HGNC Approved Gene Symbol: RCN1
Cytogenetic location: 11p13 Genomic coordinates (GRCh38): 11:32,091,074-32,105,722 (from NCBI)
The endoplasmic reticulum (ER) is the major storage compartment for calcium in most eukaryotic cells. Ozawa and Muramatsu (1993) identified cDNAs encoding mouse reticulocalbin (Rcn), a calcium-binding protein located in the lumen of the ER. By PCR using oligonucleotides based on the nucleotide sequence of mouse Rcn, Ozawa (1995) isolated cDNAs encoding RCN1 from human transitional carcinoma cell line cDNAs. The predicted 331-amino acid human RCN1 protein is 95% identical to the mouse Rcn protein. RCN1 contains a leader peptide, 6 EF-hand calcium-binding motifs, and a C-terminal HDEL sequence, which serves as an ER retention signal. By Western blot analysis of human mammalian cell extracts, antibodies against Rcn recognized 44- and 46-kD proteins. Northern blot analysis revealed that RCN1 was expressed as a 2.4-kb transcript in all tissues tested.
Kishi et al. (2007) stated that RCN proteins are highly conserved and, depending on their phosphorylation status, either stimulate or inhibit calcineurin (see PPP3CA; 114105), a Ca(2+)-dependent protein phosphatase that couples Ca(2+) signals to cellular responses. In yeast, Kishi et al. (2007) found that Cdc4 (FBXW7; 606278) bound directly to phosphorylated Rcn1, resulting in Rcn1 ubiquitination and subsequent degradation and relief of calcineurin inhibition.
Kent et al. (1997) identified the human RCN1 gene within a cosmid contig of chromosome 11p13 and localized it between the WT1 (607102) and PAX6 (607108) genes. By interspecific backcross analysis, Kent et al. (1997) mapped the mouse Rcn gene to chromosome 2, in a region showing homology of synteny with human chromosome 11p14-p13.
Kent, J., Lee, M., Schedl, A., Boyle, S., Fantes, J., Powell, M., Rushmere, N., Abbott, C., van Heyningen, V., Bickmore, W. A. The reticulocalbin gene maps to the WAGR region in human and to the Small eye Harwell deletion in mouse. Genomics 42: 260-267, 1997. [PubMed: 9192846] [Full Text: https://doi.org/10.1006/geno.1997.4706]
Kishi, T., Ikeda, A., Nagao, R., Koyama, N. The SCF(Cdc4) ubiquitin ligase regulates calcineurin signaling through degradation of phosphorylated Rcn1, an inhibitor of calcineurin. Proc. Nat. Acad. Sci. 104: 17418-17423, 2007. [PubMed: 17954914] [Full Text: https://doi.org/10.1073/pnas.0704951104]
Ozawa, M. Cloning of a human homologue of mouse reticulocalbin reveals conservation of structural domains in the novel endoplasmic reticulum resident Ca2+-binding protein with multiple EF-hand motifs. J. Biochem. 117: 1113-1119, 1995. [PubMed: 8586628] [Full Text: https://doi.org/10.1093/oxfordjournals.jbchem.a124815]
Ozawa, M., Muramatsu, T. Reticulocalbin, a novel endoplasmic reticulum resident Ca2+-binding protein with multiple EF-hand motifs and a carboxyl-terminal HDEL sequence. J. Biol. Chem. 268: 699-705, 1993. [PubMed: 8416973]