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Protein

Geranylgeranyl pyrophosphate synthase

Gene

GGPS1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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 activityi

Dimethylallyl diphosphate + isopentenyl diphosphate = diphosphate + geranyl diphosphate.1 Publication
Geranyl diphosphate + isopentenyl diphosphate = diphosphate + (2E,6E)-farnesyl diphosphate.1 Publication
(2E,6E)-farnesyl diphosphate + isopentenyl diphosphate = diphosphate + geranylgeranyl diphosphate.1 Publication

Cofactori

Mg2+CuratedNote: Binds 3 Mg2+ ions.Curated

Activity regulationi

Subject to product inhibition by geranylgeranyl diphosphate.1 Publication

Kineticsi

  1. KM=3 µM for isopentenyl diphosphate1 Publication
  2. KM=4.2 µM for farnesyl diphosphate1 Publication

    Pathwayi: farnesyl diphosphate biosynthesis

    This protein is involved in step 1 of the subpathway that synthesizes farnesyl diphosphate from geranyl diphosphate and isopentenyl diphosphate.
    Proteins known to be involved in this subpathway in this organism are:
    1. Farnesyl pyrophosphate synthase (FDPS), Geranylgeranyl pyrophosphate synthase (GGPS1)
    This subpathway is part of the pathway farnesyl diphosphate biosynthesis, which is itself part of Isoprenoid biosynthesis.
    View all proteins of this organism that are known to be involved in the subpathway that synthesizes farnesyl diphosphate from geranyl diphosphate and isopentenyl diphosphate, the pathway farnesyl diphosphate biosynthesis and in Isoprenoid biosynthesis.

    Pathwayi: geranyl diphosphate biosynthesis

    This protein is involved in step 1 of the subpathway that synthesizes geranyl diphosphate from dimethylallyl diphosphate and isopentenyl diphosphate.
    Proteins known to be involved in this subpathway in this organism are:
    1. Farnesyl pyrophosphate synthase (FDPS), Geranylgeranyl pyrophosphate synthase (GGPS1)
    This subpathway is part of the pathway geranyl diphosphate biosynthesis, which is itself part of Isoprenoid biosynthesis.
    View all proteins of this organism that are known to be involved in the subpathway that synthesizes geranyl diphosphate from dimethylallyl diphosphate and isopentenyl diphosphate, the pathway geranyl diphosphate biosynthesis and in Isoprenoid biosynthesis.

    Pathwayi: geranylgeranyl diphosphate biosynthesis

    This protein is involved in step 1 of the subpathway that synthesizes geranylgeranyl diphosphate from farnesyl diphosphate and isopentenyl diphosphate.
    Proteins known to be involved in this subpathway in this organism are:
    1. Geranylgeranyl pyrophosphate synthase (GGPS1)
    This subpathway is part of the pathway geranylgeranyl diphosphate biosynthesis, which is itself part of Isoprenoid biosynthesis.
    View all proteins of this organism that are known to be involved in the subpathway that synthesizes geranylgeranyl diphosphate from farnesyl diphosphate and isopentenyl diphosphate, the pathway geranylgeranyl diphosphate biosynthesis and in Isoprenoid biosynthesis.

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Binding sitei25Isopentenyl diphosphateBy similarity1
    Binding sitei28Isopentenyl diphosphateBy similarity1
    Binding sitei57Isopentenyl diphosphateBy similarity1
    Metal bindingi64Magnesium 11 Publication1
    Metal bindingi64Magnesium 21 Publication1
    Metal bindingi68Magnesium 11 Publication1
    Metal bindingi68Magnesium 21 Publication1
    Binding sitei73Dimethylallyl diphosphate1
    Binding sitei74Isopentenyl diphosphateBy similarity1
    Binding sitei151Dimethylallyl diphosphate1
    Binding sitei152Dimethylallyl diphosphate1
    Binding sitei185Dimethylallyl diphosphate1
    Metal bindingi188Magnesium 3By similarity1
    Binding sitei202Dimethylallyl diphosphate1
    Binding sitei212Dimethylallyl diphosphateBy similarity1

    GO - Molecular functioni

    • dimethylallyltranstransferase activity Source: Reactome
    • farnesyltranstransferase activity Source: UniProtKB
    • geranyltranstransferase activity Source: Reactome
    • identical protein binding Source: IntAct
    • metal ion binding Source: UniProtKB-KW

    GO - Biological processi

    Keywordsi

    Molecular functionTransferase
    Biological processIsoprene biosynthesis
    LigandMagnesium, Metal-binding

    Enzyme and pathway databases

    BioCyciMetaCyc:HS07859-MONOMER
    BRENDAi2.5.1.29 2681
    ReactomeiR-HSA-191273 Cholesterol biosynthesis
    R-HSA-2426168 Activation of gene expression by SREBF (SREBP)
    SABIO-RKiO95749
    UniPathwayi
    UPA00259;UER00368

    UPA00260;UER00369

    UPA00389;UER00564

    Chemistry databases

    SwissLipidsiSLP:000001316 [O95749-1]

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Geranylgeranyl pyrophosphate synthase (EC:2.5.1.-)
    Short name:
    GGPP synthase
    Short name:
    GGPPSase
    Alternative name(s):
    (2E,6E)-farnesyl diphosphate synthase
    Dimethylallyltranstransferase (EC:2.5.1.1)
    Farnesyl diphosphate synthase
    Farnesyltranstransferase (EC:2.5.1.29)
    Geranylgeranyl diphosphate synthase
    Geranyltranstransferase (EC:2.5.1.10)
    Gene namesi
    Name:GGPS1
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    Proteomesi
    • UP000005640 Componenti: Chromosome 1

    Organism-specific databases

    EuPathDBiHostDB:ENSG00000152904.11
    HGNCiHGNC:4249 GGPS1
    MIMi606982 gene
    neXtProtiNX_O95749

    Subcellular locationi

    Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

    Keywords - Cellular componenti

    Cytoplasm

    Pathology & Biotechi

    Organism-specific databases

    DisGeNETi9453
    OpenTargetsiENSG00000152904
    PharmGKBiPA28661

    Chemistry databases

    ChEMBLiCHEMBL4769
    DrugBankiDB07410 [2-(3-DIBENZOFURAN-4-YL-PHENYL)-1-HYDROXY-1-PHOSPHONO-ETHYL]-PHOSPHONIC ACID
    DB07780 FARNESYL DIPHOSPHATE
    DB04695 FARNESYL THIOPYROPHOSPHATE
    DB02552 Geranyl Diphosphate
    DB07841 GERANYLGERANYL DIPHOSPHATE
    DB04714 ISOPENTENYL PYROPHOSPHATE
    DB00399 Zoledronic acid
    GuidetoPHARMACOLOGYi643

    Polymorphism and mutation databases

    BioMutaiGGPS1

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    ChainiPRO_00001239621 – 300Geranylgeranyl pyrophosphate synthaseAdd BLAST300

    Amino acid modifications

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Modified residuei1N-acetylmethionineCombined sources1

    Keywords - PTMi

    Acetylation

    Proteomic databases

    EPDiO95749
    MaxQBiO95749
    PaxDbiO95749
    PeptideAtlasiO95749
    PRIDEiO95749
    ProteomicsDBi51020

    PTM databases

    iPTMnetiO95749
    PhosphoSitePlusiO95749

    Expressioni

    Tissue specificityi

    Abundantly expressed in testis. Found in other tissues to a lower extent.

    Gene expression databases

    BgeeiENSG00000152904 Expressed in 229 organ(s), highest expression level in sperm
    CleanExiHS_GGPS1
    ExpressionAtlasiO95749 baseline and differential
    GenevisibleiO95749 HS

    Organism-specific databases

    HPAiHPA029472

    Interactioni

    Subunit structurei

    Homohexamer; trimer of homodimers.1 Publication

    Binary interactionsi

    GO - Molecular functioni

    Protein-protein interaction databases

    BioGridi114842, 38 interactors
    IntActiO95749, 2 interactors
    STRINGi9606.ENSP00000282841

    Chemistry databases

    BindingDBiO95749

    Structurei

    Secondary structure

    1300
    Legend: HelixTurnBeta strandPDB Structure known for this area
    Show more details

    3D structure databases

    ProteinModelPortaliO95749
    SMRiO95749
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiO95749

    Family & Domainsi

    Sequence similaritiesi

    Belongs to the FPP/GGPP synthase family.Curated

    Phylogenomic databases

    eggNOGiKOG0777 Eukaryota
    COG0142 LUCA
    GeneTreeiENSGT00390000010417
    HOGENOMiHOG000169461
    HOVERGENiHBG051729
    InParanoidiO95749
    KOiK00804
    OMAiFYSKAFF
    OrthoDBiEOG091G0AO6
    PhylomeDBiO95749
    TreeFamiTF300101

    Family and domain databases

    Gene3Di1.10.600.10, 1 hit
    InterProiView protein in InterPro
    IPR008949 Isoprenoid_synthase_dom_sf
    IPR000092 Polyprenyl_synt
    IPR033749 Polyprenyl_synt_CS
    PfamiView protein in Pfam
    PF00348 polyprenyl_synt, 1 hit
    SUPFAMiSSF48576 SSF48576, 1 hit
    PROSITEiView protein in PROSITE
    PS00723 POLYPRENYL_SYNTHASE_1, 1 hit
    PS00444 POLYPRENYL_SYNTHASE_2, 1 hit

    Sequences (2+)i

    Sequence statusi: Complete.

    This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

    This entry has 2 described isoforms and 2 potential isoforms that are computationally mapped.Show allAlign All

    Isoform 1 (identifier: O95749-1) [UniParc]FASTAAdd to basket

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide
            10         20         30         40         50
    MEKTQETVQR ILLEPYKYLL QLPGKQVRTK LSQAFNHWLK VPEDKLQIII
    60 70 80 90 100
    EVTEMLHNAS LLIDDIEDNS KLRRGFPVAH SIYGIPSVIN SANYVYFLGL
    110 120 130 140 150
    EKVLTLDHPD AVKLFTRQLL ELHQGQGLDI YWRDNYTCPT EEEYKAMVLQ
    160 170 180 190 200
    KTGGLFGLAV GLMQLFSDYK EDLKPLLNTL GLFFQIRDDY ANLHSKEYSE
    210 220 230 240 250
    NKSFCEDLTE GKFSFPTIHA IWSRPESTQV QNILRQRTEN IDIKKYCVHY
    260 270 280 290 300
    LEDVGSFEYT RNTLKELEAK AYKQIDARGG NPELVALVKH LSKMFKEENE
    Length:300
    Mass (Da):34,871
    Last modified:May 1, 1999 - v1
    Checksum:iF5D1959274BEE27A
    GO
    Isoform 2 (identifier: O95749-2) [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-54: Missing.

    Note: No experimental confirmation available.
    Show »
    Length:246
    Mass (Da):28,423
    Checksum:iD1B15F57D0532D0F
    GO

    Computationally mapped potential isoform sequencesi

    There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
    EntryEntry nameProtein names
    Gene namesLengthAnnotation
    C9J6G3C9J6G3_HUMAN
    Geranylgeranyl pyrophosphate syntha...
    GGPS1
    230Annotation score:
    C9J7M1C9J7M1_HUMAN
    Geranylgeranyl pyrophosphate syntha...
    GGPS1
    242Annotation score:

    Experimental Info

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Sequence conflicti109P → Q in AAH67768 (PubMed:15489334).Curated1

    Alternative sequence

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Alternative sequenceiVSP_0565781 – 54Missing in isoform 2. 1 PublicationAdd BLAST54

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    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
    AK293278 mRNA Translation: BAH11480.1
    AL391994 Genomic DNA No translation available.
    CH471098 Genomic DNA Translation: EAW70018.1
    CH471098 Genomic DNA Translation: EAW70020.1
    BC005252 mRNA Translation: AAH05252.1
    BC067768 mRNA Translation: AAH67768.1
    CCDSiCCDS1604.1 [O95749-1]
    RefSeqiNP_001032354.1, NM_001037277.1 [O95749-1]
    UniGeneiHs.730768

    Genome annotation databases

    EnsembliENST00000282841; ENSP00000282841; ENSG00000152904 [O95749-1]
    ENST00000358966; ENSP00000351852; ENSG00000152904 [O95749-1]
    ENST00000391855; ENSP00000375728; ENSG00000152904 [O95749-2]
    ENST00000488594; ENSP00000418690; ENSG00000152904 [O95749-1]
    GeneIDi9453
    KEGGihsa:9453
    UCSCiuc001hwv.4 human [O95749-1]

    Keywords - Coding sequence diversityi

    Alternative splicing

    Similar proteinsi

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    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
    AK293278 mRNA Translation: BAH11480.1
    AL391994 Genomic DNA No translation available.
    CH471098 Genomic DNA Translation: EAW70018.1
    CH471098 Genomic DNA Translation: EAW70020.1
    BC005252 mRNA Translation: AAH05252.1
    BC067768 mRNA Translation: AAH67768.1
    CCDSiCCDS1604.1 [O95749-1]
    RefSeqiNP_001032354.1, NM_001037277.1 [O95749-1]
    UniGeneiHs.730768

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    PDB entryMethodResolution (Å)ChainPositionsPDBsum
    2Q80X-ray2.70A/B/C/D/E/F1-300[»]
    6C56X-ray2.80A/B1-300[»]
    6C57X-ray3.50A/B1-300[»]
    ProteinModelPortaliO95749
    SMRiO95749
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi114842, 38 interactors
    IntActiO95749, 2 interactors
    STRINGi9606.ENSP00000282841

    Chemistry databases

    BindingDBiO95749
    ChEMBLiCHEMBL4769
    DrugBankiDB07410 [2-(3-DIBENZOFURAN-4-YL-PHENYL)-1-HYDROXY-1-PHOSPHONO-ETHYL]-PHOSPHONIC ACID
    DB07780 FARNESYL DIPHOSPHATE
    DB04695 FARNESYL THIOPYROPHOSPHATE
    DB02552 Geranyl Diphosphate
    DB07841 GERANYLGERANYL DIPHOSPHATE
    DB04714 ISOPENTENYL PYROPHOSPHATE
    DB00399 Zoledronic acid
    GuidetoPHARMACOLOGYi643
    SwissLipidsiSLP:000001316 [O95749-1]

    PTM databases

    iPTMnetiO95749
    PhosphoSitePlusiO95749

    Polymorphism and mutation databases

    BioMutaiGGPS1

    Proteomic databases

    EPDiO95749
    MaxQBiO95749
    PaxDbiO95749
    PeptideAtlasiO95749
    PRIDEiO95749
    ProteomicsDBi51020

    Protocols and materials databases

    DNASUi9453
    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsembliENST00000282841; ENSP00000282841; ENSG00000152904 [O95749-1]
    ENST00000358966; ENSP00000351852; ENSG00000152904 [O95749-1]
    ENST00000391855; ENSP00000375728; ENSG00000152904 [O95749-2]
    ENST00000488594; ENSP00000418690; ENSG00000152904 [O95749-1]
    GeneIDi9453
    KEGGihsa:9453
    UCSCiuc001hwv.4 human [O95749-1]

    Organism-specific databases

    CTDi9453
    DisGeNETi9453
    EuPathDBiHostDB:ENSG00000152904.11
    GeneCardsiGGPS1
    HGNCiHGNC:4249 GGPS1
    HPAiHPA029472
    MIMi606982 gene
    neXtProtiNX_O95749
    OpenTargetsiENSG00000152904
    PharmGKBiPA28661
    GenAtlasiSearch...

    Phylogenomic databases

    eggNOGiKOG0777 Eukaryota
    COG0142 LUCA
    GeneTreeiENSGT00390000010417
    HOGENOMiHOG000169461
    HOVERGENiHBG051729
    InParanoidiO95749
    KOiK00804
    OMAiFYSKAFF
    OrthoDBiEOG091G0AO6
    PhylomeDBiO95749
    TreeFamiTF300101

    Enzyme and pathway databases

    UniPathwayi
    UPA00259;UER00368

    UPA00260;UER00369

    UPA00389;UER00564

    BioCyciMetaCyc:HS07859-MONOMER
    BRENDAi2.5.1.29 2681
    ReactomeiR-HSA-191273 Cholesterol biosynthesis
    R-HSA-2426168 Activation of gene expression by SREBF (SREBP)
    SABIO-RKiO95749

    Miscellaneous databases

    ChiTaRSiGGPS1 human
    EvolutionaryTraceiO95749
    GeneWikiiGGPS1
    GenomeRNAii9453
    PROiPR:O95749
    SOURCEiSearch...

    Gene expression databases

    BgeeiENSG00000152904 Expressed in 229 organ(s), highest expression level in sperm
    CleanExiHS_GGPS1
    ExpressionAtlasiO95749 baseline and differential
    GenevisibleiO95749 HS

    Family and domain databases

    Gene3Di1.10.600.10, 1 hit
    InterProiView protein in InterPro
    IPR008949 Isoprenoid_synthase_dom_sf
    IPR000092 Polyprenyl_synt
    IPR033749 Polyprenyl_synt_CS
    PfamiView protein in Pfam
    PF00348 polyprenyl_synt, 1 hit
    SUPFAMiSSF48576 SSF48576, 1 hit
    PROSITEiView protein in PROSITE
    PS00723 POLYPRENYL_SYNTHASE_1, 1 hit
    PS00444 POLYPRENYL_SYNTHASE_2, 1 hit
    ProtoNetiSearch...

    Entry informationi

    Entry nameiGGPPS_HUMAN
    AccessioniPrimary (citable) accession number: O95749
    Secondary accession number(s): A8MVQ8, Q5T2C8, Q6NW19
    Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 30, 2000
    Last sequence update: May 1, 1999
    Last modified: November 7, 2018
    This is version 177 of the entry and version 1 of the sequence. See complete history.
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny 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.

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. SIMILARITY comments
      Index of protein domains and families
    2. Human chromosome 1
      Human chromosome 1: entries, gene names and cross-references to MIM
    3. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    4. PATHWAY comments
      Index of metabolic and biosynthesis pathways
    5. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    UniProt is an ELIXIR core data resource
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