrafish and expression correlation analyses among other BBS genes in an expression quantitative trait loci data set demonstrate that TRIM32 is a BBS gene [4].
• Mutation analysis in the region of homozygosity identified a conserved homozygous missense mutation in the TRIM32 gene, a gene coding for an E3 ubiquitin ligase [4].
• On the basis of our results, the mutation in the tripartite-motif-containing gene (TRIM32) that replaces aspartate with asparagine at position 487 appears to be the causative mutation of LGMD2H [1].
• Limb-girdle muscular dystrophy type 2H (LGMD2H) is a mild autosomal recessive myopathy that was first described in the Manitoba Hutterite population [1].

Biological context of TRIM32

• The TRIM32 mutation found in the STM patients is identical to the causative mutation for LGMD2H (D487N), Haplotype analysis shows that the disease chromosomes share common ancestry [2].
• Interestingly, missense point mutation of human TRIM32 has been reported in Limb-Girdle Muscular Dystrophy Type 2H, an autosomal recessive disease [5].
• Limb girdle muscular dystrophy (LGMD) is common in the Hutterite population of North America. We previously identified a mutation in the TRIM32 gene in chromosome region 9q32, causing LGMD2H in approximately two-thirds of the 60 Hutterite LGMD patients studied to date [6].
• Sequence analysis demonstrates that HT2A is a novel member of the C3HC4 or ring finger family of zinc finger proteins that includes several known oncogenes and transcription factors [3].

Anatomical context of TRIM32

• We present data further demonstrating that the interaction between the activation domain of HIV-1 Tat and the HT2A protein can be readily detected in the mammalian cell nucleus [3].
• Trim32 expression increased the transcriptional activity of NFkappaB in epidermal keratinocytes, both under basal treatment and after UVB/TNFalpha treatment [7].
• Their interaction was induced by treatment with UVB/TNFalpha and involved redistribution of Piasy from the nucleus to the cytoplasm, where it accumulated in cytoplasmic granules that colocalized with Trim32 [7].

Associations of TRIM32 with chemical compounds

• Brain 5-HT2A receptor occupancy of deramciclane in humans after a single oral administration--a positron emission tomography study [8].
• A positron emission tomography study of the effects of treatment with valproate on brain 5-HT2A receptors in acute mania [9].

Other interactions of TRIM32

• The remaining two sons (7 and 10 years old), presented with mild decrease in stamina, had normal neuromuscular examinations and were found to be homozygous for the FKRP mutation in addition to the TRIM32 mutation [10].
• Ubiquitination of Piasy by Trim32 could be reproduced in vitro using purified components [7].

References