Regucalcin

Regucalcin
250px Rendering based on PDB 3G4E.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 3G4E, 3G4H, 4GNB, 4GNC
Identifiers
Symbols	RGN ; GNL; HEL-S-41; RC; SMP30
External IDs	OMIM: 300212 MGI: 108024 HomoloGene: 3437 GeneCards: RGN Gene
EC number	3.1.1.17
Gene ontology Molecular function • gluconolactonase activity • calcium ion binding • zinc ion binding • enzyme regulator activity Cellular component • nucleus • nucleoplasm • cytoplasm • cytosol Biological process • kidney development • negative regulation of protein kinase activity • cellular calcium ion homeostasis • spermatogenesis • aging • positive regulation of triglyceride biosynthetic process • positive regulation of glucose metabolic process • positive regulation of phosphatase activity • L-ascorbic acid biosynthetic process • negative regulation of phosphoprotein phosphatase activity • positive regulation of ATPase activity • negative regulation of GTPase activity • negative regulation of apoptotic process • positive regulation of GTPase activity • negative regulation of nitric oxide biosynthetic process • positive regulation of fatty acid biosynthetic process • negative regulation of epithelial cell proliferation • regulation of calcium-mediated signaling • negative regulation of cyclic-nucleotide phosphodiesterase activity • liver regeneration • negative regulation of sperm motility • positive regulation of superoxide dismutase activity • positive regulation of calcium-transporting ATPase activity • negative regulation of RNA biosynthetic process • negative regulation of bone development • positive regulation of proteolysis involved in cellular protein catabolic process • negative regulation of calcium-dependent ATPase activity • negative regulation of DNA catabolic process • positive regulation of dUTP diphosphatase activity • negative regulation of leucine-tRNA ligase activity • negative regulation of DNA biosynthetic process Sources: Amigo / QuickGO
RNA expression pattern
File:PBB GE RGN 210751 s at tn.png
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	9104	19733
Ensembl	ENSG00000130988	ENSMUSG00000023070
UniProt	Q15493	Q64374
RefSeq (mRNA)	NM_001282848	NM_009060
RefSeq (protein)	NP_001269777	NP_033086
Location (UCSC)	Chr X: 47.08 – 47.09 Mb	Chr X: 20.55 – 20.56 Mb
PubMed search	[1]	[2]

Regucalcin is a protein that in humans is encoded by the RGN gene.

The protein encoded by this gene is a highly conserved, calcium-binding protein, that is preferentially expressed in the liver and kidney. It may have an important role in calcium homeostasis. Studies in rats indicate that this protein may also play a role in aging, as it shows age-associated down-regulation. This gene is part of a gene cluster on chromosome Xp11.3-Xp11.23. Alternative splicing results in two transcript variants having different 5' UTRs, but encoding the same protein.

Regucalcin is a proposed name for a calcium-binding protein that was discovered in 1978. This protein is also known as Senescence Marker Protein-30 (SMP30). Regucalcin differs from calmodulin and other Ca²⁺-related proteins as it does not contain an EF-hand motif of Ca²⁺-binding domain. It may regulate the effect of Ca²⁺ on liver cell functions. From many investigations, regucalcin has been shown to play a multifunctional role in many cell types as a regulatory protein in the intracellular signaling system.

Gene

Regucalcin and its gene (rgn) are identified in 16 species consisting of regucalcin family. Regucalcin is greatly expressed in the liver of rats, although the protein is found in small amounts in other tissues and cells. The rat regucalcin gene consists of seven exons and six introns, and several consensus regulatory elements exist upstream of the 5’-flanking region. The gene is localized on the proximal end of rat chromosome Xq11.1-12 and human Xp11.3-Xp11.23. AP-1, NFI-A1, RGPR-p117, and Wnt/β-catenin/TCF4 can bind to the promoter region of the rat regucalcin gene to mediate the Ca2+ and other siganaling responses with various hormones and cytokines for transcriptional activation.

Function

Regucalcin plays a pivotal role in the keep of intracellular Ca²⁺ homeostasis due to activating Ca²⁺ pump enzymes in the plasma membrane (basolateral membrane), microsomes (endoplasmic reticulum) and mitochondria of many cells. Regucalcin is localized in the cytoplasm, mitochondria, microsomes and nucleus. Regucalcin is translocated from cytoplasm to nucleus with hormone stimulation. Regucalcin has a suppressive effect on calcium signaling from the cytoplasm to the nucleus in the proliferative cells. Also, regucalcin has been demonstrated to transport into the nucleus of cells, and it can inhibit nuclear protein kinase, protein phosphatase, and deoxyribonucleic acid and ribonucleic acid synthesis. Regucalcin can control enhancement of cell proliferation due to hormonal stimulation. Moreover, regucalcin has been shown to have an inhibitory effect on aminoacyl t-RNA synthetase, a rate limiting enzyme at translational process of protein synthesis and an activatory effect on cystein protease and superoxide dismutase in liver and kidney cells.

Regucalcin is expressed in the neuron of brain tissues, and the decrease of brain regucalcin causes accumulation of calcium in the brain microsomes. Regucalcin has an inhibitory effect on protein kinase and protein phospatase activity dependent on Ca signaling. Regucalcin has been shown to have an activatory effect on Ca pumping enzyme (Ca-ATPase) in heart sarcoplasmic reticulum. Regucalcin plays a role in the promotion of urinary calcium transport in the epithelial cells of kidney cortex. Overexpression of regucalcin suppresses cell death and apoptosis in the cloned rat hepatoma cells and normal rat kidney epithelial cells (NRK52E) induced by various signaling factors.

Thus, regucalcin plays a multifunctional role in the regulation of cell functions in liver, kidney cortex, heart and brain. Thus, regucalcin plays a pivotal role in keep of cell homeostasis and function. Regucalcin plays a pivotal role as a suppressor protein for cell signaling systems in many cell types.

Pathophysiologic role

Overexpressing of regucalcin in rats (transgenic rats) has been shown to induce bone loss and hyperlipidemia with increasing age, indicating a pathophysiologic role. Regucalcin transgenic rat may be a useful tool as animal model in osteoporosis and hyperlipidemia. Also, regucalcin/SMP30-knockout mice are known to induce a suppression in ascorbic acid biosynthesis. The disorder of regucalcin expression has been proposed to be induced cancer, brain function, heart injury, kidney failure, osteoporosis, and hyperlipidemia.