Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Glucose-6-phosphatase 2

Gene

G6PC2

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

Functioni

May hydrolyze glucose-6-phosphate to glucose in the endoplasmic reticulum. May be responsible for glucose production through glycogenolysis and gluconeogenesis (By similarity).By similarity

Catalytic activityi

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

Kineticsi

  1. KM=0.45 mM for glucose-6-phosphate (at pH 6.5)

    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 sitei115Proton donorSequence analysis1
    Binding sitei168SubstrateSequence analysis1
    Active sitei174NucleophileBy similarity1

    GO - Molecular functioni

    GO - Biological processi

    • gluconeogenesis Source: GO_Central
    • glucose 6-phosphate metabolic process Source: GO_Central
    • glucose homeostasis Source: BHF-UCL
    • glucose transport Source: Reactome
    • regulation of insulin secretion Source: BHF-UCL
    Complete GO annotation...

    Keywords - Molecular functioni

    Hydrolase

    Keywords - Biological processi

    Gluconeogenesis

    Enzyme and pathway databases

    BioCyciMetaCyc:HS14422-MONOMER.
    ZFISH:HS14422-MONOMER.
    BRENDAi3.1.3.9. 2681.
    ReactomeiR-HSA-70153. Glucose transport.
    SABIO-RKQ9NQR9.
    UniPathwayiUPA00138.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Glucose-6-phosphatase 2 (EC:3.1.3.9)
    Short name:
    G-6-Pase 2
    Short name:
    G6Pase 2
    Alternative name(s):
    Islet-specific glucose-6-phosphatase catalytic subunit-related protein
    Gene namesi
    Name:G6PC2
    Synonyms:IGRP
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    Proteomesi
    • UP000005640 Componenti: Chromosome 2

    Organism-specific databases

    HGNCiHGNC:28906. G6PC2.

    Subcellular locationi

    Topology

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Topological domaini1 – 24LumenalSequence analysisAdd BLAST24
    Transmembranei25 – 45HelicalSequence analysisAdd BLAST21
    Topological domaini46 – 56CytoplasmicSequence analysisAdd BLAST11
    Transmembranei57 – 77HelicalSequence analysisAdd BLAST21
    Topological domaini78 – 115LumenalSequence analysisAdd BLAST38
    Transmembranei116 – 136HelicalSequence analysisAdd BLAST21
    Topological domaini137 – 146CytoplasmicSequence analysis10
    Transmembranei147 – 167HelicalSequence analysisAdd BLAST21
    Topological domaini168LumenalSequence analysis1
    Transmembranei169 – 189HelicalSequence analysisAdd BLAST21
    Topological domaini190 – 211CytoplasmicSequence analysisAdd BLAST22
    Transmembranei212 – 232HelicalSequence analysisAdd BLAST21
    Topological domaini233 – 261LumenalSequence analysisAdd BLAST29
    Transmembranei262 – 282HelicalSequence analysisAdd BLAST21
    Topological domaini283 – 293CytoplasmicSequence analysisAdd BLAST11
    Transmembranei294 – 314HelicalSequence analysisAdd BLAST21
    Topological domaini315 – 318LumenalSequence analysis4
    Transmembranei319 – 339HelicalSequence analysisAdd BLAST21
    Topological domaini340 – 355CytoplasmicSequence analysisAdd BLAST16

    GO - Cellular componenti

    Complete GO annotation...

    Keywords - Cellular componenti

    Endoplasmic reticulum, Membrane

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Mutagenesisi50N → A: No effect on N-glycosylation. 1 Publication1
    Mutagenesisi92N → A: Loss of N-glycosylation. 1 Publication1
    Mutagenesisi287N → A: No effect on N-glycosylation. 1 Publication1

    Organism-specific databases

    DisGeNETi57818.
    MIMi612108. phenotype.
    OpenTargetsiENSG00000152254.
    ENSG00000278373.
    PharmGKBiPA134944773.

    Polymorphism and mutation databases

    BioMutaiG6PC2.
    DMDMi74725272.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    ChainiPRO_00003345091 – 355Glucose-6-phosphatase 2Add BLAST355

    Amino acid modifications

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Glycosylationi92N-linked (GlcNAc...)1 Publication1

    Post-translational modificationi

    N-glycosylated; the non-glycosylated form is more unstable and is degraded through the proteasome.1 Publication

    Keywords - PTMi

    Glycoprotein

    Proteomic databases

    PaxDbiQ9NQR9.
    PeptideAtlasiQ9NQR9.
    PRIDEiQ9NQR9.

    PTM databases

    DEPODiQ9NQR9.
    iPTMnetiQ9NQR9.
    PhosphoSitePlusiQ9NQR9.

    Expressioni

    Tissue specificityi

    Specifically expressed in pancreas and also detected to a lower extent in testis. Expressed by most islet cells in the pancreas (at protein level).1 Publication

    Gene expression databases

    BgeeiENSG00000152254.
    CleanExiHS_G6PC2.
    ExpressionAtlasiQ9NQR9. baseline and differential.
    GenevisibleiQ9NQR9. HS.

    Interactioni

    Protein-protein interaction databases

    STRINGi9606.ENSP00000364512.

    Structurei

    3D structure databases

    ProteinModelPortaliQ9NQR9.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Motif

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Motifi352 – 355Prevents secretion from ERSequence analysis4

    Sequence similaritiesi

    Belongs to the glucose-6-phosphatase family.Curated

    Keywords - Domaini

    Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiENOG410IDXG. Eukaryota.
    ENOG4110AJ7. LUCA.
    GeneTreeiENSGT00510000046465.
    HOGENOMiHOG000264239.
    HOVERGENiHBG003560.
    InParanoidiQ9NQR9.
    KOiK01084.
    OMAiLTWSFLW.
    OrthoDBiEOG091G0AXF.
    PhylomeDBiQ9NQR9.
    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.

    Sequences (3)i

    Sequence statusi: Complete.

    This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

    Isoform 1 (identifier: Q9NQR9-1) [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
    MDFLHRNGVL IIQHLQKDYR AYYTFLNFMS NVGDPRNIFF IYFPLCFQFN
    60 70 80 90 100
    QTVGTKMIWV AVIGDWLNLI FKWILFGHRP YWWVQETQIY PNHSSPCLEQ
    110 120 130 140 150
    FPTTCETGPG SPSGHAMGAS CVWYVMVTAA LSHTVCGMDK FSITLHRLTW
    160 170 180 190 200
    SFLWSVFWLI QISVCISRVF IATHFPHQVI LGVIGGMLVA EAFEHTPGIQ
    210 220 230 240 250
    TASLGTYLKT NLFLFLFAVG FYLLLRVLNI DLLWSVPIAK KWCANPDWIH
    260 270 280 290 300
    IDTTPFAGLV RNLGVLFGLG FAINSEMFLL SCRGGNNYTL SFRLLCALTS
    310 320 330 340 350
    LTILQLYHFL QIPTHEEHLF YVLSFCKSAS IPLTVVAFIP YSVHMLMKQS

    GKKSQ
    Length:355
    Mass (Da):40,580
    Last modified:October 1, 2000 - v1
    Checksum:iD642C37496B6C4EB
    GO
    Isoform 2 (identifier: Q9NQR9-2) [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         74-102: ILFGHRPYWWVQETQIYPNHSSPCLEQFP → KSIWPCNGRILCLVCHGNRCPEPHCLWDG
         103-355: Missing.

    Note: No experimental confirmation available.
    Show »
    Length:102
    Mass (Da):12,160
    Checksum:i45E36A48F44C0C93
    GO
    Isoform 3 (identifier: Q9NQR9-3) [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         148-154: LTWSFLW → HAGGRGL
         155-355: Missing.

    Note: No experimental confirmation available.
    Show »
    Length:154
    Mass (Da):17,757
    Checksum:i7203B17AA6D4CF40
    GO

    Polymorphismi

    Genetic variations in G6PC2 define the fasting plasma glucose levels quantitative trait locus 1 (FGQTL1) [MIMi:612108]. The normal fasting plasma glucose level in the plasma is defined as less than 100 mg per deciliter (5.55 mmol per liter). Higher fasting plasma glucose levels predict type 2 diabetes in young adults and increases the risk of mortality.

    Natural variant

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_043372171I → V.Corresponds to variant rs2232322dbSNPEnsembl.1
    Natural variantiVAR_043373207Y → S.Corresponds to variant rs2232323dbSNPEnsembl.1
    Natural variantiVAR_043374219V → L.Corresponds to variant rs492594dbSNPEnsembl.1
    Natural variantiVAR_043375324S → P.Corresponds to variant rs2232326dbSNPEnsembl.1
    Natural variantiVAR_043376340P → L.Corresponds to variant rs2232327dbSNPEnsembl.1
    Natural variantiVAR_043377342S → C.Corresponds to variant rs2232328dbSNPEnsembl.1

    Alternative sequence

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Alternative sequenceiVSP_03364874 – 102ILFGH…LEQFP → KSIWPCNGRILCLVCHGNRC PEPHCLWDG in isoform 2. 1 PublicationAdd BLAST29
    Alternative sequenceiVSP_033649103 – 355Missing in isoform 2. 1 PublicationAdd BLAST253
    Alternative sequenceiVSP_046180148 – 154LTWSFLW → HAGGRGL in isoform 3. 1 Publication7
    Alternative sequenceiVSP_046181155 – 355Missing in isoform 3. 1 PublicationAdd BLAST201

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AF283835 Genomic DNA. Translation: AAF82810.1.
    BQ777188 mRNA. No translation available.
    CR627438 mRNA. Translation: CAH10524.1.
    AC069137 Genomic DNA. No translation available.
    CH471058 Genomic DNA. Translation: EAX11291.1.
    BC104778 mRNA. Translation: AAI04779.1.
    BC113376 mRNA. Translation: AAI13377.1.
    CCDSiCCDS2230.1. [Q9NQR9-1]
    CCDS46443.1. [Q9NQR9-3]
    RefSeqiNP_001075155.1. NM_001081686.1. [Q9NQR9-3]
    NP_066999.1. NM_021176.2. [Q9NQR9-1]
    UniGeneiHs.283963.

    Genome annotation databases

    EnsembliENST00000282075; ENSP00000282075; ENSG00000152254. [Q9NQR9-2]
    ENST00000375363; ENSP00000364512; ENSG00000152254. [Q9NQR9-1]
    ENST00000429379; ENSP00000396939; ENSG00000152254. [Q9NQR9-3]
    ENST00000612807; ENSP00000481098; ENSG00000278373. [Q9NQR9-3]
    ENST00000617403; ENSP00000483899; ENSG00000278373. [Q9NQR9-2]
    ENST00000622133; ENSP00000482583; ENSG00000278373. [Q9NQR9-1]
    GeneIDi57818.
    KEGGihsa:57818.
    UCSCiuc002uem.4. human. [Q9NQR9-1]

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AF283835 Genomic DNA. Translation: AAF82810.1.
    BQ777188 mRNA. No translation available.
    CR627438 mRNA. Translation: CAH10524.1.
    AC069137 Genomic DNA. No translation available.
    CH471058 Genomic DNA. Translation: EAX11291.1.
    BC104778 mRNA. Translation: AAI04779.1.
    BC113376 mRNA. Translation: AAI13377.1.
    CCDSiCCDS2230.1. [Q9NQR9-1]
    CCDS46443.1. [Q9NQR9-3]
    RefSeqiNP_001075155.1. NM_001081686.1. [Q9NQR9-3]
    NP_066999.1. NM_021176.2. [Q9NQR9-1]
    UniGeneiHs.283963.

    3D structure databases

    ProteinModelPortaliQ9NQR9.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    STRINGi9606.ENSP00000364512.

    PTM databases

    DEPODiQ9NQR9.
    iPTMnetiQ9NQR9.
    PhosphoSitePlusiQ9NQR9.

    Polymorphism and mutation databases

    BioMutaiG6PC2.
    DMDMi74725272.

    Proteomic databases

    PaxDbiQ9NQR9.
    PeptideAtlasiQ9NQR9.
    PRIDEiQ9NQR9.

    Protocols and materials databases

    DNASUi57818.
    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsembliENST00000282075; ENSP00000282075; ENSG00000152254. [Q9NQR9-2]
    ENST00000375363; ENSP00000364512; ENSG00000152254. [Q9NQR9-1]
    ENST00000429379; ENSP00000396939; ENSG00000152254. [Q9NQR9-3]
    ENST00000612807; ENSP00000481098; ENSG00000278373. [Q9NQR9-3]
    ENST00000617403; ENSP00000483899; ENSG00000278373. [Q9NQR9-2]
    ENST00000622133; ENSP00000482583; ENSG00000278373. [Q9NQR9-1]
    GeneIDi57818.
    KEGGihsa:57818.
    UCSCiuc002uem.4. human. [Q9NQR9-1]

    Organism-specific databases

    CTDi57818.
    DisGeNETi57818.
    GeneCardsiG6PC2.
    HGNCiHGNC:28906. G6PC2.
    MIMi608058. gene.
    612108. phenotype.
    neXtProtiNX_Q9NQR9.
    OpenTargetsiENSG00000152254.
    ENSG00000278373.
    PharmGKBiPA134944773.
    GenAtlasiSearch...

    Phylogenomic databases

    eggNOGiENOG410IDXG. Eukaryota.
    ENOG4110AJ7. LUCA.
    GeneTreeiENSGT00510000046465.
    HOGENOMiHOG000264239.
    HOVERGENiHBG003560.
    InParanoidiQ9NQR9.
    KOiK01084.
    OMAiLTWSFLW.
    OrthoDBiEOG091G0AXF.
    PhylomeDBiQ9NQR9.
    TreeFamiTF324388.

    Enzyme and pathway databases

    UniPathwayiUPA00138.
    BioCyciMetaCyc:HS14422-MONOMER.
    ZFISH:HS14422-MONOMER.
    BRENDAi3.1.3.9. 2681.
    ReactomeiR-HSA-70153. Glucose transport.
    SABIO-RKQ9NQR9.

    Miscellaneous databases

    GeneWikiiG6PC2.
    GenomeRNAii57818.
    PROiQ9NQR9.
    SOURCEiSearch...

    Gene expression databases

    BgeeiENSG00000152254.
    CleanExiHS_G6PC2.
    ExpressionAtlasiQ9NQR9. baseline and differential.
    GenevisibleiQ9NQR9. 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 nameiG6PC2_HUMAN
    AccessioniPrimary (citable) accession number: Q9NQR9
    Secondary accession number(s): E9PAX2, Q6AHZ0
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: May 20, 2008
    Last sequence update: October 1, 2000
    Last modified: November 2, 2016
    This is version 117 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

    Complete proteome, Reference proteome

    Documents

    1. Human chromosome 2
      Human chromosome 2: 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.