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Protein

Glucose-6-phosphatase 3

Gene

G6PC3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Hydrolyzes glucose-6-phosphate to glucose in the endoplasmic reticulum. May form with the glucose-6-phosphate transporter (SLC37A4/G6PT) a ubiquitously expressed complex responsible for glucose production through glycogenolysis and gluconeogenesis. Probably required for normal neutrophil function.3 Publications

Catalytic activityi

D-glucose 6-phosphate + H2O = D-glucose + phosphate.1 Publication

Enzyme regulationi

Inhibited by vanadate.1 Publication

Kineticsi

8 times less active compared to G6PC under the same experimental conditions.

  1. KM=1.0 mM for glucose-6-phosphate (at pH 5.5)2 Publications
  2. KM=2.0 mM for glucose-6-phosphate (at pH 6.5)2 Publications

    Pathwayi: gluconeogenesis

    This protein is involved in the pathway gluconeogenesis, which is part of Carbohydrate biosynthesis.
    View all proteins of this organism that are known to be involved in the pathway gluconeogenesis and in Carbohydrate biosynthesis.

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Binding sitei79SubstrateSequence analysis1
    Active sitei114Proton donorSequence analysis1
    Binding sitei161SubstrateSequence analysis1
    Active sitei167Nucleophile1 Publication1

    GO - Molecular functioni

    • glucose-6-phosphatase activity Source: UniProtKB

    GO - Biological processi

    Complete GO annotation...

    Keywords - Molecular functioni

    Hydrolase

    Keywords - Biological processi

    Gluconeogenesis

    Enzyme and pathway databases

    BioCyciMetaCyc:HS13873-MONOMER.
    ZFISH:HS13873-MONOMER.
    BRENDAi3.1.3.9. 2681.
    ReactomeiR-HSA-70153. Glucose transport.
    SABIO-RKQ9BUM1.
    UniPathwayiUPA00138.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Glucose-6-phosphatase 3 (EC:3.1.3.9)
    Short name:
    G-6-Pase 3
    Short name:
    G6Pase 3
    Alternative name(s):
    Glucose-6-phosphatase beta
    Short name:
    G6Pase-beta
    Ubiquitous glucose-6-phosphatase catalytic subunit-related protein
    Gene namesi
    Name:G6PC3
    Synonyms:UGRP
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    Proteomesi
    • UP000005640 Componenti: Chromosome 17

    Organism-specific databases

    HGNCiHGNC:24861. G6PC3.

    Subcellular locationi

    Topology

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Topological domaini1 – 24LumenalSequence analysisAdd BLAST24
    Transmembranei25 – 45HelicalSequence analysisAdd BLAST21
    Topological domaini46 – 54CytoplasmicSequence analysis9
    Transmembranei55 – 75HelicalSequence analysisAdd BLAST21
    Topological domaini76 – 114LumenalSequence analysisAdd BLAST39
    Transmembranei115 – 135HelicalSequence analysisAdd BLAST21
    Topological domaini136 – 146CytoplasmicSequence analysisAdd BLAST11
    Transmembranei147 – 164HelicalSequence analysisAdd BLAST18
    Topological domaini165 – 169LumenalSequence analysis5
    Transmembranei170 – 186HelicalSequence analysisAdd BLAST17
    Topological domaini187 – 197CytoplasmicSequence analysisAdd BLAST11
    Transmembranei198 – 218HelicalSequence analysisAdd BLAST21
    Topological domaini219 – 254LumenalSequence analysisAdd BLAST36
    Transmembranei255 – 273HelicalSequence analysisAdd BLAST19
    Topological domaini274 – 283CytoplasmicSequence analysis10
    Transmembranei284 – 304HelicalSequence analysisAdd BLAST21
    Topological domaini305 – 307LumenalSequence analysis3
    Transmembranei308 – 328HelicalSequence analysisAdd BLAST21
    Topological domaini329 – 346CytoplasmicSequence analysisAdd BLAST18

    GO - Cellular componenti

    Complete GO annotation...

    Keywords - Cellular componenti

    Endoplasmic reticulum, Membrane

    Pathology & Biotechi

    Involvement in diseasei

    Neutropenia, severe congenital 4, autosomal recessive (SCN4)10 Publications
    The disease is caused by mutations affecting the gene represented in this entry.
    Disease descriptionA disorder of hematopoiesis characterized by maturation arrest of granulopoiesis at the level of promyelocytes with peripheral blood absolute neutrophil counts below 0.5 x 10(9)/l and early onset of severe bacterial infections.
    See also OMIM:612541
    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_07317444P → L in SCN4; complete loss of activity. 2 PublicationsCorresponds to variant rs762019955dbSNPEnsembl.1
    Natural variantiVAR_07275344P → S in SCN4; complete loss of activity; purified neutrophils from patients have higher levels of spontaneous and staurosporine-induced apoptosis than controls. 3 PublicationsCorresponds to variant rs775224457dbSNPEnsembl.1
    Natural variantiVAR_07275459W → R in SCN4. 1 PublicationCorresponds to variant rs752966267dbSNPEnsembl.1
    Natural variantiVAR_07275564 – 70Missing in SCN4; purified neutrophils from patients have higher levels of spontaneous and staurosporine-induced apoptosis than controls. 1 Publication7
    Natural variantiVAR_073175116M → I in SCN4; complete loss of activity. 1 Publication1
    Natural variantiVAR_064508116M → K in SCN4; the patient also carries mutation Thr-166 in ELANE; complete loss of activity. 3 Publications1
    Natural variantiVAR_072756116M → T in SCN4; complete loss of activity. 2 Publications1
    Natural variantiVAR_064509116M → V in DURSS and SCN4; complete loss of activity. 2 PublicationsCorresponds to variant rs267606834dbSNPEnsembl.1
    Natural variantiVAR_073176118T → R in SCN4; complete loss of activity. 1 PublicationCorresponds to variant rs766706036dbSNPEnsembl.1
    Natural variantiVAR_072757139S → I in SCN4; partial loss of activity. 2 Publications1
    Natural variantiVAR_072758154L → P in SCN4; complete loss of activity. 2 Publications1
    Natural variantiVAR_073177161R → Q in SCN4; complete loss of activity. 2 Publications1
    Natural variantiVAR_055156185L → P in SCN4; complete loss of activity. 2 PublicationsCorresponds to variant rs118203969dbSNPEnsembl.1
    Natural variantiVAR_064510189R → Q in SCN4; partial loss of activity. 2 PublicationsCorresponds to variant rs140294222dbSNPEnsembl.1
    Natural variantiVAR_072759208L → R in SCN4; complete loss of activity. 2 Publications1
    Natural variantiVAR_073178253R → C in SCN4. 1 PublicationCorresponds to variant rs765927570dbSNPEnsembl.1
    Natural variantiVAR_055157253R → H in SCN4; complete loss of activity; peripheral-blood patient neutrophils have an increased rate of spontaneous apoptosis; transmission electron microscopy of patient bone marrow cells shows an enlarged rough endoplasmic reticulum in myeloid progenitor cells consistent with increased ER stress. 3 PublicationsCorresponds to variant rs118203968dbSNPEnsembl.1
    Natural variantiVAR_072760260G → D in SCN4; complete loss of activity. 2 Publications1
    Natural variantiVAR_064511260G → R in SCN4; complete loss of activity. 4 PublicationsCorresponds to variant rs200478425dbSNPEnsembl.1
    Natural variantiVAR_055158262G → R in SCN4. 1 PublicationCorresponds to variant rs118203971dbSNPEnsembl.1
    Natural variantiVAR_072761325L → R in SCN4. 1 Publication1
    Dursun syndrome (DURSS)1 Publication
    The disease is caused by mutations affecting the gene represented in this entry.
    Disease descriptionA disease characterized by pulmonary arterial hypertension, cardiac abnormalities including secundum-type atrial septal defect, intermittent neutropenia, lymphopenia, monocytosis and anemia.
    See also OMIM:612541
    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_064509116M → V in DURSS and SCN4; complete loss of activity. 2 PublicationsCorresponds to variant rs267606834dbSNPEnsembl.1

    Mutagenesis

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Mutagenesisi79R → A: Loss of catalytic activity. 1 Publication1
    Mutagenesisi114H → A: Loss of catalytic activity. 1 Publication1
    Mutagenesisi167H → A: Loss of catalytic activity. 1 Publication1

    Keywords - Diseasei

    Disease mutation

    Organism-specific databases

    DisGeNETi92579.
    MalaCardsiG6PC3.
    MIMi612541. phenotype.
    OpenTargetsiENSG00000141349.
    Orphaneti331176. Autosomal recessive severe congenital neutropenia due to G6PC3 deficiency.
    PharmGKBiPA134968446.

    Polymorphism and mutation databases

    BioMutaiG6PC3.
    DMDMi74733234.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    ChainiPRO_00003345121 – 346Glucose-6-phosphatase 3Add BLAST346

    Proteomic databases

    EPDiQ9BUM1.
    MaxQBiQ9BUM1.
    PaxDbiQ9BUM1.
    PeptideAtlasiQ9BUM1.
    PRIDEiQ9BUM1.

    PTM databases

    DEPODiQ9BUM1.
    iPTMnetiQ9BUM1.
    PhosphoSitePlusiQ9BUM1.
    SwissPalmiQ9BUM1.

    Expressioni

    Tissue specificityi

    Ubiquitously expressed. Highly expressed in skeletal muscle, at intermediate levels in heart, brain, placenta, kidney, colon, thymus, spleen and pancreas. Also detected in testis, prostate, ovary, liver, lung, small intestine and peripheral blood lymphocytes.3 Publications

    Gene expression databases

    BgeeiENSG00000141349.
    CleanExiHS_G6PC3.
    ExpressionAtlasiQ9BUM1. baseline and differential.
    GenevisibleiQ9BUM1. HS.

    Interactioni

    Protein-protein interaction databases

    STRINGi9606.ENSP00000269097.

    Structurei

    3D structure databases

    ProteinModelPortaliQ9BUM1.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Sequence similaritiesi

    Belongs to the glucose-6-phosphatase family.Curated

    Keywords - Domaini

    Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiENOG410IDXG. Eukaryota.
    ENOG4110AJ7. LUCA.
    GeneTreeiENSGT00510000046465.
    HOGENOMiHOG000264239.
    HOVERGENiHBG003560.
    InParanoidiQ9BUM1.
    KOiK01084.
    OMAiHMFSAQE.
    OrthoDBiEOG091G0AXF.
    PhylomeDBiQ9BUM1.
    TreeFamiTF324388.

    Family and domain databases

    Gene3Di1.20.144.10. 1 hit.
    InterProiIPR016275. Glucose-6-phosphatase.
    IPR000326. P_Acid_Pase_2/haloperoxidase.
    [Graphical view]
    PfamiPF01569. PAP2. 1 hit.
    [Graphical view]
    PIRSFiPIRSF000905. Glucose-6-phosphatase. 1 hit.
    SMARTiSM00014. acidPPc. 1 hit.
    [Graphical view]
    SUPFAMiSSF48317. SSF48317. 1 hit.

    Sequencei

    Sequence statusi: Complete.

    Q9BUM1-1 [UniParc]FASTAAdd to basket

    « Hide

            10         20         30         40         50
    MESTLGAGIV IAEALQNQLA WLENVWLWIT FLGDPKILFL FYFPAAYYAS
    60 70 80 90 100
    RRVGIAVLWI SLITEWLNLI FKWFLFGDRP FWWVHESGYY SQAPAQVHQF
    110 120 130 140 150
    PSSCETGPGS PSGHCMITGA ALWPIMTALS SQVATRARSR WVRVMPSLAY
    160 170 180 190 200
    CTFLLAVGLS RIFILAHFPH QVLAGLITGA VLGWLMTPRV PMERELSFYG
    210 220 230 240 250
    LTALALMLGT SLIYWTLFTL GLDLSWSISL AFKWCERPEW IHVDSRPFAS
    260 270 280 290 300
    LSRDSGAALG LGIALHSPCY AQVRRAQLGN GQKIACLVLA MGLLGPLDWL
    310 320 330 340
    GHPPQISLFY IFNFLKYTLW PCLVLALVPW AVHMFSAQEA PPIHSS
    Length:346
    Mass (Da):38,735
    Last modified:March 1, 2004 - v2
    Checksum:i55C1F322E59C8439
    GO

    Natural variant

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_07317444P → L in SCN4; complete loss of activity. 2 PublicationsCorresponds to variant rs762019955dbSNPEnsembl.1
    Natural variantiVAR_07275344P → S in SCN4; complete loss of activity; purified neutrophils from patients have higher levels of spontaneous and staurosporine-induced apoptosis than controls. 3 PublicationsCorresponds to variant rs775224457dbSNPEnsembl.1
    Natural variantiVAR_07275459W → R in SCN4. 1 PublicationCorresponds to variant rs752966267dbSNPEnsembl.1
    Natural variantiVAR_07275564 – 70Missing in SCN4; purified neutrophils from patients have higher levels of spontaneous and staurosporine-induced apoptosis than controls. 1 Publication7
    Natural variantiVAR_073175116M → I in SCN4; complete loss of activity. 1 Publication1
    Natural variantiVAR_064508116M → K in SCN4; the patient also carries mutation Thr-166 in ELANE; complete loss of activity. 3 Publications1
    Natural variantiVAR_072756116M → T in SCN4; complete loss of activity. 2 Publications1
    Natural variantiVAR_064509116M → V in DURSS and SCN4; complete loss of activity. 2 PublicationsCorresponds to variant rs267606834dbSNPEnsembl.1
    Natural variantiVAR_073176118T → R in SCN4; complete loss of activity. 1 PublicationCorresponds to variant rs766706036dbSNPEnsembl.1
    Natural variantiVAR_072757139S → I in SCN4; partial loss of activity. 2 Publications1
    Natural variantiVAR_072758154L → P in SCN4; complete loss of activity. 2 Publications1
    Natural variantiVAR_073177161R → Q in SCN4; complete loss of activity. 2 Publications1
    Natural variantiVAR_055156185L → P in SCN4; complete loss of activity. 2 PublicationsCorresponds to variant rs118203969dbSNPEnsembl.1
    Natural variantiVAR_064510189R → Q in SCN4; partial loss of activity. 2 PublicationsCorresponds to variant rs140294222dbSNPEnsembl.1
    Natural variantiVAR_072759208L → R in SCN4; complete loss of activity. 2 Publications1
    Natural variantiVAR_043378216T → I.Corresponds to variant rs34406052dbSNPEnsembl.1
    Natural variantiVAR_073178253R → C in SCN4. 1 PublicationCorresponds to variant rs765927570dbSNPEnsembl.1
    Natural variantiVAR_055157253R → H in SCN4; complete loss of activity; peripheral-blood patient neutrophils have an increased rate of spontaneous apoptosis; transmission electron microscopy of patient bone marrow cells shows an enlarged rough endoplasmic reticulum in myeloid progenitor cells consistent with increased ER stress. 3 PublicationsCorresponds to variant rs118203968dbSNPEnsembl.1
    Natural variantiVAR_072760260G → D in SCN4; complete loss of activity. 2 Publications1
    Natural variantiVAR_064511260G → R in SCN4; complete loss of activity. 4 PublicationsCorresponds to variant rs200478425dbSNPEnsembl.1
    Natural variantiVAR_055158262G → R in SCN4. 1 PublicationCorresponds to variant rs118203971dbSNPEnsembl.1
    Natural variantiVAR_072761325L → R in SCN4. 1 Publication1

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    CH471178 Genomic DNA. Translation: EAW51638.1.
    BC002494 mRNA. Translation: AAH02494.2.
    BC021574 mRNA. Translation: AAH21574.1.
    CCDSiCCDS11476.1.
    RefSeqiNP_612396.1. NM_138387.3.
    UniGeneiHs.294005.

    Genome annotation databases

    EnsembliENST00000269097; ENSP00000269097; ENSG00000141349.
    GeneIDi92579.
    KEGGihsa:92579.
    UCSCiuc002iex.4. human.

    Keywords - Coding sequence diversityi

    Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    CH471178 Genomic DNA. Translation: EAW51638.1.
    BC002494 mRNA. Translation: AAH02494.2.
    BC021574 mRNA. Translation: AAH21574.1.
    CCDSiCCDS11476.1.
    RefSeqiNP_612396.1. NM_138387.3.
    UniGeneiHs.294005.

    3D structure databases

    ProteinModelPortaliQ9BUM1.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    STRINGi9606.ENSP00000269097.

    PTM databases

    DEPODiQ9BUM1.
    iPTMnetiQ9BUM1.
    PhosphoSitePlusiQ9BUM1.
    SwissPalmiQ9BUM1.

    Polymorphism and mutation databases

    BioMutaiG6PC3.
    DMDMi74733234.

    Proteomic databases

    EPDiQ9BUM1.
    MaxQBiQ9BUM1.
    PaxDbiQ9BUM1.
    PeptideAtlasiQ9BUM1.
    PRIDEiQ9BUM1.

    Protocols and materials databases

    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsembliENST00000269097; ENSP00000269097; ENSG00000141349.
    GeneIDi92579.
    KEGGihsa:92579.
    UCSCiuc002iex.4. human.

    Organism-specific databases

    CTDi92579.
    DisGeNETi92579.
    GeneCardsiG6PC3.
    H-InvDBHIX0013874.
    HGNCiHGNC:24861. G6PC3.
    MalaCardsiG6PC3.
    MIMi611045. gene.
    612541. phenotype.
    neXtProtiNX_Q9BUM1.
    OpenTargetsiENSG00000141349.
    Orphaneti331176. Autosomal recessive severe congenital neutropenia due to G6PC3 deficiency.
    PharmGKBiPA134968446.
    GenAtlasiSearch...

    Phylogenomic databases

    eggNOGiENOG410IDXG. Eukaryota.
    ENOG4110AJ7. LUCA.
    GeneTreeiENSGT00510000046465.
    HOGENOMiHOG000264239.
    HOVERGENiHBG003560.
    InParanoidiQ9BUM1.
    KOiK01084.
    OMAiHMFSAQE.
    OrthoDBiEOG091G0AXF.
    PhylomeDBiQ9BUM1.
    TreeFamiTF324388.

    Enzyme and pathway databases

    UniPathwayiUPA00138.
    BioCyciMetaCyc:HS13873-MONOMER.
    ZFISH:HS13873-MONOMER.
    BRENDAi3.1.3.9. 2681.
    ReactomeiR-HSA-70153. Glucose transport.
    SABIO-RKQ9BUM1.

    Miscellaneous databases

    ChiTaRSiG6PC3. human.
    GeneWikiiG6PC3.
    GenomeRNAii92579.
    PROiQ9BUM1.
    SOURCEiSearch...

    Gene expression databases

    BgeeiENSG00000141349.
    CleanExiHS_G6PC3.
    ExpressionAtlasiQ9BUM1. baseline and differential.
    GenevisibleiQ9BUM1. HS.

    Family and domain databases

    Gene3Di1.20.144.10. 1 hit.
    InterProiIPR016275. Glucose-6-phosphatase.
    IPR000326. P_Acid_Pase_2/haloperoxidase.
    [Graphical view]
    PfamiPF01569. PAP2. 1 hit.
    [Graphical view]
    PIRSFiPIRSF000905. Glucose-6-phosphatase. 1 hit.
    SMARTiSM00014. acidPPc. 1 hit.
    [Graphical view]
    SUPFAMiSSF48317. SSF48317. 1 hit.
    ProtoNetiSearch...

    Entry informationi

    Entry nameiG6PC3_HUMAN
    AccessioniPrimary (citable) accession number: Q9BUM1
    Secondary accession number(s): Q8WU15
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: May 20, 2008
    Last sequence update: March 1, 2004
    Last modified: November 30, 2016
    This is version 132 of the entry and version 2 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

    Caution

    According to PubMed:12370122, it has no hydrolytic activity.Curated

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. Human chromosome 17
      Human chromosome 17: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. PATHWAY comments
      Index of metabolic and biosynthesis pathways
    6. 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.