Dehydrodolichyl diphosphate synthase explained

Dehydrodolichyl diphosphate synthase is an enzyme that in humans is encoded by the DHDDS gene.^{[1] [2]}

Function

Dehydrodolichyl diphosphate (dedol-PP) synthase catalyzes cis-prenyl chain elongation to produce the polyprenyl backbone of dolichol, a glycosyl carrier lipid required for the biosynthesis of several classes of glycoproteins.

Clinical significance

It has been suggested that missense mutations in the DHDDS gene are responsible for certain variants of retinitis pigmentosa.^[3] Since it is involved in the early steps of dolichol synthesis, vital e.g. for correct N-glycosylation, a disease caused by mutations in DHDDS should be considered a congenital disorder of glycosylation (and named DHDDS-CDG according to the novel nomenclature of CDGs).^[4] Many CDG subtypes present with retinitis pigmentosa as a major feature.^[5]

Further reading

• Rual JF, Venkatesan K, Hao T . Towards a proteome-scale map of the human protein-protein interaction network. . Nature . 437 . 7062 . 1173–8 . 2005 . 16189514 . 10.1038/nature04209 . 2005Natur.437.1173R . 4427026 . etal.
• Jones J, Viswanathan K, Krag SS, Betenbaugh MJ . Polyprenyl lipid synthesis in mammalian cells expressing human cis-prenyl transferase. . Biochem. Biophys. Res. Commun. . 331 . 2 . 379–83 . 2005 . 15850770 . 10.1016/j.bbrc.2005.03.181 .
• Gerhard DS, Wagner L, Feingold EA . The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). . Genome Res. . 14 . 10B . 2121–7 . 2004 . 15489334 . 10.1101/gr.2596504 . 528928 . etal.
• Kharel Y, Takahashi S, Yamashita S, Koyama T . In vivo interaction between the human dehydrodolichyl diphosphate synthase and the Niemann-Pick C2 protein revealed by a yeast two-hybrid system. . Biochem. Biophys. Res. Commun. . 318 . 1 . 198–203 . 2004 . 15110773 . 10.1016/j.bbrc.2004.04.007 .
• Ota T, Suzuki Y, Nishikawa T . Complete sequencing and characterization of 21,243 full-length human cDNAs. . Nat. Genet. . 36 . 1 . 40–5 . 2004 . 14702039 . 10.1038/ng1285 . etal. free .
• Shridas P, Rush JS, Waechter CJ . Identification and characterization of a cDNA encoding a long-chain cis-isoprenyltranferase involved in dolichyl monophosphate biosynthesis in the ER of brain cells. . Biochem. Biophys. Res. Commun. . 312 . 4 . 1349–56 . 2004 . 14652022 . 10.1016/j.bbrc.2003.11.065 .
• Strausberg RL, Feingold EA, Grouse LH . 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 . 2003 . 12477932 . 10.1073/pnas.242603899 . 139241 . 2002PNAS...9916899M . etal. free .

External links

• GeneReviews/NCBI/NIH/UW entry on Retinitis Pigmentosa Overview

Notes and References

1. Endo S, Zhang YW, Takahashi S, Koyama T . Identification of human dehydrodolichyl diphosphate synthase gene . Biochim Biophys Acta . 1625 . 3 . 291–5 . Feb 2003 . 12591616 . 10.1016/S0167-4781(02)00628-0.
2. Web site: Entrez Gene: DHDDS dehydrodolichyl diphosphate synthase.
3. Zelinger L, Banin E, Obolensky A, Mizrahi-Meissonnier L, Beryozkin A, Bandah-Rozenfeld D, Frenkel S, Ben-Yosef T, Merin S, Schwartz SB, Cideciyan AV, Jacobson SG, Sharon D . A missense mutation in DHDDS, encoding dehydrodolichyl diphosphate synthase, is associated with autosomal-recessive retinitis pigmentosa in Ashkenazi Jews . Am. J. Hum. Genet. . 88 . 2 . 207–15 . February 2011 . 21295282 . 3035703 . 10.1016/j.ajhg.2011.01.002 .
4. Jaeken J, Hennet T, Matthijs G, Freeze HH . CDG nomenclature: time for a change! . Biochim. Biophys. Acta . 1792 . 9 . 825–6 . September 2009 . 19765534 . 10.1016/j.bbadis.2009.08.005 . 3917312 .
5. Freeze HH, Eklund EA, Ng BG, Patterson MC . Neurology of inherited glycosylation disorders . Lancet Neurol. . 11 . 5 . 453–66 . May 2012 . 22516080 . 10.1016/S1474-4422(12)70040-6. 3625645 .