AKR1B1

Available structures

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

MGI: 1353494 HomoloGene: 133743 GeneCards: AKR1B1

Targeted by Drug

sorbinil, tolrestat, zenarestat^[1]

Gene ontology
Molecular function	• aldo-keto reductase (NADP) activity • electron carrier activity • oxidoreductase activity • glyceraldehyde oxidoreductase activity • alditol:NADP+ 1-oxidoreductase activity
Cellular component	• cytoplasm • cytosol • mast cell granule • Schwann cell microvillus • Schmidt-Lanterman incisure • nucleoplasm • extracellular space • cell projection cytoplasm • perinuclear region of cytoplasm • paranodal junction • extracellular exosome
Biological process	• stress-activated protein kinase signaling cascade • cellular response to peptide • daunorubicin metabolic process • doxorubicin metabolic process • maternal process involved in female pregnancy • carbohydrate metabolic process • 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 • naphthalene metabolic process • C21-steroid hormone biosynthetic process • tissue homeostasis • inner medullary collecting duct development • oxidation-reduction process • positive regulation of JAK-STAT cascade • positive regulation of smooth muscle cell proliferation • cellular response to hydrogen peroxide • sorbitol biosynthetic process
Sources:Amigo / QuickGO

RNA expression pattern

More reference expression data

Orthologs

Species

Human

Mouse

Entrez


231


11677

Ensembl


ENSG00000085662


ENSMUSG00000001642

UniProt


P15121


P45376

RefSeq (mRNA)


NM_001628


NM_009658

RefSeq (protein)


NP_001619.1


NP_033788.3

Location (UCSC)

Chr 7: 134.44 – 134.46 Mb

Chr 6: 34.3 – 34.32 Mb

PubMed search

^[2]

^[3]

Wikidata

View/Edit Human

View/Edit Mouse

Aldo-keto reductase family 1, member B1 (aldose reductase), also known as AR, is an enzyme that in humans is encoded by the AKR1B1 gene.^[4]^[5]

Function

This gene encodes a member of the aldo/keto reductase superfamily, which consists of more than 40 known enzymes and proteins. This member catalyzes the reduction of a number of aldehydes, including the aldehyde form of glucose, and is thereby implicated in the development of diabetic complications by catalyzing the reduction of glucose to sorbitol.^[5]

Gene

There are a few putative pseudogenes for this gene, and one of them has been confirmed and mapped to chromosome 3.^[5]

References

↑ "Drugs that physically interact with Aldose reductase view/edit references on wikidata".
↑ "Human PubMed Reference:".
↑ "Mouse PubMed Reference:".
↑ Graham A, Heath P, Morten JE, Markham AF (March 1991). "The human aldose reductase gene maps to chromosome region 7q35". Hum. Genet. 86 (5): 509–14. doi:10.1007/BF00194644. PMID 1901827.
1 2 3 "Entrez Gene: AKR1B1 aldo-keto reductase family 1, member B1 (aldose reductase)".

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.

Borhani DW, Harter TM, Petrash JM (1992). "The crystal structure of the aldose reductase.NADPH binary complex.". J. Biol. Chem. 267 (34): 24841–7. PMID 1447221.
Wilson DK, Bohren KM, Gabbay KH, Quiocho FA (1992). "An unlikely sugar substrate site in the 1.65 A structure of the human aldose reductase holoenzyme implicated in diabetic complications.". Science. 257 (5066): 81–4. doi:10.1126/science.1621098. PMID 1621098.
Graham A, Heath P, Morten JE, Markham AF (1991). "The human aldose reductase gene maps to chromosome region 7q35.". Hum. Genet. 86 (5): 509–14. doi:10.1007/BF00194644. PMID 1901827.
Graham A, Brown L, Hedge PJ, et al. (1991). "Structure of the human aldose reductase gene.". J. Biol. Chem. 266 (11): 6872–7. PMID 1901857.
Grundmann U, Bohn H, Obermeier R, Amann E (1990). "Cloning and prokaryotic expression of a biologically active human placental aldose reductase.". DNA Cell Biol. 9 (3): 149–57. doi:10.1089/dna.1990.9.149. PMID 2111143.
Nishimura C, Matsuura Y, Kokai Y, et al. (1990). "Cloning and expression of human aldose reductase.". J. Biol. Chem. 265 (17): 9788–92. PMID 2112546.
Morjana NA, Lyons C, Flynn TG (1989). "Aldose reductase from human psoas muscle. Affinity labeling of an active site lysine by pyridoxal 5'-phosphate and pyridoxal 5'-diphospho-5'-adenosine.". J. Biol. Chem. 264 (5): 2912–9. PMID 2492527.
Bohren KM, Bullock B, Wermuth B, Gabbay KH (1989). "The aldo-keto reductase superfamily. cDNAs and deduced amino acid sequences of human aldehyde and aldose reductases.". J. Biol. Chem. 264 (16): 9547–51. PMID 2498333.
Chung S, LaMendola J (1989). "Cloning and sequence determination of human placental aldose reductase gene.". J. Biol. Chem. 264 (25): 14775–7. PMID 2504709.
Graham A, Hedge PJ, Powell SJ, et al. (1989). "Nucleotide sequence of cDNA for human aldose reductase". Nucleic Acids Res. 17 (20): 8368. doi:10.1093/nar/17.20.8368. PMC 334974. PMID 2510130.
Akagi Y, Kador PF, Kuwabara T, Kinoshita JH (1984). "Aldose reductase localization in human retinal mural cells". Invest. Ophthalmol. Vis. Sci. 24 (11): 1516–9. PMID 6417042.
Ko BC, Lam KS, Wat NM, Chung SS (1995). "An (A-C)n dinucleotide repeat polymorphic marker at the 5' end of the aldose reductase gene is associated with early-onset diabetic retinopathy in NIDDM patients". Diabetes. 44 (7): 727–32. doi:10.2337/diabetes.44.7.727. PMID 7789640.
Wilson DK, Tarle I, Petrash JM, Quiocho FA (1993). "Refined 1.8 A structure of human aldose reductase complexed with the potent inhibitor zopolrestat". Proc. Natl. Acad. Sci. U.S.A. 90 (21): 9847–51. doi:10.1073/pnas.90.21.9847. PMC 47669. PMID 8234324.
Tarle I, Borhani DW, Wilson DK, et al. (1994). "Probing the active site of human aldose reductase. Site-directed mutagenesis of Asp-43, Tyr-48, Lys-77, and His-110". J. Biol. Chem. 268 (34): 25687–93. PMID 8245005.
Robinson B, Hunsaker LA, Stangebye LA, Vander Jagt DL (1994). "Aldose and aldehyde reductases from human kidney cortex and medulla". Biochim. Biophys. Acta. 1203 (2): 260–6. doi:10.1016/0167-4838(93)90092-6. PMID 8268209.
Jaquinod M, Potier N, Klarskov K, et al. (1994). "Sequence of pig lens aldose reductase and electrospray mass spectrometry of non-covalent and covalent complexes". Eur. J. Biochem. 218 (3): 893–903. doi:10.1111/j.1432-1033.1993.tb18445.x. PMID 8281941.
Liu SQ, Bhatnagar A, Ansari NH, Srivastava SK (1993). "Identification of the reactive cysteine residue in human placenta aldose reductase". Biochim. Biophys. Acta. 1164 (3): 268–72. doi:10.1016/0167-4838(93)90258-S. PMID 8343525.
Nishimura C, Furue M, Ito T, et al. (1993). "Quantitative determination of human aldose reductase by enzyme-linked immunosorbent assay. Immunoassay of human aldose reductase". Biochem. Pharmacol. 46 (1): 21–8. doi:10.1016/0006-2952(93)90343-U. PMID 8347133.
Sato S, Lin LR, Reddy VN, Kador PF (1993). "Aldose reductase in human retinal pigment epithelial cells". Exp. Eye Res. 57 (2): 235–41. doi:10.1006/exer.1993.1119. PMID 8405190.
Ferraretto A, Negri A, Giuliani A, et al. (1993). "Aldose reductase is involved in long-term adaptation of EUE cells to hyperosmotic stress". Biochim. Biophys. Acta. 1175 (3): 283–8. doi:10.1016/0167-4889(93)90218-E. PMID 8435445.

PDB gallery

1abn: THE CRYSTAL STRUCTURE OF THE ALDOSE REDUCTASE NADPH BINARY COMPLEX
1ads: AN UNLIKELY SUGAR SUBSTRATE SITE IN THE 1.65 ANGSTROMS STRUCTURE OF THE HUMAN ALDOSE REDUCTASE HOLOENZYME IMPLICATED IN DIABETIC COMPLICATIONS
1az1: ALRESTATIN BOUND TO C298A/W219Y MUTANT HUMAN ALDOSE REDUCTASE
1az2: CITRATE BOUND, C298A/W219Y MUTANT HUMAN ALDOSE REDUCTASE
1ef3: FIDARESTAT BOUND TO HUMAN ALDOSE REDUCTASE
1el3: HUMAN ALDOSE REDUCTASE COMPLEXED WITH IDD384 INHIBITOR
1iei: CRYSTAL STRUCTURE OF HUMAN ALDOSE REDUCTASE COMPLEXED WITH THE INHIBITOR ZENARESTAT.
1mar: REFINED 1.8 ANGSTROMS STRUCTURE OF HUMAN ALDOSE REDUCTASE COMPLEXED WITH THE POTENT INHIBITOR ZOPOLRESTAT
1pwl: Crystal structure of human Aldose Reductase complexed with NADP and Minalrestat
1pwm: Crystal structure of human Aldose Reductase complexed with NADP and Fidarestat
1t40: Crystal structure of human aldose reductase complexed with NADP and IDD552 at ph 5
1t41: Crystal structure of human aldose reductase complexed with NADP and IDD552
1us0: HUMAN ALDOSE REDUCTASE IN COMPLEX WITH NADP+ AND THE INHIBITOR IDD594 AT 0.66 ANGSTROM
1x96: Crystal structure of Aldose Reductase with citrates bound in the active site
1x97: Crystal structure of Aldose Reductase complexed with 2R4S (Stereoisomer of Fidarestat, 2S4S)
1x98: Crystal structure of Aldose Reductase complexed with 2S4R (Stereoisomer of Fidarestat, 2S4S)
1xgd: Apo R268A human aldose reductase
1z3n: Human aldose reductase in complex with NADP+ and the inhibitor lidorestat at 1.04 angstrom
1z89: Human Aldose Reductase complexed with novel Sulfonyl-pyridazinone Inhibitor
1z8a: Human Aldose Reductase complexed with novel Sulfonyl-pyridazinone Inhibitor
2acq: AN ANION BINDING SITE IN HUMAN ALDOSE REDUCTASE: MECHANISTIC IMPLICATIONS FOR THE BINDING OF CITRATE, CACODYLATE, AND GLUCOSE-6-PHOSPHATE
2acr: AN ANION BINDING SITE IN HUMAN ALDOSE REDUCTASE: MECHANISTIC IMPLICATIONS FOR THE BINDING OF CITRATE, CACODYLATE, AND GLUCOSE-6-PHOSPHATE
2acs: AN ANION BINDING SITE IN HUMAN ALDOSE REDUCTASE: MECHANISTIC IMPLICATIONS FOR THE BINDING OF CITRATE, CACODYLATE, AND GLUCOSE-6-PHOSPHATE
2acu: TYROSINE-48 IS THE PROTON DONOR AND HISTIDINE-110 DIRECTS SUBSTRATE STEREOCHEMICAL SELECTIVITY IN THE REDUCTION REACTION OF HUMAN ALDOSE REDUCTASE: ENZYME KINETICS AND THE CRYSTAL STRUCTURE OF THE Y48H MUTANT ENZYME
2agt: Aldose Reductase Mutant Leu 300 Pro complexed with Fidarestat
2dux: Crystal structure of human Aldose Reductase complexed with zopolrestat after 3 days soaking (3days_soaked_1)
2duz: Human Aldose Reductase complexed with inhibitor zopolrestat after 3 days soaking (3days_soaked_2)
2dv0: Human Aldose Reductase complexed with zopolrestat after 6 days soaking(6days_soaked_2)
2f2k: Aldose reductase tertiary complex with NADPH and DEG
2fz8: Human Aldose reductase complexed with inhibitor zopolrestat at 1.48 A(1 day soaking).
2fz9: Human Aldose Reductase complexed with inhibitor zopolrestat after six days soaking.
2fzb: Human Aldose Reductase complexed with four tolrestat molecules at 1.5 A resolution.
2fzd: Human aldose reductase complexed with tolrestat at 1.08 A resolution.
2hv5: Human Aldose Reductase complexed with inhibitor zopolrestat after three days soaking (3days_soaked_3)
2hvn: Human Aldose Reductase-zopolrestat complex obtained by cocrystallisation after one day (1day_cocryst)
2hvo: Human Aldose Reductase-zopolrestat complex obtained by cocrystallisation (10days_cocryst)
2i16: Human aldose reductase in complex with NADP+ and the inhibitor IDD594 at temperature of 15K
2i17: Human aldose reductase in complex with NADP+ and the inhibitor IDD594 at temperature of 60K
2ikg: Aldose reductase complexed with nitrophenyl-oxadiazol type inhibitor at 1.43 A
2ikh: Human aldose reductase complexed with nitrofuryl-oxadiazol inhibitor at 1.55 A
2iki: Human aldose reductase complexed with halogenated IDD-type inhibitor
2ikj: Human aldose reductase complexed with nitro-substituted IDD-type inhibitor
2ine: Crystal Structure of Aldose Reductase complexed with Phenylacetic Acid
2inz: Crystal Structure of Aldose Reductase complexed with 2-Hydroxyphenylacetic Acid
2ipw: Crystal Structure of C298A W219Y Aldose Reductase complexed with Dichlorophenylacetic acid
2iq0: Crystal Structure of Aldose Reductase complexed with Hexanoic Acid
2iqd: Crystal Structure of Aldose Reductase complexed with Lipoic Acid
2is7: Crystal Structure of Aldose Reductase complexed with Dichlorophenylacetic acid
2isf: Crystal Structure of C298A W219Y Aldose Reductase complexed with Phenylacetic Acid
2j8t: HUMAN ALDOSE REDUCTASE IN COMPLEX WITH NADP AND CITRATE AT 0.82 ANGSTROM
2nvc: Human Aldose Reductase complexed with novel naphtho[1,2-d]isothiazole acetic acid derivative (3)
2nvd: Human Aldose Reductase complexed with novel naphtho[1,2-d]isothiazole acetic acid derivative (2)
2pev: Complex of Aldose Reductase with NADP+ and simaltaneously bound competetive inhibitors Fidarestat and IDD594. Concentration of Fidarestat in soaking solution exceeds concentration of IDD594.
2pf8: Complex of Aldose Reductase with NADP+ and simaltaneously bound competetive inhibitors Fidarestat and IDD594. Concentration of Fidarestat in soaking solution is equal to concentration of IDD594.
2pfh: Complex of Aldose Reductase with NADP+ and simaltaneously bound competetive inhibitors Fidarestat and IDD594. Concentration of Fidarestat in soaking solution is less than concentration of IDD594.

Oxidoreductases: alcohol oxidoreductases (EC 1.1)

1.1.1: NAD/NADP acceptor	3-hydroxyacyl-CoA dehydrogenase 3-hydroxybutyryl-CoA dehydrogenase Alcohol dehydrogenase Aldo-keto reductase 1A1 1B1 1B10 1C1 1C3 1C4 7A2 Aldose reductase Beta-Ketoacyl ACP reductase Carbohydrate dehydrogenases Carnitine dehydrogenase D-malate dehydrogenase (decarboxylating) DXP reductoisomerase Glucose-6-phosphate dehydrogenase Glycerol-3-phosphate dehydrogenase HMG-CoA reductase IMP dehydrogenase Isocitrate dehydrogenase Lactate dehydrogenase L-threonine dehydrogenase L-xylulose reductase Malate dehydrogenase Malate dehydrogenase (decarboxylating) Malate dehydrogenase (NADP+) Malate dehydrogenase (oxaloacetate-decarboxylating) Malate dehydrogenase (oxaloacetate-decarboxylating) (NADP+) Phosphogluconate dehydrogenase Sorbitol dehydrogenase Hydroxysteroid dehydrogenase: 3 Beta 3-beta-HSD NSDHL 11 Beta HSD11B1 HSD11B2 17 Beta

1.1.2: cytochrome acceptor	D-lactate dehydrogenase (cytochrome) D-lactate dehydrogenase (cytochrome c-553) Mannitol dehydrogenase (cytochrome)

1.1.3: oxygen acceptor	Glucose oxidase L-gulonolactone oxidase Xanthine oxidase

1.1.4: disulfide as acceptor	Vitamin K epoxide reductase Vitamin-K-epoxide reductase (warfarin-insensitive)

1.1.5: quinone/similar acceptor	Malate dehydrogenase (quinone) Quinoprotein glucose dehydrogenase

1.1.99: other acceptors	Choline dehydrogenase L2HGDH

Enzymes

Activity	Active site Binding site Catalytic triad Oxyanion hole Enzyme promiscuity Catalytically perfect enzyme Coenzyme Cofactor Enzyme catalysis Enzyme kinetics Lineweaver–Burk plot Michaelis–Menten kinetics

Regulation	Allosteric regulation Cooperativity Enzyme inhibitor

Classification	EC number Enzyme superfamily Enzyme family List of enzymes

Types	EC1 Oxidoreductases (list) EC2 Transferases (list) EC3 Hydrolases (list) EC4 Lyases (list) EC5 Isomerases (list) EC6 Ligases (list)

This article is issued from Wikipedia - version of the 12/3/2016. The text is available under the Creative Commons Attribution/Share Alike but additional terms may apply for the media files.

AKR1B1

Function

Gene

References

External links

Further reading