Ar1 (Akr1B, CG6084) encodes a cytosolic NADPH-dependent aldo-keto reductase of the AKR1B family, the Drosophila counterpart of human aldose reductase AKR1B1. It reduces glucose to sorbitol, the first step of the polyol pathway that converts glucose to fructose via sorbitol, and, like other AKR1B enzymes, has broad specificity for aldehydes and carbonyl compounds, including the reduction of prostaglandin H2 to prostaglandin F2alpha. With its paralog Ar2 it is required for hemolymph sorbitol production; this polyol pathway flux lets fat body cells sense glucose uptake through the transcription factor Mondo. In hemocytes Ar1 produces sorbitol and galactitol that act as alarmins relaying gut immune activation to the fat body, and in the ovary Akr1B-derived prostaglandin F2alpha promotes border cell migration and cluster cohesion.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0004032 aldose reductase [NAD(P)H] activity | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic inference of aldose reductase activity; Ar1 (FBgn0086254) and mammalian AKR1B enzymes are donors. Reason: Consistent with the fly genetic and biochemical data. Supporting Evidence: PMID:31350199 Aldose reductase (AR) in hemocytes, the rate-limiting enzyme of the polyol pathway, is necessary and sufficient for the increase of plasma sugar alcohols. |
| GO:0004032 aldose reductase [NAD(P)H] activity | IDA PMID:31350199 Sugar Alcohols of Polyol Pathway Serve as Alarmins to Mediat... | ACCEPT | Summary: Ar1 produces sugar alcohols (sorbitol, galactitol) in hemocytes. Reason: Core catalytic activity; the abstract-only record shows AR is necessary and sufficient for plasma sugar alcohol increase, and the curator saw activity data in the full text. Supporting Evidence: PMID:31350199 Aldose reductase (AR) in hemocytes, the rate-limiting enzyme of the polyol pathway, is necessary and sufficient for the increase of plasma sugar alcohols. |
| GO:0004032 aldose reductase [NAD(P)H] activity | IEA GO_REF:0000116 | ACCEPT | Summary: Rhea-based mapping (RHEA:12789). Reason: Consistent with experimental data. Supporting Evidence: file:DROME/Ar1/Ar1-uniprot.txt Reaction=an alditol + NADP(+) = an aldose + NADPH + H(+); |
| GO:0004032 aldose reductase [NAD(P)H] activity | ISS GO_REF:0000024 | ACCEPT | Summary: Activity transferred from human AKR1B1 (P15121). Reason: Consistent with experimental data. Supporting Evidence: file:DROME/Ar1/Ar1-uniprot.txt Key enzyme in the polyol pathway, catalyzes reduction of glucose to sorbitol during hyperglycemia. |
| GO:0005576 extracellular region | IDA PMID:31350199 Sugar Alcohols of Polyol Pathway Serve as Alarmins to Mediat... | UNDECIDED | Summary: Extracellular region localization from the alarmin study. Reason: Ar1 has no signal peptide and is otherwise cytosolic. According to the deep research report, Yang et al. refer to aldose reductase as secreted and detect increased reductase activity in hemolymph, but did not show secretion of intact Ar1 by imaging or secretion-specific assays. The cached record is abstract-only, so the basis cannot be checked directly; left undecided rather than overruling the curator. Supporting Evidence: file:DROME/Ar1/Ar1-deep-research-falcon.md Although Yang et al. refer to aldose reductase as secreted and detect increased reductase activity in hemolymph |
| GO:0005654 nucleoplasm | HDA PMID:25294944 Subcellular localisations of the CPTI collection of YFP-tagg... | KEEP AS NON CORE | Summary: Nucleoplasm localization of a YFP protein-trap line in the CPTI collection. Reason: High-throughput localization; the enzyme acts in the cytosol, but a minor nuclear pool is plausible for a small soluble protein. Gene-specific data are in the supplement. |
| GO:0005737 cytoplasm | EXP PMID:38283991 Specific prostaglandins are produced in the migratory cells ... | MODIFY | Summary: Akr1B is cytoplasmic in somatic and germline cells of the follicle. Reason: Correct but general; cytosol (GO:0005829), already annotated by HDA and IBA, is the precise compartment for this soluble enzyme. Proposed replacements: cytosol Supporting Evidence: PMID:38283991 Similar to cPGES, Akr1B is cytoplasmic in all the somatic and germline cells of the follicle |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | MODIFY | Summary: UniProt subcellular location mapping to cytoplasm. Reason: Correct but general; replace with cytosol (GO:0005829), already annotated. Proposed replacements: cytosol Supporting Evidence: file:DROME/Ar1/Ar1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm |
| GO:0005739 mitochondrion | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: Mitochondrion localization transferred from human AKR1B1. Reason: Mitochondrial association is a minor, context-dependent report for AKR1B1; fly Ar1 has no targeting sequence and was observed only in the cytoplasm. Not representative of where Ar1 acts. Supporting Evidence: PMID:38283991 Similar to cPGES, Akr1B is cytoplasmic in all the somatic and germline cells of the follicle |
| GO:0005829 cytosol | HDA PMID:25294944 Subcellular localisations of the CPTI collection of YFP-tagg... | ACCEPT | Summary: Cytosolic localization of a YFP protein-trap line. Reason: Consistent with the soluble cytosolic enzyme. |
| GO:0005829 cytosol | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic inference of cytosolic activity for AKR1B enzymes. Reason: Consistent with the fly localization data. Supporting Evidence: PMID:38283991 Similar to cPGES, Akr1B is cytoplasmic in all the somatic and germline cells of the follicle |
| GO:0006061 D-sorbitol biosynthetic process | IGI PMID:35687590 The polyol pathway is an evolutionarily conserved system for... | ACCEPT | Summary: Ar1/Ar2 double mutants have reduced hemolymph sorbitol. Reason: Ar1 catalyses the reduction of glucose to sorbitol, so it directly performs this process; the genetic interaction with Ar2 reflects redundancy. Supporting Evidence: PMID:35687590 Levels of sorbitol in the hemolymph were reduced in AR mutants and were increased in Sodh mutants PMID:35687590 CG6084 and CG10638 were doubly mutated in AR mutants. |
| GO:0006693 prostaglandin metabolic process | IEA GO_REF:0000108 | MODIFY | Summary: Prostaglandin metabolic process inferred from the prostaglandin H2 reductase activity. Reason: Correct but general; Akr1B acts as the PGF2alpha synthase in follicle cells, so prostaglandin biosynthetic process (GO:0001516) is the specific process. Like the PGH2 reductase activity rows, this is a secondary role and is not listed in core_functions. Proposed replacements: prostaglandin biosynthetic process Supporting Evidence: PMID:38283991 the PGF2Ξ± synthase Akr1B is required in the border cells for on-time migration |
| GO:0008106 alcohol dehydrogenase (NADP+) activity | IEA GO_REF:0000116 | KEEP AS NON CORE | Summary: Rhea-based alcohol dehydrogenase (NADP+) activity (aldehyde reductase reactions). Reason: AKR1B enzymes reduce many aliphatic and aromatic aldehydes; the term is correct at the level of a broad-specificity activity but is not the defining physiological activity. Supporting Evidence: file:DROME/Ar1/Ar1-uniprot.txt Catalyzes the NADPH-dependent reduction of a wide variety of carbonyl-containing compounds to their corresponding alcohols. |
| GO:0016491 oxidoreductase activity | IEA GO_REF:0000002 | MODIFY | Summary: InterPro-based generic oxidoreductase activity. Reason: Uninformative; aldose reductase activity (GO:0004032) is already annotated by IDA. Proposed replacements: aldose reductase [NAD(P)H] activity Supporting Evidence: file:DROME/Ar1/Ar1-uniprot.txt Reaction=an alditol + NADP(+) = an aldose + NADPH + H(+); |
| GO:0036130 prostaglandin H2 endoperoxidase reductase activity | IEA GO_REF:0000116 | KEEP AS NON CORE | Summary: Rhea-based prostaglandin H2 endoperoxidase reductase activity. Reason: Akr1B is described as the fly PGF2alpha synthase and is required in border cells for on-time migration, so PGH2 reduction is supported by fly genetics, although the activity itself has not been assayed with purified fly protein. Kept as a secondary, non-core activity; the matching process row is modified to prostaglandin biosynthetic process (GO:0001516), also treated as a secondary role, and neither is listed in core_functions. Supporting Evidence: PMID:38283991 the PGF2Ξ± synthase Akr1B is required in the border cells for on-time migration |
| GO:0036130 prostaglandin H2 endoperoxidase reductase activity | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: PGH2 reductase activity transferred from human AKR1B1. Reason: Akr1B is described as the fly PGF2alpha synthase and is required in border cells for on-time migration, so PGH2 reduction is supported by fly genetics, although the activity itself has not been assayed with purified fly protein. Kept as a secondary, non-core activity; the matching process row is modified to prostaglandin biosynthetic process (GO:0001516), also treated as a secondary role, and neither is listed in core_functions. Supporting Evidence: PMID:38283991 the PGF2Ξ± synthase Akr1B is required in the border cells for on-time migration |
| GO:0042572 retinol metabolic process | IEA GO_REF:0000108 | MARK AS OVER ANNOTATED | Summary: Retinol metabolic process inferred from the retinol dehydrogenase activity. Reason: Inferred from a by-similarity activity of human AKR1B1; there is no evidence that Ar1 takes part in retinoid metabolism in flies, whose visual chromophore pathway uses other enzymes. |
| GO:0042840 D-glucuronate catabolic process | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: D-glucuronate catabolic process transferred from mouse AKR1A1 (Q9JII6). Reason: The donor is AKR1A1 (aldehyde reductase, the glucuronate reductase of the uronate pathway), a paralog of the AKR1B group to which Ar1 belongs. The transfer crosses subfamilies and there is no fly evidence for a glucuronate pathway role. |
| GO:0046173 polyol biosynthetic process | IMP PMID:31350199 Sugar Alcohols of Polyol Pathway Serve as Alarmins to Mediat... | ACCEPT | Summary: AR is required for the increase of hemolymph sorbitol and galactitol after gut immune activation. Reason: Polyol biosynthetic process covers both sugar alcohols the cited experiment measured (sorbitol and galactitol), so it is the appropriate level here; Ar1 catalyses their formation from glucose and galactose. Supporting Evidence: PMID:31350199 IMD activation in guts causes elevated levels of sorbitol and galactitol in hemolymph. |
| GO:0046370 fructose biosynthetic process | IGI PMID:35687590 The polyol pathway is an evolutionarily conserved system for... | ACCEPT | Summary: Ar1/Ar2 are required for polyol-pathway conversion of glucose to fructose. Reason: Ar1 performs the first step (glucose to sorbitol) of the two-step polyol pathway that makes fructose, so it does part of the work of this process. Supporting Evidence: PMID:35687590 The polyol pathway converts glucose to fructose via sorbitol. |
| GO:0047655 allyl-alcohol dehydrogenase activity | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Allyl-alcohol dehydrogenase activity (EC 1.1.1.54) by automated mapping. Reason: Reflects acrolein reduction by AKR1B enzymes; plausible broad-specificity activity, not tested in flies. Supporting Evidence: file:DROME/Ar1/Ar1-uniprot.txt Reaction=allyl alcohol + NADP(+) = acrolein + NADPH + H(+); |
| GO:0047655 allyl-alcohol dehydrogenase activity | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Allyl-alcohol dehydrogenase activity transferred from human AKR1B1. Reason: As for the IEA row. Supporting Evidence: file:DROME/Ar1/Ar1-uniprot.txt Reaction=allyl alcohol + NADP(+) = acrolein + NADPH + H(+); |
| GO:0047681 aryl-alcohol dehydrogenase (NADP+) activity | IEA GO_REF:0000116 | KEEP AS NON CORE | Summary: Aryl-alcohol dehydrogenase (NADP+) activity by Rhea mapping. Reason: Reflects aromatic aldehyde reduction by AKR1B enzymes; plausible, untested in flies. Supporting Evidence: file:DROME/Ar1/Ar1-uniprot.txt Displays enzymatic activity towards endogenous metabolites such as aromatic and aliphatic aldehydes |
| GO:0047939 L-glucuronate reductase activity | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: L-glucuronate reductase activity transferred from mouse AKR1A1 (Q9JII6). Reason: Donor is the AKR1A1 paralog, the dedicated glucuronate reductase; Ar1 is an AKR1B enzyme and has no fly evidence for this activity. |
| GO:0047956 glycerol dehydrogenase (NADP+) activity | IEA GO_REF:0000116 | KEEP AS NON CORE | Summary: Glycerol dehydrogenase (NADP+) activity by Rhea mapping. Reason: Glyceraldehyde reduction is a known AKR1B1 activity; plausible broad-specificity activity, untested in flies. Supporting Evidence: file:DROME/Ar1/Ar1-uniprot.txt Reaction=glycerol + NADP(+) = D-glyceraldehyde + NADPH + H(+); |
| GO:0047956 glycerol dehydrogenase (NADP+) activity | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Glycerol dehydrogenase (NADP+) activity transferred from human AKR1B1. Reason: As for the IEA row. Supporting Evidence: file:DROME/Ar1/Ar1-uniprot.txt Reaction=glycerol + NADP(+) = D-glyceraldehyde + NADPH + H(+); |
| GO:0052650 all-trans-retinol dehydrogenase (NADP+) activity | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: All-trans-retinol dehydrogenase (NADP+) activity (EC 1.1.1.300). Reason: Retinal reduction is a documented AKR1B1 activity; transferred by similarity and untested in flies, so retained only as a possible broad-specificity activity. Supporting Evidence: file:DROME/Ar1/Ar1-uniprot.txt Reaction=all-trans-retinol + NADP(+) = all-trans-retinal + NADPH + |
| GO:0052650 all-trans-retinol dehydrogenase (NADP+) activity | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: All-trans-retinol dehydrogenase (NADP+) activity transferred from human AKR1B1. Reason: As for the IEA row. Supporting Evidence: file:DROME/Ar1/Ar1-uniprot.txt Reaction=all-trans-retinol + NADP(+) = all-trans-retinal + NADPH + |
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Download this section (compressed HTML)Q: Has the glucose-reducing activity and PGH2-reductase activity of purified Ar1 been measured, and how do its kinetic parameters compare with Ar2?
Experiment: Purify Ar1 and Ar2 and measure kinetics with glucose, galactose, glyceraldehyde and PGH2 to define their relative contributions to polyol and prostaglandin synthesis.
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Download this section (compressed HTML)Aldose reductase 1 (Ar1) encodes an enzyme that catalyzes the NADPH-dependent reduction of aldose sugars and other carbonyl-containing compounds to their corresponding alcohols. It is involved in the biosynthesis of D-fructose from D-glucose.
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