DSCR1

Regulator of calcineurin 1
PDB rendering based on 1wey.
Available structures PDB 1wey
Identifiers
Symbols	RCAN1; ADAPT78; CSP1; DSC1; DSCR1; MCIP1; RCN1
External IDs	OMIM: 602917 MGI: 1890564 HomoloGene: 3251 GeneCards: RCAN1 Gene
Gene Ontology Molecular function • DNA binding • sequence-specific DNA binding transcription factor activity • protein binding Cellular component • nucleus • cytoplasm Biological process • transcription, DNA-dependent • regulation of transcription, DNA-dependent • signal transduction • central nervous system development • blood circulation • calcium-mediated signaling • regulation of phosphoprotein phosphatase activity • skeletal muscle fiber development Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	1827	54720
Ensembl	ENSG00000159200	ENSMUSG00000022951
UniProt	P53805	Q7TNY3
RefSeq (mRNA)	NM_004414.5	NM_001081549
RefSeq (protein)	NP_004405.3	NP_001075018
Location (UCSC)	Chr 21: 35.89 – 35.99 Mb	Chr 16: 92.39 – 92.47 Mb
PubMed search	[1]	[2]

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]

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]

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.^[2]

Interactions

DSCR1 has been shown to interact with Calcineurin.^[3]

References

1. ^ ^{a b c} "Entrez Gene: DSCR1 Down syndrome critical region gene 1". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1827. 
2. ^ Baek K-H, Zaslavsky A, Lynch R, Britt C, Okada Y, Siarey R, Lensch M W, Park I-H, Yoon S, Minami T, Korenberg J, Folkman J, Daley G, Aird W, Galdzicki Z & Ryeom S (Jul. 2009). "Down syndrome suppression of tumor growth and the role of the calcineurin inhibitor DSCR1". Nature 459 (7250): 1126–30. doi:10.1038/nature08062. ISSN 0028-0836. PMC 2724004. PMID 19458618. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2724004. 
3. ^ Fuentes, J J; Genescà L, Kingsbury T J, Cunningham K W, Pérez-Riba M, Estivill X, de la Luna S (Jul. 2000). "DSCR1, overexpressed in Down syndrome, is an inhibitor of calcineurin-mediated signaling pathways". Hum. Mol. Genet. (ENGLAND) 9 (11): 1681–90. doi:10.1093/hmg/9.11.1681. ISSN 0964-6906. PMID 10861295. 

Further reading

• Harris CD, Ermak G, Davies KJ (2006). "Multiple roles of the DSCR1 (Adapt78 or RCAN1) gene and its protein product calcipressin 1 (or RCAN1) in disease". Cell. Mol. Life Sci. 62 (21): 2477–86. doi:10.1007/s00018-005-5085-4. PMID 16231093. 
• Keating DJ, Chen C, Pritchard MA (2006). "Alzheimer's disease and endocytic dysfunction: clues from the Down syndrome-related proteins, DSCR1 and ITSN1". Ageing Res. Rev. 5 (4): 388–401. doi:10.1016/j.arr.2005.11.001. PMID 16442855. 
• Fuentes JJ, Pritchard MA, Planas AM et al. (1996). "A new human gene from the Down syndrome critical region encodes a proline-rich protein highly expressed in fetal brain and heart". Hum. Mol. Genet. 4 (10): 1935–44. doi:10.1093/hmg/4.10.1935. PMID 8595418. 
• Andersson B, Wentland MA, Ricafrente JY et al. (1996). "A "double adaptor" method for improved shotgun library construction". Anal. Biochem. 236 (1): 107–13. doi:10.1006/abio.1996.0138. PMID 8619474. 
• Yu W, Andersson B, Worley KC et al. (1997). "Large-Scale Concatenation cDNA Sequencing". Genome Res. 7 (4): 353–8. doi:10.1101/gr.7.4.353. PMC 139146. PMID 9110174. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=139146. 
• Fuentes JJ, Pritchard MA, Estivill X (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 et al. (2000). "A protein encoded within the Down syndrome critical region is enriched in striated muscles and inhibits calcineurin signaling". J. Biol. Chem. 275 (12): 8719–25. doi:10.1074/jbc.275.12.8719. PMID 10722714. 
• Hattori M, Fujiyama A, Taylor TD et al. (2000). "The DNA sequence of human chromosome 21". Nature 405 (6784): 311–9. doi:10.1038/35012518. PMID 10830953. 
• Fuentes JJ, Genescà L, Kingsbury TJ et al. (2000). "DSCR1, overexpressed in Down syndrome, is an inhibitor of calcineurin-mediated signaling pathways". Hum. Mol. Genet. 9 (11): 1681–90. doi:10.1093/hmg/9.11.1681. PMID 10861295. 
• Ermak G, Morgan TE, Davies KJ (2001). "Chronic overexpression of the calcineurin inhibitory gene DSCR1 (Adapt78) is associated with Alzheimer's disease". J. Biol. Chem. 276 (42): 38787–94. doi:10.1074/jbc.M102829200. PMID 11483593. 
• Vega RB, Yang J, Rothermel BA et al. (2002). "Multiple domains of MCIP1 contribute to inhibition of calcineurin activity". J. Biol. Chem. 277 (33): 30401–7. doi:10.1074/jbc.M200123200. PMID 12063245. 
• Pfister SC, Machado-Santelli GM, Han SW, Henrique-Silva F (2003). "Mutational analyses of the signals involved in the subcellular location of DSCR1". BMC Cell Biol. 3: 24. doi:10.1186/1471-2121-3-24. PMC 128833. PMID 12225619. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=128833. 
• Strausberg RL, Feingold EA, Grouse LH et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=139241. 
• Genescà L, Aubareda A, Fuentes JJ et al. (2003). "Phosphorylation of calcipressin 1 increases its ability to inhibit calcineurin and decreases calcipressin half-life". Biochem. J. 374 (Pt 2): 567–75. doi:10.1042/BJ20030267. PMC 1223619. PMID 12809556. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1223619. 
• Ota T, Suzuki Y, Nishikawa T et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nat. Genet. 36 (1): 40–5. doi:10.1038/ng1285. PMID 14702039. 
• Hesser BA, Liang XH, Camenisch G et al. (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 et al. (2005). "Multiple oxidative stress-response members of the Adapt78 family". Free Radic. Biol. Med. 37 (4): 454–62. doi:10.1016/j.freeradbiomed.2004.05.014. PMID 15256217. 
• Iizuka M, Abe M, Shiiba K et al. (2004). "Down syndrome candidate region 1,a downstream target of VEGF, participates in endothelial cell migration and angiogenesis". J. Vasc. Res. 41 (4): 334–44. doi:10.1159/000079832. PMID 15263820. 
• Yao YG, Duh EJ (2004). "VEGF selectively induces Down syndrome critical region 1 gene expression in endothelial cells: a mechanism for feedback regulation of angiogenesis?". Biochem. Biophys. Res. Commun. 321 (3): 648–56. doi:10.1016/j.bbrc.2004.06.176. PMID 15358155. 
• Minami T, Horiuchi K, Miura M et al. (2005). "Vascular endothelial growth factor- and thrombin-induced termination factor, Down syndrome critical region-1, attenuates endothelial cell proliferation and angiogenesis". J. Biol. Chem. 279 (48): 50537–54. doi:10.1074/jbc.M406454200. PMID 15448146. 
• Baek, K-H, Zaslavsky A, Lynch R, Britt C, Okada Y, Siarey R, Lensch M W, Park I-H, Yoon S, Minami T, Korenberg J, Folkman J, Daley G, Aird W, Galdzicki Z & Ryeom S (2009). "Down syndrome suppression of tumor growth and the role of the calcineurin inhibitor DSCR1". Nature 459 (7250): 1126–1130. doi:10.1038/nature08062. PMC 2724004. PMID 19458618. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2724004.