Details of the Target

General Information of Target

Target ID LDTP01618
Target Name GDH/6PGL endoplasmic bifunctional protein (H6PD)
Gene Name H6PD
Gene ID 9563
Synonyms
GDH; GDH/6PGL endoplasmic bifunctional protein [Includes: Hexose-6-phosphate dehydrogenase; Glucose 1-dehydrogenase; GDH; EC 1.1.1.47; Glucose-6-phosphate dehydrogenase; EC 1.1.1.363; 6-phosphogluconolactonase; 6PGL; EC 3.1.1.31)]
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Sequence
MWNMLIVAMCLALLGCLQAQELQGHVSIILLGATGDLAKKYLWQGLFQLYLDEAGRGHSF
SFHGAALTAPKQGQELMAKALESLSCPKDMAPSHCAEHKDQFLQLSQYRQLKTAEDYQAL
NKDIEAQLQHAGLREAGRIFYFSVPPFAYEDIARNINSSCRPGPGAWLRVVLEKPFGHDH
FSAQQLATELGTFFQEEEMYRVDHYLGKQAVAQILPFRDQNRKALDGLWNRHHVERVEII
MKETVDAEGRTSFYEEYGVIRDVLQNHLTEVLTLVAMELPHNVSSAEAVLRHKLQVFQAL
RGLQRGSAVVGQYQSYSEQVRRELQKPDSFHSLTPTFAAVLVHIDNLRWEGVPFILMSGK
ALDERVGYARILFKNQACCVQSEKHWAAAQSQCLPRQLVFHIGHGDLGSPAVLVSRNLFR
PSLPSSWKEMEGPPGLRLFGSPLSDYYAYSPVRERDAHSVLLSHIFHGRKNFFITTENLL
ASWNFWTPLLESLAHKAPRLYPGGAENGRLLDFEFSSGRLFFSQQQPEQLVPGPGPAPMP
SDFQVLRAKYRESPLVSAWSEELISKLANDIEATAVRAVRRFGQFHLALSGGSSPVALFQ
QLATAHYGFPWAHTHLWLVDERCVPLSDPESNFQGLQAHLLQHVRIPYYNIHPMPVHLQQ
RLCAEEDQGAQIYAREISALVANSSFDLVLLGMGADGHTASLFPQSPTGLDGEQLVVLTT
SPSQPHRRMSLSLPLINRAKKVAVLVMGRMKREITTLVSRVGHEPKKWPISGVLPHSGQL
VWYMDYDAFLG
Target Bioclass
Enzyme
Family
Glucose-6-phosphate dehydrogenase family; Glucosamine/galactosamine-6-phosphate isomerase family, 6-phosphogluconolactonase subfamily
Subcellular location
Endoplasmic reticulum lumen
Function
Bifunctional enzyme localized in the lumen of the endoplasmic reticulum that catalyzes the first two steps of the oxidative branch of the pentose phosphate pathway/shunt, an alternative to glycolysis and a major source of reducing power and metabolic intermediates for biosynthetic processes. Has a hexose-6-phosphate dehydrogenase activity, with broad substrate specificity compared to glucose-6-phosphate 1-dehydrogenase/G6PD, and catalyzes the first step of the pentose phosphate pathway. In addition, acts as a 6-phosphogluconolactonase and catalyzes the second step of the pentose phosphate pathway. May have a dehydrogenase activity for alternative substrates including glucosamine 6-phosphate and glucose 6-sulfate. The main function of this enzyme is to provide reducing equivalents such as NADPH to maintain the adequate levels of reductive cofactors in the oxidizing environment of the endoplasmic reticulum. By producing NADPH that is needed by reductases of the lumen of the endoplasmic reticulum like corticosteroid 11-beta-dehydrogenase isozyme 1/HSD11B1, indirectly regulates their activity.
Uniprot ID
O95479
Ensemble ID
ENST00000377403.7
HGNC ID
HGNC:4795

Target Site Mutations in Different Cell Lines

Cell line Mutation details Probe for labeling this protein in this cell
HCT15 SNV: p.A78S .
IGROV1 SNV: p.G191R .
LS180 SNV: p.K496R .
MEWO SNV: p.H467Y .
MKN45 Insertion: p.V352RfsTer145 .
NCIH2286 SNV: p.P647S .
NCIH358 Substitution: p.G778N DBIA    Probe Info 
SKMEL28 SNV: p.V619G DBIA    Probe Info 
TOV21G SNV: p.L423M .

Probe(s) Labeling This Target

ABPP Probe
Click To Hide/Show 7 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
STPyne
 Probe Info  		K208(0.95); K741(6.81)  LDD0277  [1]
DBIA
 Probe Info  		C95(1.76); C404(1.58)  LDD3310  [2]
4-Iodoacetamidophenylacetylene
 Probe Info  		C86(0.00); C393(0.00)  LDD0038  [3]
IA-alkyne
 Probe Info  		C86(0.00); C393(0.00)  LDD0036  [3]
Lodoacetamide azide
 Probe Info  		C86(0.00); C623(0.00); C393(0.00); C663(0.00)  LDD0037  [3]
NHS
 Probe Info  		N.A.  LDD0010  [4]
NAIA_5
 Probe Info  		N.A.  LDD2223  [5]
PAL-AfBPP Probe
Click To Hide/Show 2 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
STS-1
 Probe Info  		N.A.  LDD0136  [6]
VE-P
 Probe Info  		N.A.  LDD0396  [7]

Competitor(s) Related to This Target

Competitor ID Name Cell line Binding Site(Ratio) Interaction ID Ref
 LDCM0022  KB02 A101D C404(1.48)  LDD2250  [2]
 LDCM0023  KB03 42-MG-BA C95(1.28)  LDD2661  [2]
 LDCM0024  KB05 COLO792 C95(1.76); C404(1.58)  LDD3310  [2]

The Interaction Atlas With This Target

The Drug(s) Related To This Target

Approved
Click To Hide/Show 1 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
Nadh Small molecular drug DB00157

References

1 A Paal-Knorr agent for chemoproteomic profiling of targets of isoketals in cells. Chem Sci. 2021 Oct 15;12(43):14557-14563. doi: 10.1039/d1sc02230j. eCollection 2021 Nov 10.
Mass spectrometry data entry: PXD028270
2 DrugMap: A quantitative pan-cancer analysis of cysteine ligandability. Cell. 2024 May 9;187(10):2536-2556.e30. doi: 10.1016/j.cell.2024.03.027. Epub 2024 Apr 22.
Mass spectrometry data entry: PXD047840
3 Enhancing Cysteine Chemoproteomic Coverage through Systematic Assessment of Click Chemistry Product Fragmentation. Anal Chem. 2022 Mar 8;94(9):3800-3810. doi: 10.1021/acs.analchem.1c04402. Epub 2022 Feb 23.
Mass spectrometry data entry: PXD028853
4 A modification-centric assessment tool for the performance of chemoproteomic probes. Nat Chem Biol. 2022 Aug;18(8):904-912. doi: 10.1038/s41589-022-01074-8. Epub 2022 Jul 21.
Mass spectrometry data entry: PXD027758 , PXD027755 , PXD027760 , PXD027762 , PXD027756 , PXD027591 , PXD007149 , PXD030064 , PXD032392 , PXD027789 , PXD027767 , PXD027764
5 N-Acryloylindole-alkyne (NAIA) enables imaging and profiling new ligandable cysteines and oxidized thiols by chemoproteomics. Nat Commun. 2023 Jun 15;14(1):3564. doi: 10.1038/s41467-023-39268-w.
Mass spectrometry data entry: PXD041264
6 Design and synthesis of minimalist terminal alkyne-containing diazirine photo-crosslinkers and their incorporation into kinase inhibitors for cell- and tissue-based proteome profiling. Angew Chem Int Ed Engl. 2013 Aug 12;52(33):8551-6. doi: 10.1002/anie.201300683. Epub 2013 Jun 10.
7 Pharmacological Targeting of Vacuolar H(+)-ATPase via Subunit V1G Combats Multidrug-Resistant Cancer. Cell Chem Biol. 2020 Nov 19;27(11):1359-1370.e8. doi: 10.1016/j.chembiol.2020.06.011. Epub 2020 Jul 9.