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O95479

- G6PE_HUMAN

UniProt

O95479 - G6PE_HUMAN

Protein

GDH/6PGL endoplasmic bifunctional protein

Gene

H6PD

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 135 (01 Oct 2014)
      Sequence version 2 (30 May 2006)
      Previous versions | rss
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    Functioni

    Oxidizes glucose-6-phosphate and glucose, as well as other hexose-6-phosphates.

    Catalytic activityi

    Beta-D-glucose + NAD(P)+ = D-glucono-1,5-lactone + NAD(P)H.PROSITE-ProRule annotation
    D-glucose 6-phosphate + NAD(P)+ = D-glucono-1,5-lactone 6-phosphate + NAD(P)H.
    6-phospho-D-glucono-1,5-lactone + H2O = 6-phospho-D-gluconate.

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei34 – 341NADPBy similarity
    Binding sitei66 – 661NADPBy similarity
    Binding sitei204 – 2041SubstratePROSITE-ProRule annotation
    Binding sitei208 – 2081SubstratePROSITE-ProRule annotation
    Active sitei267 – 2671Proton acceptorBy similarity

    GO - Molecular functioni

    1. 6-phosphogluconolactonase activity Source: UniProtKB-EC
    2. carbohydrate binding Source: Ensembl
    3. glucose 1-dehydrogenase [NAD(P)] activity Source: UniProtKB-EC
    4. glucose-6-phosphate dehydrogenase activity Source: ProtInc
    5. NADP binding Source: Ensembl

    GO - Biological processi

    1. pentose-phosphate shunt Source: Ensembl
    2. response to alcohol Source: Ensembl

    Keywords - Molecular functioni

    Hydrolase, Oxidoreductase

    Keywords - Biological processi

    Carbohydrate metabolism, Glucose metabolism

    Keywords - Ligandi

    NAD, NADP

    Enzyme and pathway databases

    BioCyciMetaCyc:HS00614-MONOMER.
    SABIO-RKO95479.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    GDH/6PGL endoplasmic bifunctional protein
    Including the following 2 domains:
    Glucose 1-dehydrogenase (EC:1.1.1.47)
    Alternative name(s):
    Hexose-6-phosphate dehydrogenase
    6-phosphogluconolactonase (EC:3.1.1.31)
    Short name:
    6PGL
    Gene namesi
    Name:H6PD
    Synonyms:GDH
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 1

    Organism-specific databases

    HGNCiHGNC:4795. H6PD.

    Subcellular locationi

    Endoplasmic reticulum lumen
    Note: Microsomes, endoplasmic reticulum lumen.

    GO - Cellular componenti

    1. endoplasmic reticulum lumen Source: UniProtKB-SubCell
    2. mitochondrion Source: Ensembl

    Keywords - Cellular componenti

    Endoplasmic reticulum

    Pathology & Biotechi

    Involvement in diseasei

    Cortisone reductase deficiency (CRD) [MIM:604931]: In CRD, activation of cortisone to cortisol does not occur, resulting in adrenocorticotropin-mediated androgen excess and a phenotype resembling polycystic ovary syndrome (PCOS).2 Publications
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti146 – 1461P → L in CRD; results in reduced enzymatic activity. 1 Publication
    VAR_069193
    Natural varianti453 – 4531R → Q in CRD; less than 50% of activity than wild-type. 3 Publications
    Corresponds to variant rs6688832 [ dbSNP | Ensembl ].
    VAR_026487

    Keywords - Diseasei

    Disease mutation

    Organism-specific databases

    MIMi604931. phenotype.
    Orphaneti168588. Hyperandrogenism due to cortisone reductase deficiency.
    PharmGKBiPA29170.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 1919By similarityAdd
    BLAST
    Chaini20 – 791772GDH/6PGL endoplasmic bifunctional proteinPRO_0000010442Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei20 – 201Pyrrolidone carboxylic acidBy similarity
    Glycosylationi157 – 1571N-linked (GlcNAc...)1 Publication
    Modified residuei208 – 2081N6-succinyllysineBy similarity
    Glycosylationi282 – 2821N-linked (GlcNAc...)1 Publication
    Glycosylationi683 – 6831N-linked (GlcNAc...)Sequence Analysis

    Keywords - PTMi

    Glycoprotein, Pyrrolidone carboxylic acid

    Proteomic databases

    MaxQBiO95479.
    PaxDbiO95479.
    PRIDEiO95479.

    PTM databases

    PhosphoSiteiO95479.

    Expressioni

    Tissue specificityi

    Present in most tissues examined, strongest in liver.

    Gene expression databases

    BgeeiO95479.
    CleanExiHS_H6PD.
    GenevestigatoriO95479.

    Organism-specific databases

    HPAiHPA004824.
    HPA005440.

    Interactioni

    Protein-protein interaction databases

    BioGridi114933. 3 interactions.
    IntActiO95479. 1 interaction.
    STRINGi9606.ENSP00000366620.

    Structurei

    3D structure databases

    ProteinModelPortaliO95479.
    SMRiO95479. Positions 29-502, 560-788.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni20 – 526507Glucose 1-dehydrogenaseAdd
    BLAST
    Regioni527 – 54014LinkerAdd
    BLAST
    Regioni541 – 7912516-phosphogluconolactonaseAdd
    BLAST

    Sequence similaritiesi

    In the N-terminal section; belongs to the glucose-6-phosphate dehydrogenase family.Curated

    Keywords - Domaini

    Signal

    Phylogenomic databases

    eggNOGiCOG0363.
    HOGENOMiHOG000231077.
    HOVERGENiHBG005780.
    InParanoidiO95479.
    KOiK13937.
    OrthoDBiEOG7BW0HS.
    PhylomeDBiO95479.
    TreeFamiTF354247.

    Family and domain databases

    Gene3Di3.40.50.720. 1 hit.
    InterProiIPR005900. 6-phosphogluconolactonase_DevB.
    IPR001282. G6P_DH.
    IPR019796. G6P_DH_AS.
    IPR022675. G6P_DH_C.
    IPR022674. G6P_DH_NAD-bd.
    IPR006148. Glc/Gal-6P_isomerase.
    IPR016040. NAD(P)-bd_dom.
    [Graphical view]
    PANTHERiPTHR23429. PTHR23429. 1 hit.
    PfamiPF02781. G6PD_C. 1 hit.
    PF00479. G6PD_N. 1 hit.
    PF01182. Glucosamine_iso. 1 hit.
    [Graphical view]
    PRINTSiPR00079. G6PDHDRGNASE.
    TIGRFAMsiTIGR01198. pgl. 1 hit.
    PROSITEiPS00069. G6P_DEHYDROGENASE. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    O95479-1 [UniParc]FASTAAdd to Basket

    « Hide

    MWNMLIVAMC LALLGCLQAQ ELQGHVSIIL LGATGDLAKK YLWQGLFQLY    50
    LDEAGRGHSF SFHGAALTAP KQGQELMAKA LESLSCPKDM APSHCAEHKD 100
    QFLQLSQYRQ LKTAEDYQAL NKDIEAQLQH AGLREAGRIF YFSVPPFAYE 150
    DIARNINSSC RPGPGAWLRV VLEKPFGHDH FSAQQLATEL GTFFQEEEMY 200
    RVDHYLGKQA VAQILPFRDQ NRKALDGLWN RHHVERVEII MKETVDAEGR 250
    TSFYEEYGVI RDVLQNHLTE VLTLVAMELP HNVSSAEAVL RHKLQVFQAL 300
    RGLQRGSAVV GQYQSYSEQV RRELQKPDSF HSLTPTFAAV LVHIDNLRWE 350
    GVPFILMSGK ALDERVGYAR ILFKNQACCV QSEKHWAAAQ SQCLPRQLVF 400
    HIGHGDLGSP AVLVSRNLFR PSLPSSWKEM EGPPGLRLFG SPLSDYYAYS 450
    PVRERDAHSV LLSHIFHGRK NFFITTENLL ASWNFWTPLL ESLAHKAPRL 500
    YPGGAENGRL LDFEFSSGRL FFSQQQPEQL VPGPGPAPMP SDFQVLRAKY 550
    RESPLVSAWS EELISKLAND IEATAVRAVR RFGQFHLALS GGSSPVALFQ 600
    QLATAHYGFP WAHTHLWLVD ERCVPLSDPE SNFQGLQAHL LQHVRIPYYN 650
    IHPMPVHLQQ RLCAEEDQGA QIYAREISAL VANSSFDLVL LGMGADGHTA 700
    SLFPQSPTGL DGEQLVVLTT SPSQPHRRMS LSLPLINRAK KVAVLVMGRM 750
    KREITTLVSR VGHEPKKWPI SGVLPHSGQL VWYMDYDAFL G 791
    Length:791
    Mass (Da):88,893
    Last modified:May 30, 2006 - v2
    Checksum:i01E179BE00C87C79
    GO

    Sequence cautioni

    The sequence CAH18137.1 differs from that shown. Reason: Erroneous initiation.

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti339 – 3391A → G in CAA10071. (PubMed:10349511)Curated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti146 – 1461P → L in CRD; results in reduced enzymatic activity. 1 Publication
    VAR_069193
    Natural varianti151 – 1511D → A.1 Publication
    Corresponds to variant rs34603401 [ dbSNP | Ensembl ].
    VAR_049117
    Natural varianti218 – 2181R → Q.
    Corresponds to variant rs35525021 [ dbSNP | Ensembl ].
    VAR_049118
    Natural varianti453 – 4531R → Q in CRD; less than 50% of activity than wild-type. 3 Publications
    Corresponds to variant rs6688832 [ dbSNP | Ensembl ].
    VAR_026487
    Natural varianti484 – 4841N → D.
    Corresponds to variant rs35404275 [ dbSNP | Ensembl ].
    VAR_049119
    Natural varianti554 – 5541P → L.
    Corresponds to variant rs17368528 [ dbSNP | Ensembl ].
    VAR_049120

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AJ012590 mRNA. Translation: CAA10071.1.
    CR749282 mRNA. Translation: CAH18137.1. Different initiation.
    Z98044 Genomic DNA. Translation: CAI95702.1.
    BC081559 mRNA. Translation: AAH81559.1.
    CCDSiCCDS101.1.
    RefSeqiNP_004276.2. NM_004285.3.
    XP_006711115.1. XM_006711052.1.
    UniGeneiHs.463511.

    Genome annotation databases

    EnsembliENST00000377403; ENSP00000366620; ENSG00000049239.
    GeneIDi9563.
    KEGGihsa:9563.
    UCSCiuc001apt.3. human.

    Keywords - Coding sequence diversityi

    Polymorphism

    Cross-referencesi

    Web resourcesi

    SHMPD

    The Singapore human mutation and polymorphism database

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AJ012590 mRNA. Translation: CAA10071.1 .
    CR749282 mRNA. Translation: CAH18137.1 . Different initiation.
    Z98044 Genomic DNA. Translation: CAI95702.1 .
    BC081559 mRNA. Translation: AAH81559.1 .
    CCDSi CCDS101.1.
    RefSeqi NP_004276.2. NM_004285.3.
    XP_006711115.1. XM_006711052.1.
    UniGenei Hs.463511.

    3D structure databases

    ProteinModelPortali O95479.
    SMRi O95479. Positions 29-502, 560-788.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 114933. 3 interactions.
    IntActi O95479. 1 interaction.
    STRINGi 9606.ENSP00000366620.

    Chemistry

    DrugBanki DB00157. NADH.

    PTM databases

    PhosphoSitei O95479.

    Proteomic databases

    MaxQBi O95479.
    PaxDbi O95479.
    PRIDEi O95479.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000377403 ; ENSP00000366620 ; ENSG00000049239 .
    GeneIDi 9563.
    KEGGi hsa:9563.
    UCSCi uc001apt.3. human.

    Organism-specific databases

    CTDi 9563.
    GeneCardsi GC01P009294.
    H-InvDB HIX0000104.
    HGNCi HGNC:4795. H6PD.
    HPAi HPA004824.
    HPA005440.
    MIMi 138090. gene.
    604931. phenotype.
    neXtProti NX_O95479.
    Orphaneti 168588. Hyperandrogenism due to cortisone reductase deficiency.
    PharmGKBi PA29170.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG0363.
    HOGENOMi HOG000231077.
    HOVERGENi HBG005780.
    InParanoidi O95479.
    KOi K13937.
    OrthoDBi EOG7BW0HS.
    PhylomeDBi O95479.
    TreeFami TF354247.

    Enzyme and pathway databases

    BioCyci MetaCyc:HS00614-MONOMER.
    SABIO-RK O95479.

    Miscellaneous databases

    ChiTaRSi H6PD. human.
    GeneWikii H6PD.
    GenomeRNAii 9563.
    NextBioi 35867.
    PROi O95479.
    SOURCEi Search...

    Gene expression databases

    Bgeei O95479.
    CleanExi HS_H6PD.
    Genevestigatori O95479.

    Family and domain databases

    Gene3Di 3.40.50.720. 1 hit.
    InterProi IPR005900. 6-phosphogluconolactonase_DevB.
    IPR001282. G6P_DH.
    IPR019796. G6P_DH_AS.
    IPR022675. G6P_DH_C.
    IPR022674. G6P_DH_NAD-bd.
    IPR006148. Glc/Gal-6P_isomerase.
    IPR016040. NAD(P)-bd_dom.
    [Graphical view ]
    PANTHERi PTHR23429. PTHR23429. 1 hit.
    Pfami PF02781. G6PD_C. 1 hit.
    PF00479. G6PD_N. 1 hit.
    PF01182. Glucosamine_iso. 1 hit.
    [Graphical view ]
    PRINTSi PR00079. G6PDHDRGNASE.
    TIGRFAMsi TIGR01198. pgl. 1 hit.
    PROSITEi PS00069. G6P_DEHYDROGENASE. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Human hexose-6-phosphate dehydrogenase (glucose 1-dehydrogenase) encoded at 1p36: coding sequence and expression."
      Mason P.J., Stevens D., Diez A., Knight S.W., Scopes D.A., Vulliamy T.J.
      Blood Cells Mol. Dis. 25:30-36(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Tissue: Bone marrow.
    2. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANTS ALA-151 AND GLN-453.
      Tissue: Salivary gland.
    3. "The DNA sequence and biological annotation of human chromosome 1."
      Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.
      , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.
      Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    4. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT GLN-453.
      Tissue: Testis.
    5. "Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry."
      Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.
      J. Proteome Res. 8:651-661(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-157 AND ASN-282.
      Tissue: Liver.
    6. "Mutations in the genes encoding 11beta-hydroxysteroid dehydrogenase type 1 and hexose-6-phosphate dehydrogenase interact to cause cortisone reductase deficiency."
      Draper N., Walker E.A., Bujalska I.J., Tomlinson J.W., Chalder S.M., Arlt W., Lavery G.G., Bedendo O., Ray D.W., Laing I., Malunowicz E., White P.C., Hewison M., Mason P.J., Connell J.M., Shackleton C.H.L., Stewart P.M.
      Nat. Genet. 34:434-439(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT CRD GLN-453, CHARACTERIZATION OF VARIANT CRD GLN-453.
    7. "Novel H6PDH mutations in two girls with premature adrenarche: 'apparent' and 'true' CRD can be differentiated by urinary steroid profiling."
      Lavery G.G., Idkowiak J., Sherlock M., Bujalska I., Ride J.P., Saqib K., Hartmann M.F., Hughes B., Wudy S.A., De Schepper J., Arlt W., Krone N., Shackleton C.H., Walker E.A., Stewart P.M.
      Eur. J. Endocrinol. 168:K19-K26(2013) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT CRD LEU-146, CHARACTERIZATION OF VARIANT CRD LEU-146.

    Entry informationi

    Entry nameiG6PE_HUMAN
    AccessioniPrimary (citable) accession number: O95479
    Secondary accession number(s): Q4TT33, Q66I35, Q68DT3
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: May 30, 2000
    Last sequence update: May 30, 2006
    Last modified: October 1, 2014
    This is version 135 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

    Keywords - Technical termi

    Complete proteome, Multifunctional enzyme, Reference proteome

    Documents

    1. Human chromosome 1
      Human chromosome 1: 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. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3