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O95479 (G6PE_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified March 19, 2014. Version 131. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
GDH/6PGL endoplasmic bifunctional protein

Including the following 2 domains:

  1. Glucose 1-dehydrogenase
    EC=1.1.1.47
    Alternative name(s):
    Hexose-6-phosphate dehydrogenase
  2. 6-phosphogluconolactonase
    Short name=6PGL
    EC=3.1.1.31
Gene names
Name:H6PD
Synonyms:GDH
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length791 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Oxidizes glucose-6-phosphate and glucose, as well as other hexose-6-phosphates.

Catalytic activity

Beta-D-glucose + NAD(P)+ = D-glucono-1,5-lactone + NAD(P)H.

D-glucose 6-phosphate + NAD(P)+ = D-glucono-1,5-lactone 6-phosphate + NAD(P)H.

6-phospho-D-glucono-1,5-lactone + H2O = 6-phospho-D-gluconate.

Subcellular location

Endoplasmic reticulum lumen. Note: Microsomes, endoplasmic reticulum lumen.

Tissue specificity

Present in most tissues examined, strongest in liver.

Involvement in disease

Cortisone reductase deficiency (CRD) [MIM:604931]: In CRD, activation of cortisone to cortisol does not occur, resulting in adrenocorticotropin-mediated androgen excess and a phenotype resembling polycystic ovary syndrome (PCOS).
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.6 Ref.7

Sequence similarities

In the N-terminal section; belongs to the glucose-6-phosphate dehydrogenase family.

In the C-terminal section; belongs to the glucosamine/galactosamine-6-phosphate isomerase family. 6-phosphogluconolactonase subfamily.

Sequence caution

The sequence CAH18137.1 differs from that shown. Reason: Erroneous initiation.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 1919 By similarity
Chain20 – 791772GDH/6PGL endoplasmic bifunctional protein
PRO_0000010442

Regions

Region20 – 526507Glucose 1-dehydrogenase
Region527 – 54014Linker
Region541 – 7912516-phosphogluconolactonase

Sites

Active site2671Proton acceptor By similarity
Binding site341NADP By similarity
Binding site661NADP By similarity
Binding site2041Substrate By similarity
Binding site2081Substrate By similarity

Amino acid modifications

Modified residue201Pyrrolidone carboxylic acid By similarity
Modified residue2081N6-succinyllysine By similarity
Glycosylation1571N-linked (GlcNAc...) Ref.5
Glycosylation2821N-linked (GlcNAc...) Ref.5
Glycosylation6831N-linked (GlcNAc...) Potential

Natural variations

Natural variant1461P → L in CRD; results in reduced enzymatic activity. Ref.7
VAR_069193
Natural variant1511D → A. Ref.2
Corresponds to variant rs34603401 [ dbSNP | Ensembl ].
VAR_049117
Natural variant2181R → Q.
Corresponds to variant rs35525021 [ dbSNP | Ensembl ].
VAR_049118
Natural variant4531R → Q in CRD; less than 50% of activity than wild-type. Ref.2 Ref.4 Ref.6
Corresponds to variant rs6688832 [ dbSNP | Ensembl ].
VAR_026487
Natural variant4841N → D.
Corresponds to variant rs35404275 [ dbSNP | Ensembl ].
VAR_049119
Natural variant5541P → L.
Corresponds to variant rs17368528 [ dbSNP | Ensembl ].
VAR_049120

Experimental info

Sequence conflict3391A → G in CAA10071. Ref.1

Sequences

Sequence LengthMass (Da)Tools
O95479 [UniParc].

Last modified May 30, 2006. Version 2.
Checksum: 01E179BE00C87C79

FASTA79188,893
        10         20         30         40         50         60 
MWNMLIVAMC LALLGCLQAQ ELQGHVSIIL LGATGDLAKK YLWQGLFQLY LDEAGRGHSF 

        70         80         90        100        110        120 
SFHGAALTAP KQGQELMAKA LESLSCPKDM APSHCAEHKD QFLQLSQYRQ LKTAEDYQAL 

       130        140        150        160        170        180 
NKDIEAQLQH AGLREAGRIF YFSVPPFAYE DIARNINSSC RPGPGAWLRV VLEKPFGHDH 

       190        200        210        220        230        240 
FSAQQLATEL GTFFQEEEMY RVDHYLGKQA VAQILPFRDQ NRKALDGLWN RHHVERVEII 

       250        260        270        280        290        300 
MKETVDAEGR TSFYEEYGVI RDVLQNHLTE VLTLVAMELP HNVSSAEAVL RHKLQVFQAL 

       310        320        330        340        350        360 
RGLQRGSAVV GQYQSYSEQV RRELQKPDSF HSLTPTFAAV LVHIDNLRWE GVPFILMSGK 

       370        380        390        400        410        420 
ALDERVGYAR ILFKNQACCV QSEKHWAAAQ SQCLPRQLVF HIGHGDLGSP AVLVSRNLFR 

       430        440        450        460        470        480 
PSLPSSWKEM EGPPGLRLFG SPLSDYYAYS PVRERDAHSV LLSHIFHGRK NFFITTENLL 

       490        500        510        520        530        540 
ASWNFWTPLL ESLAHKAPRL YPGGAENGRL LDFEFSSGRL FFSQQQPEQL VPGPGPAPMP 

       550        560        570        580        590        600 
SDFQVLRAKY RESPLVSAWS EELISKLAND IEATAVRAVR RFGQFHLALS GGSSPVALFQ 

       610        620        630        640        650        660 
QLATAHYGFP WAHTHLWLVD ERCVPLSDPE SNFQGLQAHL LQHVRIPYYN IHPMPVHLQQ 

       670        680        690        700        710        720 
RLCAEEDQGA QIYAREISAL VANSSFDLVL LGMGADGHTA SLFPQSPTGL DGEQLVVLTT 

       730        740        750        760        770        780 
SPSQPHRRMS LSLPLINRAK KVAVLVMGRM KREITTLVSR VGHEPKKWPI SGVLPHSGQL 

       790 
VWYMDYDAFL G 

« Hide

References

« Hide 'large scale' references
[1]"Human hexose-6-phosphate dehydrogenase (glucose 1-dehydrogenase) encoded at 1p36: coding sequence and expression."
Mason P.J., Stevens D., Diez A., Knight S.W., Scopes D.A., Vulliamy T.J.
Blood Cells Mol. Dis. 25:30-36(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Bone marrow.
[2]"The full-ORF clone resource of the German cDNA consortium."
Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I.
BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANTS ALA-151 AND GLN-453.
Tissue: Salivary gland.
[3]"The DNA sequence and biological annotation of human chromosome 1."
Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. expand/collapse author list , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.
Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT GLN-453.
Tissue: Testis.
[5]"Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry."
Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.
J. Proteome Res. 8:651-661(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-157 AND ASN-282.
Tissue: Liver.
[6]"Mutations in the genes encoding 11beta-hydroxysteroid dehydrogenase type 1 and hexose-6-phosphate dehydrogenase interact to cause cortisone reductase deficiency."
Draper N., Walker E.A., Bujalska I.J., Tomlinson J.W., Chalder S.M., Arlt W., Lavery G.G., Bedendo O., Ray D.W., Laing I., Malunowicz E., White P.C., Hewison M., Mason P.J., Connell J.M., Shackleton C.H.L., Stewart P.M.
Nat. Genet. 34:434-439(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT CRD GLN-453, CHARACTERIZATION OF VARIANT CRD GLN-453.
[7]"Novel H6PDH mutations in two girls with premature adrenarche: 'apparent' and 'true' CRD can be differentiated by urinary steroid profiling."
Lavery G.G., Idkowiak J., Sherlock M., Bujalska I., Ride J.P., Saqib K., Hartmann M.F., Hughes B., Wudy S.A., De Schepper J., Arlt W., Krone N., Shackleton C.H., Walker E.A., Stewart P.M.
Eur. J. Endocrinol. 168:K19-K26(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT CRD LEU-146, CHARACTERIZATION OF VARIANT CRD LEU-146.
+Additional computationally mapped references.

Web resources

SHMPD

The Singapore human mutation and polymorphism database

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AJ012590 mRNA. Translation: CAA10071.1.
CR749282 mRNA. Translation: CAH18137.1. Different initiation.
Z98044 Genomic DNA. Translation: CAI95702.1.
BC081559 mRNA. Translation: AAH81559.1.
RefSeqNP_001269516.1. NM_001282587.1.
NP_004276.2. NM_004285.3.
UniGeneHs.463511.

3D structure databases

ProteinModelPortalO95479.
SMRO95479. Positions 29-502, 560-788.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid114933. 1 interaction.
IntActO95479. 1 interaction.
STRING9606.ENSP00000366620.

Chemistry

DrugBankDB00157. NADH.

PTM databases

PhosphoSiteO95479.

Proteomic databases

PaxDbO95479.
PRIDEO95479.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000377403; ENSP00000366620; ENSG00000049239.
GeneID9563.
KEGGhsa:9563.
UCSCuc001apt.3. human.

Organism-specific databases

CTD9563.
GeneCardsGC01P009294.
H-InvDBHIX0000104.
HGNCHGNC:4795. H6PD.
HPAHPA004824.
HPA005440.
MIM138090. gene.
604931. phenotype.
neXtProtNX_O95479.
Orphanet168588. Hyperandrogenism due to cortisone reductase deficiency.
PharmGKBPA29170.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0363.
HOGENOMHOG000231077.
HOVERGENHBG005780.
InParanoidO95479.
KOK13937.
OMAFITTENL.
OrthoDBEOG7BW0HS.
PhylomeDBO95479.
TreeFamTF354247.

Enzyme and pathway databases

SABIO-RKO95479.

Gene expression databases

BgeeO95479.
CleanExHS_H6PD.
GenevestigatorO95479.

Family and domain databases

Gene3D3.40.50.720. 1 hit.
InterProIPR005900. 6-phosphogluconolactonase_DevB.
IPR001282. G6P_DH.
IPR019796. G6P_DH_AS.
IPR022675. G6P_DH_C.
IPR022674. G6P_DH_NAD-bd.
IPR006148. Glc/Gal-6P_isomerase.
IPR016040. NAD(P)-bd_dom.
[Graphical view]
PANTHERPTHR23429. PTHR23429. 1 hit.
PfamPF02781. G6PD_C. 1 hit.
PF00479. G6PD_N. 1 hit.
PF01182. Glucosamine_iso. 1 hit.
[Graphical view]
PRINTSPR00079. G6PDHDRGNASE.
TIGRFAMsTIGR01198. pgl. 1 hit.
PROSITEPS00069. G6P_DEHYDROGENASE. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSH6PD. human.
GeneWikiH6PD.
GenomeRNAi9563.
NextBio35867.
PROO95479.
SOURCESearch...

Entry information

Entry nameG6PE_HUMAN
AccessionPrimary (citable) accession number: O95479
Secondary accession number(s): Q4TT33, Q66I35, Q68DT3
Entry history
Integrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: May 30, 2006
Last modified: March 19, 2014
This is version 131 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 1

Human chromosome 1: entries, gene names and cross-references to MIM