G6PE_RABIT
ID G6PE_RABIT Reviewed; 797 AA.
AC P56201; G1SE36;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 26-FEB-2020, sequence version 3.
DT 03-AUG-2022, entry version 123.
DE RecName: Full=GDH/6PGL endoplasmic bifunctional protein {ECO:0000250|UniProtKB:Q8CFX1};
DE Includes:
DE RecName: Full=Hexose-6-phosphate dehydrogenase {ECO:0000250|UniProtKB:Q8CFX1};
DE AltName: Full=Glucose 1-dehydrogenase {ECO:0000250|UniProtKB:Q8CFX1};
DE EC=1.1.1.47 {ECO:0000250|UniProtKB:Q8CFX1};
DE AltName: Full=Glucose-6-phosphate dehydrogenase {ECO:0000303|PubMed:8506377};
DE EC=1.1.1.363 {ECO:0000250|UniProtKB:Q8CFX1};
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:0000250|UniProtKB:O95479};
OS Oryctolagus cuniculus (Rabbit).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Lagomorpha; Leporidae; Oryctolagus.
OX NCBI_TaxID=9986;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Thorbecke;
RX PubMed=21993624; DOI=10.1038/nature10530;
RA Lindblad-Toh K., Garber M., Zuk O., Lin M.F., Parker B.J., Washietl S.,
RA Kheradpour P., Ernst J., Jordan G., Mauceli E., Ward L.D., Lowe C.B.,
RA Holloway A.K., Clamp M., Gnerre S., Alfoldi J., Beal K., Chang J.,
RA Clawson H., Cuff J., Di Palma F., Fitzgerald S., Flicek P., Guttman M.,
RA Hubisz M.J., Jaffe D.B., Jungreis I., Kent W.J., Kostka D., Lara M.,
RA Martins A.L., Massingham T., Moltke I., Raney B.J., Rasmussen M.D.,
RA Robinson J., Stark A., Vilella A.J., Wen J., Xie X., Zody M.C., Baldwin J.,
RA Bloom T., Chin C.W., Heiman D., Nicol R., Nusbaum C., Young S.,
RA Wilkinson J., Worley K.C., Kovar C.L., Muzny D.M., Gibbs R.A., Cree A.,
RA Dihn H.H., Fowler G., Jhangiani S., Joshi V., Lee S., Lewis L.R.,
RA Nazareth L.V., Okwuonu G., Santibanez J., Warren W.C., Mardis E.R.,
RA Weinstock G.M., Wilson R.K., Delehaunty K., Dooling D., Fronik C.,
RA Fulton L., Fulton B., Graves T., Minx P., Sodergren E., Birney E.,
RA Margulies E.H., Herrero J., Green E.D., Haussler D., Siepel A., Goldman N.,
RA Pollard K.S., Pedersen J.S., Lander E.S., Kellis M.;
RT "A high-resolution map of human evolutionary constraint using 29 mammals.";
RL Nature 478:476-482(2011).
RN [2]
RP PARTIAL PROTEIN SEQUENCE, AND PYROGLUTAMATE FORMATION AT GLN-25.
RC STRAIN=New Zealand white; TISSUE=Liver;
RX PubMed=8506377; DOI=10.1073/pnas.90.11.5302;
RA Ozols J.;
RT "Isolation and the complete amino acid sequence of lumenal endoplasmic
RT reticulum glucose-6-phosphate dehydrogenase.";
RL Proc. Natl. Acad. Sci. U.S.A. 90:5302-5306(1993).
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. Has a hexose-6-phosphate dehydrogenase
CC activity, with broad substrate specificity compared to glucose-6-
CC phosphate 1-dehydrogenase/G6PD, and catalyzes the first step of the
CC pentose phosphate pathway. In addition, acts as a 6-
CC phosphogluconolactonase and catalyzes the second step of the pentose
CC phosphate pathway. May have a dehydrogenase activity for alternative
CC substrates including glucosamine 6-phosphate and glucose 6-sulfate. The
CC main function of this enzyme is to provide reducing equivalents such as
CC NADPH to maintain the adequate levels of reductive cofactors in the
CC oxidizing environment of the endoplasmic reticulum. 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. {ECO:0000250|UniProtKB:Q8CFX1}.
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=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:0000250|UniProtKB:Q8CFX1};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:15842;
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:0000250|UniProtKB:Q8CFX1};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:62073;
CC Evidence={ECO:0000250|UniProtKB:Q8CFX1};
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).
CC {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 2/3. {ECO:0000250|UniProtKB:Q8CFX1}.
CC -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:Q8CFX1}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum lumen
CC {ECO:0000250|UniProtKB:Q8CFX1}.
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}.
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DR EMBL; AAGW02064328; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR RefSeq; XP_008264185.1; XM_008265963.2.
DR AlphaFoldDB; P56201; -.
DR SMR; P56201; -.
DR STRING; 9986.ENSOCUP00000000694; -.
DR PRIDE; P56201; -.
DR GeneID; 100357500; -.
DR KEGG; ocu:100357500; -.
DR CTD; 9563; -.
DR eggNOG; KOG0563; Eukaryota.
DR eggNOG; KOG3147; Eukaryota.
DR HOGENOM; CLU_018975_0_0_1; -.
DR InParanoid; P56201; -.
DR OMA; DLHIFGQ; -.
DR OrthoDB; 383995at2759; -.
DR TreeFam; TF354247; -.
DR UniPathway; UPA00115; UER00409.
DR Proteomes; UP000001811; Unplaced.
DR GO; GO:0005788; C:endoplasmic reticulum lumen; ISS:UniProtKB.
DR GO; GO:0017057; F:6-phosphogluconolactonase activity; ISS:UniProtKB.
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; ISS:UniProtKB.
DR GO; GO:0050661; F:NADP binding; IEA:InterPro.
DR GO; GO:0006006; P:glucose metabolic process; IEA:UniProtKB-KW.
DR GO; GO:0009051; P:pentose-phosphate shunt, oxidative branch; ISS: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; Direct protein sequencing; Endoplasmic reticulum;
KW Glucose metabolism; Glycoprotein; Hydrolase; Multifunctional enzyme; NAD;
KW NADP; Oxidoreductase; Pyrrolidone carboxylic acid; Reference proteome;
KW Signal.
FT SIGNAL 1..24
FT /evidence="ECO:0000269|PubMed:8506377"
FT CHAIN 25..797
FT /note="GDH/6PGL endoplasmic bifunctional protein"
FT /id="PRO_0000068139"
FT REGION 25..531
FT /note="Hexose-6-phosphate dehydrogenase"
FT /evidence="ECO:0000305"
FT REGION 532..545
FT /note="Linker"
FT /evidence="ECO:0000305"
FT REGION 546..797
FT /note="6-phosphogluconolactonase"
FT /evidence="ECO:0000305"
FT ACT_SITE 272
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:P11411"
FT BINDING 37..44
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:P11413"
FT BINDING 154
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:P11413"
FT BINDING 179
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:P11413"
FT BINDING 179
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P11413"
FT BINDING 209..213
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P11413"
FT BINDING 248
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P11413"
FT BINDING 267
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P11413"
FT BINDING 365
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P11413"
FT BINDING 370
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P11413"
FT MOD_RES 25
FT /note="Pyrrolidone carboxylic acid"
FT /evidence="ECO:0000269|PubMed:8506377"
FT MOD_RES 213
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q8CFX1"
FT CARBOHYD 162
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 287
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 689
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CONFLICT 99
FT /note="R -> L (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 327
FT /note="R -> G (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 354
FT /note="W -> M (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 402
FT /note="Q -> C (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 418
FT /note="L -> V (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 617..629
FT /note="Missing (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 677
FT /note="Q -> QA (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 689
FT /note="N -> W (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 694..697
FT /note="LVLL -> EVLQ (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 733
FT /note="Q -> QQR (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 773
FT /note="K -> N (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 797 AA; 89279 MW; F94DD654DB2B55B0 CRC64;
MKCPGVWGML TVTMCVVFLG CPQAQELQGH VSVILLGATG DLAKKYLWQG LFQLFLDEAG
KGHSFSFHGA ALTAPKQGQE LMAKALESLS CPRDMAPSRC AELQAQFLRL SRYRQLKTAE
DYQALGRDIE AQVQQEGLRE AGRMFYFSVP PFAYADIARN INSSCRPGPG AWLRVVLEKP
FGHDHLSAQQ LATELGSFFQ EEEMYRVDHY LGKQAVAQIL PFRDQNRRAL DSLWNRHHVE
RVEIIMKETV DAEGRTSFYE EYGVIRDTLQ NHLTEILTLV AMELPANVSC SEAVLRHKLQ
AFRALRRLQR GSAVVGQYQT YSEQVRRELR KPAGSPSLTP TFAGVLVHVD NLRWEGVPFI
LMSGKALDER VGYVRVLFKN QAFCAQSEKH WAPAQSRCLP RQIIFYIGHG ELGHPAVLVS
RNLFRPFLPA QSWREVEDRP GLQLFGRPLS DFYAFSPVKE RDAYSILLSH IFHARKESFV
PTEHLLASWV FWTPLLESLA REVPRLYPGG ADSGRLLDFE FSGSHLSFSL GQPEQLVPGP
GSTPRPSDFQ VLGAKYRESP LISAWPDELI SKLASDIEAA AVQAVRRVGT FHLALSGGSS
PIALFQQLAS GHYGFPWAHT HLWLVDERCV PLSDPESNFQ GLQAHLLQHV RVPYYNIHPM
PVNLHQRLCA EEDRGAQAYA SEISALVTNC SFDLVLLGMG TDGHTASLFP QSPTGLDGEQ
LVVLTESPSR PHQRMSLSLP LINRAKKVAV LVMGRTKRDI TLLVSRVGRE PKKWPISGVL
PTSGQLVWYM DYEAFLG
