Affinage

AKR1A1

Aldo-keto reductase family 1 member A1 · UniProt P14550

Round 2 corrected
Length
325 aa
Mass
36.6 kDa
Annotated
2026-04-28
130 papers in source corpus 14 papers cited in narrative 14 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

AKR1A1 is a monomeric, NADPH-dependent aldo-keto reductase that catalyzes the reduction of a broad spectrum of carbonyl substrates—including aromatic and aliphatic aldehydes, quinones, methylglyoxal, succinic semialdehyde, and D-glucuronate—as well as the NADPH-dependent reduction of low-molecular-weight S-nitrosothiols (GSNO and SNO-CoA), with structurally distinct binding determinants (Arg-312 for GSNO, Lys-127 for SNO-CoA) and catalytic residues Tyr49, Lys79, and His112 essential for activity (PMID:7669785, PMID:10510318, PMID:31649033). AKR1A1 converts D-glucuronate to L-gulonate in the ascorbic acid biosynthesis pathway, as demonstrated by Akr1A1-knockout mice that develop vitamin C deficiency and osteoporosis rescued by ascorbic acid supplementation (PMID:28060768). AKR1A1 also stereo- and regioselectively oxidizes PAH trans-dihydrodiols to reactive o-quinones, constituting an alternative carcinogen-activation pathway in tissues co-expressing CYP1A1 and epoxide hydrolase (PMID:11535067). A synonymous AKR1A1 variant (c.753G>A) causes exon 8 skipping and complete loss of enzymatic activity, and has been associated with schizophrenia (PMID:34938315).

Mechanistic history

Synthesis pass · year-by-year structured walk · 9 steps
  1. 1989 High

    Cloning of AKR1A1 from human liver established it as a distinct NADPH-dependent monomeric oxidoreductase within the emerging aldo-keto reductase superfamily, resolving its molecular identity and relationship to aldose reductase.

    Evidence cDNA cloning and sequencing from human liver and placental libraries

    PMID:2498333

    Open questions at the time
    • No crystal structure available at this point
    • Substrate specificity beyond model aldehydes not yet explored
    • No in vivo functional data
  2. 1995 High

    Site-directed mutagenesis defined the catalytic triad (Tyr49, Lys79, His112) and showed that His112 governs substrate specificity, while demonstrating that AKR1A1 lacks the thiol-sensitive regulation of aldose reductase, distinguishing its catalytic mechanism within the AKR family.

    Evidence Site-directed mutagenesis with detailed steady-state kinetics and deuterium isotope effects on purified recombinant enzyme

    PMID:7669785

    Open questions at the time
    • No structural confirmation of residue roles by crystallography in this study
    • Physiological substrates in vivo still undetermined
  3. 1995 High

    Identification of in vivo glycation of rat aldehyde reductase at specific lysines with loss of catalytic efficiency provided the first evidence that AKR1A1 function is impaired in diabetes, potentially compromising 3-deoxyglucosone detoxification.

    Evidence NaB[³H]₄ labeling, peptide sequencing, mass spectrometry, and boronate affinity chromatography in streptozotocin-diabetic rat kidney

    PMID:7827091

    Open questions at the time
    • Whether glycation-mediated impairment occurs in human diabetic tissues not tested
    • Physiological impact on carbonyl detoxification in vivo not quantified
  4. 1999 High

    Comprehensive substrate profiling and tissue distribution mapping revealed AKR1A1 as a broad-specificity carbonyl reductase with highest activity toward succinic semialdehyde, aromatic aldehydes, and D-glucuronate, expressed predominantly in brain, kidney, liver, and small intestine.

    Evidence Recombinant protein kinetics with >20 substrates, Western blotting and immunohistochemistry across human tissues

    PMID:10393438 PMID:10510318

    Open questions at the time
    • In vivo contribution to each substrate pathway not yet confirmed by genetic perturbation
    • Relative contribution versus other AKR family members in each tissue unclear
  5. 2001 High

    Demonstration that AKR1A1 stereoselectively oxidizes PAH trans-dihydrodiols to reactive o-quinones established it as an alternative carcinogen-activating enzyme, expanding its functional scope beyond detoxification to potential genotoxicity.

    Evidence Recombinant enzyme kinetics with enantiopure PAH dihydrodiols, LC/MS product characterization, tissue expression arrays

    PMID:11306097 PMID:11535067

    Open questions at the time
    • In vivo contribution to PAH-induced mutagenesis or carcinogenesis not demonstrated
    • No cell-based or animal model evidence of AKR1A1-dependent PAH activation
  6. 2011 High

    siRNA knockdown studies in human cells revealed that AKR1A1 contributes to succinic semialdehyde reduction (and thus GHB metabolism) at high substrate concentrations but is not the primary enzyme for endogenous GHB biosynthesis, while in hepatocytes it catalyzes the reverse reaction (GHB oxidation to SSA).

    Evidence siRNA knockdown in astrocytoma 1321N1 and HepG2 cells with enzyme activity assays and GC/MS metabolite quantification

    PMID:21276435 PMID:25256836

    Open questions at the time
    • Identity of the primary low-Km SSA reductase for endogenous GHB synthesis remains unknown
    • In vivo relevance of GHB oxidation by AKR1A1 not confirmed in animal models
  7. 2017 High

    Genetic knockout of Akr1A1 in mice proved that AKR1A1 is essential for D-glucuronate-to-L-gulonate conversion in ascorbic acid biosynthesis in vivo, with deficiency causing vitamin C depletion and osteoporosis rescued by ascorbic acid supplementation.

    Evidence Akr1A1-knockout mouse, serum ascorbic acid measurement, micro-CT bone analysis, rescue by ascorbic acid supplementation

    PMID:28060768

    Open questions at the time
    • Whether other phenotypes beyond bone arise from AKR1A1 loss (e.g. carbonyl stress, S-nitrosothiol accumulation) not systematically assessed
    • KO resulted from transgene insertion; a clean targeted deletion would strengthen the model
  8. 2019 High

    Biochemical purification and knockout validation identified AKR1A1 as the primary NADPH-dependent GSNO reductase in mammalian tissues, with distinct substrate-binding residues for GSNO (Arg-312) and SNO-CoA (Lys-127), establishing a previously unrecognized role in nitric oxide signaling through S-nitrosothiol metabolism.

    Evidence De novo purification from tissues, kinetics, site-directed mutagenesis, AKR1A1-KO and GSNOR-KO cross-validation in mice

    PMID:31649033

    Open questions at the time
    • Physiological consequences of impaired S-nitrosothiol reduction in AKR1A1-deficient animals not characterized
    • Whether AKR1A1 and ADH5/GSNOR coordinate or are redundant in vivo is not resolved
  9. 2021 High

    A synonymous AKR1A1 variant (c.753G>A) was shown to disrupt exon 8 splicing, producing a truncated, enzymatically dead protein, linking AKR1A1 loss-of-function to a human genetic context (schizophrenia association).

    Evidence Minigene splicing assay, recombinant truncated protein activity assay, qRT-PCR in patient samples

    PMID:34938315

    Open questions at the time
    • Schizophrenia association reported from a single cohort; independent replication in larger populations is lacking
    • Mechanism linking AKR1A1 loss to neuropsychiatric phenotype is not established

Open questions

Synthesis pass · forward-looking unresolved questions
  • Outstanding questions include: (1) the relative in vivo contributions of AKR1A1 versus other reductases to carbonyl detoxification and S-nitrosothiol homeostasis across tissues; (2) whether AKR1A1-mediated PAH activation contributes to carcinogenesis in animal models; and (3) the mechanistic basis for a potential AKR1A1–schizophrenia link.
  • No conditional or tissue-specific knockout studies exist
  • No structural basis for SNO-CoA versus GSNO selectivity beyond modeling and mutagenesis
  • PAH activation role untested in vivo

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016491 oxidoreductase activity 6
Localization
GO:0005829 cytosol 1
Pathway
R-HSA-1430728 Metabolism 4

Evidence

Reading pass · 14 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1989 Human aldehyde reductase (AKR1A1) was cloned from a human liver cDNA library, revealing a 325-amino acid NADPH-dependent monomeric oxidoreductase with 65% identity to aldose reductase, establishing AKR1A1 as a founding member of the aldo-keto reductase (AKR) superfamily. cDNA cloning and sequencing from human liver and placental libraries The Journal of biological chemistry High 2498333
1995 Active-site mutagenesis of human aldehyde reductase (AKR1A1) identified Tyr49, Lys79, and His112 as critical catalytic residues: Tyr49 and Lys79 mutations abolish activity, while His112 mutation dramatically reduces catalytic efficiency (up to 4200-fold for aromatic substrates) and determines substrate specificity. Unlike aldose reductase, AKR1A1 lacks thiol sensitivity at the C-terminal loop, and nucleotide exchange is only partially rate-limiting (deuterium isotope effect on kcat = 1.48). Site-directed mutagenesis, kinetic analysis, deuterium isotope effects, inhibitor binding assays Biochemistry High 7669785
1995 Rat aldehyde reductase (ortholog of AKR1A1) is glycated in vivo at lysines 67, 84, and 140, reducing its catalytic efficiency (kcat/Km). In streptozotocin-induced diabetic rats, kidney glycated aldehyde reductase is significantly increased, implicating impaired 3-deoxyglucosone detoxification under diabetic conditions. NaB[3H]4 labeling, peptide sequencing, mass spectrometry, boronate affinity chromatography, enzymatic activity assays Biochemistry High 7827091
1999 AKR1A1 substrate specificity was comprehensively characterized using recombinant protein expressed in E. coli: it reduces a broad spectrum of carbonyl compounds with highest activity toward succinic semialdehyde (SSA), aromatic aldehydes (4-nitrobenzaldehyde, 4-carboxybenzaldehyde), pyridine aldehydes, 4-hydroxynonenal, methylglyoxal, 1,2-naphthoquinone, 16-ketoestrone, and d-glucuronic acid. Tissue distribution by Western blotting showed AKR1A1 expression primarily in brain, kidney, liver, and small intestine, with distinct patterns from related AKR family members. Recombinant protein expression in E. coli, enzyme kinetics, Western blotting, immunohistochemistry, anion-exchange chromatography The Biochemical journal High 10510318
1999 The human AKR1A1 gene was characterized: it spans approximately 16 kb, contains 8 exons encoding the entire coding region and 3'-UTR, and was mapped to chromosome 1p33→p32 by fluorescence in situ hybridization (FISH). Genomic DNA isolation, restriction mapping, sequencing, FISH Cytogenetics and cell genetics High 10393438
2001 AKR1A1 (ubiquitous aldehyde reductase) oxidizes potent proximate carcinogen trans-dihydrodiols (e.g., benzo[a]pyrene-7,8-dihydrodiol) to reactive o-quinones in a stereo- and regioselective manner. AKR1A1 displayed the highest Vmax/Km ratio among human AKRs for (+/-)-trans-7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene, preferentially oxidizing non-K-region trans-dihydrodiols and specifically the metabolically relevant (-)-[7R,8R] enantiomer. The product benzo[a]pyrene-7,8-dione was confirmed as a thioether conjugate by LC/MS trapping. Co-expression of AKR1A1 with CYP1A1 and epoxide hydrolase in multiple human tissues was demonstrated. cDNA cloning from HepG2, E. coli overexpression, enzyme purification, kinetic analysis, circular dichroism spectrometry, LC/MS product characterization, multiple tissue expression array Biochemistry High 11535067
2001 AKR1A1 preferentially oxidizes the metabolically relevant (-)-[3R,4R]-dihydroxy-3,4-dihydrobenz[a]anthracene among tested PAH trans-dihydrodiols and displays high Vmax/Km for multiple methylated benz[a]anthracene diols. Co-expression of AKR1A1 with CYP1A1 and epoxide hydrolase at PAH target tissues supports a role for AKR1A1 in a widespread alternative pathway of PAH carcinogen activation. Recombinant AKR1A1 expression in E. coli, enzyme kinetics, multiple tissue expression arrays Chemico-biological interactions Medium 11306097
2007 Site-specific immobilization of AKR1A1 via C-terminal biotin (expressed protein ligation/intein strategy) onto streptavidin templates preserves full catalytic activity comparable to the enzyme in solution, while randomly adsorbed AKR1A1 retains only 0.3–1.7% activity. The immobilized enzyme retained >35% activity after 50 days, demonstrating exceptional stability. Intein-mediated expressed protein ligation, biotin labeling, streptavidin immobilization, kinetic parameter measurement Chembiochem Medium 17508367
2011 siRNA-mediated knockdown of AKR1A1 in human astrocytoma 1321N1 cells (88% mRNA, 94% protein reduction) caused a 30% decrease in aldehyde reductase activity (pNBA reductase assay) and reduced succinic semialdehyde reductase activity at high (1 mM) but not low (10 μM) substrate concentrations, suggesting AKR1A1 contributes to GHB biosynthesis at high SSA concentrations but is not the primary enzyme for endogenous GHB production in this cell line. siRNA knockdown, qRT-PCR, Western blot, enzyme activity assays, GC/MS measurement of GHB Chemico-biological interactions Medium 21276435
2014 siRNA knockdown of AKR1A1 in HepG2 cells (92% mRNA, 93% protein reduction) caused an 82% decrease in NADP-dependent GHB-dehydrogenase activity at high GHB concentrations (10 mM) and a 2-fold increase in intracellular GHB levels when exposed to 50 μM GHB. This demonstrates that AKR1A1 catalyzes NADP-dependent oxidation of GHB (reverse reaction: GHB→SSA) in the liver at pharmacologically relevant concentrations, but does not contribute to endogenous GHB biosynthesis. siRNA knockdown, qRT-PCR, Western blot, enzyme activity assay, GC/MS quantification of intracellular and extracellular GHB Biochemical pharmacology High 25256836
2017 Knockout of Akr1A1 in mice (via transgene integration causing 30-kb genomic deletion) results in insufficient serum ascorbic acid levels, confirming AKR1A1's role in catalyzing D-glucuronate to L-gulonate conversion in the ascorbic acid biosynthesis pathway. Akr1A1 KO mice develop abnormal bone development and osteoporosis that is rescued by ascorbic acid administration, linking AKR1A1 enzymatic function to bone formation through ascorbic acid availability. Gene knockout mouse model, serum ascorbic acid measurement, micro-CT bone analysis, osteocalcin assay, ascorbic acid supplementation rescue experiment Oncotarget High 28060768
2019 AKR1A1 was identified as a primary mediator of NADPH-coupled GSNO (S-nitroso-glutathione) reductase activity in mammalian tissues. Purification of NADPH-dependent GSNOR activity from tissues identified AKR1A1 as the responsible enzyme. Kinetic analyses showed substrate preference SNO-CoA > GSNO. AKR1A1 deletion from murine tissues dramatically lowered NADPH-dependent GSNOR activity; conversely, GSNOR-deficient mice had increased AKR1A1 activity. Molecular modeling and mutagenesis identified Arg-312 as a key residue for GSNO interaction, while Lys-127 (SNO-CoA binding residue) minimally affects GSNO reduction, demonstrating structurally distinct binding sites for the two LMW-SNO substrates. Biochemical purification from tissues, kinetic analysis, AKR1A1 knockout mice, GSNOR knockout mice, molecular modeling, site-directed mutagenesis The Journal of biological chemistry High 31649033
2021 A silent AKR1A1 variant c.753G>A (rs745484618, p.Arg251Arg) located at the first position of exon 8 was associated with schizophrenia. Minigene assay demonstrated that this variant induces exon 8 skipping, causing a frameshift and truncation of the AKR1A1 protein. Recombinant truncated AKR1A1 protein completely lacks enzymatic activity. Individuals with this variant showed lower AKR1A1 mRNA expression and lower AKR activity, expected to result in glucuronate accumulation that promotes drug excretion. Minigene splicing assay, recombinant protein expression, enzyme activity assay, qRT-PCR in patient samples Frontiers in genetics High 34938315
2022 Kefir peptide treatment of AKR1A1 knockout (vitamin C-deficient) mice rescues osteoporosis by promoting osteoblast differentiation (via Runx2, β-catenin, BMP-2, NFATc1 upregulation) and inhibiting osteoclast differentiation (suppressing RANKL-induced p38, NF-κB, Akt, PLCγ2, CREB-1 phosphorylation and NFATc1/c-Fos nuclear translocation). This further validates the Akr1A1 KO mouse as a model of vitamin C deficiency-driven osteoporosis. AKR1A1 KO mouse model, micro-CT, nanoindentation, ELISA for bone markers, Western blot of signaling pathway components, osteoblast/osteoclast differentiation assays Biomedicine & pharmacotherapy Medium 36252352

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2015 The BioPlex Network: A Systematic Exploration of the Human Interactome. Cell 1118 26186194
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
1999 DD3: a new prostate-specific gene, highly overexpressed in prostate cancer. Cancer research 790 10606244
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2008 Large-scale proteomics and phosphoproteomics of urinary exosomes. Journal of the American Society of Nephrology : JASN 607 19056867
2021 Multilevel proteomics reveals host perturbations by SARS-CoV-2 and SARS-CoV. Nature 532 33845483
2003 DD3(PCA3)-based molecular urine analysis for the diagnosis of prostate cancer. European urology 531 12814669
2002 DD3(PCA3), a very sensitive and specific marker to detect prostate tumors. Cancer research 462 11980670
2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome research 438 15489334
2022 OpenCell: Endogenous tagging for the cartography of human cellular organization. Science (New York, N.Y.) 432 35271311
2005 Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes. Genome research 409 16344560
2015 Panorama of ancient metazoan macromolecular complexes. Nature 407 26344197
1989 The aldo-keto reductase superfamily. cDNAs and deduced amino acid sequences of human aldehyde and aldose reductases. The Journal of biological chemistry 392 2498333
2006 Knockdown of ALR (MLL2) reveals ALR target genes and leads to alterations in cell adhesion and growth. Molecular and cellular biology 313 17178841
2009 Proteomic analysis of human parotid gland exosomes by multidimensional protein identification technology (MudPIT). Journal of proteome research 237 19199708
2001 An essential function of the mitochondrial sulfhydryl oxidase Erv1p/ALR in the maturation of cytosolic Fe/S proteins. EMBO reports 233 11493598
2010 MHC class II-associated proteins in B-cell exosomes and potential functional implications for exosome biogenesis. Immunology and cell biology 221 20458337
1999 Major differences exist in the function and tissue-specific expression of human aflatoxin B1 aldehyde reductase and the principal human aldo-keto reductase AKR1 family members. The Biochemical journal 182 10510318
1994 Cloning and sequence analysis of the rat augmenter of liver regeneration (ALR) gene: expression of biologically active recombinant ALR and demonstration of tissue distribution. Proceedings of the National Academy of Sciences of the United States of America 158 8058770
2019 Circular RNA FOXP1 promotes tumor progression and Warburg effect in gallbladder cancer by regulating PKLR expression. Molecular cancer 154 31623628
2011 Spectrum of MLL2 (ALR) mutations in 110 cases of Kabuki syndrome. American journal of medical genetics. Part A 149 21671394
2020 Comparative Application of BioID and TurboID for Protein-Proximity Biotinylation. Cells 146 32344865
2022 A comprehensive SARS-CoV-2-human protein-protein interactome reveals COVID-19 pathobiology and potential host therapeutic targets. Nature biotechnology 140 36217030
2013 In-depth proteomic analyses of exosomes isolated from expressed prostatic secretions in urine. Proteomics 138 23533145
2014 The PYRIN domain-only protein POP3 inhibits ALR inflammasomes and regulates responses to infection with DNA viruses. Nature immunology 135 24531343
2013 Proteomic analysis of podocyte exosome-enriched fraction from normal human urine. Journal of proteomics 126 23376485
2000 An African swine fever virus ERV1-ALR homologue, 9GL, affects virion maturation and viral growth in macrophages and viral virulence in swine. Journal of virology 126 10627538
2000 A viral member of the ERV1/ALR protein family participates in a cytoplasmic pathway of disulfide bond formation. Proceedings of the National Academy of Sciences of the United States of America 125 11035794
2004 A protein interaction framework for human mRNA degradation. Genome research 123 15231747
1995 Mechanism of human aldehyde reductase: characterization of the active site pocket. Biochemistry 120 7669785
2001 The ubiquitous aldehyde reductase (AKR1A1) oxidizes proximate carcinogen trans-dihydrodiols to o-quinones: potential role in polycyclic aromatic hydrocarbon activation. Biochemistry 101 11535067
2006 Polymorphisms in oxidative stress genes and risk for non-Hodgkin lymphoma. Carcinogenesis 98 16543247
1986 Biosynthetic alanine racemase of Salmonella typhimurium: purification and characterization of the enzyme encoded by the alr gene. Biochemistry 96 3524677
2011 Molecular recognition and substrate mimicry drive the electron-transfer process between MIA40 and ALR. Proceedings of the National Academy of Sciences of the United States of America 95 21383138
2003 New targets for therapy in prostate cancer: differential display code 3 (DD3(PCA3)), a highly prostate cancer-specific gene. Urology 95 14607216
2010 Genome-wide YFP fluorescence complementation screen identifies new regulators for telomere signaling in human cells. Molecular & cellular proteomics : MCP 93 21044950
2020 Inhibition of Drp1 SUMOylation by ALR protects the liver from ischemia-reperfusion injury. Cell death and differentiation 84 33110216
2001 Expression and activities of aldo-keto oxidoreductases in Alzheimer disease. Journal of neuropathology and experimental neurology 82 11444797
1997 Structure and expression pattern of human ALR, a novel gene with strong homology to ALL-1 involved in acute leukemia and to Drosophila trithorax. Oncogene 82 9247308
2020 Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins and Uncovers Widespread Protein Aggregation in Affected Brains. Cell reports 79 32814053
1996 Analysis of the structure and expression of the augmenter of liver regeneration (ALR) gene. Molecular medicine (Cambridge, Mass.) 79 8900538
2013 Shotgun proteomics reveals specific modulated protein patterns in tears of patients with primary open angle glaucoma naïve to therapy. Molecular bioSystems 77 23580065
2019 The midbody interactome reveals unexpected roles for PP1 phosphatases in cytokinesis. Nature communications 74 31586073
2013 Nrf2 activates augmenter of liver regeneration (ALR) via antioxidant response element and links oxidative stress to liver regeneration. Molecular medicine (Cambridge, Mass.) 71 23887691
2006 Gain of function in an ERV/ALR sulfhydryl oxidase by molecular engineering of the shuttle disulfide. Journal of molecular biology 70 16893552
1995 In vivo glycation of aldehyde reductase, a major 3-deoxyglucosone reducing enzyme: identification of glycation sites. Biochemistry 69 7827091
2021 Histone deacetylase inhibitors inhibit cervical cancer growth through Parkin acetylation-mediated mitophagy. Acta pharmaceutica Sinica. B 66 35256949
2000 Augmenter of liver regeneration (ALR) may promote liver regeneration by reducing natural killer (NK) cell activity in human liver diseases. Journal of gastroenterology 66 10680666
2002 Use of the alr gene as a food-grade selection marker in lactic acid bacteria. Applied and environmental microbiology 63 12406763
2005 Expression of augmenter of liver regeneration (ALR) in human liver cirrhosis and carcinoma. Histopathology 58 15982324
2007 Identification of PCA3 (DD3) in prostatic carcinoma by in situ hybridization. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 52 17873893
1986 Biosynthetic alr alanine racemase from Salmonella typhimurium: DNA and protein sequence determination. Biochemistry 49 3524676
2013 Expression and functional analysis of the CorA-MRS2-ALR-type magnesium transporter family in rice. Plant & cell physiology 47 23926064
2012 Disulfide bond formation: sulfhydryl oxidase ALR controls mitochondrial biogenesis of human MIA40. Traffic (Copenhagen, Denmark) 46 23186364
2005 Mechanisms underlying resistance of pancreatic islets from ALR/Lt mice to cytokine-induced destruction. Journal of immunology (Baltimore, Md. : 1950) 44 16002729
2001 Unusual resistance of ALR/Lt mouse beta cells to autoimmune destruction: role for beta cell-expressed resistance determinants. Proceedings of the National Academy of Sciences of the United States of America 44 11136257
2010 Augmenter of liver regeneration (ALR) protects human hepatocytes against apoptosis. Biochemical and biophysical research communications 43 21108930
2019 AKR1A1 is a novel mammalian S-nitroso-glutathione reductase. The Journal of biological chemistry 39 31649033
1999 Highly divergent amino termini of the homologous human ALR and yeast scERV1 gene products define species specific differences in cellular localization. European journal of cell biology 39 10384986
2012 An electron-transfer path through an extended disulfide relay system: the case of the redox protein ALR. Journal of the American Chemical Society 36 22224850
2010 Upregulation of MetC is essential for D-alanine-independent growth of an alr/dadX-deficient Escherichia coli strain. Journal of bacteriology 36 21193606
2005 Regulation of chemosensory and GABAergic motor neuron development by the C. elegans Aristaless/Arx homolog alr-1. Development (Cambridge, England) 36 15790968
2005 mt-Nd2 Allele of the ALR/Lt mouse confers resistance against both chemically induced and autoimmune diabetes. Diabetologia 35 15692809
2012 Augmenter of liver regeneration (alr) promotes liver outgrowth during zebrafish hepatogenesis. PloS one 34 22292055
2003 Genetic analysis of resistance to Type-1 Diabetes in ALR/Lt mice, a NOD-related strain with defenses against autoimmune-mediated diabetogenic stress. Immunogenetics 34 14513297
2010 Liver regeneration associated protein (ALR) exhibits antimetastatic potential in hepatocellular carcinoma. Molecular medicine (Cambridge, Mass.) 33 21152698
2002 The alanine racemase gene alr is an alternative to antibiotic resistance genes in cloning systems for industrial Corynebacterium glutamicum strains. Journal of biotechnology 33 12204559
2000 Isolation and characterization of the promoter of the human prostate cancer-specific DD3 gene. The Journal of biological chemistry 33 10982808
1999 Resistance of ALR/Lt islets to free radical-mediated diabetogenic stress is inherited as a dominant trait. Diabetes 31 10535453
2008 Transcription factor Ap2delta associates with Ash2l and ALR, a trithorax family histone methyltransferase, to activate Hoxc8 transcription. Proceedings of the National Academy of Sciences of the United States of America 30 18495928
2010 Differential display code 3 (DD3/PCA3) in prostate cancer diagnosis. Anticancer research 29 20332487
1993 The 92-min region of the Escherichia coli chromosome: location and cloning of the ubiA and alr genes. Gene 29 8335265
2012 Targeting and maturation of Erv1/ALR in the mitochondrial intermembrane space. ACS chemical biology 28 22296668
2010 Cholera toxin-sensitive GTP-binding protein-coupled activation of augmenter of liver regeneration (ALR) receptor and its function in rat kupffer cells. Journal of cellular physiology 28 19859909
2001 Metabolic activation of polycyclic aromatic hydrocarbon trans-dihydrodiols by ubiquitously expressed aldehyde reductase (AKR1A1). Chemico-biological interactions 28 11306097
2001 Novel human HALR (MLL3) gene encodes a protein homologous to ALR and to ALL-1 involved in leukemia, and maps to chromosome 7q36 associated with leukemia and developmental defects. Cancer detection and prevention 28 11718452
2013 Augmenter of liver regeneration (ALR) is a novel biomarker of hepatocellular stress/inflammation: in vitro, in vivo and in silico studies. Molecular medicine (Cambridge, Mass.) 27 23073658
2009 The combination of urine DD3(PCA3) mRNA and PSA mRNA as molecular markers of prostate cancer. Biomarkers : biochemical indicators of exposure, response, and susceptibility to chemicals 27 19489685
2017 ALR encoding dCMP deaminase is critical for DNA damage repair, cell cycle progression and plant development in rice. Journal of experimental botany 26 29186482
2007 Specifically immobilised aldo/keto reductase AKR1A1 shows a dramatic increase in activity relative to the randomly immobilised enzyme. Chembiochem : a European journal of chemical biology 26 17508367
2015 The aspartate-less receiver (ALR) domains: distribution, structure and function. PLoS pathogens 25 25875291
2010 Targeting Gene-ViroTherapy for prostate cancer by DD3-driven oncolytic virus-harboring interleukin-24 gene. International journal of cancer 25 19950222
2002 Genetic control of neutrophil superoxide production in diabetes-resistant ALR/Lt mice. Free radical biology & medicine 25 11937300
2005 Expression of the sulfhydryl oxidase ALR (Augmenter of Liver Regeneration) in adult rat brain. Brain research 24 15916753
2012 Prostate cancer-specific and potent antitumor effect of a DD3-controlled oncolytic virus harboring the PTEN gene. PloS one 23 22509396
2006 Expression of human telomerase reverse transcriptase, Survivin, DD3 and PCGEM1 messenger RNA in archival prostate carcinoma tissue. The Canadian journal of urology 23 16515751
2005 The Caenorhabditis elegans aristaless orthologue, alr-1, is required for maintaining the functional and structural integrity of the amphid sensory organs. Molecular biology of the cell 22 16055504
2017 A novel osteoporosis model with ascorbic acid deficiency in Akr1A1 gene knockout mice. Oncotarget 20 28060768
2018 Augmenter of liver regeneration (ALR) regulates acute pancreatitis via inhibiting HMGB1/TLR4/NF-κB signaling pathway. American journal of translational research 19 29511434
2010 Foxa2 (HNF-3beta) regulates expression of hepatotrophic factor ALR in liver cells. Biochemical and biophysical research communications 18 20382118
2020 The role of PIAS3, p-STAT3 and ALR in colorectal cancer: new translational molecular features for an old disease. European review for medical and pharmacological sciences 17 33155205
2018 Bile acid-induced apoptosis and bile acid synthesis are reduced by over-expression of Augmenter of Liver Regeneration (ALR) in a STAT3-dependent mechanism. Experimental cell research 17 30500391
2006 Expression of alr gene from Corynebacterium glutamicum ATCC 13032 in Escherichia coli and molecular characterization of the recombinant alanine racemase. Journal of biotechnology 17 16707184
2011 Augmenter of liver regeneration (ALR) gene therapy attenuates CCl₄-induced liver injury and fibrosis in rats. Biochemical and biophysical research communications 16 22033404
2024 Multiomics Analyses Identify AKR1A1 as a Biomarker for Diabetic Kidney Disease. Diabetes 15 38394643
2019 Overexpression of augmenter of liver regeneration (ALR) mitigates the effect of H2O2-induced endoplasmic reticulum stress in renal tubule epithelial cells. Apoptosis : an international journal on programmed cell death 14 30680481
2019 Santacruzamate A Ameliorates AD-Like Pathology by Enhancing ER Stress Tolerance Through Regulating the Functions of KDELR and Mia40-ALR in vivo and in vitro. Frontiers in cellular neuroscience 14 30886573
2003 Is DD3 a new prostate-specific gene? Anticancer research 14 12680228
2022 Identification of Putative Plant-Based ALR-2 Inhibitors to Treat Diabetic Peripheral Neuropathy. Current issues in molecular biology 13 35877418
2022 Kefir peptides ameliorate osteoporosis in AKR1A1 knockout mice with vitamin C deficiency by promoting osteoblastogenesis and inhibiting osteoclastogenesis. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 13 36252352
2003 Expression of p65, DD3 and c-erbB2 genes in prostate cancer. Neoplasma 13 12740642
2022 Imbalance in ALR ubiquitination accelerates the progression of nonalcoholic steatohepatitis to hepatocellular carcinoma. Oncogene 12 36434180
2017 Augmenter of liver regeneration (ALR) exhibits a dual signaling impact on hepatic acute-phase response. Experimental and molecular pathology 12 28506765
2008 Comparative analysis of the islet proteome between NOD/Lt and ALR/Lt mice. Annals of the New York Academy of Sciences 12 19120270
2017 Assessment of Metabolic Changes in Mycobacterium smegmatis Wild-Type and alr Mutant Strains: Evidence of a New Pathway of d-Alanine Biosynthesis. Journal of proteome research 10 28121156
2011 The role of aldehyde reductase AKR1A1 in the metabolism of γ-hydroxybutyrate in 1321N1 human astrocytoma cells. Chemico-biological interactions 10 21276435
1997 [In vitro stimulation of HTC hepatoma cell growth by recombinant human augmenter of liver regeneration (ALR)]. Sheng li xue bao : [Acta physiologica Sinica] 10 9813496
2018 Bile acids down-regulate the expression of Augmenter of Liver Regeneration (ALR) via SHP/HNF4α1 and independent of Egr-1. Experimental and molecular pathology 9 30243934
2016 Sexually Dimorphic Expression of eGFP Transgene in the Akr1A1 Locus of Mouse Liver Regulated by Sex Hormone-Related Epigenetic Remodeling. Scientific reports 9 27087367
2014 High expression of 23 kDa protein of augmenter of liver regeneration (ALR) in human hepatocellular carcinoma. OncoTargets and therapy 9 24940072
2014 Metabolism of gamma hydroxybutyrate in human hepatoma HepG2 cells by the aldo-keto reductase AKR1A1. Biochemical pharmacology 8 25256836
2017 The alr-groEL1 operon in Mycobacterium tuberculosis: an interplay of multiple regulatory elements. Scientific reports 7 28256563
2016 Augmenter of liver regeneration (ALR) restrains concanavalin A-induced hepatitis in mice. International immunopharmacology 7 27085679
2010 Polygenic inheritance of sensorineural hearing loss (Snhl2, -3, and -4) and organ of Corti patterning defect in the ALR/LtJ mouse strain. Hearing research 7 21185929
1994 Dexamethasone-mediated induction of MMTV-myf5 in DD3 myoblasts increases endogenous myogenin expression but does not transactivate myf5. Experimental cell research 7 8187825
2023 Identification and Expression of the CorA/MRS2/ALR Type Magnesium Transporters in Tomato. Plants (Basel, Switzerland) 6 37447072
2021 AKR1A1 Variant Associated With Schizophrenia Causes Exon Skipping, Leading to Loss of Enzymatic Activity. Frontiers in genetics 6 34938315
2018 Prostate Cancer-Specific of DD3-driven Oncolytic Virus-harboring mK5 Gene. Open medicine (Warsaw, Poland) 6 30613790
2014 Exogenous augmenter of liver regeneration (ALR) attenuates inflammatory response in renal hypoxia re-oxygenation injury. Renal failure 6 24392837
1990 Genetic profile of alloxan-induced diabetes-susceptible mice (ALS) and-resistant mice (ALR). Jikken dobutsu. Experimental animals 6 2361527
2025 ALR inhibits HBV replication and autophagosome formation by ameliorating HBV-induced ROS production in hepatic cells. Virus genes 5 39934594
2022 Multiple Alr genes exhibit allorecognition-associated variation in the colonial cnidarian Hydractinia. Immunogenetics 5 35761101
2022 Correlation between 25-hydroxyvitamin D/D3 Deficiency and COVID-19 Disease Severity in Adults from Northern Colorado. Nutrients 5 36558362
2015 The Level of ALR is Regulated by the Quantity of Mitochondrial DNA. Pathology oncology research : POR 5 26584568
2012 Benzo(a)pyrene induces hepatic AKR1A1 mRNA expression in tilapia fish (Oreochromis niloticus). Toxicology mechanisms and methods 5 22394341
2005 Functional analysis of a novel gene, DD3-3, from Dictyostelium discoideum. Biochemical and biophysical research communications 5 15883003
1999 The structural organization of the human aldehyde reductase gene, AKR1A1, and mapping to chromosome 1p33-->p32. Cytogenetics and cell genetics 5 10393438
1991 [Diabetic peculiarity of the ALS-Ay and ALR-Ay strains]. Jikken dobutsu. Experimental animals 5 1915599