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

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

Stable Identifier

R-HSA-4419978

Type

Reaction [transition]

Species

Homo sapiens

Compartment

endoplasmic reticulum membrane, cytosol, integral component of cytoplasmic side of endoplasmic reticulum membrane

Locations in the PathwayBrowser

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Metabolism of proteins (Homo sapiens)

- Post-translational protein modification (Homo sapiens)
  - Asparagine N-linked glycosylation (Homo sapiens)
    - Biosynthesis of the N-glycan precursor (dolichol lipid-linked oligosaccharide, LLO) and transfer to a nascent protein (Homo sapiens)
      - Synthesis of substrates in N-glycan biosythesis (Homo sapiens)
        
        Synthesis of Dolichyl-phosphate (Homo sapiens)
        
        DHDDS:NUS1 elongates E,E-FPP with (n)IPPP to form pPPP (Homo sapiens)

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

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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 Züchner, 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