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Protein

Geranylgeranyl pyrophosphate synthase

Gene

GGPS1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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

Enzyme 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. Geranylgeranyl pyrophosphate synthase (GGPS1), Farnesyl pyrophosphate synthase (FDPS)
    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. Geranylgeranyl pyrophosphate synthase (GGPS1), Farnesyl pyrophosphate synthase (FDPS)
    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)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei25 – 251Isopentenyl diphosphateBy similarity
    Binding sitei28 – 281Isopentenyl diphosphateBy similarity
    Binding sitei57 – 571Isopentenyl diphosphateBy similarity
    Metal bindingi64 – 641Magnesium 11 Publication
    Metal bindingi64 – 641Magnesium 21 Publication
    Metal bindingi68 – 681Magnesium 11 Publication
    Metal bindingi68 – 681Magnesium 21 Publication
    Binding sitei73 – 731Dimethylallyl diphosphate
    Binding sitei74 – 741Isopentenyl diphosphateBy similarity
    Binding sitei151 – 1511Dimethylallyl diphosphate
    Binding sitei152 – 1521Dimethylallyl diphosphate
    Binding sitei185 – 1851Dimethylallyl diphosphate
    Metal bindingi188 – 1881Magnesium 3By similarity
    Binding sitei202 – 2021Dimethylallyl diphosphate
    Binding sitei212 – 2121Dimethylallyl diphosphateBy similarity

    GO - Molecular functioni

    GO - Biological processi

    Complete GO annotation...

    Keywords - Molecular functioni

    Transferase

    Keywords - Biological processi

    Isoprene biosynthesis

    Keywords - Ligandi

    Magnesium, 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-RKO95749.
    UniPathwayiUPA00259; UER00368.
    UPA00260; UER00369.
    UPA00389; UER00564.

    Chemistry

    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

    HGNCiHGNC:4249. GGPS1.

    Subcellular locationi

    GO - Cellular componenti

    Complete GO annotation...

    Keywords - Cellular componenti

    Cytoplasm

    Pathology & Biotechi

    Organism-specific databases

    PharmGKBiPA28661.

    Chemistry

    ChEMBLiCHEMBL4769.
    DrugBankiDB00399. Zoledronate.
    GuidetoPHARMACOLOGYi643.

    Polymorphism and mutation databases

    BioMutaiGGPS1.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 300300Geranylgeranyl pyrophosphate synthasePRO_0000123962Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei1 – 11N-acetylmethionineCombined sources

    Keywords - PTMi

    Acetylation

    Proteomic databases

    EPDiO95749.
    MaxQBiO95749.
    PaxDbiO95749.
    PeptideAtlasiO95749.
    PRIDEiO95749.

    PTM databases

    iPTMnetiO95749.
    PhosphoSiteiO95749.

    Expressioni

    Tissue specificityi

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

    Gene expression databases

    BgeeiENSG00000152904.
    CleanExiHS_GGPS1.
    ExpressionAtlasiO95749. baseline and differential.
    GenevisibleiO95749. HS.

    Organism-specific databases

    HPAiHPA029472.

    Interactioni

    Subunit structurei

    Homohexamer; trimer of homodimers.1 Publication

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    ATOX1O002443EBI-10179283,EBI-10179267

    Protein-protein interaction databases

    BioGridi114842. 30 interactions.
    IntActiO95749. 1 interaction.
    STRINGi9606.ENSP00000282841.

    Chemistry

    BindingDBiO95749.

    Structurei

    Secondary structure

    1
    300
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Helixi8 – 125Combined sources
    Helixi14 – 196Combined sources
    Helixi25 – 3915Combined sources
    Helixi43 – 6826Combined sources
    Beta strandi71 – 733Combined sources
    Helixi79 – 835Combined sources
    Helixi85 – 10420Combined sources
    Helixi111 – 13424Combined sources
    Helixi141 – 16525Combined sources
    Helixi174 – 19421Combined sources
    Helixi206 – 2105Combined sources
    Helixi215 – 2239Combined sources
    Helixi229 – 2357Combined sources
    Helixi241 – 25313Combined sources
    Helixi256 – 27722Combined sources
    Helixi282 – 29211Combined sources

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    2Q80X-ray2.70A/B/C/D/E/F1-300[»]
    ProteinModelPortaliO95749.
    SMRiO95749. Positions 6-295.
    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.
    OMAiHWLNVPE.
    OrthoDBiEOG091G0AO6.
    PhylomeDBiO95749.
    TreeFamiTF300101.

    Family and domain databases

    Gene3Di1.10.600.10. 1 hit.
    InterProiIPR008949. Isoprenoid_synthase_dom.
    IPR000092. Polyprenyl_synt.
    IPR017446. Polyprenyl_synth-rel.
    [Graphical view]
    PANTHERiPTHR12001. PTHR12001. 1 hit.
    PfamiPF00348. polyprenyl_synt. 1 hit.
    [Graphical view]
    SUPFAMiSSF48576. SSF48576. 1 hit.
    PROSITEiPS00723. POLYPRENYL_SYNTHASE_1. 1 hit.
    PS00444. POLYPRENYL_SYNTHASE_2. 1 hit.
    [Graphical view]

    Sequences (2)i

    Sequence statusi: Complete.

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

    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

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti109 – 1091P → Q in AAH67768 (PubMed:15489334).Curated

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei1 – 5454Missing in isoform 2. 1 PublicationVSP_056578Add
    BLAST

    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. Translation: CAI13753.1.
    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

    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. Translation: CAI13753.1.
    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
    EntryMethodResolution (Å)ChainPositionsPDBsum
    2Q80X-ray2.70A/B/C/D/E/F1-300[»]
    ProteinModelPortaliO95749.
    SMRiO95749. Positions 6-295.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi114842. 30 interactions.
    IntActiO95749. 1 interaction.
    STRINGi9606.ENSP00000282841.

    Chemistry

    BindingDBiO95749.
    ChEMBLiCHEMBL4769.
    DrugBankiDB00399. Zoledronate.
    GuidetoPHARMACOLOGYi643.
    SwissLipidsiSLP:000001316. [O95749-1]

    PTM databases

    iPTMnetiO95749.
    PhosphoSiteiO95749.

    Polymorphism and mutation databases

    BioMutaiGGPS1.

    Proteomic databases

    EPDiO95749.
    MaxQBiO95749.
    PaxDbiO95749.
    PeptideAtlasiO95749.
    PRIDEiO95749.

    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.
    GeneCardsiGGPS1.
    HGNCiHGNC:4249. GGPS1.
    HPAiHPA029472.
    MIMi606982. gene.
    neXtProtiNX_O95749.
    PharmGKBiPA28661.
    GenAtlasiSearch...

    Phylogenomic databases

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

    Enzyme and pathway databases

    UniPathwayiUPA00259; 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-RKO95749.

    Miscellaneous databases

    ChiTaRSiGGPS1. human.
    EvolutionaryTraceiO95749.
    GeneWikiiGGPS1.
    GenomeRNAii9453.
    PROiO95749.
    SOURCEiSearch...

    Gene expression databases

    BgeeiENSG00000152904.
    CleanExiHS_GGPS1.
    ExpressionAtlasiO95749. baseline and differential.
    GenevisibleiO95749. HS.

    Family and domain databases

    Gene3Di1.10.600.10. 1 hit.
    InterProiIPR008949. Isoprenoid_synthase_dom.
    IPR000092. Polyprenyl_synt.
    IPR017446. Polyprenyl_synth-rel.
    [Graphical view]
    PANTHERiPTHR12001. PTHR12001. 1 hit.
    PfamiPF00348. polyprenyl_synt. 1 hit.
    [Graphical view]
    SUPFAMiSSF48576. SSF48576. 1 hit.
    PROSITEiPS00723. POLYPRENYL_SYNTHASE_1. 1 hit.
    PS00444. POLYPRENYL_SYNTHASE_2. 1 hit.
    [Graphical view]
    ProtoNetiSearch...

    Entry informationi

    Entry nameiGGPPS_HUMAN
    AccessioniPrimary (citable) accession number: O95749
    Secondary accession number(s): A8MVQ8, Q5T2C8, Q6NW19
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: May 30, 2000
    Last sequence update: May 1, 1999
    Last modified: September 7, 2016
    This is version 162 of the entry and version 1 of the sequence. [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. Human chromosome 1
      Human chromosome 1: entries, gene names and cross-references to MIM
    2. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    3. PATHWAY comments
      Index of metabolic and biosynthesis pathways
    4. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    5. SIMILARITY comments
      Index of protein domains and families

    Similar proteinsi

    Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
    100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
    90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
    50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.