G6PD_RAT
ID G6PD_RAT Reviewed; 515 AA.
AC P05370;
DT 01-NOV-1988, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 176.
DE RecName: Full=Glucose-6-phosphate 1-dehydrogenase;
DE Short=G6PD;
DE EC=1.1.1.49 {ECO:0000250|UniProtKB:P11413};
GN Name=G6pdx; Synonyms=G6pd;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Sprague-Dawley; TISSUE=Liver;
RX PubMed=3412913; DOI=10.1093/nar/16.15.7746;
RA Ho Y., Howard A.J., Crapo J.D.;
RT "Cloning and sequence of a cDNA encoding rat glucose-6-phosphate
RT dehydrogenase.";
RL Nucleic Acids Res. 16:7746-7746(1988).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Kidney;
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 [3]
RP PROTEIN SEQUENCE OF 2-514, CLEAVAGE OF INITIATOR METHIONINE, AND
RP ACETYLATION AT ALA-2.
RC STRAIN=Wistar; TISSUE=Liver;
RX PubMed=2606104; DOI=10.1111/j.1432-1033.1989.tb15242.x;
RA Jeffery J., Barros-Soederling J., Murray L., Wood I., Hansen R.,
RA Szepesi B., Joernvall H.;
RT "Glucose-6-phosphate dehydrogenase. Characteristics revealed by the rat
RT liver enzyme structure.";
RL Eur. J. Biochem. 186:551-556(1989).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 41-515.
RA Fritz R.S., Kletzien R.F.;
RL Submitted (NOV-1989) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP PROTEIN SEQUENCE OF 58-72; 176-192 AND 228-257, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RC STRAIN=Sprague-Dawley; TISSUE=Spinal cord;
RA Lubec G., Afjehi-Sadat L.;
RL Submitted (NOV-2006) to UniProtKB.
CC -!- FUNCTION: Cytosolic glucose-6-phosphate dehydrogenase that catalyzes
CC the first and rate-limiting step of the oxidative branch within the
CC pentose phosphate pathway/shunt, an alternative route to glycolysis for
CC the dissimilation of carbohydrates and a major source of reducing power
CC and metabolic intermediates for fatty acid and nucleic acid
CC biosynthetic processes. {ECO:0000250|UniProtKB:P11413}.
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=1.1.1.49;
CC Evidence={ECO:0000250|UniProtKB:P11413};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:15842;
CC Evidence={ECO:0000250|UniProtKB:P11413};
CC -!- PATHWAY: Carbohydrate degradation; pentose phosphate pathway; D-
CC ribulose 5-phosphate from D-glucose 6-phosphate (oxidative stage): step
CC 1/3. {ECO:0000250|UniProtKB:P11413}.
CC -!- SUBUNIT: Homotetramer; dimer of dimers. Interacts with SIRT2; the
CC interaction is enhanced by H(2)O(2) treatment (By similarity).
CC {ECO:0000250|UniProtKB:P11413}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol
CC {ECO:0000250|UniProtKB:P11413}. Membrane
CC {ECO:0000250|UniProtKB:P11413}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:P11413}.
CC -!- PTM: Acetylated by ELP3 at Lys-403; acetylation inhibits its
CC homodimerization and enzyme activity. Deacetylated by SIRT2 at Lys-403;
CC deacetylation stimulates its enzyme activity (By similarity).
CC {ECO:0000250|UniProtKB:P11413}.
CC -!- MISCELLANEOUS: Has NADP both as cofactor (bound to the N-terminal
CC domain) and as structural element bound to the C-terminal domain.
CC -!- SIMILARITY: Belongs to the glucose-6-phosphate dehydrogenase family.
CC {ECO:0000305}.
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DR EMBL; X07467; CAA30355.1; -; mRNA.
DR EMBL; BC081820; AAH81820.1; -; mRNA.
DR EMBL; M26655; AAA41179.1; -; Genomic_DNA.
DR EMBL; M26653; AAA41179.1; JOINED; Genomic_DNA.
DR EMBL; M26654; AAA41179.1; JOINED; Genomic_DNA.
DR PIR; S01233; S01233.
DR RefSeq; NP_058702.1; NM_017006.2.
DR AlphaFoldDB; P05370; -.
DR SMR; P05370; -.
DR BioGRID; 246548; 2.
DR IntAct; P05370; 4.
DR STRING; 10116.ENSRNOP00000053157; -.
DR iPTMnet; P05370; -.
DR PhosphoSitePlus; P05370; -.
DR World-2DPAGE; 0004:P05370; -.
DR jPOST; P05370; -.
DR PaxDb; P05370; -.
DR PRIDE; P05370; -.
DR Ensembl; ENSRNOT00000080887; ENSRNOP00000075297; ENSRNOG00000056728.
DR GeneID; 24377; -.
DR KEGG; rno:24377; -.
DR CTD; 2539; -.
DR RGD; 2645; G6pdx.
DR eggNOG; KOG0563; Eukaryota.
DR GeneTree; ENSGT00530000063435; -.
DR HOGENOM; CLU_013524_2_3_1; -.
DR InParanoid; P05370; -.
DR OMA; VEICVYE; -.
DR OrthoDB; 383995at2759; -.
DR PhylomeDB; P05370; -.
DR TreeFam; TF300584; -.
DR BRENDA; 1.1.1.49; 5301.
DR Reactome; R-RNO-5628897; TP53 Regulates Metabolic Genes.
DR Reactome; R-RNO-71336; Pentose phosphate pathway.
DR SABIO-RK; P05370; -.
DR UniPathway; UPA00115; UER00408.
DR PRO; PR:P05370; -.
DR Proteomes; UP000002494; Chromosome X.
DR Bgee; ENSRNOG00000056728; Expressed in ovary and 20 other tissues.
DR Genevisible; P05370; RN.
DR GO; GO:0034451; C:centriolar satellite; IEA:Ensembl.
DR GO; GO:0009898; C:cytoplasmic side of plasma membrane; ISO:RGD.
DR GO; GO:0005829; C:cytosol; IDA:RGD.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:RGD.
DR GO; GO:0005634; C:nucleus; IDA:RGD.
DR GO; GO:0030246; F:carbohydrate binding; IDA:RGD.
DR GO; GO:0005536; F:glucose binding; IDA:RGD.
DR GO; GO:0004345; F:glucose-6-phosphate dehydrogenase activity; IDA:RGD.
DR GO; GO:0042802; F:identical protein binding; ISO:RGD.
DR GO; GO:0050661; F:NADP binding; IDA:RGD.
DR GO; GO:0042803; F:protein homodimerization activity; ISO:RGD.
DR GO; GO:0001998; P:angiotensin-mediated vasoconstriction involved in regulation of systemic arterial blood pressure; ISO:RGD.
DR GO; GO:0002033; P:angiotensin-mediated vasodilation involved in regulation of systemic arterial blood pressure; ISO:RGD.
DR GO; GO:0034599; P:cellular response to oxidative stress; ISO:RGD.
DR GO; GO:0006695; P:cholesterol biosynthetic process; ISO:RGD.
DR GO; GO:0048821; P:erythrocyte development; ISO:RGD.
DR GO; GO:0043249; P:erythrocyte maturation; ISO:RGD.
DR GO; GO:0051156; P:glucose 6-phosphate metabolic process; IDA:RGD.
DR GO; GO:0006006; P:glucose metabolic process; IBA:GO_Central.
DR GO; GO:0006749; P:glutathione metabolic process; ISO:RGD.
DR GO; GO:0006741; P:NADP biosynthetic process; ISO:RGD.
DR GO; GO:0006739; P:NADP metabolic process; ISS:UniProtKB.
DR GO; GO:0006740; P:NADPH regeneration; ISO:RGD.
DR GO; GO:0061052; P:negative regulation of cell growth involved in cardiac muscle cell development; IMP:RGD.
DR GO; GO:0010734; P:negative regulation of protein glutathionylation; ISO:RGD.
DR GO; GO:2000378; P:negative regulation of reactive oxygen species metabolic process; IMP:RGD.
DR GO; GO:0019322; P:pentose biosynthetic process; ISO:RGD.
DR GO; GO:0006098; P:pentose-phosphate shunt; IDA:RGD.
DR GO; GO:0009051; P:pentose-phosphate shunt, oxidative branch; IMP:RGD.
DR GO; GO:1904879; P:positive regulation of calcium ion transmembrane transport via high voltage-gated calcium channel; IMP:RGD.
DR GO; GO:0040014; P:regulation of multicellular organism growth; ISO:RGD.
DR GO; GO:0043523; P:regulation of neuron apoptotic process; IDA:RGD.
DR GO; GO:0045471; P:response to ethanol; IDA:RGD.
DR GO; GO:0032094; P:response to food; IEP:RGD.
DR GO; GO:0010041; P:response to iron(III) ion; IEP:RGD.
DR GO; GO:0014070; P:response to organic cyclic compound; IEP:RGD.
DR GO; GO:0006979; P:response to oxidative stress; ISO:RGD.
DR GO; GO:0046390; P:ribose phosphate biosynthetic process; ISO:RGD.
DR HAMAP; MF_00966; G6PD; 1.
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; IPR036291; NAD(P)-bd_dom_sf.
DR PANTHER; PTHR23429; PTHR23429; 1.
DR Pfam; PF02781; G6PD_C; 1.
DR Pfam; PF00479; G6PD_N; 1.
DR PIRSF; PIRSF000110; G6PD; 1.
DR PRINTS; PR00079; G6PDHDRGNASE.
DR SUPFAM; SSF51735; SSF51735; 1.
DR TIGRFAMs; TIGR00871; zwf; 1.
DR PROSITE; PS00069; G6P_DEHYDROGENASE; 1.
PE 1: Evidence at protein level;
KW Acetylation; Carbohydrate metabolism; Cytoplasm; Direct protein sequencing;
KW Glucose metabolism; Hydroxylation; Membrane; NADP; Oxidoreductase;
KW Phosphoprotein; Reference proteome.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:2606104"
FT CHAIN 2..515
FT /note="Glucose-6-phosphate 1-dehydrogenase"
FT /id="PRO_0000068087"
FT ACT_SITE 263
FT /note="Proton acceptor"
FT /evidence="ECO:0000250"
FT BINDING 38..45
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 72
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 147
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 171
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 171
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 201..205
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 239
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 258
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 357
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 360
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 365
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 366
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 370
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 393
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 395
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 401..403
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 421..423
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 487
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 503
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 509
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000269|PubMed:2606104"
FT MOD_RES 8
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P11413"
FT MOD_RES 10
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P11413"
FT MOD_RES 89
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P11413"
FT MOD_RES 171
FT /note="N6-(2-hydroxyisobutyryl)lysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P11413"
FT MOD_RES 171
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P11413"
FT MOD_RES 403
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P11413"
FT MOD_RES 432
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P11413"
FT MOD_RES 497
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P11413"
FT MOD_RES 503
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P11413"
FT CONFLICT 320
FT /note="N -> D (in Ref. 3; AA sequence)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 515 AA; 59376 MW; 8E92FFF3BF5A959B CRC64;
MAEQVALSRT QVCGILREEL YQGDAFHQAD THIFIIMGAS GDLAKKKIYP TIWWLFRDGL
LPEDTFIVGY ARSRLTVDDI RKQSEPFFKV TPEERPKLEE FFARNSYVAG QYDDPASYKH
LNSHMNALHQ GMQANRLFYL ALPPTVYEAV TKNIQEICMS QTGWNRIIVE KPFGRDLQSS
NQLSNHISSL FREDQIYRID HYLGKEMVQN LMVLRFANRI FGPIWNRDNI ACVILTFKEP
FGTEGRGGYF DEFGIIRDVM QNHLLQMLCL VAMEKPASTD SDDVRDEKVK VLKCISEVET
DNVVLGQYVG NPSGEGEATN GYLDDPTVPH GSTTATFAAA VLYVENERWD GVPFILRCGK
ALNERKAEVR LQFRDVAGDI FHQQCKRNEL VIRVQPNEAV YTKMMTKKPG MFFNPEESEL
DLTYGNRYKN VKLPDAYERL ILDVFCGSQM HFVRSDELRE AWRIFTPLLH KIDREKPQPI
PYVYGSRGPT EADELMKRVG FQYEGTYKWV NPHKL
