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 27-MAR-2024, entry version 146. 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, RC Spleen, 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 CC 6-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}; 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; 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 GlyCosmos; Q8CFX1; 3 sites, 2 glycans. DR GlyGen; Q8CFX1; 5 sites, 2 N-linked glycans (1 site), 1 O-linked glycan (2 sites). DR iPTMnet; Q8CFX1; -. DR PhosphoSitePlus; Q8CFX1; -. DR SwissPalm; Q8CFX1; -. DR EPD; Q8CFX1; -. DR jPOST; Q8CFX1; -. DR MaxQB; Q8CFX1; -. DR PaxDb; 10090-ENSMUSP00000030830; -. DR ProteomicsDB; 271657; -. DR Pumba; Q8CFX1; -. DR Antibodypedia; 1350; 350 antibodies from 28 providers. DR DNASU; 100198; -. DR Ensembl; ENSMUST00000084117.13; ENSMUSP00000081134.7; ENSMUSG00000028980.15. DR GeneID; 100198; -. DR KEGG; mmu:100198; -. DR UCSC; uc008vxh.2; mouse. DR AGR; MGI:2140356; -. 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; YCPQSGT; -. DR OrthoDB; 989808at2759; -. DR SABIO-RK; Q8CFX1; -. DR UniPathway; UPA00115; UER00409. DR BioGRID-ORCS; 100198; 1 hit in 77 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 193 other cell types or tissues. DR ExpressionAtlas; Q8CFX1; baseline and differential. DR GO; GO:0005783; C:endoplasmic reticulum; IMP:MGI. DR GO; GO:0005788; C:endoplasmic reticulum lumen; ISS:UniProtKB. 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: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 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; Q8CFX1; MM. 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 //