G6PE_MOUSE
ID G6PE_MOUSE Reviewed; 789 AA.
AC Q8CFX1; A2A7A9; B2KGW7; Q8BLH1;
DT 30-MAY-2006, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 137.
DE RecName: Full=GDH/6PGL endoplasmic bifunctional protein {ECO:0000305|PubMed:12831846};
DE Includes:
DE RecName: Full=Hexose-6-phosphate dehydrogenase {ECO:0000303|PubMed:4169027};
DE AltName: Full=Glucose 1-dehydrogenase {ECO:0000305|PubMed:4169027};
DE EC=1.1.1.47 {ECO:0000269|PubMed:4169027};
DE AltName: Full=Glucose-6-phosphate dehydrogenase {ECO:0000305|PubMed:4169027};
DE EC=1.1.1.363 {ECO:0000269|PubMed:12831846, ECO:0000269|PubMed:4169027};
DE Includes:
DE RecName: Full=6-phosphogluconolactonase {ECO:0000303|PubMed:12831846};
DE Short=6PGL {ECO:0000303|PubMed:12831846};
DE EC=3.1.1.31 {ECO:0000269|PubMed:12831846};
DE Flags: Precursor;
GN Name=H6pd {ECO:0000312|MGI:MGI:2140356};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Liver;
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 [4]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, SUBSTRATE
RP SPECIFICITY, PATHWAY, AND TISSUE SPECIFICITY.
RX PubMed=4169027; DOI=10.1016/s0021-9258(18)99426-3;
RA Beutler E., Morrison M.;
RT "Localization and characteristics of hexose 6-phosphate dehydrogenase
RT (glucose dehydrogenase).";
RL J. Biol. Chem. 242:5289-5293(1967).
RN [5]
RP FUNCTION, CATALYTIC ACTIVITY, SUBSTRATE SPECIFICITY, BIOPHYSICOCHEMICAL
RP PROPERTIES, PATHWAY, SUBUNIT, AND SUBCELLULAR LOCATION.
RX PubMed=12831846; DOI=10.1016/s0003-9861(03)00229-7;
RA Clarke J.L., Mason P.J.;
RT "Murine hexose-6-phosphate dehydrogenase: a bifunctional enzyme with broad
RT substrate specificity and 6-phosphogluconolactonase activity.";
RL Arch. Biochem. Biophys. 415:229-234(2003).
RN [6]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=16356929; DOI=10.1074/jbc.m512635200;
RA Lavery G.G., Walker E.A., Draper N., Jeyasuria P., Marcos J.,
RA Shackleton C.H., Parker K.L., White P.C., Stewart P.M.;
RT "Hexose-6-phosphate dehydrogenase knock-out mice lack 11 beta-
RT hydroxysteroid dehydrogenase type 1-mediated glucocorticoid generation.";
RL J. Biol. Chem. 281:6546-6551(2006).
RN [7]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=17656460; DOI=10.1210/en.2007-0593;
RA Rogoff D., Ryder J.W., Black K., Yan Z., Burgess S.C., McMillan D.R.,
RA White P.C.;
RT "Abnormalities of glucose homeostasis and the hypothalamic-pituitary-
RT adrenal axis in mice lacking hexose-6-phosphate dehydrogenase.";
RL Endocrinology 148:5072-5080(2007).
RN [8]
RP TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE.
RX PubMed=18218694; DOI=10.1210/en.2007-1705;
RA Bujalska I.J., Hewitt K.N., Hauton D., Lavery G.G., Tomlinson J.W.,
RA Walker E.A., Stewart P.M.;
RT "Lack of hexose-6-phosphate dehydrogenase impairs lipid mobilization from
RT mouse adipose tissue.";
RL Endocrinology 149:2584-2591(2008).
RN [9]
RP FUNCTION, CATALYTIC ACTIVITY, TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE.
RX PubMed=18222920; DOI=10.1074/jbc.m710067200;
RA Lavery G.G., Walker E.A., Turan N., Rogoff D., Ryder J.W., Shelton J.M.,
RA Richardson J.A., Falciani F., White P.C., Stewart P.M., Parker K.L.,
RA McMillan D.R.;
RT "Deletion of hexose-6-phosphate dehydrogenase activates the unfolded
RT protein response pathway and induces skeletal myopathy.";
RL J. Biol. Chem. 283:8453-8461(2008).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas, Spleen,
RC and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [11]
RP SUCCINYLATION [LARGE SCALE ANALYSIS] AT LYS-205 AND LYS-424, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=23806337; DOI=10.1016/j.molcel.2013.06.001;
RA Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y.,
RA Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.;
RT "SIRT5-mediated lysine desuccinylation impacts diverse metabolic
RT pathways.";
RL Mol. Cell 50:919-930(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 (PubMed:4169027, PubMed:12831846,
CC PubMed:16356929, PubMed:18222920). 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:4169027, PubMed:12831846,
CC PubMed:18222920). In addition, acts as a 6-phosphogluconolactonase and
CC catalyzes the second step of the pentose phosphate pathway
CC (PubMed:12831846). May have a dehydrogenase activity for alternative
CC substrates including glucosamine 6-phosphate and glucose 6-sulfate
CC (PubMed:12831846). The main function of this enzyme is to provide
CC reducing equivalents such as NADPH to maintain the adequate levels of
CC reductive cofactors in the oxidizing environment of the endoplasmic
CC reticulum (PubMed:12831846, PubMed:16356929, PubMed:17656460,
CC PubMed:18222920). By producing NADPH that is needed by reductases of
CC the lumen of the endoplasmic reticulum like corticosteroid 11-beta-
CC dehydrogenase isozyme 1/HSD11B1, indirectly regulates their activity
CC (PubMed:16356929). {ECO:0000269|PubMed:12831846,
CC ECO:0000269|PubMed:16356929, ECO:0000269|PubMed:17656460,
CC ECO:0000269|PubMed:18222920, ECO:0000269|PubMed:4169027}.
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:0000269|PubMed:4169027};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38216;
CC Evidence={ECO:0000305|PubMed:4169027};
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:12831846, ECO:0000269|PubMed:4169027};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:15842;
CC Evidence={ECO:0000305|PubMed:4169027};
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:0000269|PubMed:12831846};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:12557;
CC Evidence={ECO:0000305|PubMed:12831846};
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:0000269|PubMed:4169027};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:62065;
CC Evidence={ECO:0000305|PubMed:4169027};
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:0000269|PubMed:12831846, ECO:0000269|PubMed:18222920,
CC ECO:0000269|PubMed:4169027};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:62069;
CC Evidence={ECO:0000305|PubMed:4169027};
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:12831846,
CC ECO:0000269|PubMed:4169027};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:62073;
CC Evidence={ECO:0000305|PubMed:4169027};
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:0000269|PubMed:4169027};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:62077;
CC Evidence={ECO:0000305|PubMed:4169027};
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:0000269|PubMed:12831846};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:62089;
CC Evidence={ECO:0000305|PubMed:12831846};
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:0000269|PubMed:4169027};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:14294;
CC Evidence={ECO:0000305|PubMed:4169027};
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:0000269|PubMed:4169027};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:14406;
CC Evidence={ECO:0000305|PubMed:4169027};
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:0000269|PubMed:12831846};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:62081;
CC Evidence={ECO:0000305|PubMed:12831846};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=4065 mM for D-glucose (at pH 7.1 in the presence of NADP)
CC {ECO:0000269|PubMed:4169027};
CC KM=725 mM for D-glucose (at pH 7.1 in the presence of NAD)
CC {ECO:0000269|PubMed:4169027};
CC KM=532 mM for D-glucose (at pH 9.6 in the presence of NAD)
CC {ECO:0000269|PubMed:4169027};
CC KM=120 uM for D-glucose 6-phosphate (at pH 9.6 in the presence of
CC NADP) {ECO:0000269|PubMed:4169027};
CC KM=28 uM for D-glucose 6-phosphate (at pH 9.6 in the presence of NAD)
CC {ECO:0000269|PubMed:4169027};
CC KM=66 uM for 2-deoxy-D-glucose 6-phosphate (at pH 7.1 in the presence
CC of NADP) {ECO:0000269|PubMed:4169027};
CC KM=12 uM for 2-deoxy-D-glucose 6-phosphate (at pH 7.1 in the presence
CC of NAD) {ECO:0000269|PubMed:4169027};
CC KM=5.89 mM for 2-deoxy-D-glucose 6-phosphate (at pH 9.6 in the
CC presence of NADP) {ECO:0000269|PubMed:4169027};
CC KM=4.35 mM for 2-deoxy-D-glucose 6-phosphate (at pH 9.6 in the
CC presence of NAD) {ECO:0000269|PubMed:4169027};
CC KM=7 uM for D-galactopyranose 6-phosphate (at pH 7.1 in the presence
CC of NADP) {ECO:0000269|PubMed:4169027};
CC KM=504 uM for D-galactopyranose 6-phosphate (at pH 9.6 in the
CC presence of NADP) {ECO:0000269|PubMed:4169027};
CC KM=223 uM for D-galactopyranose 6-phosphate (at pH 7.1 in the
CC presence of NAD) {ECO:0000269|PubMed:4169027};
CC KM=9 uM for NADP (at pH 7.1 in the presence of galactose 6-phosphate)
CC {ECO:0000269|PubMed:4169027};
CC KM=14 uM for NADP (at pH 9.6 in the presence of galactose 6-
CC phosphate) {ECO:0000269|PubMed:4169027};
CC KM=4 uM for NADP (at pH 9.6 in the presence of D-glucose 6-phosphate)
CC {ECO:0000269|PubMed:4169027};
CC KM=12 uM for NADP (at pH 7.1 in the presence of D-glucose)
CC {ECO:0000269|PubMed:4169027};
CC KM=52 uM for NAD (at pH 7.1 in the presence of D-glucose)
CC {ECO:0000269|PubMed:4169027};
CC KM=47 uM for NADP (at pH 9.6 in the presence of D-glucose)
CC {ECO:0000269|PubMed:4169027};
CC KM=261 uM for NAD (at pH 9.6 in the presence of D-glucose)
CC {ECO:0000269|PubMed:4169027};
CC KM=34 uM for NAD (at pH 7.1 in the presence of D-glucose)
CC {ECO:0000269|PubMed:4169027};
CC KM=72 uM for NAD (at pH 9.6 in the presence of D-glucose)
CC {ECO:0000269|PubMed:4169027};
CC pH dependence:
CC Optimum pH is 6.0-8.0. {ECO:0000269|PubMed:12831846};
CC -!- PATHWAY: Carbohydrate degradation; pentose phosphate pathway; D-
CC ribulose 5-phosphate from D-glucose 6-phosphate (oxidative stage).
CC {ECO:0000269|PubMed:12831846, ECO:0000269|PubMed:4169027}.
CC -!- PATHWAY: Carbohydrate degradation; pentose phosphate pathway; D-
CC ribulose 5-phosphate from D-glucose 6-phosphate (oxidative stage): step
CC 2/3. {ECO:0000269|PubMed:12831846}.
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:12831846}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum lumen
CC {ECO:0000305|PubMed:12831846}.
CC -!- TISSUE SPECIFICITY: Expressed in liver (at protein level)
CC (PubMed:4169027). Expressed in muscles (PubMed:18222920). Expressed in
CC adipose tissues (PubMed:18218694). {ECO:0000269|PubMed:18218694,
CC ECO:0000269|PubMed:18222920, ECO:0000269|PubMed:4169027}.
CC -!- DISRUPTION PHENOTYPE: Mice lacking H6pd are born at the expected
CC Mendelian frequency and do not show overt phenotype (PubMed:16356929).
CC However, they display cellular inability to convert 11-
CC dehydrocorticosterone (11-DHC) to corticosterone and present increased
CC corticosterone to 11-DHC conversion associated with adrenal hyperplasia
CC (PubMed:16356929). Mutant mice also display fasting hypoglycemia and
CC perturbed lipid mobilization that are probably due to the
CC aforementioned effect on corticosterone metabolism and blunted
CC intracellular action of the hormone (PubMed:17656460, PubMed:18218694).
CC Skeletal myopathy associated with a dysregulation of the expression of
CC proteins associated with calcium homeostasis in the sarcoplasmic
CC reticulum and an activation of the unfolded protein response are also
CC observed (PubMed:18222920). {ECO:0000269|PubMed:16356929,
CC ECO:0000269|PubMed:17656460, ECO:0000269|PubMed:18218694,
CC ECO:0000269|PubMed:18222920}.
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 -!- SEQUENCE CAUTION:
CC Sequence=BAC32260.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AK045199; BAC32260.1; ALT_INIT; mRNA.
DR EMBL; AK159373; BAE35029.1; -; mRNA.
DR EMBL; AL606914; CAM16119.1; -; Genomic_DNA.
DR EMBL; CU463327; CAQ51682.1; -; Genomic_DNA.
DR EMBL; BC042677; AAH42677.1; -; mRNA.
DR CCDS; CCDS71524.1; -.
DR RefSeq; NP_001277933.1; NM_001291004.1.
DR RefSeq; NP_775547.2; NM_173371.4.
DR AlphaFoldDB; Q8CFX1; -.
DR SMR; Q8CFX1; -.
DR BioGRID; 221399; 2.
DR STRING; 10090.ENSMUSP00000030830; -.
DR GlyConnect; 2334; 2 N-Linked glycans (1 site).
DR GlyGen; Q8CFX1; 3 sites, 2 N-linked glycans (1 site).
DR iPTMnet; Q8CFX1; -.
DR PhosphoSitePlus; Q8CFX1; -.
DR SwissPalm; Q8CFX1; -.
DR EPD; Q8CFX1; -.
DR jPOST; Q8CFX1; -.
DR MaxQB; Q8CFX1; -.
DR PaxDb; Q8CFX1; -.
DR PRIDE; Q8CFX1; -.
DR ProteomicsDB; 271657; -.
DR Antibodypedia; 1350; 318 antibodies from 28 providers.
DR DNASU; 100198; -.
DR Ensembl; ENSMUST00000084117; ENSMUSP00000081134; ENSMUSG00000028980.
DR GeneID; 100198; -.
DR KEGG; mmu:100198; -.
DR UCSC; uc008vxh.2; mouse.
DR CTD; 9563; -.
DR MGI; MGI:2140356; H6pd.
DR VEuPathDB; HostDB:ENSMUSG00000028980; -.
DR eggNOG; KOG0563; Eukaryota.
DR eggNOG; KOG3147; Eukaryota.
DR GeneTree; ENSGT00530000063435; -.
DR HOGENOM; CLU_018975_0_0_1; -.
DR InParanoid; Q8CFX1; -.
DR OMA; DLHIFGQ; -.
DR OrthoDB; 383995at2759; -.
DR SABIO-RK; Q8CFX1; -.
DR UniPathway; UPA00115; UER00409.
DR BioGRID-ORCS; 100198; 0 hits in 72 CRISPR screens.
DR PRO; PR:Q8CFX1; -.
DR Proteomes; UP000000589; Chromosome 4.
DR RNAct; Q8CFX1; protein.
DR Bgee; ENSMUSG00000028980; Expressed in left lobe of liver and 191 other tissues.
DR ExpressionAtlas; Q8CFX1; baseline and differential.
DR Genevisible; Q8CFX1; MM.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005783; C:endoplasmic reticulum; IMP:MGI.
DR GO; GO:0005788; C:endoplasmic reticulum lumen; ISS:UniProtKB.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:MGI.
DR GO; GO:0005739; C:mitochondrion; ISO:MGI.
DR GO; GO:0016529; C:sarcoplasmic reticulum; IMP:MGI.
DR GO; GO:0017057; F:6-phosphogluconolactonase activity; IDA:MGI.
DR GO; GO:0030246; F:carbohydrate binding; ISO:MGI.
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:MGI.
DR GO; GO:0050661; F:NADP binding; ISO:MGI.
DR GO; GO:0005975; P:carbohydrate metabolic process; ISO:MGI.
DR GO; GO:0006006; P:glucose metabolic process; IBA:GO_Central.
DR GO; GO:0006739; P:NADP metabolic process; ISO:MGI.
DR GO; GO:0006098; P:pentose-phosphate shunt; IDA:MGI.
DR GO; GO:0009051; P:pentose-phosphate shunt, oxidative branch; ISS:UniProtKB.
DR GO; GO:2000064; P:regulation of cortisol biosynthetic process; IMP:UniProtKB.
DR CDD; cd01400; 6PGL; 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 PANTHER; PTHR23429; PTHR23429; 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; SSF100950; SSF100950; 1.
DR SUPFAM; SSF51735; SSF51735; 1.
DR TIGRFAMs; TIGR01198; pgl; 1.
DR PROSITE; PS00069; G6P_DEHYDROGENASE; 1.
PE 1: Evidence at protein level;
KW Carbohydrate metabolism; Endoplasmic reticulum; Glucose metabolism;
KW Glycoprotein; Hydrolase; Multifunctional enzyme; NAD; NADP; Oxidoreductase;
KW Pyrrolidone carboxylic acid; Reference proteome; Signal.
FT SIGNAL 1..16
FT /evidence="ECO:0000250|UniProtKB:P56201"
FT CHAIN 17..789
FT /note="GDH/6PGL endoplasmic bifunctional protein"
FT /id="PRO_0000236794"
FT REGION 17..524
FT /note="Hexose-6-phosphate dehydrogenase"
FT /evidence="ECO:0000305"
FT REGION 525..538
FT /note="Linker"
FT /evidence="ECO:0000305"
FT REGION 539..789
FT /note="6-phosphogluconolactonase"
FT /evidence="ECO:0000305"
FT ACT_SITE 264
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:P11411"
FT BINDING 29..36
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:P11413"
FT BINDING 146
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:P11413"
FT BINDING 171
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:P11413"
FT BINDING 171
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P11413"
FT BINDING 201..205
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P11413"
FT BINDING 240
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P11413"
FT BINDING 259
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P11413"
FT BINDING 357
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P11413"
FT BINDING 362
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P11413"
FT MOD_RES 17
FT /note="Pyrrolidone carboxylic acid"
FT /evidence="ECO:0000250|UniProtKB:P56201"
FT MOD_RES 205
FT /note="N6-succinyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 424
FT /note="N6-succinyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT CARBOHYD 154
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 279
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 681
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CONFLICT 77
FT /note="V -> A (in Ref. 1; BAE35029, 2; CAQ51682 and 3;
FT AAH42677)"
FT /evidence="ECO:0000305"
FT CONFLICT 106
FT /note="R -> H (in Ref. 1; BAE35029, 2; CAQ51682 and 3;
FT AAH42677)"
FT /evidence="ECO:0000305"
FT CONFLICT 285
FT /note="A -> T (in Ref. 1; BAE35029, 2; CAQ51682 and 3;
FT AAH42677)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 789 AA; 88928 MW; E970CE8B35D3E1E5 CRC64;
MLLAAMCLAL LGCLQAQELK GHVSIILLGA TGDLAKKYLW QGLFQLYLDE AGKGHSFSFH
GAALTAPQQG QKLMDKVLES LSCPKDLVPS RCDELKGQFL QLSQYRQLKT VEDYQTLNKD
IETQVQQDGL WEAGRIFYFS VPPFAYADIA RNINSSCRPH PGAWLRVVFE KPFGHDHLSA
QQLASELGSF FQEEEMYRVD HYLGKQAVAQ ILPFRDQNRK ALDGLWNRHH VERVEIILKE
TIDAEGRASF YEEYGVIRDT LQNHLTEILT LVAMELPLNI SSSAAVLQHK LWAFQALRGL
QKSSAILGQY QAYSGQVRRE LQKPDGFQSL TPTFAGVLVH IDNLRWEGVP FILMSGKALD
ERVGYVRIVF KNRAYCTQSE RHWVPEQSRC LPQQIIFYIG HGELGHPAIL VSRNLFKPSL
PTQKWKEVQD QPGLRLFGRP LSDYYAYRPV REQDAYSTLL SHIFHCRKES FITTENLLAS
WVFWTPLLDS LAFEVPRPYP GGAENGQLLD FEFSGGQLTF SQQQLEVLIP DLGSVPKPSD
FQVLGARYRQ SPLITAWPEE LISKLASDIE AAAVQAVRHF GKFHLALSGG SSPIALFQQL
ATGHYSFPWA HTHLWLVDER CVPLSDPDSN FQGLQAHLLQ HVRVPYYNIH PMPVHLHQRL
CAEEDQGAQT YASEISALVA NSSFDLVLLG MGTDGHTASL FPQSPTGLDG DQLVVLTESP
FRPHQRMSLS LPLINRAKKV AVLVMGRTKR EITTLVSRVG HEPKKWPISG VVPLSGQLVW
YMDYEAFLG
