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Protein

Glucose-6-phosphatase 3

Gene

G6PC3

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

Caution

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

Catalytic activityi

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

Activity 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

    • gluconeogenesis Source: GO_Central
    • glucose 6-phosphate metabolic process Source: GO_Central
    • glucose-6-phosphate transport Source: Ensembl

    Keywordsi

    Molecular functionHydrolase
    Biological processGluconeogenesis

    Enzyme and pathway databases

    BioCyciMetaCyc:HS13873-MONOMER
    BRENDAi3.1.3.9 2681
    ReactomeiR-HSA-3282872 Severe congenital neutropenia type 4 (G6PC3)
    R-HSA-70263 Gluconeogenesis
    SABIO-RKiQ9BUM1
    UniPathwayi
    UPA00138

    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

    EuPathDBiHostDB:ENSG00000141349.8
    HGNCiHGNC:24861 G6PC3
    MIMi611045 gene
    neXtProtiNX_Q9BUM1

    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

    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

    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 dbSNP:rs762019955Ensembl.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 dbSNP:rs775224457EnsemblClinVar.1
    Natural variantiVAR_07275459W → R in SCN4. 1 PublicationCorresponds to variant dbSNP:rs752966267Ensembl.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_073176118T → R in SCN4; complete loss of activity. 1 PublicationCorresponds to variant dbSNP:rs766706036Ensembl.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 PublicationsCorresponds to variant dbSNP:rs1485073209Ensembl.1
    Natural variantiVAR_055156185L → P in SCN4; complete loss of activity. 2 PublicationsCorresponds to variant dbSNP:rs118203969EnsemblClinVar.1
    Natural variantiVAR_064510189R → Q in SCN4; partial loss of activity. 2 PublicationsCorresponds to variant dbSNP:rs140294222EnsemblClinVar.1
    Natural variantiVAR_072759208L → R in SCN4; complete loss of activity. 2 Publications1
    Natural variantiVAR_073178253R → C in SCN4. 1 PublicationCorresponds to variant dbSNP:rs765927570Ensembl.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 dbSNP:rs118203968EnsemblClinVar.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 dbSNP:rs200478425EnsemblClinVar.1
    Natural variantiVAR_055158262G → R in SCN4. 1 PublicationCorresponds to variant dbSNP:rs118203971EnsemblClinVar.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

    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
    ProteomicsDBi79110

    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 Expressed in 220 organ(s), highest expression level in adenohypophysis
    CleanExiHS_G6PC3
    ExpressionAtlasiQ9BUM1 baseline and differential
    GenevisibleiQ9BUM1 HS

    Organism-specific databases

    HPAiHPA067052

    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
    OMAiTLWPCLV
    OrthoDBiEOG091G0AXF
    PhylomeDBiQ9BUM1
    TreeFamiTF324388

    Family and domain databases

    InterProiView protein in InterPro
    IPR016275 Glucose-6-phosphatase
    IPR036938 P_Acid_Pase_2/haloperoxi_sf
    IPR000326 P_Acid_Pase_2/haloperoxidase
    PfamiView protein in Pfam
    PF01569 PAP2, 1 hit
    PIRSFiPIRSF000905 Glucose-6-phosphatase, 1 hit
    SMARTiView protein in SMART
    SM00014 acidPPc, 1 hit
    SUPFAMiSSF48317 SSF48317, 1 hit

    Sequence (1+)i

    Sequence statusi: Complete.

    This entry has 1 described isoform and 4 potential isoforms that are computationally mapped.Show allAlign All

    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

    Computationally mapped potential isoform sequencesi

    There are 4 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
    EntryEntry nameProtein names
    Gene namesLengthAnnotation
    K7ESE6K7ESE6_HUMAN
    Glucose-6-phosphatase 3
    G6PC3
    243Annotation score:
    K7EQ13K7EQ13_HUMAN
    Glucose-6-phosphatase 3
    G6PC3
    72Annotation score:
    K7ENK1K7ENK1_HUMAN
    Glucose-6-phosphatase 3
    G6PC3
    73Annotation score:
    K7EJC5K7EJC5_HUMAN
    Glucose-6-phosphatase 3
    G6PC3
    69Annotation score:

    Natural variant

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_07317444P → L in SCN4; complete loss of activity. 2 PublicationsCorresponds to variant dbSNP:rs762019955Ensembl.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 dbSNP:rs775224457EnsemblClinVar.1
    Natural variantiVAR_07275459W → R in SCN4. 1 PublicationCorresponds to variant dbSNP:rs752966267Ensembl.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 dbSNP:rs267606834EnsemblClinVar.1
    Natural variantiVAR_073176118T → R in SCN4; complete loss of activity. 1 PublicationCorresponds to variant dbSNP:rs766706036Ensembl.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 PublicationsCorresponds to variant dbSNP:rs1485073209Ensembl.1
    Natural variantiVAR_055156185L → P in SCN4; complete loss of activity. 2 PublicationsCorresponds to variant dbSNP:rs118203969EnsemblClinVar.1
    Natural variantiVAR_064510189R → Q in SCN4; partial loss of activity. 2 PublicationsCorresponds to variant dbSNP:rs140294222EnsemblClinVar.1
    Natural variantiVAR_072759208L → R in SCN4; complete loss of activity. 2 Publications1
    Natural variantiVAR_043378216T → I. Corresponds to variant dbSNP:rs34406052EnsemblClinVar.1
    Natural variantiVAR_073178253R → C in SCN4. 1 PublicationCorresponds to variant dbSNP:rs765927570Ensembl.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 dbSNP:rs118203968EnsemblClinVar.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 dbSNP:rs200478425EnsemblClinVar.1
    Natural variantiVAR_055158262G → R in SCN4. 1 PublicationCorresponds to variant dbSNP:rs118203971EnsemblClinVar.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

    Similar proteinsi

    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
    ProteomicsDBi79110

    Protocols and materials databases

    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

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

    Organism-specific databases

    CTDi92579
    DisGeNETi92579
    EuPathDBiHostDB:ENSG00000141349.8
    GeneCardsiG6PC3
    H-InvDBiHIX0013874
    HGNCiHGNC:24861 G6PC3
    HPAiHPA067052
    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
    OMAiTLWPCLV
    OrthoDBiEOG091G0AXF
    PhylomeDBiQ9BUM1
    TreeFamiTF324388

    Enzyme and pathway databases

    UniPathwayi
    UPA00138

    BioCyciMetaCyc:HS13873-MONOMER
    BRENDAi3.1.3.9 2681
    ReactomeiR-HSA-3282872 Severe congenital neutropenia type 4 (G6PC3)
    R-HSA-70263 Gluconeogenesis
    SABIO-RKiQ9BUM1

    Miscellaneous databases

    ChiTaRSiG6PC3 human
    GeneWikiiG6PC3
    GenomeRNAii92579
    PROiPR:Q9BUM1
    SOURCEiSearch...

    Gene expression databases

    BgeeiENSG00000141349 Expressed in 220 organ(s), highest expression level in adenohypophysis
    CleanExiHS_G6PC3
    ExpressionAtlasiQ9BUM1 baseline and differential
    GenevisibleiQ9BUM1 HS

    Family and domain databases

    InterProiView protein in InterPro
    IPR016275 Glucose-6-phosphatase
    IPR036938 P_Acid_Pase_2/haloperoxi_sf
    IPR000326 P_Acid_Pase_2/haloperoxidase
    PfamiView protein in Pfam
    PF01569 PAP2, 1 hit
    PIRSFiPIRSF000905 Glucose-6-phosphatase, 1 hit
    SMARTiView protein in SMART
    SM00014 acidPPc, 1 hit
    SUPFAMiSSF48317 SSF48317, 1 hit
    ProtoNetiSearch...

    Entry informationi

    Entry nameiG6PC3_HUMAN
    AccessioniPrimary (citable) accession number: Q9BUM1
    Secondary accession number(s): Q8WU15
    Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 20, 2008
    Last sequence update: March 1, 2004
    Last modified: November 7, 2018
    This is version 143 of the entry and version 2 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

    Complete proteome, Reference proteome

    Documents

    1. SIMILARITY comments
      Index of protein domains and families
    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. Human chromosome 17
      Human chromosome 17: entries, gene names and cross-references to MIM
    UniProt is an ELIXIR core data resource
    Main funding by: National Institutes of Health

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