Alternative titles; symbols
HGNC Approved Gene Symbol: RCN2
Cytogenetic location: 15q24.3 Genomic coordinates (GRCh38): 15:76,931,749-76,954,393 (from NCBI)
ERC55 is an EF-hand calcium-binding protein that specifically localizes in the endoplasmic reticulum (ER), the major calcium storage compartment in nonmuscle eukaryotic cells (Weis et al., 1994).
By screening a HeLa cell cDNA expression library with autoimmune serum from a patient, Weis et al. (1994) cloned a human cDNA encoding an EF-hand protein, ERC55 (RCN2). The predicted 317-amino acid ERC55 protein contains an N-terminal signal sequence, 6 copies of the EF-hand motif, and a C-terminal His-Asp-Glu-Leu (HDEL) sequence, which was originally defined as an ER retention motif in yeast proteins. Immunocytolocalization and cell fractionation studies demonstrated that ERC55 is a resident ER protein; the HDEL motif is required for its ER retention. ERC55 was detected by antibodies in all cell lines tested. It binds calcium in vitro. By Western blotting, in vitro translated ERC55 protein has a molecular mass of 55 kD.
Chen et al. (1995) identified RCN2 using a yeast 2-hybrid screen to identify proteins that interact with human papillomavirus transforming protein E6. They named the RCN2 protein 'E6-binding protein' (E6BP). E6BP also interacted with bovine papillomavirus type 1 (BPV1) E6, and the transforming activity of BPV1 E6 mutants correlated with their E6BP-binding ability.
Using the yeast 2-hybrid system to identify coactivators that specifically mediate the ligand-dependent activity of the AF-2 transcription-activating domain of the vitamin D receptor (VDR; 601769), Imai et al. (1997) cloned a mouse cDNA encoding Rcn2. They named the Rcn2 protein 'vitamin D receptor-associated factor' (Vaf1). The Vaf1-Vdr interaction was ligand-independent, leading Imai et al. (1997) to suggest that Vaf1 is a specific cofactor that modulates Vdr function. The mouse Vaf1 protein is 92% identical to human RCN2.
The RCN2 gene was assigned by a radiation hybrid panel to human chromosome 15, between D15S215 and D15S206 by Genethon, and between D15S114 and D15S1041 by the Stanford Human Genome Center (Schuler et al., 1996). By fluorescence in situ hybridization, Wang et al. (1997) mapped the RCN2 gene to 15q23.
Chen, J. J., Reid, C. E., Band, V., Androphy, E. J. Interaction of papillomavirus E6 oncoproteins with a putative calcium-binding protein. Science 269: 529-531, 1995. [PubMed: 7624774] [Full Text: https://doi.org/10.1126/science.7624774]
Imai, T., Matsuda, K., Shimojima, T., Hashimoto, T., Masuhiro, Y., Kitamoto, T., Sugita, A., Suzuki, K., Matsumoto, H., Masushige, S., Nogi, Y., Muramatsu, M., Handa, H., Kato, S. ERC-55, a binding protein for the papilloma virus E6 oncoprotein, specifically interacts with vitamin D receptor among nuclear receptors. Biochem. Biophys. Res. Commun. 233: 765-769, 1997. [PubMed: 9168930] [Full Text: https://doi.org/10.1006/bbrc.1997.6531]
Schuler, G. D., Boguski, M. S., Stewart, E. A., Stein, L. D., Gyapay, G., Rice, K., White, R. E., Rodriguez-Tome, P., Aggarwal, A., Bajorek, E., Bentolila, S., Birren, B. B., Butler, A., Castle, A. B., Chiannilkulchai, N., Chu, A., Clee, C., Cowles, S., Day, P. J. R., Dibling, T., and 84 others. A gene map of the human genome. Science 274: 540-546, 1996. [PubMed: 8849440]
Wang, J. Y., Zhen, D. K., Bianchi, D. W., Androphy, E. J., Chen, J. J. Assignment of the gene for ERC-55 (RCN2) to human chromosome band 15q22.33-q24.1 by in situ hybridization. Cytogenet. Cell Genet. 79: 60-61, 1997. [PubMed: 9533013] [Full Text: https://doi.org/10.1159/000134683]
Weis, K., Griffiths, G., Lamond, A. I. The endoplasmic reticulum calcium-binding protein of 55 kDa is a novel EF-hand protein retained in the endoplasmic reticulum by a carboxyl-terminal His-Asp-Glu-Leu motif. J. Biol. Chem. 269: 19142-19150, 1994. [PubMed: 8034671]