Regucalcin

Revision as of 01:10, 11 November 2017 by en>JCW-CleanerBot (→‎Further reading: task, replaced: Acta Crystallographica. Section D, Biological Crystallography → Acta Crystallographica Section D using AWB)
(diff) ← Older revision | Latest revision (diff) | Newer revision → (diff)
Jump to navigation Jump to search
VALUE_ERROR (nil)
Identifiers
Aliases
External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez

n/a

n/a

Ensembl

n/a

n/a

UniProt

n/a

n/a

RefSeq (mRNA)

n/a

n/a

RefSeq (protein)

n/a

n/a

Location (UCSC)n/an/a
PubMed searchn/an/a
Wikidata
View/Edit Human

Regucalcin is a protein that in humans is encoded by the RGN gene.[1][2]

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.[2]

Regucalcin is a proposed name for a calcium-binding protein that was discovered in 1978.[3][4][5] This protein is also known as Senescence Marker Protein-30 (SMP30).[6][7] Regucalcin differs from calmodulin and other Ca2+-related proteins as it does not contain an EF-hand motif of Ca2+-binding domain.[3][8] It may regulate the effect of Ca2+ on liver cell functions.[5] 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.[9][10] 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.[11] 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.[12]

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.[13] 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.[14] 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.[15] Regucalcin plays a novel role as a suppressor in carcinogenesis of human patients with various types of cancer including pancreatic cancer, breast cancer, hepatoma, and lung cancer.[16][17][15]

References

  1. ↑ Fujita T, Mandel JL, Shirasawa T, Hino O, Shirai T, Maruyama N (September 1995). "Isolation of cDNA clone encoding human homologue of senescence marker protein-30 (SMP30) and its location on the X chromosome". Biochimica et Biophysica Acta. 1263 (3): 249–52. doi:10.1016/0167-4781(95)00120-6. PMID 7548213.
  2. ↑ 2.0 2.1 "Entrez Gene: RGN regucalcin (senescence marker protein-30)".
  3. ↑ 3.0 3.1 Yamaguchi M, Yamamoto T (June 1978). "Purification of calcium binding substance from soluble fraction of normal rat liver". Chemical & Pharmaceutical Bulletin. 26 (6): 1915–8. doi:10.1248/cpb.26.1915. PMID 699201.
  4. ↑ Yamaguchi M (January 1988). "Physicochemical properties of calcium-binding protein isolated from rat liver cytosol: Ca2+-induced conformational changes". Chemical & Pharmaceutical Bulletin. 36 (1): 286–90. doi:10.1248/cpb.36.286. PMID 3378291.
  5. ↑ 5.0 5.1 Yamaguchi M (1992). "A novel Ca2+-binding protein regucalcin and calcium inhibition. Regulatory role in liver cell function". Calcium Inhibition. Boca Raton: CRC Press. pp. 19–41.
  6. ↑ Fujita T, Uchida K, Maruyama N (April 1992). "Purification of senescence marker protein-30 (SMP30) and its androgen-independent decrease with age in the rat liver". Biochimica et Biophysica Acta. 1116 (2): 122–8. doi:10.1016/0304-4165(92)90108-7. PMID 1581340.
  7. ↑ Fujita T, Shirasawa T, Uchida K, Maruyama N (October 1992). "Isolation of cDNA clone encoding rat senescence marker protein-30 (SMP30) and its tissue distribution". Biochimica et Biophysica Acta. 1132 (3): 297–305. doi:10.1016/0167-4781(92)90164-u. PMID 1420310.
  8. ↑
  9. ↑ Shimokawa N, Yamaguchi M (August 1993). "Molecular cloning and sequencing of the cDNA coding for a calcium-binding protein regucalcin from rat liver". FEBS Letters. 327 (3): 251–5. doi:10.1016/0014-5793(93)80998-a. PMID 8348951.
  10. ↑ Misawa H, Yamaguchi M (August 2000). "The gene of Ca2+-binding protein regucalcin is highly conserved in vertebrate species". International Journal of Molecular Medicine. 6 (2): 191–6. doi:10.3892/ijmm.6.2.191. PMID 10891565.
  11. ↑ Yamaguchi M, Makino R, Shimokawa N (December 1996). "The 5' end sequences and exon organization in rat regucalcin gene". Molecular and Cellular Biochemistry. 165 (2): 145–50. doi:10.1007/bf00229476. PMID 8979263.
  12. ↑ Yamaguchi M (January 2011). "The transcriptional regulation of regucalcin gene expression". Molecular and Cellular Biochemistry. 346 (1–2): 147–71. doi:10.1007/s11010-010-0601-8. PMID 20936536.
  13. ↑ Yamaguchi M (March 2005). "Role of regucalcin in maintaining cell homeostasis and function (review)". International Journal of Molecular Medicine. 15 (3): 371–89. doi:10.3892/ijmm.15.3.371. PMID 15702226.
  14. ↑ Yamaguchi M (August 2010). "Regucalcin and metabolic disorders: osteoporosis and hyperlipidemia are induced in regucalcin transgenic rats". Molecular and Cellular Biochemistry. 341 (1–2): 119–33. doi:10.1007/s11010-010-0443-4. PMID 20349117.
  15. ↑ 15.0 15.1 Yamaguchi M (2017). The Role of Regucalcin in Cell Homeostasis and Disorder. New York: Nova Science Publishers. pp. 1–288. ISBN 978-3-319-39855-6.
  16. ↑ Yamaguchi M (August 2015). "Involvement of regucalcin as a suppressor protein in human carcinogenesis: Insight into the gene therapy". Journal of Cancer Research and Clinical Oncology. 141 (8): 133–1341. doi:10.1007/s00432-014-1831-z. PMID 25230901.
  17. ↑ Yamaguchi M, Osuka S, Weitzmann MN, El-Rayes BF, Shoji M, Murata T (May 2016). "Prolonged survival in pancreatic cancer patients with increased regucalcin gene expression: Overexpression of regucalcin suppresses the proliferation in human pancreatic cancer MIA PaCa-2 cells in vitro". International Journal of Oncology. 48: 1955–1964. doi:10.3892/ijo.2016.3409. PMID 26935290.

Further reading

  • Fujita T, Shirasawa T, Maruyama N (March 1999). "Expression and structure of senescence marker protein-30 (SMP30) and its biological significance". Mechanisms of Ageing and Development. 107 (3): 271–80. doi:10.1016/S0047-6374(98)00136-5. PMID 10360682.
  • Maruyama K, Sugano S (January 1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene. 138 (1–2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.
  • Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S (October 1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene. 200 (1–2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149.
  • Misawa H, Yamaguchi M (March 2000). "Transcript heterogeneity of the human gene for Ca2+-binding protein regucalcin". International Journal of Molecular Medicine. 5 (3): 283–7. doi:10.3892/ijmm.5.3.283. PMID 10677570.
  • Thiselton DL, McDowall J, Brandau O, Ramser J, d'Esposito F, Bhattacharya SS, Ross MT, Hardcastle AJ, Meindl A (April 2002). "An integrated, functionally annotated gene map of the DXS8026-ELK1 interval on human Xp11.3-Xp11.23: potential hotspot for neurogenetic disorders". Genomics. 79 (4): 560–72. doi:10.1006/geno.2002.6733. PMID 11944989.
  • Ishigami A, Handa S, Maruyama N, Supakar PC (January 2003). "Nuclear localization of senescence marker protein-30, SMP30, in cultured mouse hepatocytes and its similarity to RNA polymerase". Bioscience, Biotechnology, and Biochemistry. 67 (1): 158–60. doi:10.1271/bbb.67.158. PMID 12619687.
  • Matsuyama S, Kitamura T, Enomoto N, Fujita T, Ishigami A, Handa S, Maruyama N, Zheng D, Ikejima K, Takei Y, Sato N (August 2004). "Senescence marker protein-30 regulates Akt activity and contributes to cell survival in Hep G2 cells". Biochemical and Biophysical Research Communications. 321 (2): 386–90. doi:10.1016/j.bbrc.2004.06.161. PMID 15358188.
  • Warizaya M, Kinoshita T, Yamaoka M, Shibata T, Saito N, Nakajima H, Fujii T (November 2004). "Expression, purification, crystallization and preliminary X-ray diffraction studies of human liver regucalcin". Acta Crystallographica Section D. 60 (Pt 11): 2019–21. doi:10.1107/S0907444904020608. PMID 15502314.
  • Ishigami A, Fujita T, Inoue H, Handa S, Kubo S, Kondo Y, Maruyama N (May 2005). "Senescence marker protein-30 (SMP30) induces formation of microvilli and bile canaliculi in Hep G2 cells". Cell and Tissue Research. 320 (2): 243–9. doi:10.1007/s00441-004-1073-5. PMID 15714273.
  • Yamaguchi M, Daimon Y (August 2005). "Overexpression of regucalcin suppresses cell proliferation in cloned rat hepatoma H4-II-E cells: involvement of intracellular signaling factors and cell cycle-related genes". Journal of Cellular Biochemistry. 95 (6): 1169–77. doi:10.1002/jcb.20490. PMID 15962315.
Retrieved from "https://www.wikidoc.org/index.php?title=Regucalcin&oldid=1423253"