ID GGPPS_HUMAN Reviewed; 300 AA. AC O95749; Q5T2C8; Q6NW19; DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot. DT 01-MAY-1999, sequence version 1. DT 04-NOV-2008, entry version 80. DE RecName: Full=Geranylgeranyl pyrophosphate synthetase; DE Short=GGPP synthetase; DE Short=GGPPSase; DE AltName: Full=Geranylgeranyl diphosphate synthase; DE Includes: DE RecName: Full=Dimethylallyltranstransferase; DE EC=2.5.1.1; DE Includes: DE RecName: Full=Geranyltranstransferase; DE EC=2.5.1.10; DE Includes: DE RecName: Full=Farnesyltranstransferase; DE EC=2.5.1.29; GN Name=GGPS1; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Fetal heart; RX MEDLINE=98412715; PubMed=9741684; RA Ericsson J., Greene J.M., Carter K.C., Shell B.K., Duan D.R., RA Florence C., Edwards P.A.; RT "Human geranylgeranyl diphosphate synthase: isolation of the cDNA, RT chromosomal mapping and tissue expression."; RL J. Lipid Res. 39:1731-1739(1998). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Testis; RX MEDLINE=99150380; PubMed=10026212; DOI=10.1074/jbc.274.9.5888; RA Kuzuguchi T., Morita Y., Sagami I., Sagami H., Ogura K.; RT "Human geranylgeranyl diphosphate synthase. cDNA cloning and RT expression."; RL J. Biol. Chem. 274:5888-5894(1999). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA]. RA Misawa N., Okazaki H., Noguchi Y., Tatsuno I., Saito Y., Yasuda T., RA Hirai A.; RT "Study on isolation of a geranylgeranyl pyrophosphate (GGPP) synthase RT cDNA and its expression -- development of a new assay system of gene RT functions."; RL Proc. Jpn. Conf. Biochem. Lipids 41:293-296(1999). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Pituitary; RX MEDLINE=20402571; PubMed=10931946; DOI=10.1073/pnas.160270997; RA Hu R.-M., Han Z.-G., Song H.-D., Peng Y.-D., Huang Q.-H., Ren S.-X., RA Gu Y.-J., Huang C.-H., Li Y.-B., Jiang C.-L., Fu G., Zhang Q.-H., RA Gu B.-W., Dai M., Mao Y.-F., Gao G.-F., Rong R., Ye M., Zhou J., RA Xu S.-H., Gu J., Shi J.-X., Jin W.-R., Zhang C.-K., Wu T.-M., RA Huang G.-Y., Chen Z., Chen M.-D., Chen J.-L.; RT "Gene expression profiling in the human hypothalamus-pituitary-adrenal RT axis and full-length cDNA cloning."; RL Proc. Natl. Acad. Sci. U.S.A. 97:9543-9548(2000). RN [5] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Liver, and Spleen; RX MEDLINE=99203156; PubMed=10101267; DOI=10.1016/S1388-1981(99)00028-1; RA Kainou T., Kawamura K., Tanaka K., Matsuda H., Kawamukai M.; RT "Identification of the GGPS1 genes encoding geranylgeranyl diphosphate RT synthases from mouse and human."; RL Biochim. Biophys. Acta 1437:333-340(1999). RN [6] RP NUCLEOTIDE SEQUENCE [MRNA]. RA Zhang M., Yu L., Hu P., Bi A., Zhang Q., Xu M., Zhao S.; RT "Molecular cloning and expression analysis of a novel human cDNA RT encoding a protein homologous to Neurospora crassa geranylgeranyl RT pyrophosphate synthetase."; RL Submitted (APR-1998) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16710414; DOI=10.1038/nature04727; RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., RA Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., RA Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., RA McDonald L., Evans R., Phillips K., Atkinson A., Cooper R., Jones C., RA Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., RA Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., RA Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., RA Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., RA Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., RA Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., RA Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., RA Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., RA Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., RA Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., RA Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., RA Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., RA Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., RA Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., RA Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., RA Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., RA Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., RA Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., RA Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., RA Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., RA Beck S., Rogers J., Bentley D.R.; RT "The DNA sequence and biological annotation of human chromosome 1."; RL Nature 441:315-321(2006). RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Kidney, and Testis; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). CC -!- FUNCTION: Catalyzes the trans-addition of the three molecules of CC IPP onto DMAPP to form geranylgeranyl pyrophosphate, an important CC precursor of carotenoids and geranylated proteins. CC -!- CATALYTIC ACTIVITY: Dimethylallyl diphosphate + isopentenyl CC diphosphate = diphosphate + geranyl diphosphate. CC -!- CATALYTIC ACTIVITY: Geranyl diphosphate + isopentenyl diphosphate CC = diphosphate + trans,trans-farnesyl diphosphate. CC -!- CATALYTIC ACTIVITY: Trans,trans-farnesyl diphosphate + isopentenyl CC diphosphate = diphosphate + geranylgeranyl diphosphate. CC -!- PATHWAY: Isoprenoid biosynthesis; farnesyl-PP biosynthesis; CC farnesyl-PP from geranyl-PP and isopentenyl-PP: step 1/1. CC -!- PATHWAY: Isoprenoid biosynthesis; geranyl-PP biosynthesis; CC geranyl-PP from dimethylallyl-PP and isopentenyl-PP: step 1/1. CC -!- PATHWAY: Isoprenoid biosynthesis; geranylgeranyl-PP biosynthesis; CC geranylgeranyl-PP from farnesyl-PP and isopentenyl-PP: step 1/1. CC -!- SUBUNIT: Homooctamer. CC -!- SUBCELLULAR LOCATION: Cytoplasm. CC -!- TISSUE SPECIFICITY: Abundantly expressed in testis. Found in other CC tissues to a lower extent. CC -!- SIMILARITY: Belongs to the FPP/GGPP synthetase family. CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution-NoDerivs License CC ----------------------------------------------------------------------- DR EMBL; AB017971; BAA75909.1; -; mRNA. DR EMBL; AB019036; BAA77251.1; -; mRNA. DR EMBL; AF125394; AAD43050.1; -; mRNA. DR EMBL; AB016043; BAA76511.1; -; mRNA. DR EMBL; AF057698; AAG45581.1; -; mRNA. DR EMBL; AL391994; CAI13753.1; -; Genomic_DNA. DR EMBL; BC005252; AAH05252.1; -; mRNA. DR EMBL; BC067768; AAH67768.1; -; mRNA. DR RefSeq; NP_001032354.1; -. DR RefSeq; NP_001032355.1; -. DR RefSeq; NP_004828.1; -. DR UniGene; Hs.647791; -. DR PDB; 2Q80; X-ray; 2.70 A; A/B/C/D/E/F=1-300. DR PDBsum; 2Q80; -. DR Ensembl; ENSG00000152904; Homo sapiens. DR GeneID; 9453; -. DR KEGG; hsa:9453; -. DR H-InvDB; HIX0001713; -. DR HGNC; HGNC:4249; GGPS1. DR MIM; 606982; gene. DR PharmGKB; PA28661; -. DR HOGENOM; O95749; -. DR HOVERGEN; O95749; -. DR Reactome; REACT_602; Lipid and lipoprotein metabolism. DR NextBio; 35412; -. DR ArrayExpress; O95749; -. DR CleanEx; HS_GGPS1; -. DR GermOnline; ENSG00000152904; Homo sapiens. DR GO; GO:0005625; C:soluble fraction; IDA:UniProtKB. DR GO; GO:0004311; F:farnesyltranstransferase activity; IDA:UniProtKB. DR GO; GO:0006720; P:isoprenoid metabolic process; IDA:UniProtKB. DR InterPro; IPR000092; Polyprenyl_synt. DR InterPro; IPR017446; Polyprenyl_synth-rel. DR InterPro; IPR008949; Terpenoid_synth. DR Gene3D; G3DSA:1.10.600.10; Terpenoid_synth; 1. DR PANTHER; PTHR12001; Polyprenyl_synt; 1. DR Pfam; PF00348; polyprenyl_synt; 1. DR PROSITE; PS00723; POLYPRENYL_SYNTHET_1; 1. DR PROSITE; PS00444; POLYPRENYL_SYNTHET_2; 1. PE 1: Evidence at protein level; KW 3D-structure; Cytoplasm; Isoprene biosynthesis; KW Multifunctional enzyme; Transferase. FT CHAIN 1 300 Geranylgeranyl pyrophosphate synthetase. FT /FTId=PRO_0000123962. FT CONFLICT 109 109 P -> Q (in Ref. 8; AAH67768). FT HELIX 9 13 FT HELIX 15 20 FT HELIX 26 40 FT HELIX 44 69 FT STRAND 72 74 FT HELIX 80 84 FT HELIX 86 105 FT HELIX 112 135 FT HELIX 142 166 FT HELIX 175 195 FT HELIX 207 211 FT HELIX 216 224 FT HELIX 230 236 FT HELIX 242 254 FT HELIX 257 278 FT HELIX 283 293 SQ SEQUENCE 300 AA; 34871 MW; F5D1959274BEE27A CRC64; MEKTQETVQR ILLEPYKYLL QLPGKQVRTK LSQAFNHWLK VPEDKLQIII EVTEMLHNAS LLIDDIEDNS KLRRGFPVAH SIYGIPSVIN SANYVYFLGL EKVLTLDHPD AVKLFTRQLL ELHQGQGLDI YWRDNYTCPT EEEYKAMVLQ KTGGLFGLAV GLMQLFSDYK EDLKPLLNTL GLFFQIRDDY ANLHSKEYSE NKSFCEDLTE GKFSFPTIHA IWSRPESTQV QNILRQRTEN IDIKKYCVHY LEDVGSFEYT RNTLKELEAK AYKQIDARGG NPELVALVKH LSKMFKEENE //