Alternative titles; symbols
HGNC Approved Gene Symbol: RNF5
Cytogenetic location: 6p21.32 Genomic coordinates (GRCh38): 6:32,178,405-32,180,793 (from NCBI)
The RING finger is a unique zinc-chelating domain involved in mediating protein-protein interactions. The extensive sequence homology within the RING finger domain permitted Kyushiki et al. (1997) to clone RNF5, a novel member of the RING finger family of genes. RNF5 encodes a predicted 1,620-amino acid protein that shares significant homology with a hypothetical protein encoded by Caenorhabditis elegans. Expression of RNF5 was detected as a 1.2-kb transcript in a variety of human tissues.
Cystic fibrosis (219700) arises from misfolding and premature degradation of CFTR (602421) containing a deletion of phe508 (delF508; 602421.0001). Younger et al. (2006) identified an endoplasmic reticulum (ER) membrane-associated ubiquitin ligase complex containing the E3 RMA1, the E2 UBC6E (UBE2J1; 616175), and derlin-1 (DERL1; 608813) that cooperated with the cytosolic HSC70 (HSPA8; 600816)/CHIP (STUB1; 607207) E3 complex to triage CFTR and delFl508. Derlin-1 retained CFTR in the ER membrane and interacted with RMA1 and UBC6E to promote proteasomal degradation of CFTR. RMA1 could recognize folding defects in delF508 coincident with translation, whereas CHIP appeared to act posttranslationally. A folding defect in delF508 detected by RMA1 involved the inability of the second membrane-spanning domain of CFTR to productively interact with N-terminal domains. Younger et al. (2006) concluded that the RMA1 and CHIP E3 ubiquitin ligases act sequentially in ER membrane and cytosol to monitor the folding status of CFTR and delF508.
Using a yeast 2-hybrid screen, Zhong et al. (2009) identified RNF5 as an MITA (TMEM173; 612374)-interacting protein. Coimmunoprecipitation and mutation analyses showed that the RNF5 C terminus was required for the interaction, which was induced by viral infection. RNF5 ubiquitinated MITA at lys150, leading to MITA degradation and inhibition of virus-induced IRF3 (603734) activation, IFNB1 (147640) expression, and cellular antiviral response. Zhong et al. (2009) concluded that RNF5 negatively regulates virus-induced signaling by targeting MITA for ubiquitination and degradation at the mitochondria.
Kyushiki et al. (1997) determined that the RNF5 gene contains 6 exons.
Kyushiki et al. (1997) mapped the RNF5 gene to chromosome 6p21.31 by fluorescence in situ hybridization. Radiation hybrid mapping likewise assigned RNF5 to a region proximal to the major histocompatibility complex (MHC) on chromosome 6p. RNF5 was the third RING finger gene identified in the region proximal to MHC, raising the possibility that this family of genes may exist as a cluster in that area of the genome. The others are RING finger protein-1 (602045) and RING finger protein-3 (601540).
Kyushiki, H., Kuga, Y., Suzuki, M., Takahashi, E., Horie, M. Cloning, expression and mapping of a novel RING-finger gene (RNF5), a human homologue of a putative zinc-finger gene from Caenorhabditis elegans. Cytogenet. Cell Genet. 79: 114-117, 1997. [PubMed: 9533025] [Full Text: https://doi.org/10.1159/000134695]
Younger, J. M., Chen, L., Ren, H.-Y., Rosser, M. F. N., Turnbull, E. L., Fan, C.-Y., Patterson, C., Cyr, D. M. Sequential quality-control checkpoints triage misfolded cystic fibrosis transmembrane conductance regulator. Cell 126: 571-582, 2006. [PubMed: 16901789] [Full Text: https://doi.org/10.1016/j.cell.2006.06.041]
Zhong, B., Zhang, L., Lei, C., Li, Y., Mao, A.-P., Yang, Y., Wang, Y.-Y., Zhang, X.-L., Shu, H.-B. The ubiquitin ligase RNF5 regulates antiviral responses by mediating degradation of the adaptor protein MITA. Immunity 30: 397-407, 2009. [PubMed: 19285439] [Full Text: https://doi.org/10.1016/j.immuni.2009.01.008]