Alternative titles; symbols
HGNC Approved Gene Symbol: RNF40
Cytogenetic location: 16p11.2 Genomic coordinates (GRCh38) : 16:30,761,612-30,776,307 (from NCBI)
Using yeast 2-hybrid analysis to identify syntaxin-1 (see 186590)-interacting proteins, Chin et al. (2002) identified rat Rnf40, which they called Staring. By searching EST databases, they identified human RNF40. The human RNF40 protein contains 1,001 amino acids and shares about 93% amino acid identity with the rat protein. Both proteins have 6 coiled-coil domains and a C-terminal RING finger motif. Northern blot analysis of human and rat tissue panels showed that RNF40 is expressed ubiquitously. Western blot analysis showed expression of Rnf40 throughout rat brain, where it exists in both cytosolic and membrane-associated pools.
Hwang et al. (2003) identified an S. cerevisiae protein, Bre1, as an evolutionarily conserved RING finger protein that is required in vivo for both ubiquitination of histone H2B and methylation of histone H3 on lys4 (see 142711 for information on histones). They identified 2 human homologs of Bre1, RNF20 (607699) and RNF40, which they termed BRE1A and BRE1B, respectively.
Chin et al. (2002) showed that the rat Rpf40 protein binds and recruits the brain-enriched E2 ubiquitin-conjugating enzyme Ubch8 (603890) to syntaxin-1 and facilitates the ubiquitination and proteasome-dependent degradation of syntaxin-1. These findings suggested that RPF40 is a novel E3 ubiquitin-protein ligase that targets syntaxin-1 for degradation by the ubiquitin-proteasome pathway.
Hwang et al. (2003) showed that the S. cerevisiae Bre1 protein is required in vivo for both H2B ubiquitination and H3 lys4 methylation. They determined that the RING domain of Bre1 is essential for both of these modifications, as is large-1 (Lge1), a protein required for cell size control that copurifies with Bre1. In cells lacking the euchromatin-associated histone variant H2A.Z, Bre1, Rad6 (see 312180), and Lge1 were each essential for cell viability, supporting redundant functions for H2B ubiquitination and H2A substitution in the formation of active chromatin. Analysis of mutants demonstrated a function for Bre1/Lge1-dependent H2B monoubiquitination in the control of cell size.
Wood et al. (2003) showed that the RING finger of S. cerevisiae Bre1 is required for ubiquitination of H2B, methylation of lys4 and lys79 of H3, and for telomeric silencing. Chromatin immunoprecipitation experiments indicated that both Rad6 and Bre1 are recruited to a promoter. The authors determined that Bre1 is essential for this recruitment of Rad6 and is dedicated to the transcriptional pathway of Rad6. The results suggested that Bre1 is the likely E3 enzyme that directs Rad6 to modify chromatin and ultimately to affect gene expression.
Chin, L.-S., Vavalle, J. P., Li, L. Staring, a novel E3 ubiquitin-protein ligase that targets syntaxin 1 for degradation. J. Biol. Chem. 277: 35071-35079, 2002. [PubMed: 12121982] [Full Text: https://doi.org/10.1074/jbc.M203300200]
Hwang, W. W., Venkatasubrahmanyam, S., Ianculescu, A. G., Tong, A., Boone, C., Madhani, H. D. A conserved RING finger protein required for histone H2B monoubiquitination and cell size control. Molec. Cell 11: 261-266, 2003. [PubMed: 12535538] [Full Text: https://doi.org/10.1016/s1097-2765(02)00826-2]
Wood, A., Krogan, N. J., Dover, J., Schneider, J., Heidt, J., Boateng, M. A., Dean, K., Golshani, A., Zhang, Y., Greenblatt, J. F., Johnston, M., Shilatifard, A. Bre1, an E3 ubiquitin ligase required for recruitment and substrate selection of Rad6 at a promoter. Molec. Cell 11: 267-274, 2003. [PubMed: 12535539] [Full Text: https://doi.org/10.1016/s1097-2765(02)00802-x]