Alternative titles; symbols
HGNC Approved Gene Symbol: COMMD5
Cytogenetic location: 8q24.3 Genomic coordinates (GRCh38) : 8:144,837,978-144,853,556 (from NCBI)
Solban et al. (2000) cloned rat Hcarg from a cDNA library constructed from the spontaneously hypertensive rat parathyroid gland. The deduced 224-amino acid protein has a calculated molecular mass of about 22.5 kD. Hcarg has a 67% alpha helix content, a calcium-binding EF-hand motif, 4 putative leucine zipper motifs, a nuclear receptor-binding domain, and no transmembrane domain. It also contains several putative phosphorylation sites and an N-glycosylation site. Using rat Hcarg as probe, Solban et al. (2000) cloned human HCARG from a vascular smooth muscle cell cDNA library. The deduced 224-amino acid protein shares 80% homology with rat Hcarg. Multiple-tissue expression array analysis detected high expression in heart, stomach, jejunum, kidney, liver, and adrenal gland. Expression was generally higher in adult organs than in fetal tissues, particularly in heart, kidney, and liver. In situ hybridization of rat tissues detected expression in the medulla and zona fasciculata of the adrenal cortex and in the tubules of the kidney, but showed no expression in renal glomeruli. Immunofluorescence microscopy of transfected COS-7 cells and immunohistochemical staining of rat pituitary detected Hcarg predominantly localized to the nucleus, with some staining at sites of protein synthesis.
By database analysis to identify proteins similar to MURR1 (COMMD1; 607238), followed PCR amplification, Burstein et al. (2005) cloned COMMD5. The deduced protein has a C-terminal copper metabolism MURR1 (COMM) domain that is leucine-rich and was predicted to form a beta sheet. Database analysis revealed COMMD5 expression in all 13 human tissues examined, with highest expression in heart, lung, brain, and liver, and lowest expression in skin.
Solban et al. (2000) found that expression of Hcarg was higher in the adrenal cortex and kidney tubules of hypertensive rats compared with their normotensive controls. Rat Hcarg inhibited cell proliferation in human embryonic kidney cells following transfection.
By coimmunoprecipitation analysis, Burstein et al. (2005) found that COMMD5 interacted with endogenous COMMD1 from HEK293 cells. COMMD5 robustly inhibited TNF (191160)-mediated activation of NF-kappa-B (see NFKB1, 164011). Protein pull-down assays showed that COMMD5 associated with the NF-kappa-B subunits RELA, RELB (604758), and p105 (NFKB1), but not with p100 (NFKB2; 164012) or CREL (REL; 164910).
Mao et al. (2011) found that COMMD5 interacted with epitope-tagged cullins CUL2 (603135), CUL3 (603136), CUL4A (603137), and CUL7 (609577). COMMD5 that was precipitated from human cell lines supported polyubiquitination in vitro, presumably due to its interaction with cullin RING ligases (CRLs; see CUL, 603134), multimeric ubiquitin ligase complexes that include cullins among their components.
By genomic sequence analysis, Solban et al. (2002) mapped the COMMD5 gene to chromosome 8q24.3.
Burstein, E., Hoberg, J. E., Wilkinson, A. S., Rumble, J. M., Csomos, R. A., Komarck, C. M., Maine, G. N., Wilkinson, J. C., Mayo, M. W., Duckett, C. S. COMMD proteins, a novel family of structural and functional homologs of MURR1. J. Biol. Chem. 280: 22222-22232, 2005. [PubMed: 15799966] [Full Text: https://doi.org/10.1074/jbc.M501928200]
Mao, X., Gluck, N., Chen, B., Starokadomskyy, P., Li, H., Maine, G. N., Burstein, E. COMMD1 (copper metabolism MURR1 domain-containing protein 1) regulates cullin RING ligases by preventing CAND1 (cullin-associated Nedd8-dissociated protein 1) binding. J. Biol. Chem. 286: 32355-32365, 2011. [PubMed: 21778237] [Full Text: https://doi.org/10.1074/jbc.M111.278408]
Solban, N., Dumas, P., Gossard, F., Sun, Y., Pravenec, M., Kren, V., Lewanczuk, R., Hamet, P., Tremblay, J. Chromosomal mapping of HCaRG, a novel hypertension-related, calcium-regulated gene. Folia Biologica 48: 9-14, 2002. [PubMed: 11871861]
Solban, N., Jia, H.-P., Richard, S., Tremblay, S., Devlin, A. M., Peng, J., Gossard, F., Guo, D.-F., Morel, G., Hamet, P., Lewanczuk, R., Tremblay, J. HCaRG, a novel calcium-regulated gene coding for a nuclear protein, is potentially involved in the regulation of cell proliferation. J. Biol. Chem. 275: 32234-32243, 2000. [PubMed: 10918053] [Full Text: https://doi.org/10.1074/jbc.M001352200]