CPLM-018624

Genbank Nucleotide ID

Farnesyl pyrophosphate synthase

Protein Synonyms/Alias

FPP synthase; FPS; (2E,6E)-farnesyl diphosphate synthase; Cholesterol-regulated 39 kDa protein; CR 39; Dimethylallyltranstransferase; Farnesyl diphosphate synthase; Geranyltranstransferase

Mus musculus (Mouse)

Position	Peptide	Type	References
6	**MNGNQKLDAYNQE	ubiquitination	[1]
14	LDAYNQEKQNFIQHF	acetylation	[2, 3, 4, 5]
14	LDAYNQEKQNFIQHF	ubiquitination	[1]
26	QHFSQIVKVLTEKEL	acetylation	[2]
31	IVKVLTEKELGHPEI	acetylation	[2, 3, 5, 6, 7, 8]
31	IVKVLTEKELGHPEI	ubiquitination	[1]
46	GDAIARLKEVLEYNA	acetylation	[2]
46	GDAIARLKEVLEYNA	ubiquitination	[1]
57	EYNALGGKYNRGLTV	acetylation	[2, 3, 4, 5, 6, 8, 9]
57	EYNALGGKYNRGLTV	phosphoglycerylation	[10]
57	EYNALGGKYNRGLTV	succinylation	[4]
57	EYNALGGKYNRGLTV	ubiquitination	[1]
75	FQELVEPKKQDAESL	ubiquitination	[1]
144	ASIYRLLKFYCREQP	acetylation	[2]
293	LEENYGQKDPEKVAR	acetylation	[2, 6]
293	LEENYGQKDPEKVAR	ubiquitination	[1]
297	YGQKDPEKVARVKAL	acetylation	[2]
297	YGQKDPEKVARVKAL	ubiquitination	[1]
302	PEKVARVKALYEALD	acetylation	[2]
302	PEKVARVKALYEALD	ubiquitination	[1]

[1] Proteomic analyses reveal divergent ubiquitylation site patterns in murine tissues.
Wagner SA, Beli P, Weinert BT, Schölz C, Kelstrup CD, Young C, Nielsen ML, Olsen JV, Brakebusch C, Choudhary C.
Mol Cell Proteomics. 2012 Dec;11(12):1578-85. [PMID: 22790023]
[2] Quantitative acetylome analysis reveals the roles of SIRT1 in regulating diverse substrates and cellular pathways.
Chen Y, Zhao W, Yang JS, Cheng Z, Luo H, Lu Z, Tan M, Gu W, Zhao Y.
Mol Cell Proteomics. 2012 Oct;11(10):1048-62. [PMID: 22826441]
[3] Proteomic investigations of lysine acetylation identify diverse substrates of mitochondrial deacetylase sirt3.
Sol EM, Wagner SA, Weinert BT, Kumar A, Kim HS, Deng CX, Choudhary C.
PLoS One. 2012;7(12):e50545. [PMID: 23236377]
[4] SIRT5-Mediated Lysine Desuccinylation Impacts Diverse Metabolic Pathways.
Park J, Chen Y, Tishkoff DX, Peng C, Tan M, Dai L, Xie Z, Zhang Y, Zwaans BM, Skinner ME, Lombard DB, Zhao Y.
Mol Cell. 2013 Jun 27;50(6):919-30. [PMID: 23806337]
[5] Quantification of mitochondrial acetylation dynamics highlights prominent sites of metabolic regulation.
Still AJ, Floyd BJ, Hebert AS, Bingman CA, Carson JJ, Gunderson DR, Dolan BK, Grimsrud PA, Dittenhafer-Reed KE, Stapleton DS, Keller MP, Westphall MS, Denu JM, Attie AD, Coon JJ, Pagliarini DJ.
J Biol Chem. 2013 Jul 17;. [PMID: 23864654]
[6] Calorie restriction and SIRT3 trigger global reprogramming of the mitochondrial protein acetylome.
Hebert AS, Dittenhafer-Reed KE, Yu W, Bailey DJ, Selen ES, Boersma MD, Carson JJ, Tonelli M, Balloon AJ, Higbee AJ, Westphall MS, Pagliarini DJ, Prolla TA, Assadi-Porter F, Roy S, Denu JM, Coon JJ.
Mol Cell. 2013 Jan 10;49(1):186-99. [PMID: 23201123]
[7] Circadian acetylome reveals regulation of mitochondrial metabolic pathways.
Masri S, Patel VR, Eckel-Mahan KL, Peleg S, Forne I, Ladurner AG, Baldi P, Imhof A, Sassone-Corsi P.
Proc Natl Acad Sci U S A. 2013 Feb 26;110(9):3339-44. [PMID: 23341599]
[8] Label-free quantitative proteomics of the lysine acetylome in mitochondria identifies substrates of SIRT3 in metabolic pathways.
Rardin MJ, Newman JC, Held JM, Cusack MP, Sorensen DJ, Li B, Schilling B, Mooney SD, Kahn CR, Verdin E, Gibson BW.
Proc Natl Acad Sci U S A. 2013 Apr 16;110(16):6601-6. [PMID: 23576753]
[9] Quantitative assessment of the impact of the gut microbiota on lysine epsilon-acetylation of host proteins using gnotobiotic mice.
Simon GM, Cheng J, Gordon JI.
Proc Natl Acad Sci U S A. 2012 Jul 10;109(28):11133-8. [PMID: 22733758]
[10] Functional lysine modification by an intrinsically reactive primary glycolytic metabolite.
Moellering RE, Cravatt BF.
Science. 2013 Aug 2;341(6145):549-53. [PMID: 23908237]

Functional Description

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 (By similarity).

METAL 103 103 Magnesium 1 (By similarity).
METAL 103 103 Magnesium 2 (By similarity).
METAL 107 107 Magnesium 1 (By similarity).
METAL 107 107 Magnesium 2 (By similarity).
METAL 243 243 Magnesium 3 (By similarity).
BINDING 57 57 Isopentenyl diphosphate (By similarity).
BINDING 60 60 Isopentenyl diphosphate (By similarity).
BINDING 96 96 Isopentenyl diphosphate (By similarity).
BINDING 112 112 Dimethylallyl diphosphate (By
BINDING 113 113 Isopentenyl diphosphate (By similarity).
BINDING 200 200 Dimethylallyl diphosphate (By
BINDING 201 201 Dimethylallyl diphosphate (By
BINDING 240 240 Dimethylallyl diphosphate (By
BINDING 257 257 Dimethylallyl diphosphate (By
BINDING 266 266 Dimethylallyl diphosphate (By
MOD_RES 57 57 N6-acetyllysine (By similarity).

Acetylation; Cholesterol biosynthesis; Cholesterol metabolism; Complete proteome; Cytoplasm; Isoprene biosynthesis; Lipid biosynthesis; Lipid metabolism; Magnesium; Metal-binding; Reference proteome; Steroid biosynthesis; Steroid metabolism; Sterol biosynthesis; Sterol metabolism; Transferase.

UniProt (SWISSPROT/TrEMBL); GenBank; EMBL

GO:0005739; C:mitochondrion; IDA:MGI.
GO:0005634; C:nucleus; IEA:Compara.
GO:0004161; F:dimethylallyltranstransferase activity; IEA:EC.
GO:0004337; F:geranyltranstransferase activity; IEA:EC.
GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
GO:0006695; P:cholesterol biosynthetic process; IEA:UniProtKB-KW.
GO:0045337; P:farnesyl diphosphate biosynthetic process; IEA:UniProtKB-UniPathway.
GO:0033384; P:geranyl diphosphate biosynthetic process; IEA:UniProtKB-UniPathway.

IPR000092; Polyprenyl_synt.
IPR008949; Terpenoid_synth.

PF00348; polyprenyl_synt

PS00723; POLYPRENYL_SYNTHASE_1
PS00444; POLYPRENYL_SYNTHASE_2