GGPPS_HUMAN
ID GGPPS_HUMAN Reviewed; 300 AA.
AC O95749; A8MVQ8; Q5T2C8; Q6NW19;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1999, sequence version 1.
DT 03-AUG-2022, entry version 199.
DE RecName: Full=Geranylgeranyl pyrophosphate synthase;
DE Short=GGPP synthase;
DE Short=GGPPSase;
DE EC=2.5.1.-;
DE AltName: Full=(2E,6E)-farnesyl diphosphate synthase;
DE AltName: Full=Dimethylallyltranstransferase;
DE EC=2.5.1.1;
DE AltName: Full=Farnesyl diphosphate synthase;
DE AltName: Full=Farnesyltranstransferase;
DE EC=2.5.1.29;
DE AltName: Full=Geranylgeranyl diphosphate synthase;
DE AltName: Full=Geranyltranstransferase;
DE EC=2.5.1.10;
GN Name=GGPS1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Fetal heart;
RX PubMed=9741684;
RA Ericsson J., Greene J.M., Carter K.C., Shell B.K., Duan D.R., Florence C.,
RA 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] (ISOFORM 1).
RC TISSUE=Testis;
RX 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 expression.";
RL J. Biol. Chem. 274:5888-5894(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
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 cDNA
RT 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] (ISOFORM 1).
RC TISSUE=Pituitary;
RX 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., Gu B.-W.,
RA Dai M., Mao Y.-F., Gao G.-F., Rong R., Ye M., Zhou J., Xu S.-H., Gu J.,
RA Shi J.-X., Jin W.-R., Zhang C.-K., Wu T.-M., Huang G.-Y., Chen Z.,
RA Chen M.-D., Chen J.-L.;
RT "Gene expression profiling in the human hypothalamus-pituitary-adrenal axis
RT and full-length cDNA cloning.";
RL Proc. Natl. Acad. Sci. U.S.A. 97:9543-9548(2000).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Liver, and Spleen;
RX 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] (ISOFORM 1).
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 encoding a
RT protein homologous to Neurospora crassa geranylgeranyl pyrophosphate
RT synthetase.";
RL Submitted (APR-1998) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [8]
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., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., 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., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., 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., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., 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 [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
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 project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [12]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [13]
RP INVOLVEMENT IN MDHLO, VARIANTS MDHLO SER-15; CYS-257; CYS-259; GLY-261 AND
RP HIS-261, CHARACTERIZATION OF VARIANTS MDHLO SER-15; CYS-257; CYS-259;
RP GLY-261 AND HIS-261, FUNCTION, SUBCELLULAR LOCATION, AND TISSUE
RP SPECIFICITY.
RX PubMed=32403198; DOI=10.1002/ana.25772;
RA Foley A.R., Zou Y., Dunford J.E., Rooney J., Chandra G., Xiong H.,
RA Straub V., Voit T., Romero N., Donkervoort S., Hu Y., Markello T., Horn A.,
RA Qebibo L., Dastgir J., Meilleur K.G., Finkel R.S., Fan Y., Mamchaoui K.,
RA Duguez S., Nelson I., Laporte J., Santi M., Malfatti E., Maisonobe T.,
RA Touraine P., Hirano M., Hughes I., Bushby K., Oppermann U., Boehm J.,
RA Jaiswal J.K., Stojkovic T., Boennemann C.G.;
RT "GGPS1 Mutations Cause Muscular Dystrophy/Hearing Loss/Ovarian
RT Insufficiency Syndrome.";
RL Ann. Neurol. 88:332-347(2020).
RN [14]
RP X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) IN COMPLEX WITH MAGNESIUM AND
RP GERANYLGERANYL PHOSPHATE, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL
RP PROPERTIES, ACTIVITY REGULATION, AND SUBUNIT.
RX PubMed=16698791; DOI=10.1074/jbc.m602603200;
RA Kavanagh K.L., Dunford J.E., Bunkoczi G., Russell R.G., Oppermann U.;
RT "The crystal structure of human geranylgeranyl pyrophosphate synthase
RT reveals a novel hexameric arrangement and inhibitory product binding.";
RL J. Biol. Chem. 281:22004-22012(2006).
CC -!- FUNCTION: Catalyzes the trans-addition of the three molecules of IPP
CC onto DMAPP to form geranylgeranyl pyrophosphate, an important precursor
CC of carotenoids and geranylated proteins. {ECO:0000269|PubMed:32403198}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=dimethylallyl diphosphate + isopentenyl diphosphate = (2E)-
CC geranyl diphosphate + diphosphate; Xref=Rhea:RHEA:22408,
CC ChEBI:CHEBI:33019, ChEBI:CHEBI:57623, ChEBI:CHEBI:58057,
CC ChEBI:CHEBI:128769; EC=2.5.1.1;
CC Evidence={ECO:0000269|PubMed:16698791};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(2E)-geranyl diphosphate + isopentenyl diphosphate = (2E,6E)-
CC farnesyl diphosphate + diphosphate; Xref=Rhea:RHEA:19361,
CC ChEBI:CHEBI:33019, ChEBI:CHEBI:58057, ChEBI:CHEBI:128769,
CC ChEBI:CHEBI:175763; EC=2.5.1.10;
CC Evidence={ECO:0000269|PubMed:16698791};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(2E,6E)-farnesyl diphosphate + isopentenyl diphosphate =
CC (2E,6E,10E)-geranylgeranyl diphosphate + diphosphate;
CC Xref=Rhea:RHEA:17653, ChEBI:CHEBI:33019, ChEBI:CHEBI:58756,
CC ChEBI:CHEBI:128769, ChEBI:CHEBI:175763; EC=2.5.1.29;
CC Evidence={ECO:0000269|PubMed:16698791};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000305};
CC Note=Binds 3 Mg(2+) ions. {ECO:0000305};
CC -!- ACTIVITY REGULATION: Subject to product inhibition by geranylgeranyl
CC diphosphate. {ECO:0000269|PubMed:16698791}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=3 uM for isopentenyl diphosphate {ECO:0000269|PubMed:16698791};
CC KM=4.2 uM for farnesyl diphosphate {ECO:0000269|PubMed:16698791};
CC -!- PATHWAY: Isoprenoid biosynthesis; farnesyl diphosphate biosynthesis;
CC farnesyl diphosphate from geranyl diphosphate and isopentenyl
CC diphosphate: step 1/1.
CC -!- PATHWAY: Isoprenoid biosynthesis; geranyl diphosphate biosynthesis;
CC geranyl diphosphate from dimethylallyl diphosphate and isopentenyl
CC diphosphate: step 1/1.
CC -!- PATHWAY: Isoprenoid biosynthesis; geranylgeranyl diphosphate
CC biosynthesis; geranylgeranyl diphosphate from farnesyl diphosphate and
CC isopentenyl diphosphate: step 1/1.
CC -!- SUBUNIT: Homohexamer; trimer of homodimers.
CC {ECO:0000269|PubMed:16698791}.
CC -!- INTERACTION:
CC O95749; O00244: ATOX1; NbExp=3; IntAct=EBI-10179283, EBI-10179267;
CC O95749; O95749: GGPS1; NbExp=7; IntAct=EBI-10179283, EBI-10179283;
CC O95749; O00560: SDCBP; NbExp=3; IntAct=EBI-10179283, EBI-727004;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:32403198}.
CC Cytoplasm, perinuclear region {ECO:0000269|PubMed:32403198}. Cytoplasm,
CC myofibril, sarcomere, Z line {ECO:0000269|PubMed:32403198}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=O95749-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O95749-2; Sequence=VSP_056578;
CC -!- TISSUE SPECIFICITY: Abundantly expressed in testis (PubMed:9741684,
CC PubMed:10026212). Found in other tissues to a lower extent
CC (PubMed:9741684, PubMed:10026212). Expressed in dermal fibroblast and
CC skeletal muscle (PubMed:32403198). {ECO:0000269|PubMed:10026212,
CC ECO:0000269|PubMed:32403198, ECO:0000269|PubMed:9741684}.
CC -!- DISEASE: Muscular dystrophy, congenital hearing loss, and ovarian
CC insufficiency syndrome (MDHLO) [MIM:619518]: An autosomal recessive
CC disorder characterized by early-onset progressive muscle weakness,
CC sensorineural hearing loss, and primary amenorrhea due to ovarian
CC insufficiency. Some patients become wheelchair-bound by the second
CC decade, whereas others have a milder phenotype and maintain independent
CC ambulation into adulthood. Most patients have respiratory
CC insufficiency. {ECO:0000269|PubMed:32403198}. Note=The disease is
CC caused by variants affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the FPP/GGPP synthase family. {ECO:0000305}.
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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; AK293278; BAH11480.1; -; mRNA.
DR EMBL; AL391994; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471098; EAW70018.1; -; Genomic_DNA.
DR EMBL; CH471098; EAW70020.1; -; Genomic_DNA.
DR EMBL; BC005252; AAH05252.1; -; mRNA.
DR EMBL; BC067768; AAH67768.1; -; mRNA.
DR CCDS; CCDS1604.1; -. [O95749-1]
DR RefSeq; NP_001032354.1; NM_001037277.1. [O95749-1]
DR PDB; 2Q80; X-ray; 2.70 A; A/B/C/D/E/F=1-300.
DR PDB; 6C56; X-ray; 2.80 A; A/B=1-300.
DR PDB; 6C57; X-ray; 3.50 A; A/B=1-300.
DR PDB; 6G31; X-ray; 3.00 A; A/B/C/D/E/F/G/H/I/J/K/L=1-300.
DR PDB; 6G32; X-ray; 3.28 A; A/B/C/D/E/F=1-300.
DR PDB; 6R4V; X-ray; 2.20 A; A/B/C/D/E/F=1-300.
DR PDBsum; 2Q80; -.
DR PDBsum; 6C56; -.
DR PDBsum; 6C57; -.
DR PDBsum; 6G31; -.
DR PDBsum; 6G32; -.
DR PDBsum; 6R4V; -.
DR AlphaFoldDB; O95749; -.
DR SMR; O95749; -.
DR BioGRID; 114842; 62.
DR IntAct; O95749; 26.
DR STRING; 9606.ENSP00000282841; -.
DR BindingDB; O95749; -.
DR ChEMBL; CHEMBL4769; -.
DR DrugBank; DB06830; (1-HYDROXYHEPTANE-1,1-DIYL)BIS(PHOSPHONIC ACID).
DR DrugBank; DB06931; (1-HYDROXYNONANE-1,1-DIYL)BIS(PHOSPHONIC ACID).
DR DrugBank; DB07221; (2,2-DIPHOSPHONOETHYL)(DODECYL)DIMETHYLPHOSPHONIUM.
DR DrugBank; DB08529; (6E,11E)-HEPTADECA-6,11-DIENE-9,9-DIYLBIS(PHOSPHONIC ACID).
DR DrugBank; DB07410; [2-(3-DIBENZOFURAN-4-YL-PHENYL)-1-HYDROXY-1-PHOSPHONO-ETHYL]-PHOSPHONIC ACID.
DR DrugBank; DB07780; Farnesyl diphosphate.
DR DrugBank; DB04695; Farnesyl thiopyrophosphate.
DR DrugBank; DB02552; Geranyl Diphosphate.
DR DrugBank; DB07841; Geranylgeranyl diphosphate.
DR DrugBank; DB00710; Ibandronate.
DR DrugBank; DB04714; ISOPENTENYL PYROPHOSPHATE.
DR DrugBank; DB07873; Lauryl alcohol diphosphonic acid.
DR DrugBank; DB06548; Minodronic acid.
DR DrugBank; DB00282; Pamidronic acid.
DR DrugBank; DB00399; Zoledronic acid.
DR DrugCentral; O95749; -.
DR GuidetoPHARMACOLOGY; 643; -.
DR SwissLipids; SLP:000001316; -. [O95749-1]
DR iPTMnet; O95749; -.
DR PhosphoSitePlus; O95749; -.
DR BioMuta; GGPS1; -.
DR EPD; O95749; -.
DR jPOST; O95749; -.
DR MassIVE; O95749; -.
DR MaxQB; O95749; -.
DR PaxDb; O95749; -.
DR PeptideAtlas; O95749; -.
DR PRIDE; O95749; -.
DR ProteomicsDB; 2198; -.
DR ProteomicsDB; 51020; -. [O95749-1]
DR Antibodypedia; 34695; 445 antibodies from 30 providers.
DR DNASU; 9453; -.
DR Ensembl; ENST00000282841.9; ENSP00000282841.5; ENSG00000152904.11. [O95749-1]
DR Ensembl; ENST00000358966.6; ENSP00000351852.2; ENSG00000152904.11. [O95749-1]
DR Ensembl; ENST00000391855.2; ENSP00000375728.2; ENSG00000152904.11. [O95749-2]
DR Ensembl; ENST00000488594.5; ENSP00000418690.1; ENSG00000152904.11. [O95749-1]
DR GeneID; 9453; -.
DR KEGG; hsa:9453; -.
DR MANE-Select; ENST00000282841.9; ENSP00000282841.5; NM_004837.4; NP_004828.1.
DR UCSC; uc001hwv.4; human. [O95749-1]
DR CTD; 9453; -.
DR DisGeNET; 9453; -.
DR GeneCards; GGPS1; -.
DR HGNC; HGNC:4249; GGPS1.
DR HPA; ENSG00000152904; Low tissue specificity.
DR MIM; 606982; gene.
DR MIM; 619518; phenotype.
DR neXtProt; NX_O95749; -.
DR OpenTargets; ENSG00000152904; -.
DR PharmGKB; PA28661; -.
DR VEuPathDB; HostDB:ENSG00000152904; -.
DR eggNOG; KOG0777; Eukaryota.
DR GeneTree; ENSGT00940000153498; -.
DR InParanoid; O95749; -.
DR OMA; FYSKAFF; -.
DR PhylomeDB; O95749; -.
DR TreeFam; TF300101; -.
DR BioCyc; MetaCyc:HS07859-MON; -.
DR BRENDA; 2.5.1.29; 2681.
DR PathwayCommons; O95749; -.
DR Reactome; R-HSA-191273; Cholesterol biosynthesis.
DR Reactome; R-HSA-2426168; Activation of gene expression by SREBF (SREBP).
DR SABIO-RK; O95749; -.
DR SignaLink; O95749; -.
DR UniPathway; UPA00259; UER00368.
DR UniPathway; UPA00260; UER00369.
DR UniPathway; UPA00389; UER00564.
DR BioGRID-ORCS; 9453; 718 hits in 1047 CRISPR screens.
DR ChiTaRS; GGPS1; human.
DR EvolutionaryTrace; O95749; -.
DR GeneWiki; GGPS1; -.
DR GenomeRNAi; 9453; -.
DR Pharos; O95749; Tchem.
DR PRO; PR:O95749; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; O95749; protein.
DR Bgee; ENSG00000152904; Expressed in sperm and 208 other tissues.
DR ExpressionAtlas; O95749; baseline and differential.
DR Genevisible; O95749; HS.
DR GO; GO:0005737; C:cytoplasm; IMP:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IMP:UniProtKB.
DR GO; GO:0030018; C:Z disc; IMP:UniProtKB.
DR GO; GO:0004161; F:dimethylallyltranstransferase activity; IEA:UniProtKB-EC.
DR GO; GO:0004311; F:farnesyltranstransferase activity; IDA:UniProtKB.
DR GO; GO:0004337; F:geranyltranstransferase activity; IEA:UniProtKB-EC.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004659; F:prenyltransferase activity; IBA:GO_Central.
DR GO; GO:0045337; P:farnesyl diphosphate biosynthetic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0033384; P:geranyl diphosphate biosynthetic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0033386; P:geranylgeranyl diphosphate biosynthetic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0008299; P:isoprenoid biosynthetic process; IBA:GO_Central.
DR GO; GO:0006720; P:isoprenoid metabolic process; IDA:UniProtKB.
DR CDD; cd00685; Trans_IPPS_HT; 1.
DR Gene3D; 1.10.600.10; -; 1.
DR InterPro; IPR008949; Isoprenoid_synthase_dom_sf.
DR InterPro; IPR000092; Polyprenyl_synt.
DR InterPro; IPR033749; Polyprenyl_synt_CS.
DR Pfam; PF00348; polyprenyl_synt; 1.
DR SUPFAM; SSF48576; SSF48576; 1.
DR PROSITE; PS00723; POLYPRENYL_SYNTHASE_1; 1.
DR PROSITE; PS00444; POLYPRENYL_SYNTHASE_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing;
KW Congenital muscular dystrophy; Cytoplasm; Deafness; Disease variant;
KW Isoprene biosynthesis; Lipid metabolism; Magnesium; Metal-binding;
KW Reference proteome; Transferase.
FT CHAIN 1..300
FT /note="Geranylgeranyl pyrophosphate synthase"
FT /id="PRO_0000123962"
FT BINDING 25
FT /ligand="isopentenyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:128769"
FT /evidence="ECO:0000250|UniProtKB:P14324"
FT BINDING 28
FT /ligand="isopentenyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:128769"
FT /evidence="ECO:0000250|UniProtKB:P14324"
FT BINDING 57
FT /ligand="isopentenyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:128769"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 64
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:16698791"
FT BINDING 64
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:16698791"
FT BINDING 68
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:16698791"
FT BINDING 68
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:16698791"
FT BINDING 73
FT /ligand="dimethylallyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:57623"
FT BINDING 74
FT /ligand="isopentenyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:128769"
FT /evidence="ECO:0000250|UniProtKB:P14324"
FT BINDING 151
FT /ligand="dimethylallyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:57623"
FT BINDING 152
FT /ligand="dimethylallyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:57623"
FT BINDING 185
FT /ligand="dimethylallyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:57623"
FT BINDING 202
FT /ligand="dimethylallyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:57623"
FT BINDING 212
FT /ligand="dimethylallyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:57623"
FT /evidence="ECO:0000250"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0007744|PubMed:22814378"
FT VAR_SEQ 1..54
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_056578"
FT VARIANT 15
FT /note="P -> S (in MDHLO; unknown pathological significance;
FT shows no change in farnesyltranstransferase activity)"
FT /evidence="ECO:0000269|PubMed:32403198"
FT /id="VAR_086458"
FT VARIANT 257
FT /note="F -> C (in MDHLO; shows slightly decreased
FT farnesyltranstransferase activity)"
FT /evidence="ECO:0000269|PubMed:32403198"
FT /id="VAR_086459"
FT VARIANT 259
FT /note="Y -> C (in MDHLO; shows slightly decreased
FT farnesyltranstransferase activity)"
FT /evidence="ECO:0000269|PubMed:32403198"
FT /id="VAR_086460"
FT VARIANT 261
FT /note="R -> G (in MDHLO; shows slightly decreased
FT farnesyltranstransferase activity)"
FT /evidence="ECO:0000269|PubMed:32403198"
FT /id="VAR_086461"
FT VARIANT 261
FT /note="R -> H (in MDHLO; shows slightly decreased
FT farnesyltranstransferase activity)"
FT /evidence="ECO:0000269|PubMed:32403198"
FT /id="VAR_086462"
FT CONFLICT 109
FT /note="P -> Q (in Ref. 10; AAH67768)"
FT /evidence="ECO:0000305"
FT HELIX 6..21
FT /evidence="ECO:0007829|PDB:6R4V"
FT HELIX 27..39
FT /evidence="ECO:0007829|PDB:6R4V"
FT HELIX 43..67
FT /evidence="ECO:0007829|PDB:6R4V"
FT STRAND 71..73
FT /evidence="ECO:0007829|PDB:2Q80"
FT HELIX 79..83
FT /evidence="ECO:0007829|PDB:6R4V"
FT HELIX 85..104
FT /evidence="ECO:0007829|PDB:6R4V"
FT HELIX 111..134
FT /evidence="ECO:0007829|PDB:6R4V"
FT HELIX 141..151
FT /evidence="ECO:0007829|PDB:6R4V"
FT HELIX 153..164
FT /evidence="ECO:0007829|PDB:6R4V"
FT HELIX 174..194
FT /evidence="ECO:0007829|PDB:6R4V"
FT HELIX 206..210
FT /evidence="ECO:0007829|PDB:6R4V"
FT HELIX 215..223
FT /evidence="ECO:0007829|PDB:6R4V"
FT STRAND 224..226
FT /evidence="ECO:0007829|PDB:6G32"
FT HELIX 229..235
FT /evidence="ECO:0007829|PDB:6R4V"
FT HELIX 241..253
FT /evidence="ECO:0007829|PDB:6R4V"
FT HELIX 256..276
FT /evidence="ECO:0007829|PDB:6R4V"
FT TURN 277..279
FT /evidence="ECO:0007829|PDB:6R4V"
FT HELIX 282..291
FT /evidence="ECO:0007829|PDB:6R4V"
FT HELIX 292..294
FT /evidence="ECO:0007829|PDB:6R4V"
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
