Alternative titles; symbols
HGNC Approved Gene Symbol: TRIM3
Cytogenetic location: 11p15.4 Genomic coordinates (GRCh38) : 11:6,448,613-6,474,459 (from NCBI)
El-Husseini and Vincent (1999) screened rat cerebellar mRNA for nucleotide-binding proteins. Using the resulting RT-PCR product as a probe to screen a rat brain cDNA library, they isolated a novel ring finger cDNA, Rnf22, which they designated Berp. Berp encodes a member of the RBCC subgroup of RING finger proteins characterized by 3 motifs: an N-terminal ring finger, a B-box zinc finger, and a coiled-coil domain. The rat Berp protein contains a 130-amino acid region that is 41% identical to a repeat domain present in actin-binding proteins. Its C terminus contains 6 repeats that are predicted to form a circular beta-propeller similar to that in WD and kelch proteins. Northern blot analysis detected highest expression of Berp in cerebellum, with weaker expression in other brain regions as well as in lung, liver, kidney, and heart. Using a yeast 2-hybrid system and immunoprecipitation experiments, Berp was expressed in cytoplasm with a punctate pattern similar to that of endogenous myosin Va (MYO5A; 160777), a pattern characteristic of organelle-associated proteins.
Using rat Berp to screen a hippocampus cDNA library, followed by EST database analysis and RT-PCR of cerebellar total RNA, El-Husseini et al. (2001) cloned human BERP. The deduced 744-amino aid protein has an N-terminal RING finger, followed by B-box motifs, a coiled-coil domain, a putative actin-binding protein-like beta-sheet structure, and a predicted C-terminal 6-blade beta-propeller domain. Human BERP shares 98% amino acid identity with rat and mouse Berp and about 30% identity with the putative C. elegans ortholog. Northern blot analysis detected a major 3-kb transcript in human brain. EST database analysis suggested that BERP is also expressed in breast, heart, uterus, and testis.
El-Husseini and Vincent (1999) demonstrated that the RBCC domain of rat BERP could homodimerize. Additionally, the C-terminal repeats of Berp interacted with class V myosins. El-Husseini and Vincent (1999) hypothesized that BERP may mediate interactions with various proteins, allowing cargo transport via a myosin V-mediated pathway. BERP interactions with class V myosins may also be important in organelle transport and neurite outgrowth.
El-Husseini et al. (2000) demonstrated interaction between the RBCC domain of rat BERP and a rat brain cDNA for a nonmuscle isoform of alpha-actinin, Actn4 (604638). Using immunohistochemistry, El-Husseini et al. (2000) showed that both Berp and Actn4 were expressed in a punctate pattern throughout the cytoplasm and neuritic processes of differentiated PC12 cells. They concluded that BERP may serve to anchor class V myosin to particular cell domains via its interaction with ACTN4.
Using mutation analysis and reporter gene assays, Cheung et al. (2010) found that only 1 of 4 putative p53 (TP53; 191170)-binding sites in the promoter region of human BERP activated BERP expression. Similarly, treatment with pentylenetetrazol upregulated Berp expression in p53 +/+ mouse hippocampal neurons, but not in p53 -/- hippocampal neurons.
El-Husseini et al. (2001) determined that the TRIM3 gene contains 11 coding exons.
Cheung et al. (2010) identified a functional p53-binding site within intron 1 of the TRIM3 gene.
Using FISH, El-Husseini et al. (2001) mapped the TRIM3 gene to chromosome 11p15.5.
Cheung et al. (2010) found that Berp -/- mice were born at the expected mendelian ratio and were viable, healthy, and fertile, with no gross or histologic abnormalities. Berp -/- mice were more resistant to pentylenetetrazol-induced seizures than wildtype mice. Patch-clamp recordings showed that cortical neurons from Berp -/- mice exhibited reduced mean miniature inhibitory postsynaptic current frequency and amplitude compared with wildtype neurons, which appeared to be due to reduced surface expression of the Gabrg2 (137164) GABA receptor subunit. Gabrg2 mRNA content was not altered in Berp -/- neurons.
Cheung, C. C., Yang, C., Berger, T., Zaugg, K., Reilly, P., Elia, A. J., Wakeham, A., You-Ten, A., Chang, N., Li, L., Wan, Q., Mak, T. W. Identification of BERP (brain-expressed RING finger protein) as a p53 target gene that modulates seizure susceptibility through interacting with GABA(A) receptors. Proc. Nat. Acad. Sci. 107: 11883-11888, 2010. [PubMed: 20543135] [Full Text: https://doi.org/10.1073/pnas.1006529107]
El-Husseini, A. E., Kwasnicka, D., Yamada, T., Hirohashi, S., Vincent, S. R. BERP, a novel ring finger protein, binds to alpha-actinin-4. Biochem. Biophys. Res. Commun. 267: 906-911, 2000. [PubMed: 10673389] [Full Text: https://doi.org/10.1006/bbrc.1999.2045]
El-Husseini, A. E., Vincent, S. R. Cloning and characterization of a novel RING finger protein that interacts with class V myosins. J. Biol. Chem. 274: 19771-19777, 1999. [PubMed: 10391919] [Full Text: https://doi.org/10.1074/jbc.274.28.19771]
El-Husseini, A. E.-D., Fretier, P., Vincent, S. R. Cloning and characterization of a gene (RNF22) encoding a novel brain expressed ring finger protein (BERP) that maps to human chromosome 11p15.5. Genomics 71: 363-367, 2001. [PubMed: 11170753] [Full Text: https://doi.org/10.1006/geno.2000.6452]