Farnesyl pyrophosphate synthase

Function

Key enzyme in isoprenoid biosynthesis which catalyzes the formation of farnesyl diphosphate (FPP), a precursor for several classes of essential metabolites including sterols, dolichols, carotenoids, and ubiquinones. FPP also serves as substrate for protein farnesylation and geranylgeranylation. Catalyzes the sequential condensation of isopentenyl pyrophosphate with the allylic pyrophosphates, dimethylallyl pyrophosphate, and then with the resultant geranylpyrophosphate to the ultimate product farnesyl pyrophosphate.

Classification

Family (Pfam)

PF00348 polyprenyl_synt

InterPro

FPS1-like, Isoprenoid_synthase_dom_sf, Polyprenyl_synt, Polyprenyl_synt_CS

Functional cluster

Membrane Channels & Lipid-Anchored Proteins

Experimental structures · PDB · 92

• 1YQ7 X-ray 2.20A
• 1YV5 X-ray 2.00A
• 1ZW5 X-ray 2.30A
• 2F7M X-ray 2.30A
• 2F89 X-ray 2.60A
• 2F8C X-ray 2.20A
• 2F8Z X-ray 2.60A
• 2F92 X-ray 2.15A
• 2F94 X-ray 1.94A
• 2F9K X-ray 2.06A
• 2OPM X-ray 2.40A
• 2OPN X-ray 2.70A
• … and 80 more

A predicted model is available from AlphaFold.

Gene Ontology · 16

• GO:0005737 cytoplasm
• GO:0005829 cytosol
• GO:0005759 mitochondrial matrix
• GO:0005777 peroxisome
• GO:0004337 (2E,6E)-farnesyl diphosphate synthase activity
• GO:0004161 dimethylallyltranstransferase activity
• GO:0046872 metal ion binding
• GO:0003723 RNA binding
• GO:0006695 cholesterol biosynthetic process
• GO:0033489 cholesterol biosynthetic process via desmosterol
• GO:0033490 cholesterol biosynthetic process via lathosterol
• GO:0045337 farnesyl diphosphate biosynthetic process
• GO:0010142 farnesyl diphosphate biosynthetic process, mevalonate pathway
• GO:0033384 geranyl diphosphate biosynthetic process
• GO:0033386 geranylgeranyl diphosphate biosynthetic process
• GO:0036197 zymosterol biosynthetic process

Disease associations

• porokeratosis 9, multiple types MONDO:0014713

Drugs targeting this protein · 6

• RISEDRONATE SODIUM inhibitor
• MINODRONIC ACID inhibitor
• PAMIDRONATE DISODIUM inhibitor
• IBANDRONATE SODIUM inhibitor
• ZOLEDRONIC ACID inhibitor
• ALENDRONATE SODIUM inhibitor

Related proteins · sequence + function similarity

• Farnesyl pyrophosphate synthase 0.89
• Farnesyl pyrophosphate synthase 0.89
• Farnesyl pyrophosphate synthase 0.88
• Farnesyl pyrophosphate synthase 0.88
• Farnesyl pyrophosphate synthase 0.78
• Farnesyl pyrophosphate synthase 0.78
• Farnesyl pyrophosphate synthase 0.77
• Bifunctional chrysanthemol synthase, chloroplastic 0.75
• Geranylgeranyl pyrophosphate synthase 0.72
• Farnesyl pyrophosphate synthase 1, mitochondrial 0.72
• Farnesyl pyrophosphate synthase 0.72
• Monoterpene synthase FDS-5, chloroplastic 0.72

Co-cited proteins · studied together in the literature

• Farnesyl pyrophosphate synthase 1 shared papers
• S-adenosylmethionine-dependent nucleotide dehydratase RSAD2 1 shared papers
• Diphosphomevalonate decarboxylase 1 shared papers
• Phosphomevalonate kinase 1 shared papers
• Hydroxyacyl-coenzyme A dehydrogenase, mitochondrial 1 shared papers
• Prostaglandin reductase 1 1 shared papers
• Adenosylhomocysteinase 1 shared papers
• Histone acetyltransferase mst1 1 shared papers
• Hydroxysteroid dehydrogenase-like protein 2 1 shared papers
• Histone H4 1 shared papers
• Heat shock protein HSP 90-alpha A2 1 shared papers
• Acyl-CoA-binding protein 1 shared papers

Literature · 21 cited papers

• Landscape of the regulatory elements for lysine 2-hydroxyisobutyrylation pathway. Cell Res. · 2018
• Genomic variations of the mevalonate pathway in porokeratosis. Elife · 2015
• N-terminome analysis of the human mitochondrial proteome. Proteomics · 2015
• An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J. Proteomics · 2014
• N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB. Proc. Natl. Acad. Sci. U.S.A. · 2012
• Comparative large-scale characterisation of plant vs. mammal proteins reveals similar and idiosyncratic N-alpha acetylation features. Mol. Cell. Proteomics · 2012
• Initial characterization of the human central proteome. BMC Syst. Biol. · 2011
• Lysine acetylation targets protein complexes and co-regulates major cellular functions. Science · 2009
• Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach. Anal. Chem. · 2009
• Lipophilic bisphosphonates as dual farnesyl/geranylgeranyl diphosphate synthase inhibitors: an X-ray and NMR investigation. J. Am. Chem. Soc. · 2009
• The interferon-inducible protein viperin inhibits influenza virus release by perturbing lipid rafts. Cell Host Microbe · 2007
• Structural basis for the exceptional in vivo efficacy of bisphosphonate drugs. ChemMedChem · 2006
• … and 9 more in the literature graph