24-dehydrocholesterol reductase

24-dehydrocholesterol reductase
Identifiers
Symbols	DHCR24 ; DCE; Nbla03646; SELADIN1; seladin-1
External IDs	OMIM: 606418 MGI: 1922004 HomoloGene: 8850 GeneCards: DHCR24 Gene
EC number	1.3.1.72
Gene ontology Molecular function • delta24(24-1) sterol reductase activity • UDP-N-acetylmuramate dehydrogenase activity • oxidoreductase activity, acting on the CH-CH group of donors, NAD or NADP as acceptor • enzyme binding • peptide antigen binding • delta24-sterol reductase activity • flavin adenine dinucleotide binding Cellular component • Golgi membrane • nucleus • cytoplasm • endoplasmic reticulum • endoplasmic reticulum membrane • cytosol • cytoskeleton • membrane • integral component of membrane Biological process • cholesterol biosynthetic process • apoptotic process • response to oxidative stress • cell cycle arrest • Ras protein signal transduction • protein localization • negative regulation of cell proliferation • response to hormone • tissue development • male genitalia development • plasminogen activation • amyloid precursor protein catabolic process • negative regulation of apoptotic process • negative regulation of cysteine-type endopeptidase activity involved in apoptotic process • skin development • small molecule metabolic process • oxidation-reduction process • membrane organization • regulation of neuron death Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	1718	74754
Ensembl	ENSG00000116133	ENSMUSG00000034926
UniProt	Q15392	Q8VCH6
RefSeq (mRNA)	NM_014762	NM_053272
RefSeq (protein)	NP_055577	NP_444502
Location (UCSC)	Chr 1: 54.85 – 54.89 Mb	Chr 4: 106.56 – 106.59 Mb
PubMed search

24-dehydrocholesterol reductase is a protein that in humans is encoded by the DHCR24 gene.^[1][2]

This gene encodes a flavin adenine dinucleotide (FAD)-dependent oxidoreductase, which catalyzes the reduction of the delta-24 double bond of sterol intermediates during cholesterol biosynthesis. The protein contains a leader sequence that directs it to the endoplasmic reticulum membrane. Missense mutations in this gene have been associated with desmosterolosis. Also, reduced expression of the gene occurs in the temporal cortex of Alzheimer disease patients and overexpression has been observed in adrenal gland cancer cells.^[2]

Model organisms

Dhcr24 knockout mouse phenotype

Characteristic	Phenotype
Homozygote viability	Abnormal
Recessive lethal study	Abnormal
Fertility	Normal
Body weight	Normal
Anxiety	Normal
Neurological assessment	Normal
Grip strength	Normal
Hot plate	Normal
Dysmorphology	Normal
Indirect calorimetry	Normal
Glucose tolerance test	Normal
Auditory brainstem response	Normal
DEXA	Normal
Radiography	Normal
Body temperature	Normal
Eye morphology	Normal
Clinical chemistry	Normal
Plasma immunoglobulins	Normal
Haematology	Normal
Peripheral blood lymphocytes	Normal
Micronucleus test	Normal
Heart weight	Normal
Skin Histopathology	Normal
Brain histopathology	Normal
Salmonella infection	Normal[3]
Citrobacter infection	Normal[4]
All tests and analysis from[5][6]

Model organisms have been used in the study of DHCR24 function. A conditional knockout mouse line, called Dhcr24^{tm1a(EUCOMM)Wtsi[7][8]} was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists.^[9][10][11]

Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.^[5][12] Twenty-six tests were carried out on mutant mice and two significant abnormalities were observed.^[5] Few homozygous mutant embryos were identified during gestation, and none survived until weaning. The remaining tests were carried out on heterozygous mutant adult mice and no further abmornalities were observed.^[5]

References

1. Waterham HR, Koster J, Romeijn GJ, Hennekam RC, Vreken P, Andersson HC, FitzPatrick DR, Kelley RI, Wanders RJ (Sep 2001). "Mutations in the 3beta-hydroxysterol Delta24-reductase gene cause desmosterolosis, an autosomal recessive disorder of cholesterol biosynthesis.". Am J Hum Genet 69 (4): 685–94. doi:10.1086/323473. PMC 1226055. PMID 11519011.
2. "Entrez Gene: DHCR24 24-dehydrocholesterol reductase".
3. "Salmonella infection data for Dhcr24". Wellcome Trust Sanger Institute.
4. "Citrobacter infection data for Dhcr24". Wellcome Trust Sanger Institute.
5. White JK, Gerdin AK, Karp NA; et al. (July 2013). "Genome-wide Generation and Systematic Phenotyping of Knockout Mice Reveals New Roles for Many Genes". Cell 154 (2): 452–64. doi:10.1016/j.cell.2013.06.022. PMC 3717207. PMID 23870131.
6. Mouse Resources Portal, Wellcome Trust Sanger Institute.
7. "International Knockout Mouse Consortium".
8. "Mouse Genome Informatics".
9. Skarnes, W. C.; Rosen, B.; West, A. P.; Koutsourakis, M.; Bushell, W.; Iyer, V.; Mujica, A. O.; Thomas, M.; Harrow, J.; Cox, T.; Jackson, D.; Severin, J.; Biggs, P.; Fu, J.; Nefedov, M.; De Jong, P. J.; Stewart, A. F.; Bradley, A. (2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature 474 (7351): 337–342. doi:10.1038/nature10163. PMC 3572410. PMID 21677750.
10. Dolgin E (2011). "Mouse library set to be knockout". Nature 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.
11. Collins FS, Rossant J, Wurst W (2007). "A Mouse for All Reasons". Cell 128 (1): 9–13. doi:10.1016/j.cell.2006.12.018. PMID 17218247.
12. van der Weyden L, White JK, Adams DJ, Logan DW (2011). "The mouse genetics toolkit: revealing function and mechanism.". Genome Biol 12 (6): 224. doi:10.1186/gb-2011-12-6-224. PMC 3218837. PMID 21722353.

Further reading

• Peri A, Danza G, Serio M (2005). "Seladin-1 as a target of estrogen receptor activation in the brain: a new gene for a rather old story?". J. Endocrinol. Invest. 28 (3): 285–93. doi:10.1007/bf03345387. PMID 15954227.
• Nomura N, Miyajima N, Sazuka T; et al. (1995). "Prediction of the coding sequences of unidentified human genes. I. The coding sequences of 40 new genes (KIAA0001-KIAA0040) deduced by analysis of randomly sampled cDNA clones from human immature myeloid cell line KG-1.". DNA Res. 1 (1): 27–35. doi:10.1093/dnares/1.1.27. PMID 7584026.
• Nomura N, Miyajima N, Sazuka T; et al. (1995). "Prediction of the coding sequences of unidentified human genes. I. The coding sequences of 40 new genes (KIAA0001-KIAA0040) deduced by analysis of randomly sampled cDNA clones from human immature myeloid cell line KG-1 (supplement).". DNA Res. 1 (1): 47–56. doi:10.1093/dnares/1.1.47. PMID 7584028.
• Greeve I, Hermans-Borgmeyer I, Brellinger C; et al. (2001). "The human DIMINUTO/DWARF1 homolog seladin-1 confers resistance to Alzheimer's disease-associated neurodegeneration and oxidative stress.". J. Neurosci. 20 (19): 7345–52. PMID 11007892.
• Andersson HC, Kratz L, Kelley R (2003). "Desmosterolosis presenting with multiple congenital anomalies and profound developmental delay.". Am. J. Med. Genet. 113 (4): 315–9. doi:10.1002/ajmg.b.10873. PMID 12457401.
• 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.
• Luciani P, Ferruzzi P, Arnaldi G; et al. (2004). "Expression of the novel adrenocorticotropin-responsive gene selective Alzheimer's disease indicator-1 in the normal adrenal cortex and in adrenocortical adenomas and carcinomas.". J. Clin. Endocrinol. Metab. 89 (3): 1332–9. doi:10.1210/jc.2003-031065. PMID 15001630.
• Suzuki Y, Yamashita R, Shirota M; et al. (2004). "Sequence comparison of human and mouse genes reveals a homologous block structure in the promoter regions.". Genome Res. 14 (9): 1711–8. doi:10.1101/gr.2435604. PMC 515316. PMID 15342556.
• Gerhard DS, Wagner L, Feingold EA; et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334.
• Wu C, Miloslavskaya I, Demontis S; et al. (2005). "Regulation of cellular response to oncogenic and oxidative stress by Seladin-1.". Nature 432 (7017): 640–5. doi:10.1038/nature03173. PMID 15577914.
• Di Stasi D, Vallacchi V, Campi V; et al. (2005). "DHCR24 gene expression is upregulated in melanoma metastases and associated to resistance to oxidative stress-induced apoptosis.". Int. J. Cancer 115 (2): 224–30. doi:10.1002/ijc.20885. PMID 15688385.
• Crameri A, Biondi E, Kuehnle K; et al. (2006). "The role of seladin-1/DHCR24 in cholesterol biosynthesis, APP processing and Abeta generation in vivo.". EMBO J. 25 (2): 432–43. doi:10.1038/sj.emboj.7600938. PMC 1383521. PMID 16407971.
• Benvenuti S, Saccardi R, Luciani P; et al. (2006). "Neuronal differentiation of human mesenchymal stem cells: changes in the expression of the Alzheimer's disease-related gene seladin-1.". Exp. Cell Res. 312 (13): 2592–604. doi:10.1016/j.yexcr.2006.04.016. PMID 16762343.
• Lämsä R, Helisalmi S, Hiltunen M; et al. (2007). "The association study between DHCR24 polymorphisms and Alzheimer's disease.". Am. J. Med. Genet. B Neuropsychiatr. Genet. 144 (7): 906–10. doi:10.1002/ajmg.b.30532. PMID 17510943.