O95479 (G6PE_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	791 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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	Defects in H6PD are a cause of 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).
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.

Ontologies

Keywords
Biological process	Carbohydrate metabolism Glucose metabolism
Cellular component	Endoplasmic reticulum
Coding sequence diversity	Polymorphism
Disease	Disease mutation
Domain	Signal
Ligand	NAD NADP
Molecular function	Hydrolase Oxidoreductase
PTM	Glycoprotein Phosphoprotein Pyrrolidone carboxylic acid
Technical term	Complete proteome Multifunctional enzyme Reference proteome
Gene Ontology (GO)
Cellular component	endoplasmic reticulum lumen Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	6-phosphogluconolactonase activity Inferred from electronic annotation. Source: EC glucose 1-dehydrogenase [NAD(P)] activity Inferred from electronic annotation. Source: EC glucose-6-phosphate dehydrogenase activity Traceable author statement. Source: ProtInc
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 19	19	By similarity
	Chain	20 – 791	772	GDH/6PGL endoplasmic bifunctional protein		PRO_0000010442
Regions
	Region	20 – 526	507	Glucose 1-dehydrogenase
	Region	527 – 540	14	Linker
	Region	541 – 791	251	6-phosphogluconolactonase
Sites
	Active site	267	1	Proton acceptor By similarity
	Binding site	34	1	NADP By similarity
	Binding site	66	1	NADP By similarity
	Binding site	204	1	Substrate By similarity
	Binding site	208	1	Substrate By similarity
Amino acid modifications
	Modified residue	20	1	Pyrrolidone carboxylic acid By similarity
	Modified residue	316	1	Phosphotyrosine Ref.5
	Glycosylation	157	1	N-linked (GlcNAc...) Ref.6
	Glycosylation	282	1	N-linked (GlcNAc...) Ref.6
	Glycosylation	683	1	N-linked (GlcNAc...) Potential
Natural variations
	Natural variant	151	1	D → A. Ref.2 Corresponds to variant rs34603401 [ dbSNP | Ensembl ].		VAR_049117
	Natural variant	218	1	R → Q. Corresponds to variant rs35525021 [ dbSNP | Ensembl ].		VAR_049118
	Natural variant	453	1	R → Q in CDR; less than 50% of activity than wild-type. Ref.2 Ref.4 Ref.7 Corresponds to variant rs6688832 [ dbSNP | Ensembl ].		VAR_026487
	Natural variant	484	1	N → D. Corresponds to variant rs35404275 [ dbSNP | Ensembl ].		VAR_049119
	Natural variant	554	1	P → L. Corresponds to variant rs17368528 [ dbSNP | Ensembl ].		VAR_049120
Experimental info
	Sequence conflict	339	1	A → G in CAA10071. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	O95479 [UniParc]. Last modified May 30, 2006. Version 2. Checksum: 01E179BE00C87C79	FASTA	791	88,893
	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

References

	« Hide 'large scale' referencesShow '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: 10349511] [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: 17974005] [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. , 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: 16710414] [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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT GLN-453. Tissue: Testis.
[5]	"Tyrosine phosphorylated Par3 regulates epithelial tight junction assembly promoted by EGFR signaling." Wang Y., Du D., Fang L., Yang G., Zhang C., Zeng R., Ullrich A., Lottspeich F., Chen Z. EMBO J. 25:5058-5070(2006) [PubMed: 17053785] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-316, MASS SPECTROMETRY. Tissue: Embryonic kidney.
[6]	"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: 19159218] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-157 AND ASN-282, MASS SPECTROMETRY. Tissue: Liver.
[7]	"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: 12858176] [Abstract] Cited for: VARIANT CDR GLN-453, CHARACTERIZATION OF VARIANT CDR GLN-453.
+	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.
IPI	IPI00607861.
RefSeq	NP_004276.2. NM_004285.3.
UniGene	Hs.463511.
3D structure databases
ProteinModelPortal	O95479.
SMR	O95479. Positions 25-524, 556-790.
ModBase	Search...
Protein-protein interaction databases
IntAct	O95479. 1 interaction.
STRING	O95479.
PTM databases
PhosphoSite	O95479.
Proteomic databases
PRIDE	O95479.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000377403; ENSP00000366620; ENSG00000049239.
GeneID	9563.
KEGG	hsa:9563.
NMPDR	fig|9606.3.peg.223.
UCSC	uc001apt.1. human.
Organism-specific databases
CTD	9563.
GeneCards	GC01P009294.
H-InvDB	HIX0000104.
HGNC	HGNC:4795. H6PD.
HPA	HPA004824. HPA005440.
MIM	138090. gene. 604931. phenotype.
neXtProt	NX_O95479.
Orphanet	168588. Hyperandrogenism due to cortisone reductase deficiency.
PharmGKB	PA29170.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG14296.
GeneTree	ENSGT00530000063435.
HOGENOM	HBG356361.
HOVERGEN	HBG005780.
InParanoid	O95479.
OMA	NIHPMPV.
OrthoDB	EOG4QC14P.
PhylomeDB	O95479.
Gene expression databases
ArrayExpress	O95479.
Bgee	O95479.
CleanEx	HS_H6PD.
Genevestigator	O95479.
GermOnline	ENSG00000049239. Homo sapiens.
Family and domain databases
InterPro	IPR005900. 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]
Gene3D	G3DSA:3.40.50.720. NAD(P)-bd. 1 hit.
KO	K13937.
PANTHER	PTHR23429. G6PDH. 1 hit.
Pfam	PF02781. G6PD_C. 1 hit. PF00479. G6PD_N. 1 hit. PF01182. Glucosamine_iso. 1 hit. [Graphical view]
PRINTS	PR00079. G6PDHDRGNASE.
TIGRFAMs	TIGR01198. Pgl. 1 hit.
PROSITE	PS00069. G6P_DEHYDROGENASE. 1 hit. [Graphical view]
ProtoNet	Search...
Other
DrugBank	DB00157. NADH.
NextBio	35867.
SOURCE	Search...

Entry information

Entry name

G6PE_HUMAN

Accession

Primary (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:	January 25, 2012
This is version 113 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.