DHDDS:NUS1 elongates E,E-FPP with (n)IPPP to form pPPP

Stable Identifier
R-HSA-4419978
Type
Reaction [transition]
Species
Homo sapiens
Compartment
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The ER membrane-associated enzyme dehydrodolichyl diphosphate synthase (DHDDS) mediates the sequential head-to-tail cis addition of multiple isopentyl pyrophosphate (IPP) molecules to farnesyl pyrophosphate (E,E-FPP) to produce polyprenol pyrophosphate (pPPP) (Shridas et al. 2003). Dolichol in humans contain homologues ranging from 17-23 isoprene units, the most common homologues contain 19 or 20 isoprene units (Freeman et al. 1980). Dehydrodolichyl diphosphate syntase complex subunit NUS1 (NUS1, aka Nogo-B receptor NgBR) interacts with DHDDS, enhancing its stability and promoting Dol-P production (Harrison et al. 2011).

Defects in DHDDS cause retinitis pigmentosa 59 (RP59; MIM:613861), a pigment retinopathy, characterised by retinal pigment deposits (visible on fundus examination) and primary loss of rod photoreceptors followed by secondary loss of cone photoreceptors. Sufferers typically have night vision blindness and loss of mid to peripheral vision. As the condition progresses, they lose far peripheral vision and eventually central vision (Zuchner et al. 2011).

Literature References
PubMed ID Title Journal Year
21295283 Whole-exome sequencing links a variant in DHDDS to retinitis pigmentosa

Z├╝chner, S, Dallman, J, Wen, R, Beecham, G, Naj, A, Farooq, A, Kohli, MA, Whitehead, PL, Hulme, W, Konidari, I, Edwards, YJ, Cai, G, Peter, I, Seo, D, Buxbaum, JD, Haines, JL, Blanton, S, Young, J, Alfonso, E, Vance, JM, Lam, BL, Pericak-Vance, MA

Am. J. Hum. Genet. 2011
7374371 Analysis of dolichol in human tissues by high pressure liquid chromatography

Freeman, DJ, Rupar, CA, Carroll, KK

Lipids 1980
21572394 Nogo-B receptor is necessary for cellular dolichol biosynthesis and protein N-glycosylation

Harrison, KD, Park, EJ, Gao, N, Kuo, A, Rush, JS, Waechter, CJ, Lehrman, MA, Sessa, WC

EMBO J. 2011
14652022 Identification and characterization of a cDNA encoding a long-chain cis-isoprenyltranferase involved in dolichyl monophosphate biosynthesis in the ER of brain cells

Shridas, P, Rush, JS, Waechter, CJ

Biochem. Biophys. Res. Commun. 2003
Participants
Participant Of
Catalyst Activity
Catalyst Activity
Title
transferase activity, transferring alkyl or aryl (other than methyl) groups of DHDDS:NUS1 [endoplasmic reticulum membrane]
Physical Entity
Activity
Orthologous Events
Authored
Reviewed
Created