UniProt Accession

 FPPS_HUMAN; P14324; D3DV91; E9PCI9; Q96G29 

Genbank Protein ID

 J05262; D14697; AK291084; AL139410; CH471121; CH471121; CH471121; BC010004; BQ062616; M29863 

Genbank Nucleotide ID

 AAA52423.1; BAA03523.2; BAF83773.1; CAI12715.1; EAW53076.1; EAW53077.1; EAW53078.1; AAH10004.1; AAA35820.1 

Protein Name

 Farnesyl pyrophosphate synthase 

Protein Synonyms/Alias

 FPP synthase; FPS; (2E,6E)-farnesyl diphosphate synthase; Dimethylallyltranstransferase; Farnesyl diphosphate synthase; Geranyltranstransferase 

Gene Name

 FDPS 

Gene Synonyms/Alias

 FPS; KIAA1293 

Created Date

 July 27, 2013 

Organism

 Homo sapiens (Human) 

NCBI Taxa ID

 9606 

Lysine Modification

Position	Peptide	Type	References
80	SDVYAQEKQDFVQHF	acetylation	[1]
80	SDVYAQEKQDFVQHF	ubiquitination	[2, 3, 4]
112	GDAIARLKEVLEYNA	ubiquitination	[2, 3, 4, 5, 6, 7, 8, 9]
123	EYNAIGGKYNRGLTV	acetylation	[1, 4, 10, 11, 12]
123	EYNAIGGKYNRGLTV	ubiquitination	[2, 3, 4, 5, 8, 9, 13, 14]
142	RELVEPRKQDADSLQ	ubiquitination	[3, 5]
187	GQICWYQKPGVGLDA	ubiquitination	[3, 4, 6, 15]
210	ACIYRLLKLYCREQP	ubiquitination	[3, 4, 5, 6, 8]
260	RFTEKRYKSIVKYKT	ubiquitination	[3]
264	KRYKSIVKYKTAFYS	ubiquitination	[3]
332	GTDIQDNKCSWLVVQ	ubiquitination	[2, 3, 4, 5, 6, 15]
353	PEQYQILKENYGQKE	acetylation	[10]
353	PEQYQILKENYGQKE	ubiquitination	[2, 3, 4, 5, 8, 13, 14]
359	LKENYGQKEAEKVAR	ubiquitination	[3, 4, 5]
363	YGQKEAEKVARVKAL	ubiquitination	[3]

Reference

 [1] 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]
 [2] Methods for quantification of in vivo changes in protein ubiquitination following proteasome and deubiquitinase inhibition.
 Udeshi ND, Mani DR, Eisenhaure T, Mertins P, Jaffe JD, Clauser KR, Hacohen N, Carr SA.
 Mol Cell Proteomics. 2012 May;11(5):148-59. [PMID: 22505724]
 [3] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
 [4] Integrated proteomic analysis of post-translational modifications by serial enrichment.
 Mertins P, Qiao JW, Patel J, Udeshi ND, Clauser KR, Mani DR, Burgess MW, Gillette MA, Jaffe JD, Carr SA.
 Nat Methods. 2013 Jul;10(7):634-7. [PMID: 23749302]
 [5] Systematic and quantitative assessment of the ubiquitin-modified proteome.
 Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
 Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983]
 [6] Global identification of modular cullin-RING ligase substrates.
 Emanuele MJ, Elia AE, Xu Q, Thoma CR, Izhar L, Leng Y, Guo A, Chen YN, Rush J, Hsu PW, Yen HC, Elledge SJ.
 Cell. 2011 Oct 14;147(2):459-74. [PMID: 21963094]
 [7] Proteome-wide identification of ubiquitylation sites by conjugation of engineered lysine-less ubiquitin.
 Oshikawa K, Matsumoto M, Oyamada K, Nakayama KI.
 J Proteome Res. 2012 Feb 3;11(2):796-807. [PMID: 22053931]
 [8] Systems-wide analysis of ubiquitylation dynamics reveals a key role for PAF15 ubiquitylation in DNA-damage bypass.
 Povlsen LK, Beli P, Wagner SA, Poulsen SL, Sylvestersen KB, Poulsen JW, Nielsen ML, Bekker-Jensen S, Mailand N, Choudhary C.
 Nat Cell Biol. 2012 Oct;14(10):1089-98. [PMID: 23000965]
 [9] Landscape of the PARKIN-dependent ubiquitylome in response to mitochondrial depolarization.
 Sarraf SA, Raman M, Guarani-Pereira V, Sowa ME, Huttlin EL, Gygi SP, Harper JW.
 Nature. 2013 Apr 18;496(7445):372-6. [PMID: 23503661]
 [10] Lysine acetylation targets protein complexes and co-regulates major cellular functions.
 Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M.
 Science. 2009 Aug 14;325(5942):834-40. [PMID: 19608861]
 [11] Regulation of cellular metabolism by protein lysine acetylation.
 Zhao S, Xu W, Jiang W, Yu W, Lin Y, Zhang T, Yao J, Zhou L, Zeng Y, Li H, Li Y, Shi J, An W, Hancock SM, He F, Qin L, Chin J, Yang P, Chen X, Lei Q, Xiong Y, Guan KL.
 Science. 2010 Feb 19;327(5968):1000-4. [PMID: 20167786]
 [12] Proteomic investigations reveal a role for RNA processing factor THRAP3 in the DNA damage response.
 Beli P, Lukashchuk N, Wagner SA, Weinert BT, Olsen JV, Baskcomb L, Mann M, Jackson SP, Choudhary C.
 Mol Cell. 2012 Apr 27;46(2):212-25. [PMID: 22424773]
 [13] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
 Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
 Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473]
 [14] hCKSAAP_UbSite: improved prediction of human ubiquitination sites by exploiting amino acid pattern and properties.
 Chen Z, Zhou Y, Song J, Zhang Z.
 Biochim Biophys Acta. 2013 Aug;1834(8):1461-7. [PMID: 23603789]
 [15] Ubiquitin ligase substrate identification through quantitative proteomics at both the protein and peptide levels.
 Lee KA, Hammerle LP, Andrews PS, Stokes MP, Mustelin T, Silva JC, Black RA, Doedens JR.
 J Biol Chem. 2011 Dec 2;286(48):41530-8. [PMID: 21987572] 

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. 

Sequence Annotation

 METAL 169 169 Magnesium 1.
 METAL 169 169 Magnesium 2.
 METAL 173 173 Magnesium 1.
 METAL 173 173 Magnesium 2.
 METAL 309 309 Magnesium 3.
 BINDING 123 123 Isopentenyl diphosphate.
 BINDING 126 126 Isopentenyl diphosphate.
 BINDING 162 162 Isopentenyl diphosphate.
 BINDING 178 178 Dimethylallyl diphosphate.
 BINDING 179 179 Isopentenyl diphosphate.
 BINDING 266 266 Dimethylallyl diphosphate.
 BINDING 267 267 Dimethylallyl diphosphate.
 BINDING 306 306 Dimethylallyl diphosphate.
 BINDING 323 323 Dimethylallyl diphosphate.
 BINDING 332 332 Dimethylallyl diphosphate (By
 MOD_RES 123 123 N6-acetyllysine.
 MOD_RES 353 353 N6-acetyllysine.  

Keyword

 3D-structure; Acetylation; Alternative splicing; Cholesterol biosynthesis; Cholesterol metabolism; Complete proteome; Cytoplasm; Host-virus interaction; Isoprene biosynthesis; Lipid biosynthesis; Lipid metabolism; Magnesium; Metal-binding; Polymorphism; Reference proteome; Steroid biosynthesis; Steroid metabolism; Sterol biosynthesis; Sterol metabolism; Transferase. 

Sequence Source

 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 

Protein Length

 419 AA 

Protein Sequence

Gene Ontology

 GO:0005829; C:cytosol; TAS:Reactome.
 GO:0005739; C:mitochondrion; IEA:Compara.
 GO:0005634; C:nucleus; IDA:HPA.
 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; TAS:Reactome.
 GO:0045337; P:farnesyl diphosphate biosynthetic process; IEA:UniProtKB-UniPathway.
 GO:0033384; P:geranyl diphosphate biosynthetic process; IEA:UniProtKB-UniPathway.
 GO:0019048; P:virus-host interaction; IEA:UniProtKB-KW. 

Interpro

 IPR000092; Polyprenyl_synt.
 IPR008949; Terpenoid_synth. 

Pfam

 PF00348; polyprenyl_synt 

SMART

  

PROSITE

 PS00723; POLYPRENYL_SYNTHASE_1
 PS00444; POLYPRENYL_SYNTHASE_2 

PRINTS