GGPPS_MOUSE
ID GGPPS_MOUSE Reviewed; 300 AA.
AC Q9WTN0;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1999, sequence version 1.
DT 03-AUG-2022, entry version 159.
DE RecName: Full=Geranylgeranyl pyrophosphate synthase {ECO:0000305|PubMed:10101267};
DE Short=GGPP synthase;
DE Short=GGPPSase;
DE EC=2.5.1.- {ECO:0000305|PubMed:10101267};
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 {ECO:0000305|PubMed:10101267};
DE AltName: Full=Geranylgeranyl diphosphate synthase {ECO:0000303|PubMed:10101267};
DE AltName: Full=Geranyltranstransferase;
DE EC=2.5.1.10;
GN Name=Ggps1 {ECO:0000312|MGI:MGI:1341724};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND CATALYTIC ACTIVITY.
RC STRAIN=C57BL/6J; TISSUE=Lymph node;
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Eye;
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 [3]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Heart, Lung, Pancreas, Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [4]
RP MUTAGENESIS OF TYR-259.
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).
CC -!- FUNCTION: Catalyzes the trans-addition of the three molecules of
CC isopentenyl diphosphate (IPP) onto dimethylallyl pyrophosphate (DMAPP)
CC to form geranylgeranyl pyrophosphate, an important precursor of
CC carotenoids and geranylated proteins. {ECO:0000250|UniProtKB:O95749}.
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 -!- 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 -!- 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:0000305|PubMed:10101267};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17654;
CC Evidence={ECO:0000305|PubMed:10101267};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250};
CC Note=Binds 2 Mg(2+) ions per subunit. {ECO:0000250};
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. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000305}. Cytoplasm, perinuclear
CC region {ECO:0000250|UniProtKB:O95749}. Cytoplasm, myofibril, sarcomere,
CC Z line {ECO:0000250|UniProtKB:O95749}.
CC -!- SIMILARITY: Belongs to the FPP/GGPP synthase family. {ECO:0000305}.
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DR EMBL; AB016044; BAA76512.1; -; mRNA.
DR EMBL; BC069913; AAH69913.1; -; mRNA.
DR CCDS; CCDS26248.1; -.
DR RefSeq; NP_001318048.1; NM_001331119.1.
DR RefSeq; NP_001318105.1; NM_001331176.1.
DR RefSeq; NP_001318106.1; NM_001331177.1.
DR RefSeq; NP_001318107.1; NM_001331178.1.
DR RefSeq; NP_001318109.1; NM_001331180.1.
DR RefSeq; NP_034412.1; NM_010282.3.
DR RefSeq; XP_006516612.1; XM_006516549.3.
DR RefSeq; XP_017170874.1; XM_017315385.1.
DR AlphaFoldDB; Q9WTN0; -.
DR SMR; Q9WTN0; -.
DR BioGRID; 199910; 2.
DR STRING; 10090.ENSMUSP00000126603; -.
DR iPTMnet; Q9WTN0; -.
DR PhosphoSitePlus; Q9WTN0; -.
DR EPD; Q9WTN0; -.
DR MaxQB; Q9WTN0; -.
DR PaxDb; Q9WTN0; -.
DR PRIDE; Q9WTN0; -.
DR ProteomicsDB; 271214; -.
DR Antibodypedia; 34695; 445 antibodies from 30 providers.
DR DNASU; 14593; -.
DR Ensembl; ENSMUST00000170957; ENSMUSP00000126603; ENSMUSG00000021302.
DR GeneID; 14593; -.
DR KEGG; mmu:14593; -.
DR UCSC; uc007pmw.2; mouse.
DR CTD; 9453; -.
DR MGI; MGI:1341724; Ggps1.
DR VEuPathDB; HostDB:ENSMUSG00000021302; -.
DR eggNOG; KOG0777; Eukaryota.
DR GeneTree; ENSGT00940000153498; -.
DR HOGENOM; CLU_014015_6_0_1; -.
DR InParanoid; Q9WTN0; -.
DR OMA; FYSKAFF; -.
DR OrthoDB; 981769at2759; -.
DR PhylomeDB; Q9WTN0; -.
DR TreeFam; TF300101; -.
DR BRENDA; 2.5.1.29; 3474.
DR Reactome; R-MMU-191273; Cholesterol biosynthesis.
DR UniPathway; UPA00259; UER00368.
DR UniPathway; UPA00260; UER00369.
DR UniPathway; UPA00389; UER00564.
DR BioGRID-ORCS; 14593; 31 hits in 75 CRISPR screens.
DR ChiTaRS; Ggps1; mouse.
DR PRO; PR:Q9WTN0; -.
DR Proteomes; UP000000589; Chromosome 13.
DR RNAct; Q9WTN0; protein.
DR Bgee; ENSMUSG00000021302; Expressed in rostral migratory stream and 249 other tissues.
DR ExpressionAtlas; Q9WTN0; baseline and differential.
DR Genevisible; Q9WTN0; MM.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISS:UniProtKB.
DR GO; GO:0030018; C:Z disc; ISS:UniProtKB.
DR GO; GO:0004161; F:dimethylallyltranstransferase activity; IEA:UniProtKB-EC.
DR GO; GO:0004311; F:farnesyltranstransferase activity; ISS:UniProtKB.
DR GO; GO:0004337; F:geranyltranstransferase activity; IDA:MGI.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
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; ISS: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 Acetylation; Cytoplasm; Isoprene biosynthesis; Lipid metabolism; Magnesium;
KW Metal-binding; Reference proteome; Transferase.
FT CHAIN 1..300
FT /note="Geranylgeranyl pyrophosphate synthase"
FT /id="PRO_0000123963"
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:0000250|UniProtKB:P14324"
FT BINDING 64
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P14324"
FT BINDING 68
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P14324"
FT BINDING 68
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P14324"
FT BINDING 73
FT /ligand="dimethylallyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:57623"
FT /evidence="ECO:0000250"
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 /evidence="ECO:0000250"
FT BINDING 152
FT /ligand="dimethylallyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:57623"
FT /evidence="ECO:0000250"
FT BINDING 185
FT /ligand="dimethylallyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:57623"
FT /evidence="ECO:0000250"
FT BINDING 202
FT /ligand="dimethylallyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:57623"
FT /evidence="ECO:0000250"
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:0000250|UniProtKB:O95749"
FT MUTAGEN 259
FT /note="Y->C: Results in prenatal animals lethality."
FT /evidence="ECO:0000269|PubMed:32403198"
SQ SEQUENCE 300 AA; 34707 MW; 13ECB67EA17EEE63 CRC64;
MEKTKEKAER ILLEPYRYLL QLPGKQVRSK LSQAFNHWLK VPEDKLQIII EVTEMLHNAS
LLIDDIEDSS KLRRGFPVAH SIYGVPSVIN SANYVYFLGL EKVLTLDHPD AVKLFTRQLL
ELHQGQGLDI YWRDTYTCPT EEEYKAMVLQ KTGGLFGLAV GLMQLFSDYK EDLKPLLDTL
GLFFQIRDDY ANLHSKEYSE NKSFCEDLTE GKFSFPTIHA IWSRPESTQV QNILRQRTEN
IDIKKYCVQY LEDVGSFAYT RHTLRELEAK AYKQIEACGG NPSLVALVKH LSKMFTEENK
