DSCR1

Regulator of calcineurin 1

PDB rendering based on 1wey.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols RCAN1 ; ADAPT78; CSP1; DSC1; DSCR1; MCIP1; RCN1
External IDs OMIM: 602917 MGI: 1890564 HomoloGene: 3251 GeneCards: RCAN1 Gene
RNA expression pattern
More reference expression data
Orthologs
Species Human Mouse
Entrez 1827 54720
Ensembl ENSG00000159200 ENSMUSG00000022951
UniProt P53805 Q9JHG6
RefSeq (mRNA) NM_001285389 NM_001081549
RefSeq (protein) NP_001272318 NP_001075018
Location (UCSC) Chr 21:
34.51 – 34.62 Mb		 Chr 16:
92.39 – 92.47 Mb
PubMed search

Down syndrome critical region gene 1, also known as DSCR1, is a protein that in humans is encoded by the DSCR1 gene.[1]

Function

The protein encoded by this gene interacts with calcineurin A and inhibits calcineurin-dependent signaling pathways of genetic transcription, possibly affecting central nervous system development. Three transcript variants encoding three different isoforms have been found for this gene.[1] In endothelial cells, VEGF stimulates RCAN1.4 expression which regulates gene expression, cell migration and tubular morphogenesis.[2]

Clinical significance

This gene is located in the minimal candidate region for the Down syndrome phenotype, and is overexpressed in the brain of Down syndrome fetuses. Chronic overexpression of this gene may lead to neurofibrillary tangles such as those associated with Alzheimer's disease.[1][3]

It is suggested that the reason patients with Down's Syndrome are less predisposed to certain cancers is due to the impact of this gene of reducing blood supply to tumour cells.[4]

Interactions

DSCR1 has been shown to interact with Calcineurin.[5]

References

  1. 1 2 3 "Entrez Gene: DSCR1 Down syndrome critical region gene 1".
  2. ↑ Holmes K, Chapman E, See V, Cross MJ (July 2010). "VEGF stimulates RCAN1.4 expression in endothelial cells via a pathway requiring Ca2+/calcineurin and protein kinase C-delta". PLOS ONE 5 (7): e11435. doi:10.1371/journal.pone.0011435. PMC 2897886. PMID 20625401.
  3. ↑ Martin KR, Corlett A, Dubach D, Mustafa T, Coleman HA, Parkington HC, Merson TD, Bourne JA, Porta S, Arbonés ML, Finkelstein DI, Pritchard MA (Jul 2012). "Over-expression of RCAN1 causes Down syndrome-like hippocampal deficits that alter learning and memory". Human Molecular Genetics 21 (13): 3025–3041. doi:10.1093/hmg/dds134.
  4. ↑ Baek KH, Zaslavsky A, Lynch RC, Britt C, Okada Y, Siarey RJ, Lensch MW, Park IH, Yoon SS, Minami T, Korenberg JR, Folkman J, Daley GQ, Aird WC, Galdzicki Z, Ryeom S (Jun 2009). "Down's syndrome suppression of tumour growth and the role of the calcineurin inhibitor DSCR1". Nature 459 (7250): 1126–30. doi:10.1038/nature08062. PMC 2724004. PMID 19458618.
  5. ↑ Fuentes JJ, Genescà L, Kingsbury TJ, Cunningham KW, Pérez-Riba M, Estivill X, de la Luna S (Jul 2000). "DSCR1, overexpressed in Down syndrome, is an inhibitor of calcineurin-mediated signaling pathways". Human Molecular Genetics 9 (11): 1681–90. doi:10.1093/hmg/9.11.1681. PMID 10861295.

Further reading

  • Harris CD, Ermak G, Davies KJ (Nov 2005). "Multiple roles of the DSCR1 (Adapt78 or RCAN1) gene and its protein product calcipressin 1 (or RCAN1) in disease". Cellular and Molecular Life Sciences : CMLS 62 (21): 2477–86. doi:10.1007/s00018-005-5085-4. PMID 16231093.  Check date values in: |year= / |date= mismatch (help)
  • Keating DJ, Chen C, Pritchard MA (Nov 2006). "Alzheimer's disease and endocytic dysfunction: clues from the Down syndrome-related proteins, DSCR1 and ITSN1". Ageing Research Reviews 5 (4): 388–401. doi:10.1016/j.arr.2005.11.001. PMID 16442855. 
  • Fuentes JJ, Pritchard MA, Planas AM, Bosch A, Ferrer I, Estivill X (Oct 1995). "A new human gene from the Down syndrome critical region encodes a proline-rich protein highly expressed in fetal brain and heart". Human Molecular Genetics 4 (10): 1935–44. doi:10.1093/hmg/4.10.1935. PMID 8595418.  Check date values in: |year= / |date= mismatch (help)
  • Andersson B, Wentland MA, Ricafrente JY, Liu W, Gibbs RA (Apr 1996). "A "double adaptor" method for improved shotgun library construction". Analytical Biochemistry 236 (1): 107–13. doi:10.1006/abio.1996.0138. PMID 8619474. 
  • Yu W, Andersson B, Worley KC, Muzny DM, Ding Y, Liu W, Ricafrente JY, Wentland MA, Lennon G, Gibbs RA (Apr 1997). "Large-scale concatenation cDNA sequencing". Genome Research 7 (4): 353–8. doi:10.1101/gr.7.4.353. PMC 139146. PMID 9110174. 
  • Fuentes JJ, Pritchard MA, Estivill X (Sep 1997). "Genomic organization, alternative splicing, and expression patterns of the DSCR1 (Down syndrome candidate region 1) gene". Genomics 44 (3): 358–61. doi:10.1006/geno.1997.4866. PMID 9325060. 
  • Rothermel B, Vega RB, Yang J, Wu H, Bassel-Duby R, Williams RS (Mar 2000). "A protein encoded within the Down syndrome critical region is enriched in striated muscles and inhibits calcineurin signaling". The Journal of Biological Chemistry 275 (12): 8719–25. doi:10.1074/jbc.275.12.8719. PMID 10722714. 
  • Fuentes JJ, Genescà L, Kingsbury TJ, Cunningham KW, Pérez-Riba M, Estivill X, de la Luna S (Jul 2000). "DSCR1, overexpressed in Down syndrome, is an inhibitor of calcineurin-mediated signaling pathways". Human Molecular Genetics 9 (11): 1681–90. doi:10.1093/hmg/9.11.1681. PMID 10861295. 
  • Ermak G, Morgan TE, Davies KJ (Oct 2001). "Chronic overexpression of the calcineurin inhibitory gene DSCR1 (Adapt78) is associated with Alzheimer's disease". The Journal of Biological Chemistry 276 (42): 38787–94. doi:10.1074/jbc.M102829200. PMID 11483593. 
  • Vega RB, Yang J, Rothermel BA, Bassel-Duby R, Williams RS (Aug 2002). "Multiple domains of MCIP1 contribute to inhibition of calcineurin activity". The Journal of Biological Chemistry 277 (33): 30401–7. doi:10.1074/jbc.M200123200. PMID 12063245. 
  • Pfister SC, Machado-Santelli GM, Han SW, Henrique-Silva F (Sep 2002). "Mutational analyses of the signals involved in the subcellular location of DSCR1". BMC Cell Biology 3: 24. doi:10.1186/1471-2121-3-24. PMC 128833. PMID 12225619.  Check date values in: |year= / |date= mismatch (help)
  • Genescà L, Aubareda A, Fuentes JJ, Estivill X, De La Luna S, Pérez-Riba M (Sep 2003). "Phosphorylation of calcipressin 1 increases its ability to inhibit calcineurin and decreases calcipressin half-life". The Biochemical Journal 374 (Pt 2): 567–75. doi:10.1042/BJ20030267. PMC 1223619. PMID 12809556. 
  • Hesser BA, Liang XH, Camenisch G, Yang S, Lewin DA, Scheller R, Ferrara N, Gerber HP (Jul 2004). "Down syndrome critical region protein 1 (DSCR1), a novel VEGF target gene that regulates expression of inflammatory markers on activated endothelial cells". Blood 104 (1): 149–58. doi:10.1182/blood-2004-01-0273. PMID 15016650. 
  • Michtalik HJ, Narayan AV, Bhatt N, Lin HY, Mulligan MT, Zhang SL, Crawford DR (Aug 2004). "Multiple oxidative stress-response members of the Adapt78 family". Free Radical Biology & Medicine 37 (4): 454–62. doi:10.1016/j.freeradbiomed.2004.05.014. PMID 15256217.  Check date values in: |year= / |date= mismatch (help)
  • Iizuka M, Abe M, Shiiba K, Sasaki I, Sato Y (2004). "Down syndrome candidate region 1,a downstream target of VEGF, participates in endothelial cell migration and angiogenesis". Journal of Vascular Research 41 (4): 334–44. doi:10.1159/000079832. PMID 15263820. 
  • Yao YG, Duh EJ (Aug 2004). "VEGF selectively induces Down syndrome critical region 1 gene expression in endothelial cells: a mechanism for feedback regulation of angiogenesis?". Biochemical and Biophysical Research Communications 321 (3): 648–56. doi:10.1016/j.bbrc.2004.06.176. PMID 15358155. 
  • Minami T, Horiuchi K, Miura M, Abid MR, Takabe W, Noguchi N, Kohro T, Ge X, Aburatani H, Hamakubo T, Kodama T, Aird WC (Nov 2004). "Vascular endothelial growth factor- and thrombin-induced termination factor, Down syndrome critical region-1, attenuates endothelial cell proliferation and angiogenesis". The Journal of Biological Chemistry 279 (48): 50537–54. doi:10.1074/jbc.M406454200. PMID 15448146.  Check date values in: |year= / |date= mismatch (help)
  • Baek KH, Zaslavsky A, Lynch RC, Britt C, Okada Y, Siarey RJ, Lensch MW, Park IH, Yoon SS, Minami T, Korenberg JR, Folkman J, Daley GQ, Aird WC, Galdzicki Z, Ryeom S (Jun 2009). "Down's syndrome suppression of tumour growth and the role of the calcineurin inhibitor DSCR1". Nature 459 (7250): 1126–1130. doi:10.1038/nature08062. PMC 2724004. PMID 19458618. 


This article is issued from Wikipedia - version of the Sunday, January 24, 2016. The text is available under the Creative Commons Attribution/Share Alike but additional terms may apply for the media files.