Reviewed, UniProtKB/Swiss-Prot O95749 (GGPPS_HUMAN)

Names and origin

Protein names

Recommended name:
Geranylgeranyl pyrophosphate synthase
Short name=GGPP synthase
Short name=GGPPSase

Alternative name(s):
Geranylgeranyl diphosphate synthase

Including the following 3 domains:

1. Dimethylallyltranstransferase
   EC=2.5.1.1
2. Geranyltranstransferase
   EC=2.5.1.10
3. Farnesyltranstransferase
   EC=2.5.1.29

Gene names

Name:

GGPS1

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	300 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Catalyzes the trans-addition of the three molecules of IPP onto DMAPP to form geranylgeranyl pyrophosphate, an important precursor of carotenoids and geranylated proteins.
Catalytic activity	Dimethylallyl diphosphate + isopentenyl diphosphate = diphosphate + geranyl diphosphate. Ref.11 Geranyl diphosphate + isopentenyl diphosphate = diphosphate + trans,trans-farnesyl diphosphate. Ref.11 Trans,trans-farnesyl diphosphate + isopentenyl diphosphate = diphosphate + geranylgeranyl diphosphate. Ref.11
Cofactor	Binds 3 magnesium ions Probable.
Enzyme regulation	Subject to product inhibition by geranylgeranyl diphosphate. Ref.11
Pathway	Isoprenoid biosynthesis; farnesyl diphosphate biosynthesis; farnesyl diphosphate from geranyl diphosphate and isopentenyl diphosphate: step 1/1. Isoprenoid biosynthesis; geranyl diphosphate biosynthesis; geranyl diphosphate from dimethylallyl diphosphate and isopentenyl diphosphate: step 1/1. Isoprenoid biosynthesis; geranylgeranyl diphosphate biosynthesis; geranylgeranyl diphosphate from farnesyl diphosphate and isopentenyl diphosphate: step 1/1.
Subunit structure	Homohexamer; trimer of homodimers. Ref.11
Subcellular location	Cytoplasm.
Tissue specificity	Abundantly expressed in testis. Found in other tissues to a lower extent.
Sequence similarities	Belongs to the FPP/GGPP synthase family.
Biophysicochemical properties	Kinetic parameters: KM=3 µM for isopentenyl diphosphate KM=4.2 µM for farnesyl diphosphate

Ontologies

Keywords
Biological process	Isoprene biosynthesis
Cellular component	Cytoplasm
Ligand	Magnesium Metal-binding
Molecular function	Transferase
PTM	Acetylation
Technical term	3D-structure Complete proteome Multifunctional enzyme
Gene Ontology (GO)
Biological process	isoprenoid biosynthetic process Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell soluble fraction Ref.1 Inferred from direct assay. Source: UniProtKB
Molecular function	dimethylallyltranstransferase activity Inferred from electronic annotation. Source: EC farnesyltranstransferase activity Ref.1 Ref.2 Inferred from direct assay. Source: UniProtKB geranyltranstransferase activity Inferred from electronic annotation. Source: EC magnesium ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 300

300

Geranylgeranyl pyrophosphate synthase

PRO_0000123962

Sites

Metal binding

64

1

Magnesium 1

Metal binding

64

1

Magnesium 2

Metal binding

68

1

Magnesium 1

Metal binding

68

1

Magnesium 2

Metal binding

188

1

Magnesium 3 By similarity

Binding site

25

1

Isopentenyl diphosphate By similarity

Binding site

28

1

Isopentenyl diphosphate By similarity

Binding site

57

1

Isopentenyl diphosphate By similarity

Binding site

73

1

Dimethylallyl diphosphate

Binding site

74

1

Isopentenyl diphosphate By similarity

Binding site

151

1

Dimethylallyl diphosphate

Binding site

152

1

Dimethylallyl diphosphate

Binding site

185

1

Dimethylallyl diphosphate

Binding site

202

1

Dimethylallyl diphosphate

Binding site

212

1

Dimethylallyl diphosphate By similarity

Amino acid modifications

Modified residue

25

1

N6-acetyllysine Ref.10

Experimental info

Sequence conflict

109

1

P → Q in AAH67768. Ref.8

Secondary structure

1

.

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300

Helix Strand Turn

Details...

Helix

9 – 13

5

Helix

15 – 20

6

Helix

26 – 40

15

Helix

44 – 69

26

Beta strand

72 – 74

3

Helix

80 – 84

5

Helix

86 – 105

20

Helix

112 – 135

24

Helix

142 – 166

25

Helix

175 – 195

21

Helix

207 – 211

5

Helix

216 – 224

9

Helix

230 – 236

7

Helix

242 – 254

13

Helix

257 – 278

22

Helix

283 – 293

11

Sequences

	Sequence		Length	Mass (Da)
	O95749-1 [UniParc]. Last modified May 1, 1999. Version 1. Checksum: F5D1959274BEE27A	FASTA	300	34,871
	10 20 30 40 50 60 MEKTQETVQR ILLEPYKYLL QLPGKQVRTK LSQAFNHWLK VPEDKLQIII EVTEMLHNAS 70 80 90 100 110 120 LLIDDIEDNS KLRRGFPVAH SIYGIPSVIN SANYVYFLGL EKVLTLDHPD AVKLFTRQLL 130 140 150 160 170 180 ELHQGQGLDI YWRDNYTCPT EEEYKAMVLQ KTGGLFGLAV GLMQLFSDYK EDLKPLLNTL 190 200 210 220 230 240 GLFFQIRDDY ANLHSKEYSE NKSFCEDLTE GKFSFPTIHA IWSRPESTQV QNILRQRTEN 250 260 270 280 290 300 IDIKKYCVHY LEDVGSFEYT RNTLKELEAK AYKQIDARGG NPELVALVKH LSKMFKEENE

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Human geranylgeranyl diphosphate synthase: isolation of the cDNA, chromosomal mapping and tissue expression." Ericsson J., Greene J.M., Carter K.C., Shell B.K., Duan D.R., Florence C., Edwards P.A. J. Lipid Res. 39:1731-1739(1998) [PubMed: 9741684] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Fetal heart.
[2]	"Human geranylgeranyl diphosphate synthase. cDNA cloning and expression." Kuzuguchi T., Morita Y., Sagami I., Sagami H., Ogura K. J. Biol. Chem. 274:5888-5894(1999) [PubMed: 10026212] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Testis.
[3]	"Study on isolation of a geranylgeranyl pyrophosphate (GGPP) synthase cDNA and its expression -- development of a new assay system of gene functions." Misawa N., Okazaki H., Noguchi Y., Tatsuno I., Saito Y., Yasuda T., Hirai A. Proc. Jpn. Conf. Biochem. Lipids 41:293-296(1999) Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]	"Gene expression profiling in the human hypothalamus-pituitary-adrenal axis and full-length cDNA cloning." Hu R.-M., Han Z.-G., Song H.-D., Peng Y.-D., Huang Q.-H., Ren S.-X., Gu Y.-J., Huang C.-H., Li Y.-B., Jiang C.-L., Fu G., Zhang Q.-H., Gu B.-W., Dai M., Mao Y.-F., Gao G.-F., Rong R., Ye M. , Zhou J., Xu S.-H., Gu J., Shi J.-X., Jin W.-R., Zhang C.-K., Wu T.-M., Huang G.-Y., Chen Z., Chen M.-D., Chen J.-L. Proc. Natl. Acad. Sci. U.S.A. 97:9543-9548(2000) [PubMed: 10931946] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Pituitary.
[5]	"Identification of the GGPS1 genes encoding geranylgeranyl diphosphate synthases from mouse and human." Kainou T., Kawamura K., Tanaka K., Matsuda H., Kawamukai M. Biochim. Biophys. Acta 1437:333-340(1999) [PubMed: 10101267] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Liver and Spleen.
[6]	"Molecular cloning and expression analysis of a novel human cDNA encoding a protein homologous to Neurospora crassa geranylgeranyl pyrophosphate synthetase." Zhang M., Yu L., Hu P., Bi A., Zhang Q., Xu M., Zhao S. Submitted (APR-1998) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[7]	"The DNA sequence and biological annotation of human chromosome 1." Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R. Nature 441:315-321(2006) [PubMed: 16710414] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Kidney and Testis.
[9]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[10]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed: 19608861] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-25, MASS SPECTROMETRY.
[11]	"The crystal structure of human geranylgeranyl pyrophosphate synthase reveals a novel hexameric arrangement and inhibitory product binding." Kavanagh K.L., Dunford J.E., Bunkoczi G., Russell R.G., Oppermann U. J. Biol. Chem. 281:22004-22012(2006) [PubMed: 16698791] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) IN COMPLEX WITH MAGNESIUM AND GERANYLGERANYL PHOSPHATE, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, ENZYME REGULATION, SUBUNIT.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AB017971 mRNA. Translation: BAA75909.1.
AB019036 mRNA. Translation: BAA77251.1.
AF125394 mRNA. Translation: AAD43050.1.
AB016043 mRNA. Translation: BAA76511.1.
AF057698 mRNA. Translation: AAG45581.1.
AL391994 Genomic DNA. Translation: CAI13753.1.
BC005252 mRNA. Translation: AAH05252.1.
BC067768 mRNA. Translation: AAH67768.1.

IPI

IPI00032892.

RefSeq

NP_001032354.1.
NP_001032355.1.
NP_004828.1.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2Q80	X-ray	2.70	A/B/C/D/E/F	1-300	[»]

ModBase

Search...

Protein-protein interaction databases

STRING

O95749.

PTM databases

PhosphoSite

O95749.

Proteomic databases

PRIDE

O95749.

Genome annotation databases

Ensembl

ENST00000282841; ENSP00000282841; ENSG00000152904; Homo sapiens. [Genome view]
ENST00000358966; ENSP00000351852; ENSG00000152904; Homo sapiens. [Genome view]
ENST00000476121; ENSP00000420183; ENSG00000152904; Homo sapiens. [Genome view]
ENST00000488594; ENSP00000418690; ENSG00000152904; Homo sapiens. [Genome view]

GeneID

9453.

KEGG

hsa:9453.

UCSC

uc001hwv.1. human.

Organism-specific databases

CTD

9453.

GeneCards

GC01P233558.

H-InvDB

HIX0001713.

HGNC

HGNC:4249. GGPS1.

MIM

606982. gene.

PharmGKB

PA28661.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG19203.

HOGENOM

HBG397395.

HOVERGEN

HBG051729.

InParanoid

O95749.

OMA

LLEPYRY.

OrthoDB

EOG9G7FJM.

PhylomeDB

O95749.

Enzyme and pathway databases

BioCyc

MetaCyc:ENSG00000152904-MONOMER.

BRENDA

2.5.1.1. 247.
2.5.1.10. 247.
2.5.1.29. 247.

Reactome

REACT_602. Metabolism of lipids and lipoproteins.

Gene expression databases

ArrayExpress

O95749.

Bgee

O95749.

CleanEx

HS_GGPS1.

Genevestigator

O95749.

GermOnline

ENSG00000152904. Homo sapiens.

Family and domain databases

InterPro

IPR000092. Polyprenyl_synt.
IPR017446. Polyprenyl_synth-rel.
IPR008949. Terpenoid_synth.
[Graphical view]

Gene3D

G3DSA:1.10.600.10. Terpenoid_synth. 1 hit.

PANTHER

PTHR12001. Polyprenyl_synt. 1 hit.

Pfam

PF00348. polyprenyl_synt. 1 hit.
[Graphical view]

SUPFAM

SSF48576. Terpenoid_synth. 1 hit.

PROSITE

PS00723. POLYPRENYL_SYNTHET_1. 1 hit.
PS00444. POLYPRENYL_SYNTHET_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

35412.

SOURCE

Search...

Entry information

Entry name

GGPPS_HUMAN

Accession

Primary (citable) accession number: O95749
Secondary accession number(s): Q5T2C8, Q6NW19

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 30, 2000
Last sequence update:	May 1, 1999
Last modified:	March 2, 2010
This is version 99 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.