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Overview

Uniprot IDO95479
Protein NameGDH/6PGL endoplasmic bifunctional protein
Gene NameH6PD
OrganismHomo sapiens

Kla Sites from experimental identification

Position Flanking peptide
208 RVDHYLGKQAVAQIL
293 AEAVLRHKLQVFQAL

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 (By similarity). 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 (PubMed:12858176, PubMed:18628520, PubMed:23132696). In addition, acts as a 6-phosphogluconolactonase and catalyzes the second step of the pentose phosphate pathway (By similarity). May have a dehydrogenase activity for alternative substrates including glucosamine 6-phosphate and glucose 6-sulfate (By similarity). 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 (PubMed:12858176, PubMed:18628520, PubMed:23132696). 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 (PubMed:18628520)

Protein Sequence

10 MWNMLIVAMC 20 LALLGCLQAQ 30 ELQGHVSIIL 40 LGATGDLAKK 50 YLWQGLFQLY 60 LDEAGRGHSF 70 SFHGAALTAP 80 KQGQELMAKA 90 LESLSCPKDM 100 APSHCAEHKD 110 QFLQLSQYRQ 120 LKTAEDYQAL 130 NKDIEAQLQH 140 AGLREAGRIF 150 YFSVPPFAYE 160 DIARNINSSC 170 RPGPGAWLRV 180 VLEKPFGHDH 190 FSAQQLATEL 200 GTFFQEEEMY 210 RVDHYLGKQA 220 VAQILPFRDQ 230 NRKALDGLWN 240 RHHVERVEII 250 MKETVDAEGR 260 TSFYEEYGVI 270 RDVLQNHLTE 280 VLTLVAMELP 290 HNVSSAEAVL 300 RHKLQVFQAL 310 RGLQRGSAVV 320 GQYQSYSEQV 330 RRELQKPDSF 340 HSLTPTFAAV 350 LVHIDNLRWE 360 GVPFILMSGK 370 ALDERVGYAR 380 ILFKNQACCV 390 QSEKHWAAAQ 400 SQCLPRQLVF 410 HIGHGDLGSP 420 AVLVSRNLFR 430 PSLPSSWKEM 440 EGPPGLRLFG 450 SPLSDYYAYS 460 PVRERDAHSV 470 LLSHIFHGRK 480 NFFITTENLL 490 ASWNFWTPLL 500 ESLAHKAPRL 510 YPGGAENGRL 520 LDFEFSSGRL 530 FFSQQQPEQL 540 VPGPGPAPMP 550 SDFQVLRAKY 560 RESPLVSAWS 570 EELISKLAND 580 IEATAVRAVR 590 RFGQFHLALS 600 GGSSPVALFQ 610 QLATAHYGFP 620 WAHTHLWLVD 630 ERCVPLSDPE 640 SNFQGLQAHL 650 LQHVRIPYYN 660 IHPMPVHLQQ 670 RLCAEEDQGA 680 QIYAREISAL 690 VANSSFDLVL 700 LGMGADGHTA 710 SLFPQSPTGL 720 DGEQLVVLTT 730 SPSQPHRRMS 740 LSLPLINRAK 750 KVAVLVMGRM 760 KREITTLVSR 770 VGHEPKKWPI 780 SGVLPHSGQL 790 VWYMDYDAFL G

Gene Ontology

Classification GO ID Description
Cellular Component GO:0005783 endoplasmic reticulum
Cellular Component GO:0005788 endoplasmic reticulum lumen
Cellular Component GO:0016529 sarcoplasmic reticulum
Molecular Function GO:0017057 6-phosphogluconolactonase activity
Molecular Function GO:0030246 carbohydrate binding
Molecular Function GO:0047934 glucose 1-dehydrogenase (NAD+) activity
Molecular Function GO:0047935 glucose 1-dehydrogenase (NADP+) activity
Molecular Function GO:0004345 glucose-6-phosphate dehydrogenase activity
Molecular Function GO:0050661 NADP binding
Biological Process GO:0006006 glucose metabolic process
Biological Process GO:0009051 pentose-phosphate shunt, oxidative branch
Biological Process GO:2000064 regulation of cortisol biosynthetic process
Biological Process GO:0097305 response to alcohol
Biological Process GO:0031667 response to nutrient levels

Reference

[1] Yang Z, Yan C, Ma J, Peng P, Ren X et al.. Lactylome analysis suggests lactylation-dependent mechanisms of metabolic adaptation in hepatocellular carcinoma.. Nat Metab 5(1):61-79. 2023 Jan. PMID: 36593272.