ID   G6PE_HUMAN              Reviewed;         791 AA.
AC   O95479; Q4TT33; Q66I35; Q68DT3; R4GMU1;
DT   30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT   30-MAY-2006, sequence version 2.
DT   27-MAR-2024, entry version 194.
DE   RecName: Full=GDH/6PGL endoplasmic bifunctional protein {ECO:0000250|UniProtKB:Q8CFX1};
DE   Includes:
DE     RecName: Full=Hexose-6-phosphate dehydrogenase {ECO:0000303|PubMed:10349511};
DE     AltName: Full=Glucose 1-dehydrogenase {ECO:0000303|PubMed:10349511};
DE              Short=GDH {ECO:0000303|PubMed:10349511};
DE              EC=1.1.1.47 {ECO:0000250|UniProtKB:Q8CFX1};
DE     AltName: Full=Glucose-6-phosphate dehydrogenase {ECO:0000305|PubMed:18628520};
DE              EC=1.1.1.363 {ECO:0000269|PubMed:18628520};
DE   Includes:
DE     RecName: Full=6-phosphogluconolactonase {ECO:0000250|UniProtKB:Q8CFX1};
DE              Short=6PGL {ECO:0000250|UniProtKB:Q8CFX1};
DE              EC=3.1.1.31 {ECO:0000250|UniProtKB:Q8CFX1};
DE   Flags: Precursor;
GN   Name=H6PD {ECO:0000312|HGNC:HGNC:4795}; Synonyms=GDH;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RC   TISSUE=Bone marrow;
RX   PubMed=10349511; DOI=10.1006/bcmd.1999.0224;
RA   Mason P.J., Stevens D., Diez A., Knight S.W., Scopes D.A., Vulliamy T.J.;
RT   "Human hexose-6-phosphate dehydrogenase (glucose 1-dehydrogenase) encoded
RT   at 1p36: coding sequence and expression.";
RL   Blood Cells Mol. Dis. 25:30-36(1999).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), VARIANT CORTRD1
RP   GLN-453, AND VARIANT ALA-151.
RC   TISSUE=Salivary gland;
RX   PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA   Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA   Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA   Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA   Wiemann S., Schupp I.;
RT   "The full-ORF clone resource of the German cDNA consortium.";
RL   BMC Genomics 8:399-399(2007).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=16710414; DOI=10.1038/nature04727;
RA   Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA   Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA   Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA   Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA   Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA   Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA   Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA   Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA   Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA   Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA   Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA   Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA   Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA   Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA   Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA   Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA   Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA   Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA   Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA   McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA   Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA   Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA   Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA   Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA   Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA   White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA   Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA   Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA   Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT   "The DNA sequence and biological annotation of human chromosome 1.";
RL   Nature 441:315-321(2006).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT GLN-453.
RC   TISSUE=Testis;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [5]
RP   GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-157 AND ASN-282.
RC   TISSUE=Liver;
RX   PubMed=19159218; DOI=10.1021/pr8008012;
RA   Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.;
RT   "Glycoproteomics analysis of human liver tissue by combination of multiple
RT   enzyme digestion and hydrazide chemistry.";
RL   J. Proteome Res. 8:651-661(2009).
RN   [6]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Liver;
RX   PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA   Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA   Ye M., Zou H.;
RT   "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT   phosphoproteome.";
RL   J. Proteomics 96:253-262(2014).
RN   [7]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=25944712; DOI=10.1002/pmic.201400617;
RA   Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA   Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT   "N-terminome analysis of the human mitochondrial proteome.";
RL   Proteomics 15:2519-2524(2015).
RN   [8]
RP   VARIANT CORTRD1 GLN-453, CHARACTERIZATION OF VARIANT CORTRD1 GLN-453,
RP   FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY.
RX   PubMed=12858176; DOI=10.1038/ng1214;
RA   Draper N., Walker E.A., Bujalska I.J., Tomlinson J.W., Chalder S.M.,
RA   Arlt W., Lavery G.G., Bedendo O., Ray D.W., Laing I., Malunowicz E.,
RA   White P.C., Hewison M., Mason P.J., Connell J.M., Shackleton C.H.L.,
RA   Stewart P.M.;
RT   "Mutations in the genes encoding 11beta-hydroxysteroid dehydrogenase type 1
RT   and hexose-6-phosphate dehydrogenase interact to cause cortisone reductase
RT   deficiency.";
RL   Nat. Genet. 34:434-439(2003).
RN   [9]
RP   VARIANTS CORTRD1 316-TYR--GLY-791 DEL AND ASP-359, CHARACTERIZATION OF
RP   VARIANTS CORTRD1 316-TYR--GLY-791 DEL; ASP-359 AND GLN-453, FUNCTION,
RP   CATALYTIC ACTIVITY, PATHWAY, AND SUBCELLULAR LOCATION.
RX   PubMed=18628520; DOI=10.1210/jc.2008-0743;
RA   Lavery G.G., Walker E.A., Tiganescu A., Ride J.P., Shackleton C.H.,
RA   Tomlinson J.W., Connell J.M., Ray D.W., Biason-Lauber A., Malunowicz E.M.,
RA   Arlt W., Stewart P.M.;
RT   "Steroid biomarkers and genetic studies reveal inactivating mutations in
RT   hexose-6-phosphate dehydrogenase in patients with cortisone reductase
RT   deficiency.";
RL   J. Clin. Endocrinol. Metab. 93:3827-3832(2008).
RN   [10]
RP   VARIANTS CORTRD1 LEU-146; 325-GLN--GLY-791 DEL AND 446-TYR--GLY-791 DEL,
RP   CHARACTERIZATION OF VARIANTS CORTRD1 LEU-146; 325-GLN--GLY-791 DEL AND
RP   446-TYR--GLY-791 DEL, FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY.
RX   PubMed=23132696; DOI=10.1530/eje-12-0628;
RA   Lavery G.G., Idkowiak J., Sherlock M., Bujalska I., Ride J.P., Saqib K.,
RA   Hartmann M.F., Hughes B., Wudy S.A., De Schepper J., Arlt W., Krone N.,
RA   Shackleton C.H., Walker E.A., Stewart P.M.;
RT   "Novel H6PDH mutations in two girls with premature adrenarche: 'apparent'
RT   and 'true' CRD can be differentiated by urinary steroid profiling.";
RL   Eur. J. Endocrinol. 168:K19-K26(2013).
CC   -!- FUNCTION: Bifunctional enzyme localized in the lumen of the endoplasmic
CC       reticulum that catalyzes the first two steps of the oxidative branch of
CC       the pentose phosphate pathway/shunt, an alternative to glycolysis and a
CC       major source of reducing power and metabolic intermediates for
CC       biosynthetic processes (By similarity). Has a hexose-6-phosphate
CC       dehydrogenase activity, with broad substrate specificity compared to
CC       glucose-6-phosphate 1-dehydrogenase/G6PD, and catalyzes the first step
CC       of the pentose phosphate pathway (PubMed:12858176, PubMed:18628520,
CC       PubMed:23132696). In addition, acts as a 6-phosphogluconolactonase and
CC       catalyzes the second step of the pentose phosphate pathway (By
CC       similarity). May have a dehydrogenase activity for alternative
CC       substrates including glucosamine 6-phosphate and glucose 6-sulfate (By
CC       similarity). The main function of this enzyme is to provide reducing
CC       equivalents such as NADPH to maintain the adequate levels of reductive
CC       cofactors in the oxidizing environment of the endoplasmic reticulum
CC       (PubMed:12858176, PubMed:18628520, PubMed:23132696). By producing NADPH
CC       that is needed by reductases of the lumen of the endoplasmic reticulum
CC       like corticosteroid 11-beta-dehydrogenase isozyme 1/HSD11B1, indirectly
CC       regulates their activity (PubMed:18628520).
CC       {ECO:0000250|UniProtKB:Q8CFX1, ECO:0000269|PubMed:12858176,
CC       ECO:0000269|PubMed:18628520, ECO:0000269|PubMed:23132696}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=D-glucose 6-phosphate + NADP(+) = 6-phospho-D-glucono-1,5-
CC         lactone + H(+) + NADPH; Xref=Rhea:RHEA:15841, ChEBI:CHEBI:15378,
CC         ChEBI:CHEBI:57783, ChEBI:CHEBI:57955, ChEBI:CHEBI:58349,
CC         ChEBI:CHEBI:61548; EC=1.1.1.363;
CC         Evidence={ECO:0000269|PubMed:18628520, ECO:0000269|PubMed:23132696};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:15842;
CC         Evidence={ECO:0000305|PubMed:18628520};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=D-glucose 6-phosphate + NAD(+) = 6-phospho-D-glucono-1,5-
CC         lactone + H(+) + NADH; Xref=Rhea:RHEA:38215, ChEBI:CHEBI:15378,
CC         ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:57955,
CC         ChEBI:CHEBI:61548; EC=1.1.1.363;
CC         Evidence={ECO:0000250|UniProtKB:Q8CFX1};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38216;
CC         Evidence={ECO:0000250|UniProtKB:Q8CFX1};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=6-phospho-D-glucono-1,5-lactone + H2O = 6-phospho-D-gluconate
CC         + H(+); Xref=Rhea:RHEA:12556, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC         ChEBI:CHEBI:57955, ChEBI:CHEBI:58759; EC=3.1.1.31;
CC         Evidence={ECO:0000250|UniProtKB:Q8CFX1};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:12557;
CC         Evidence={ECO:0000250|UniProtKB:Q8CFX1};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=2-deoxy-D-glucose 6-phosphate + NAD(+) = 2-deoxy-6-phospho-D-
CC         glucono-1,5-lactone + H(+) + NADH; Xref=Rhea:RHEA:62064,
CC         ChEBI:CHEBI:15378, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945,
CC         ChEBI:CHEBI:84760, ChEBI:CHEBI:145420;
CC         Evidence={ECO:0000250|UniProtKB:Q8CFX1};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:62065;
CC         Evidence={ECO:0000250|UniProtKB:Q8CFX1};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=2-deoxy-D-glucose 6-phosphate + NADP(+) = 2-deoxy-6-phospho-D-
CC         glucono-1,5-lactone + H(+) + NADPH; Xref=Rhea:RHEA:62068,
CC         ChEBI:CHEBI:15378, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349,
CC         ChEBI:CHEBI:84760, ChEBI:CHEBI:145420;
CC         Evidence={ECO:0000250|UniProtKB:Q8CFX1};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:62069;
CC         Evidence={ECO:0000250|UniProtKB:Q8CFX1};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=D-galactose 6-phosphate + NADP(+) = 6-phospho-D-galactono-1,5-
CC         lactone + H(+) + NADPH; Xref=Rhea:RHEA:62072, ChEBI:CHEBI:15378,
CC         ChEBI:CHEBI:57783, ChEBI:CHEBI:58349, ChEBI:CHEBI:91004,
CC         ChEBI:CHEBI:145419; Evidence={ECO:0000269|PubMed:12858176};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:62073;
CC         Evidence={ECO:0000305|PubMed:12858176};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=D-galactose 6-phosphate + NAD(+) = 6-phospho-D-galactono-1,5-
CC         lactone + H(+) + NADH; Xref=Rhea:RHEA:62076, ChEBI:CHEBI:15378,
CC         ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:91004,
CC         ChEBI:CHEBI:145419; Evidence={ECO:0000250|UniProtKB:Q8CFX1};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:62077;
CC         Evidence={ECO:0000250|UniProtKB:Q8CFX1};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=D-glucosamine 6-phosphate + NADP(+) = 2-amino-2-deoxy-6-
CC         phospho-D-glucono-1,5-lactone + 2 H(+) + NADPH; Xref=Rhea:RHEA:62088,
CC         ChEBI:CHEBI:15378, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349,
CC         ChEBI:CHEBI:58725, ChEBI:CHEBI:145423;
CC         Evidence={ECO:0000250|UniProtKB:Q8CFX1};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:62089;
CC         Evidence={ECO:0000250|UniProtKB:Q8CFX1};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=D-glucose + NAD(+) = D-glucono-1,5-lactone + H(+) + NADH;
CC         Xref=Rhea:RHEA:14293, ChEBI:CHEBI:4167, ChEBI:CHEBI:15378,
CC         ChEBI:CHEBI:16217, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=1.1.1.47;
CC         Evidence={ECO:0000250|UniProtKB:Q8CFX1};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:14294;
CC         Evidence={ECO:0000250|UniProtKB:Q8CFX1};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=D-glucose + NADP(+) = D-glucono-1,5-lactone + H(+) + NADPH;
CC         Xref=Rhea:RHEA:14405, ChEBI:CHEBI:4167, ChEBI:CHEBI:15378,
CC         ChEBI:CHEBI:16217, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; EC=1.1.1.47;
CC         Evidence={ECO:0000250|UniProtKB:Q8CFX1};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:14406;
CC         Evidence={ECO:0000250|UniProtKB:Q8CFX1};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=D-glucose 6-sulfate + NADP(+) = 6-sulfo-D-glucono-1,5-lactone
CC         + H(+) + NADPH; Xref=Rhea:RHEA:62080, ChEBI:CHEBI:15378,
CC         ChEBI:CHEBI:57783, ChEBI:CHEBI:58349, ChEBI:CHEBI:145424,
CC         ChEBI:CHEBI:145427; Evidence={ECO:0000250|UniProtKB:Q8CFX1};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:62081;
CC         Evidence={ECO:0000250|UniProtKB:Q8CFX1};
CC   -!- PATHWAY: Carbohydrate degradation; pentose phosphate pathway; D-
CC       ribulose 5-phosphate from D-glucose 6-phosphate (oxidative stage): step
CC       1/3. {ECO:0000269|PubMed:12858176, ECO:0000269|PubMed:18628520,
CC       ECO:0000269|PubMed:23132696}.
CC   -!- PATHWAY: Carbohydrate degradation; pentose phosphate pathway; D-
CC       ribulose 5-phosphate from D-glucose 6-phosphate (oxidative stage): step
CC       2/3. {ECO:0000250|UniProtKB:Q8CFX1}.
CC   -!- PATHWAY: Carbohydrate degradation; pentose phosphate pathway; D-
CC       ribulose 5-phosphate from D-glucose 6-phosphate (oxidative stage).
CC       {ECO:0000250|UniProtKB:Q8CFX1}.
CC   -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:Q8CFX1}.
CC   -!- SUBCELLULAR LOCATION: Endoplasmic reticulum lumen
CC       {ECO:0000305|PubMed:18628520}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=O95479-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=O95479-2; Sequence=VSP_060485;
CC   -!- TISSUE SPECIFICITY: Present in most tissues examined, strongest in
CC       liver. {ECO:0000269|PubMed:10349511}.
CC   -!- DISEASE: Cortisone reductase deficiency 1 (CORTRD1) [MIM:604931]: An
CC       autosomal recessive error of cortisone metabolism characterized by a
CC       failure to regenerate cortisol from cortisone, resulting in increased
CC       cortisol clearance, activation of the hypothalamic-pituitary axis and
CC       ACTH-mediated adrenal androgen excess. Clinical features include
CC       hyperandrogenism resulting in hirsutism, oligo-amenorrhea, and
CC       infertility in females and premature pseudopuberty in males.
CC       {ECO:0000269|PubMed:12858176, ECO:0000269|PubMed:17974005,
CC       ECO:0000269|PubMed:18628520, ECO:0000269|PubMed:23132696}. Note=The
CC       disease is caused by variants affecting the gene represented in this
CC       entry.
CC   -!- SIMILARITY: In the N-terminal section; belongs to the glucose-6-
CC       phosphate dehydrogenase family. {ECO:0000305}.
CC   -!- SIMILARITY: In the C-terminal section; belongs to the
CC       glucosamine/galactosamine-6-phosphate isomerase family. 6-
CC       phosphogluconolactonase subfamily. {ECO:0000305}.
CC   -!- WEB RESOURCE: Name=SHMPD; Note=The Singapore human mutation and
CC       polymorphism database;
CC       URL="http://shmpd.bii.a-star.edu.sg/gene.php?genestart=C&genename=H6PD";
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DR   EMBL; AJ012590; CAA10071.1; -; mRNA.
DR   EMBL; CR749282; CAH18137.1; -; mRNA.
DR   EMBL; Z98044; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC081559; AAH81559.1; -; mRNA.
DR   CCDS; CCDS101.1; -. [O95479-1]
DR   CCDS; CCDS72697.1; -. [O95479-2]
DR   RefSeq; NP_001269516.1; NM_001282587.1. [O95479-2]
DR   RefSeq; NP_004276.2; NM_004285.3. [O95479-1]
DR   RefSeq; XP_006711115.1; XM_006711052.3. [O95479-1]
DR   RefSeq; XP_016858354.1; XM_017002865.1. [O95479-1]
DR   PDB; 8EM2; EM; 3.02 A; A/B=1-791.
DR   PDBsum; 8EM2; -.
DR   AlphaFoldDB; O95479; -.
DR   EMDB; EMD-26425; -.
DR   EMDB; EMD-28232; -.
DR   SMR; O95479; -.
DR   BioGRID; 114933; 39.
DR   IntAct; O95479; 4.
DR   STRING; 9606.ENSP00000473348; -.
DR   BindingDB; O95479; -.
DR   DrugBank; DB00157; NADH.
DR   GlyConnect; 1264; 3 N-Linked glycans (1 site).
DR   GlyCosmos; O95479; 3 sites, 3 glycans.
DR   GlyGen; O95479; 3 sites, 5 N-linked glycans (2 sites).
DR   iPTMnet; O95479; -.
DR   PhosphoSitePlus; O95479; -.
DR   SwissPalm; O95479; -.
DR   BioMuta; H6PD; -.
DR   EPD; O95479; -.
DR   jPOST; O95479; -.
DR   MassIVE; O95479; -.
DR   MaxQB; O95479; -.
DR   PaxDb; 9606-ENSP00000473348; -.
DR   PeptideAtlas; O95479; -.
DR   ProteomicsDB; 50910; -.
DR   Pumba; O95479; -.
DR   Antibodypedia; 1350; 350 antibodies from 28 providers.
DR   DNASU; 9563; -.
DR   Ensembl; ENST00000377403.7; ENSP00000366620.2; ENSG00000049239.13. [O95479-1]
DR   Ensembl; ENST00000602477.1; ENSP00000473348.1; ENSG00000049239.13. [O95479-2]
DR   GeneID; 9563; -.
DR   KEGG; hsa:9563; -.
DR   MANE-Select; ENST00000377403.7; ENSP00000366620.2; NM_004285.4; NP_004276.2.
DR   UCSC; uc001apt.4; human. [O95479-1]
DR   AGR; HGNC:4795; -.
DR   CTD; 9563; -.
DR   DisGeNET; 9563; -.
DR   GeneCards; H6PD; -.
DR   HGNC; HGNC:4795; H6PD.
DR   HPA; ENSG00000049239; Tissue enhanced (liver).
DR   MalaCards; H6PD; -.
DR   MIM; 138090; gene.
DR   MIM; 604931; phenotype.
DR   neXtProt; NX_O95479; -.
DR   OpenTargets; ENSG00000049239; -.
DR   Orphanet; 168588; Hyperandrogenism due to cortisone reductase deficiency.
DR   PharmGKB; PA29170; -.
DR   VEuPathDB; HostDB:ENSG00000049239; -.
DR   eggNOG; KOG0563; Eukaryota.
DR   eggNOG; KOG3147; Eukaryota.
DR   GeneTree; ENSGT00530000063435; -.
DR   HOGENOM; CLU_018975_0_0_1; -.
DR   InParanoid; O95479; -.
DR   OrthoDB; 989808at2759; -.
DR   PhylomeDB; O95479; -.
DR   TreeFam; TF354247; -.
DR   BioCyc; MetaCyc:HS00614-MONOMER; -.
DR   PathwayCommons; O95479; -.
DR   SABIO-RK; O95479; -.
DR   SignaLink; O95479; -.
DR   UniPathway; UPA00115; UER00408.
DR   UniPathway; UPA00115; UER00409.
DR   BioGRID-ORCS; 9563; 4 hits in 1146 CRISPR screens.
DR   ChiTaRS; H6PD; human.
DR   GeneWiki; H6PD; -.
DR   GenomeRNAi; 9563; -.
DR   Pharos; O95479; Tbio.
DR   PRO; PR:O95479; -.
DR   Proteomes; UP000005640; Chromosome 1.
DR   RNAct; O95479; Protein.
DR   Bgee; ENSG00000049239; Expressed in parotid gland and 197 other cell types or tissues.
DR   GO; GO:0005783; C:endoplasmic reticulum; IBA:GO_Central.
DR   GO; GO:0005788; C:endoplasmic reticulum lumen; IDA:UniProtKB.
DR   GO; GO:0017057; F:6-phosphogluconolactonase activity; ISS:UniProtKB.
DR   GO; GO:0030246; F:carbohydrate binding; IEA:Ensembl.
DR   GO; GO:0047934; F:glucose 1-dehydrogenase (NAD+) activity; IEA:RHEA.
DR   GO; GO:0047935; F:glucose 1-dehydrogenase (NADP+) activity; IEA:RHEA.
DR   GO; GO:0047936; F:glucose 1-dehydrogenase [NAD(P)] activity; IEA:UniProtKB-EC.
DR   GO; GO:0004345; F:glucose-6-phosphate dehydrogenase activity; IDA:UniProtKB.
DR   GO; GO:0050661; F:NADP binding; IEA:Ensembl.
DR   GO; GO:0006006; P:glucose metabolic process; IBA:GO_Central.
DR   GO; GO:0009051; P:pentose-phosphate shunt, oxidative branch; IMP:UniProtKB.
DR   GO; GO:2000064; P:regulation of cortisol biosynthetic process; IMP:UniProtKB.
DR   GO; GO:0097305; P:response to alcohol; IEA:Ensembl.
DR   GO; GO:0031667; P:response to nutrient levels; IEA:Ensembl.
DR   CDD; cd01400; 6PGL; 1.
DR   Gene3D; 3.40.50.1360; -; 1.
DR   Gene3D; 3.40.50.720; NAD(P)-binding Rossmann-like Domain; 1.
DR   InterPro; IPR005900; 6-phosphogluconolactonase_DevB.
DR   InterPro; IPR001282; G6P_DH.
DR   InterPro; IPR019796; G6P_DH_AS.
DR   InterPro; IPR022675; G6P_DH_C.
DR   InterPro; IPR022674; G6P_DH_NAD-bd.
DR   InterPro; IPR006148; Glc/Gal-6P_isomerase.
DR   InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR   InterPro; IPR037171; NagB/RpiA_transferase-like.
DR   NCBIfam; TIGR01198; pgl; 1.
DR   PANTHER; PTHR23429:SF7; GDH_6PGL ENDOPLASMIC BIFUNCTIONAL PROTEIN; 1.
DR   PANTHER; PTHR23429; GLUCOSE-6-PHOSPHATE 1-DEHYDROGENASE G6PD; 1.
DR   Pfam; PF02781; G6PD_C; 1.
DR   Pfam; PF00479; G6PD_N; 1.
DR   Pfam; PF01182; Glucosamine_iso; 1.
DR   PRINTS; PR00079; G6PDHDRGNASE.
DR   SUPFAM; SSF55347; Glyceraldehyde-3-phosphate dehydrogenase-like, C-terminal domain; 1.
DR   SUPFAM; SSF51735; NAD(P)-binding Rossmann-fold domains; 1.
DR   SUPFAM; SSF100950; NagB/RpiA/CoA transferase-like; 1.
DR   PROSITE; PS00069; G6P_DEHYDROGENASE; 1.
DR   Genevisible; O95479; HS.
PE   1: Evidence at protein level;
KW   3D-structure; Alternative splicing; Carbohydrate metabolism;
KW   Disease variant; Endoplasmic reticulum; Glucose metabolism; Glycoprotein;
KW   Hydrolase; Multifunctional enzyme; NAD; NADP; Oxidoreductase;
KW   Pyrrolidone carboxylic acid; Reference proteome; Signal.
FT   SIGNAL          1..19
FT                   /evidence="ECO:0000250|UniProtKB:P56201"
FT   CHAIN           20..791
FT                   /note="GDH/6PGL endoplasmic bifunctional protein"
FT                   /id="PRO_0000010442"
FT   REGION          20..526
FT                   /note="Hexose-6-phosphate dehydrogenase"
FT                   /evidence="ECO:0000305"
FT   REGION          527..540
FT                   /note="Linker"
FT                   /evidence="ECO:0000305"
FT   REGION          541..791
FT                   /note="6-phosphogluconolactonase"
FT                   /evidence="ECO:0000305"
FT   ACT_SITE        267
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000250|UniProtKB:P11411"
FT   BINDING         32..39
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250|UniProtKB:P11413"
FT   BINDING         149
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250|UniProtKB:P11413"
FT   BINDING         174
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250|UniProtKB:P11413"
FT   BINDING         174
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:P11413"
FT   BINDING         204..208
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:P11413"
FT   BINDING         243
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:P11413"
FT   BINDING         262
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:P11413"
FT   BINDING         360
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:P11413"
FT   BINDING         365
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:P11413"
FT   MOD_RES         20
FT                   /note="Pyrrolidone carboxylic acid"
FT                   /evidence="ECO:0000250|UniProtKB:P56201"
FT   MOD_RES         208
FT                   /note="N6-succinyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:Q8CFX1"
FT   CARBOHYD        157
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:19159218"
FT   CARBOHYD        282
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:19159218"
FT   CARBOHYD        683
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   VAR_SEQ         1
FT                   /note="M -> MLAEPFNWHPGM (in isoform 2)"
FT                   /id="VSP_060485"
FT   VARIANT         146
FT                   /note="P -> L (in CORTRD1; no effect on protein abundance;
FT                   decreased glucose-6-phosphate dehydrogenase activity)"
FT                   /evidence="ECO:0000269|PubMed:23132696"
FT                   /id="VAR_069193"
FT   VARIANT         151
FT                   /note="D -> A (in dbSNP:rs34603401)"
FT                   /evidence="ECO:0000269|PubMed:17974005"
FT                   /id="VAR_049117"
FT   VARIANT         218
FT                   /note="R -> Q (in dbSNP:rs35525021)"
FT                   /id="VAR_049118"
FT   VARIANT         316..791
FT                   /note="Missing (in CORTRD1; loss of glucose-6-phosphate
FT                   dehydrogenase activity)"
FT                   /evidence="ECO:0000269|PubMed:18628520"
FT                   /id="VAR_083053"
FT   VARIANT         325..791
FT                   /note="Missing (in CORTRD1; loss of glucose-6-phosphate
FT                   dehydrogenase activity)"
FT                   /evidence="ECO:0000269|PubMed:23132696"
FT                   /id="VAR_083054"
FT   VARIANT         359
FT                   /note="G -> D (in CORTRD1; loss of glucose-6-phosphate
FT                   dehydrogenase activity; dbSNP:rs387907167)"
FT                   /evidence="ECO:0000269|PubMed:18628520"
FT                   /id="VAR_083055"
FT   VARIANT         446..791
FT                   /note="Missing (in CORTRD1; loss of glucose-6-phosphate
FT                   dehydrogenase activity)"
FT                   /evidence="ECO:0000269|PubMed:23132696"
FT                   /id="VAR_083056"
FT   VARIANT         453
FT                   /note="R -> Q (in CORTRD1; uncertain significance; no
FT                   effect on glucose-6-phosphate dehydrogenase activity;
FT                   however an effect was originally observed;
FT                   dbSNP:rs6688832)"
FT                   /evidence="ECO:0000269|PubMed:12858176,
FT                   ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:17974005,
FT                   ECO:0000269|PubMed:18628520"
FT                   /id="VAR_026487"
FT   VARIANT         484
FT                   /note="N -> D (in dbSNP:rs35404275)"
FT                   /id="VAR_049119"
FT   VARIANT         554
FT                   /note="P -> L (in dbSNP:rs17368528)"
FT                   /id="VAR_049120"
FT   CONFLICT        339
FT                   /note="A -> G (in Ref. 1; CAA10071)"
FT                   /evidence="ECO:0000305"
FT   STRAND          25..30
FT                   /evidence="ECO:0007829|PDB:8EM2"
FT   HELIX           36..40
FT                   /evidence="ECO:0007829|PDB:8EM2"
FT   HELIX           42..53
FT                   /evidence="ECO:0007829|PDB:8EM2"
FT   STRAND          60..68
FT                   /evidence="ECO:0007829|PDB:8EM2"
FT   HELIX           70..82
FT                   /evidence="ECO:0007829|PDB:8EM2"
FT   HELIX           92..105
FT                   /evidence="ECO:0007829|PDB:8EM2"
FT   STRAND          107..110
FT                   /evidence="ECO:0007829|PDB:8EM2"
FT   STRAND          112..114
FT                   /evidence="ECO:0007829|PDB:8EM2"
FT   HELIX           115..131
FT                   /evidence="ECO:0007829|PDB:8EM2"
FT   STRAND          135..141
FT                   /evidence="ECO:0007829|PDB:8EM2"
FT   HELIX           150..158
FT                   /evidence="ECO:0007829|PDB:8EM2"
FT   STRAND          163..165
FT                   /evidence="ECO:0007829|PDB:8EM2"
FT   STRAND          170..172
FT                   /evidence="ECO:0007829|PDB:8EM2"
FT   HELIX           180..191
FT                   /evidence="ECO:0007829|PDB:8EM2"
FT   TURN            196..198
FT                   /evidence="ECO:0007829|PDB:8EM2"
FT   STRAND          200..202
FT                   /evidence="ECO:0007829|PDB:8EM2"
FT   HELIX           205..207
FT                   /evidence="ECO:0007829|PDB:8EM2"
FT   HELIX           211..213
FT                   /evidence="ECO:0007829|PDB:8EM2"
FT   HELIX           214..219
FT                   /evidence="ECO:0007829|PDB:8EM2"
FT   TURN            223..228
FT                   /evidence="ECO:0007829|PDB:8EM2"
FT   HELIX           231..233
FT                   /evidence="ECO:0007829|PDB:8EM2"
FT   STRAND          234..242
FT                   /evidence="ECO:0007829|PDB:8EM2"
FT   STRAND          247..249
FT                   /evidence="ECO:0007829|PDB:8EM2"
FT   TURN            252..257
FT                   /evidence="ECO:0007829|PDB:8EM2"
FT   HELIX           258..262
FT                   /evidence="ECO:0007829|PDB:8EM2"
FT   HELIX           263..267
FT                   /evidence="ECO:0007829|PDB:8EM2"
FT   HELIX           268..275
FT                   /evidence="ECO:0007829|PDB:8EM2"
FT   HELIX           287..298
FT                   /evidence="ECO:0007829|PDB:8EM2"
FT   STRAND          308..313
FT                   /evidence="ECO:0007829|PDB:8EM2"
FT   HELIX           314..323
FT                   /evidence="ECO:0007829|PDB:8EM2"
FT   STRAND          336..342
FT                   /evidence="ECO:0007829|PDB:8EM2"
FT   STRAND          346..351
FT                   /evidence="ECO:0007829|PDB:8EM2"
FT   STRAND          354..361
FT                   /evidence="ECO:0007829|PDB:8EM2"
FT   STRAND          366..373
FT                   /evidence="ECO:0007829|PDB:8EM2"
FT   HELIX           383..385
FT                   /evidence="ECO:0007829|PDB:8EM2"
FT   TURN            388..390
FT                   /evidence="ECO:0007829|PDB:8EM2"
FT   STRAND          392..394
FT                   /evidence="ECO:0007829|PDB:8EM2"
FT   STRAND          397..404
FT                   /evidence="ECO:0007829|PDB:8EM2"
FT   TURN            405..407
FT                   /evidence="ECO:0007829|PDB:8EM2"
FT   STRAND          411..415
FT                   /evidence="ECO:0007829|PDB:8EM2"
FT   TURN            416..418
FT                   /evidence="ECO:0007829|PDB:8EM2"
FT   STRAND          427..429
FT                   /evidence="ECO:0007829|PDB:8EM2"
FT   HELIX           443..445
FT                   /evidence="ECO:0007829|PDB:8EM2"
FT   STRAND          446..453
FT                   /evidence="ECO:0007829|PDB:8EM2"
FT   HELIX           457..467
FT                   /evidence="ECO:0007829|PDB:8EM2"
FT   HELIX           470..472
FT                   /evidence="ECO:0007829|PDB:8EM2"
FT   HELIX           476..492
FT                   /evidence="ECO:0007829|PDB:8EM2"
FT   STRAND          499..501
FT                   /evidence="ECO:0007829|PDB:8EM2"
FT   HELIX           504..506
FT                   /evidence="ECO:0007829|PDB:8EM2"
FT   STRAND          513..516
FT                   /evidence="ECO:0007829|PDB:8EM2"
FT   STRAND          519..524
FT                   /evidence="ECO:0007829|PDB:8EM2"
SQ   SEQUENCE   791 AA;  88893 MW;  01E179BE00C87C79 CRC64;
     MWNMLIVAMC LALLGCLQAQ ELQGHVSIIL LGATGDLAKK YLWQGLFQLY LDEAGRGHSF
     SFHGAALTAP KQGQELMAKA LESLSCPKDM APSHCAEHKD QFLQLSQYRQ LKTAEDYQAL
     NKDIEAQLQH AGLREAGRIF YFSVPPFAYE DIARNINSSC RPGPGAWLRV VLEKPFGHDH
     FSAQQLATEL GTFFQEEEMY RVDHYLGKQA VAQILPFRDQ NRKALDGLWN RHHVERVEII
     MKETVDAEGR TSFYEEYGVI RDVLQNHLTE VLTLVAMELP HNVSSAEAVL RHKLQVFQAL
     RGLQRGSAVV GQYQSYSEQV RRELQKPDSF HSLTPTFAAV LVHIDNLRWE GVPFILMSGK
     ALDERVGYAR ILFKNQACCV QSEKHWAAAQ SQCLPRQLVF HIGHGDLGSP AVLVSRNLFR
     PSLPSSWKEM EGPPGLRLFG SPLSDYYAYS PVRERDAHSV LLSHIFHGRK NFFITTENLL
     ASWNFWTPLL ESLAHKAPRL YPGGAENGRL LDFEFSSGRL FFSQQQPEQL VPGPGPAPMP
     SDFQVLRAKY RESPLVSAWS EELISKLAND IEATAVRAVR RFGQFHLALS GGSSPVALFQ
     QLATAHYGFP WAHTHLWLVD ERCVPLSDPE SNFQGLQAHL LQHVRIPYYN IHPMPVHLQQ
     RLCAEEDQGA QIYAREISAL VANSSFDLVL LGMGADGHTA SLFPQSPTGL DGEQLVVLTT
     SPSQPHRRMS LSLPLINRAK KVAVLVMGRM KREITTLVSR VGHEPKKWPI SGVLPHSGQL
     VWYMDYDAFL G
//