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";
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
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 Genevisible; O95479; HS.
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.
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
//
