ID G6PE_HUMAN Reviewed; 791 AA. AC O95479; Q4TT33; Q66I35; Q68DT3; DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot. DT 30-MAY-2006, sequence version 2. DT 13-FEB-2019, entry version 168. DE RecName: Full=GDH/6PGL endoplasmic bifunctional protein; DE Includes: DE RecName: Full=Glucose 1-dehydrogenase; DE EC=1.1.1.47; DE AltName: Full=Glucose-6-phosphate dehydrogenase; DE EC=1.1.1.363; DE Includes: DE RecName: Full=6-phosphogluconolactonase; DE Short=6PGL; DE EC=3.1.1.31; DE Flags: Precursor; GN Name=H6PD; Synonyms=GDH; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. 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., RA Vulliamy T.J.; RT "Human hexose-6-phosphate dehydrogenase (glucose 1-dehydrogenase) RT encoded at 1p36: coding sequence and expression."; RL Blood Cells Mol. Dis. 25:30-36(1999). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANTS ALA-151 AND RP GLN-453. 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., RA Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., RA Ottenwaelder B., Poustka A., 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., RA Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., RA Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., RA McDonald L., Evans R., Phillips K., Atkinson A., Cooper R., Jones C., RA Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., RA Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., RA Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., RA Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., RA Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., RA Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., RA 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., RA Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., RA Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., RA Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., RA Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., RA Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., RA Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., RA Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., RA 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., RA Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., RA Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., RA Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., RA Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., RA Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., RA 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 RT project: 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 RT multiple 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., RA Wang L., Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human RT liver 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., RA Ayoub D., 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, AND CHARACTERIZATION OF VARIANT CORTRD1 RP GLN-453. 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 RT type 1 and hexose-6-phosphate dehydrogenase interact to cause RT cortisone reductase deficiency."; RL Nat. Genet. 34:434-439(2003). RN [9] RP VARIANT CORTRD1 LEU-146, AND CHARACTERIZATION OF VARIANT CORTRD1 RP LEU-146. RX PubMed=23132696; DOI=10.1530/EJE-12-0628; RA Lavery G.G., Idkowiak J., Sherlock M., Bujalska I., Ride J.P., RA Saqib K., Hartmann M.F., Hughes B., Wudy S.A., De Schepper J., RA Arlt W., Krone N., Shackleton C.H., Walker E.A., Stewart P.M.; RT "Novel H6PDH mutations in two girls with premature adrenarche: RT 'apparent' and 'true' CRD can be differentiated by urinary steroid RT profiling."; RL Eur. J. Endocrinol. 168:K19-K26(2013). CC -!- FUNCTION: Oxidizes glucose-6-phosphate and glucose, as well as CC other hexose-6-phosphates. 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; CC EC=1.1.1.47; Evidence={ECO:0000255|PROSITE-ProRule:PRU10005}; CC -!- CATALYTIC ACTIVITY: CC Reaction=D-glucose + NADP(+) = D-glucono-1,5-lactone + H(+) + CC NADPH; Xref=Rhea:RHEA:14405, ChEBI:CHEBI:4167, CC ChEBI:CHEBI:15378, ChEBI:CHEBI:16217, ChEBI:CHEBI:57783, CC ChEBI:CHEBI:58349; EC=1.1.1.47; Evidence={ECO:0000255|PROSITE- CC ProRule:PRU10005}; 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 -!- CATALYTIC ACTIVITY: CC Reaction=D-glucose 6-phosphate + NADP(+) = 6-phospho-D-glucono- CC 1,5-lactone + H(+) + NADPH; Xref=Rhea:RHEA:15841, CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57783, ChEBI:CHEBI:57955, CC ChEBI:CHEBI:58349, ChEBI:CHEBI:61548; EC=1.1.1.363; CC -!- CATALYTIC ACTIVITY: CC Reaction=6-phospho-D-glucono-1,5-lactone + H2O = 6-phospho-D- CC gluconate + H(+); Xref=Rhea:RHEA:12556, ChEBI:CHEBI:15377, CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57955, ChEBI:CHEBI:58759; CC EC=3.1.1.31; CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum lumen. CC Note=Microsomes, endoplasmic reticulum lumen. CC -!- TISSUE SPECIFICITY: Present in most tissues examined, strongest in CC liver. CC -!- DISEASE: Cortisone reductase deficiency 1 (CORTRD1) [MIM:604931]: CC An autosomal recessive error of cortisone metabolism characterized CC by a failure to regenerate cortisol from cortisone, resulting in CC increased cortisol clearance, activation of the CC hypothalamic- pituitary axis and ACTH-mediated adrenal androgen CC excess. Clinical features include hyperandrogenism resulting in CC hirsutism, oligo- amenorrhea, and infertility in females and CC premature pseudopuberty in males. {ECO:0000269|PubMed:12858176, CC ECO:0000269|PubMed:23132696}. Note=The disease is caused by CC mutations affecting the gene represented in this 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 -!- SEQUENCE CAUTION: CC Sequence=CAH18137.1; Type=Erroneous initiation; Evidence={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=A&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; ALT_INIT; mRNA. DR EMBL; Z98044; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC081559; AAH81559.1; -; mRNA. DR CCDS; CCDS101.1; -. DR RefSeq; NP_004276.2; NM_004285.3. DR RefSeq; XP_006711115.1; XM_006711052.3. DR RefSeq; XP_016858354.1; XM_017002865.1. DR UniGene; Hs.463511; -. DR ProteinModelPortal; O95479; -. DR SMR; O95479; -. DR BioGrid; 114933; 5. DR IntAct; O95479; 1. DR STRING; 9606.ENSP00000366620; -. DR BindingDB; O95479; -. DR DrugBank; DB00157; NADH. DR GlyConnect; 1264; -. DR iPTMnet; O95479; -. DR PhosphoSitePlus; O95479; -. DR BioMuta; H6PD; -. DR EPD; O95479; -. DR jPOST; O95479; -. DR MaxQB; O95479; -. DR PaxDb; O95479; -. DR PeptideAtlas; O95479; -. DR PRIDE; O95479; -. DR ProteomicsDB; 50910; -. DR Ensembl; ENST00000377403; ENSP00000366620; ENSG00000049239. DR GeneID; 9563; -. DR KEGG; hsa:9563; -. DR UCSC; uc001apt.4; human. DR CTD; 9563; -. DR DisGeNET; 9563; -. DR EuPathDB; HostDB:ENSG00000049239.12; -. DR GeneCards; H6PD; -. DR H-InvDB; HIX0000104; -. DR HGNC; HGNC:4795; H6PD. DR HPA; HPA004824; -. DR HPA; HPA005440; -. 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 eggNOG; KOG0563; Eukaryota. DR eggNOG; KOG3147; Eukaryota. DR eggNOG; COG0363; LUCA. DR eggNOG; COG0364; LUCA. DR GeneTree; ENSGT00530000063435; -. DR HOGENOM; HOG000231077; -. DR HOVERGEN; HBG005780; -. DR InParanoid; O95479; -. DR KO; K13937; -. DR OrthoDB; 383995at2759; -. DR PhylomeDB; O95479; -. DR TreeFam; TF354247; -. DR BioCyc; MetaCyc:HS00614-MONOMER; -. DR SABIO-RK; O95479; -. DR ChiTaRS; H6PD; human. DR GeneWiki; H6PD; -. DR GenomeRNAi; 9563; -. DR PRO; PR:O95479; -. DR Proteomes; UP000005640; Chromosome 1. DR Bgee; ENSG00000049239; Expressed in 225 organ(s), highest expression level in saliva-secreting gland. DR ExpressionAtlas; O95479; baseline and differential. DR Genevisible; O95479; HS. DR GO; GO:0005788; C:endoplasmic reticulum lumen; IEA:UniProtKB-SubCell. DR GO; GO:0017057; F:6-phosphogluconolactonase activity; IEA:UniProtKB-EC. DR GO; GO:0047936; F:glucose 1-dehydrogenase [NAD(P)] activity; IEA:UniProtKB-EC. DR GO; GO:0004345; F:glucose-6-phosphate dehydrogenase activity; TAS:ProtInc. DR GO; GO:0050661; F:NADP binding; IEA:InterPro. DR GO; GO:0006006; P:glucose metabolic process; IEA:UniProtKB-KW. DR GO; GO:0006098; P:pentose-phosphate shunt; IEA:InterPro. 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; Complete proteome; Disease mutation; KW Endoplasmic reticulum; Glucose metabolism; Glycoprotein; Hydrolase; KW Multifunctional enzyme; NAD; NADP; Oxidoreductase; Polymorphism; KW Pyrrolidone carboxylic acid; Reference proteome; Signal. FT SIGNAL 1 19 {ECO:0000250}. FT CHAIN 20 791 GDH/6PGL endoplasmic bifunctional FT protein. FT /FTId=PRO_0000010442. FT REGION 20 526 Glucose 1-dehydrogenase. FT REGION 527 540 Linker. FT REGION 541 791 6-phosphogluconolactonase. FT ACT_SITE 267 267 Proton acceptor. {ECO:0000250}. FT BINDING 34 34 NADP. {ECO:0000250}. FT BINDING 66 66 NADP. {ECO:0000250}. FT BINDING 204 204 Substrate. {ECO:0000255|PROSITE- FT ProRule:PRU10005}. FT BINDING 208 208 Substrate. {ECO:0000255|PROSITE- FT ProRule:PRU10005}. FT MOD_RES 20 20 Pyrrolidone carboxylic acid. FT {ECO:0000250|UniProtKB:P56201}. FT MOD_RES 208 208 N6-succinyllysine. FT {ECO:0000250|UniProtKB:Q8CFX1}. FT CARBOHYD 157 157 N-linked (GlcNAc...) asparagine. FT {ECO:0000269|PubMed:19159218}. FT CARBOHYD 282 282 N-linked (GlcNAc...) asparagine. FT {ECO:0000269|PubMed:19159218}. FT CARBOHYD 683 683 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT VARIANT 146 146 P -> L (in CORTRD1; results in reduced FT enzymatic activity). FT {ECO:0000269|PubMed:23132696}. FT /FTId=VAR_069193. FT VARIANT 151 151 D -> A (in dbSNP:rs34603401). FT {ECO:0000269|PubMed:17974005}. FT /FTId=VAR_049117. FT VARIANT 218 218 R -> Q (in dbSNP:rs35525021). FT /FTId=VAR_049118. FT VARIANT 453 453 R -> Q (in CORTRD1; less than 50% of FT activity than wild-type; FT dbSNP:rs6688832). FT {ECO:0000269|PubMed:12858176, FT ECO:0000269|PubMed:15489334, FT ECO:0000269|PubMed:17974005}. FT /FTId=VAR_026487. FT VARIANT 484 484 N -> D (in dbSNP:rs35404275). FT /FTId=VAR_049119. FT VARIANT 554 554 P -> L (in dbSNP:rs17368528). FT /FTId=VAR_049120. FT CONFLICT 339 339 A -> G (in Ref. 1; CAA10071). FT {ECO:0000305}. 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 //