AKR1B1

AKR1B1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2PDQ, 1IEI, 2ACQ, 2FZB, 2IKH, 2PDH, 3LD5, 2IQ0, 1T40, 2PDG, 2PDB, 3GHR, 2NVD, 2PD5, 2PDU, 3M4H, 4GCA, 2PDX, 2I17, 1US0, 1AZ1, 2R24, 3M64, 1MAR, 3ONC, 1Z3N, 3ONB, 2ACR, 2DUZ, 2DUX, 2HVO, 2FZ8, 4PUW, 4XZH, 4QBX, 4JIR, 2PD9, 3LQL, 1ABN, 2PDW, 4PR4, 2PDI, 3LEP, 2PDJ, 4PUU, 2DV0, 3LEN, 3G5E, 1EF3, 4LB3, 2PDC, 3LBO, 2PDP, 2FZD, 4NKC, 2PZN, 2ISF, 3RX4, 2PDL, 3Q65, 4PRT, 4Q7B, 4QX4, 2FZ9, 2IKJ, 2J8T, 4IGS, 2IS7, 3V35, 1Z8A, 1XGD, 3T42, 2QXW, 4QR6, 1X96, 4RPQ, 2HV5, 2NVC, 2F2K, 3BCJ, 3LZ3, 3V36, 2PDK, 3GHU, 3GHS, 2ACU, 2PDM, 4LAZ, 1T41, 2IKG, 3MB9, 2PDF, 4PRR, 2PDN, 3LQG, 4XZI, 3LZ5, 2AGT, 3S3G, 1PWL, 3M0I, 2PF8, 3RX2, 2IPW, 3MC5, 3DN5, 4QXI, 2HVN, 2INZ, 1X97, 2PDY, 3RX3, 1PWM, 4LBR, 3Q67, 4LAU, 1Z89, 2IKI, 3P2V, 1X98, 1AZ2, 2PFH, 3U2C, 2ACS, 3GHT, 4LB4, 2INE, 1EL3, 2I16, 2IQD, 2PEV, 4LBS, 1ADS, 4YU1, 4YS1
Identifiers
Aliases	AKR1B1, ADR, ALDR1, ALR2, AR, aldo-keto reductase family 1, member B1 (aldose reductase), aldo-keto reductase family 1 member B
External IDs	OMIM: 103880; MGI: 1353494; HomoloGene: 133743; GeneCards: AKR1B1; OMA:AKR1B1 - orthologs
Gene location (Human) Chr. Chromosome 7 (human)[1] Band 7q33 Start 134,442,356 bp[1] End 134,459,284 bp[1]
Gene location (Mouse) Chr. Chromosome 6 (mouse)[2] Band 6 14.87 cM|6 B1 Start 34,279,369 bp[2] End 34,294,413 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in right adrenal cortex left adrenal gland left adrenal cortex olfactory bulb spinal ganglia seminal vesicula apex of heart Skeletal muscle tissue of rectus abdominis trigeminal ganglion gastrocnemius muscle Top expressed in urinary bladder primary oocyte secondary oocyte zygote adrenal gland quadriceps femoris muscle spermatocyte muscle tissue skeletal muscle tissue right kidney More reference expression data BioGPS More reference expression data
Gene ontology Molecular function aldo-keto reductase (NADP) activity electron transfer activity oxidoreductase activity glyceraldehyde oxidoreductase activity alditol:NADP+ 1-oxidoreductase activity alcohol dehydrogenase (NADP+) activity retinal dehydrogenase activity allyl-alcohol dehydrogenase activity NADP-retinol dehydrogenase activity Cellular component mast cell granule Schwann cell microvillus Schmidt-Lanterman incisure nucleoplasm plasma membrane bounded cell projection cytoplasm perinuclear region of cytoplasm paranodal junction extracellular exosome extracellular space cytoplasm cytosol Biological process stress-activated protein kinase signaling cascade cellular response to peptide daunorubicin metabolic process doxorubicin metabolic process maternal process involved in female pregnancy monosaccharide metabolic process norepinephrine metabolic process fructose biosynthetic process response to thyroid hormone response to stress response to water deprivation cellular response to methylglyoxal response to organic substance C21-steroid hormone biosynthetic process tissue homeostasis inner medullary collecting duct development positive regulation of receptor signaling pathway via JAK-STAT positive regulation of smooth muscle cell proliferation cellular response to hydrogen peroxide sorbitol biosynthetic process renal water homeostasis regulation of urine volume negative regulation of apoptotic process renal system development carbohydrate metabolic process electron transport chain cellular hyperosmotic salinity response retinoid metabolic process metanephric collecting duct development retinol metabolic process Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 231 11677 Ensembl ENSG00000085662 ENSMUSG00000001642 UniProt P15121 P45376 RefSeq (mRNA) NM_001628 NM_001346142 NM_009658 RefSeq (protein) NP_001333071 NP_001619 NP_033788 Location (UCSC) Chr 7: 134.44 – 134.46 Mb Chr 6: 34.28 – 34.29 Mb PubMed search [3] [4]
Wikidata
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Aldo-keto reductase family 1, member B1 (AKR1B1), also known as aldose reductase, is an enzyme that is encoded by the AKR1B1 gene in humans.^[5][6] It is a reduced nicotinamide-adenine dinucleotide phosphate (NADPH)-dependent enzyme catalyzing the reduction of various aldehydes and ketones to the corresponding alcohol. The involvement of AKR1B1 in oxidative stress diseases, cell signal transduction, and cell proliferation process endows AKR1B1 with potential as a therapeutic target.

Structure

Gene

The AKR1B1 gene lies on the chromosome location of 7q33 and consists of 10 exons. There are a few putative pseudogenes for this gene, and one of them has been confirmed and mapped to chromosome 3.^[6]

Protein

AKR1B1 consists of 316 amino acid residues and weighs 35853Da. It does not possess the traditional dinucleotide binding fold. The way it binds NADPH differs from other nucleotide adenine dinucleotide-dependent enzymes. The active site pocket of human aldose reductase is relatively hydrophobic, lined by seven aromatic and four other non-polar residues.^[7]

Function

AR belongs to the aldehyde-keto reductase superfamily, with a widely expression in human organs including the kidney, lens, retina, nerve, heart, placenta, brain, skeletal muscle, testis, blood vessels, lung, and liver.^[8] It is a reduced nicotinamide-adenine dinucleotide phosphate (NADPH)-dependent enzyme catalyzing the reduction of various aldehydes and ketones to the corresponding alcohol. It also participates in glucose metabolism and osmoregulation and plays a protective role against toxic aldehydes derived from lipid peroxidation and steroidogenesis.^[9]

Clinical significance

Under diabetic conditions AR converts glucose into sorbitol, which is then converted to fructose. 20466987 It has been found to play an important role in many diabetes complications such as diabetes retinopathy and renopathy.^[10][11][12] It is also involved in many oxidative stress diseases, cell signal transduction, and cell proliferation process including cardiovascular disorders, sepsis, and cancer.^[13]

It has been reported that the action of AR contributes to the activation of retinal microglia, suggesting that inhibition of AR may be of a therapeutic importance to reduce inflammation associated with activation of RMG.^[14] Adapting AR inhibitors could as well prevent sepsis complications, prevent angiogenesis, ameliorate mild or asymptomatic diabetic cardiovascular autonomic neuropathy and may be a promising strategy for the treatment of endotoxemia and other ROS-induced inflammatory diseases.^[12]

Interactions

AKR1B1 has been found to interact with:

• ginsenoside 20(S)-Rh2^[15]
• alkaloid^[16]
• carboxylic acid derivatives^[12]
• spirohydantoins^[12]
• cyclic amides^[12]

References

Further reading

External links

• Human AKR1B1 genome location and AKR1B1 gene details page in the UCSC Genome Browser.
• Human AR genome location and AR gene details page in the UCSC Genome Browser.