Alternative titles; symbols
HGNC Approved Gene Symbol: CUL5
Cytogenetic location: 11q22.3 Genomic coordinates (GRCh38): 11:108,008,898-108,107,761 (from NCBI)
Arginine vasopressin (AVP)-activated calcium-mobilizing receptor-1 (VACM1) is a cell surface protein involved in intracellular signal transduction. The gene encoding rabbit Vacm1 was isolated by Burnatowska-Hledin et al. (1995) from a renal medullary cDNA library by expression cloning in Xenopus laevis oocytes. While searching for expressed genes in the ataxia-telangiectasia (208900) gene (ATM; 607585) region on chromosome 11q22-q23, Byrd et al. (1997) identified the gene encoding the human homolog of rabbit Vacm1 and determined the complete amino acid sequence for the protein. The 780-amino acid predicted polypeptide differs from the rabbit sequence by only 7 residues. Northern hybridization analysis showed expression in a wide range of human tissues. Byrd et al. (1997) noted that the human VACM1 gene shares homology with the C. elegans gene Cul5, a member of the family of cullin genes that are involved in cell cycle regulation.
An et al. (2007) determined that the CUL5 gene contains 19 exons and spans about 100 kb.
Byrd et al. (1997) mapped the CUL5 gene to chromosome 11q22-q23.
Since human immunodeficiency virus (HIV)-1 viral infectivity factor (Vif) interacts with CUL5 to mediate degradation of the anti-HIV-1 enzyme APOBEC3G (607113), An et al. (2007) investigated whether genetic variation in CUL5 affects the course of HIV-1 infection. SNP analysis showed that CUL5 genetic variation did not affect susceptibility to HIV-1 infection. Some CUL5 haplotypes were associated with a rapid loss of CD4 (186940)-positive T cells and increased viral loads after infection, whereas other CUL5 haplotypes showed a delayed CD4-positive T-cell depletion. Gel-shift analysis suggested that there may be differential nuclear protein binding efficiencies between the CUL5 haplotypes. An et al. (2007) proposed that inhibitors that block interaction between HIV-1 Vif and CUL5 may have potential as an anti-HIV-1 therapeutic strategy.
An, P., Duggal, P., Wang, L. H., O'Brien, S. J., Donfield, S., Goedert, J. J., Phair, J., Buchbinder, S., Kirk, G. D., Winkler, C. A. Polymorphisms of CUL5 are associated with CD4+ T cell loss in HIV-1 infected individuals. PLoS Genet. 3: e19, 2007. Note: Electronic Article. [PubMed: 17257057] [Full Text: https://doi.org/10.1371/journal.pgen.0030019]
Burnatowska-Hledin, M. A., Spielman, W. S., Smith, W. L., Shi, P., Meyer, J. M., Dewitt, D. L. Expression cloning of an AVP-activated, calcium-mobilizing receptor from rabbit kidney medulla. Am. J. Physiol. 268: F1198-F1210, 1995. [PubMed: 7611460] [Full Text: https://doi.org/10.1152/ajprenal.1995.268.6.F1198]
Byrd, P. J., Stankovic, T., McConville, C. M., Smith, A. D., Cooper, P. R., Taylor, A. M. R. Identification and analysis of expression of human VACM-1, a cullin gene family member located on chromosome 11q22-23. Genome Res. 7: 71-75, 1997. [PubMed: 9037604] [Full Text: https://doi.org/10.1101/gr.7.1.71]