ID ALDR_RAT Reviewed; 316 AA. AC P07943; DT 01-AUG-1988, integrated into UniProtKB/Swiss-Prot. DT 23-JAN-2007, sequence version 3. DT 24-JAN-2024, entry version 175. DE RecName: Full=Aldo-keto reductase family 1 member B1; DE EC=1.1.1.21 {ECO:0000250|UniProtKB:P15121}; DE EC=1.1.1.300 {ECO:0000250|UniProtKB:P15121}; DE EC=1.1.1.372 {ECO:0000250|UniProtKB:P15121}; DE EC=1.1.1.54 {ECO:0000250|UniProtKB:P15121}; DE AltName: Full=Aldehyde reductase; DE AltName: Full=Aldose reductase; DE Short=AR; GN Name=Akr1b1; Synonyms=Akr1b4, Aldr1; OS Rattus norvegicus (Rat). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Rattus. OX NCBI_TaxID=10116; RN [1] RP NUCLEOTIDE SEQUENCE, AND PARTIAL PROTEIN SEQUENCE. RC STRAIN=Sprague-Dawley; TISSUE=Lens; RX PubMed=3111886; DOI=10.1016/0014-5793(87)80905-5; RA Carper D., Nishimura C., Shinohara T., Dietzchold B., Wistow G., Craft C., RA Kador P., Kinoshita J.H.; RT "Aldose reductase and p-crystallin belong to the same protein superfamily RT as aldehyde reductase."; RL FEBS Lett. 220:209-213(1987). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=1748296; DOI=10.1016/0378-1119(91)90326-7; RA Graham C.E., Szpirer C., Levan G., Carper D.; RT "Characterization of the aldose reductase-encoding gene family in rat."; RL Gene 107:259-267(1991). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Prostate; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [4] RP PROTEIN SEQUENCE OF 42-53; 156-169; 178-195; 276-294 AND 307-316, AND RP IDENTIFICATION BY MASS SPECTROMETRY. RC STRAIN=Sprague-Dawley; TISSUE=Spinal cord; RA Lubec G., Afjehi-Sadat L.; RL Submitted (NOV-2006) to UniProtKB. RN [5] RP PROTEIN SEQUENCE OF 156-169 AND 205-210. RC TISSUE=Astrocyte; RX PubMed=7498172; DOI=10.1002/elps.11501601205; RA Laeng P., Bouillon P., Taupenot L., Labourdette G.; RT "Long-term induction of an aldose reductase protein by basic fibroblast RT growth factor in rat astrocytes in vitro."; RL Electrophoresis 16:1240-1250(1995). RN [6] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-3, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=22673903; DOI=10.1038/ncomms1871; RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C., RA Olsen J.V.; RT "Quantitative maps of protein phosphorylation sites across 14 different rat RT organs and tissues."; RL Nat. Commun. 3:876-876(2012). CC -!- FUNCTION: Catalyzes the NADPH-dependent reduction of a wide variety of CC carbonyl-containing compounds to their corresponding alcohols with a CC broad range of catalytic efficiencies. CC -!- FUNCTION: Catalyzes the NADPH-dependent reduction of a wide variety of CC carbonyl-containing compounds to their corresponding alcohols. Displays CC enzymatic activity towards endogenous metabolites such as aromatic and CC aliphatic aldehydes, ketones, monosacharides, bile acids and CC xenobiotics substrates. Key enzyme in the polyol pathway, catalyzes CC reduction of glucose to sorbitol during hyperglycemia. Reduces steroids CC and their derivatives and prostaglandins. Displays low enzymatic CC activity toward all-trans-retinal, 9-cis-retinal, and 13-cis-retinal. CC Catalyzes the reduction of diverse phospholipid aldehydes such as 1- CC palmitoyl-2-(5-oxovaleroyl)-sn -glycero-3-phosphoethanolamin (POVPC) CC and related phospholipid aldehydes that are generated from the CC oxydation of phosphotidylcholine and phosphatdyleethanolamides. Plays a CC role in detoxifying dietary and lipid-derived unsaturated carbonyls, CC such as crotonaldehyde, 4-hydroxynonenal, trans-2-hexenal, trans-2,4- CC hexadienal and their glutathione-conjugates carbonyls (GS-carbonyls). CC {ECO:0000250|UniProtKB:P15121}. CC -!- CATALYTIC ACTIVITY: CC Reaction=an alditol + NADP(+) = an aldose + H(+) + NADPH; CC Xref=Rhea:RHEA:12789, Rhea:RHEA-COMP:9554, Rhea:RHEA-COMP:9555, CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15693, ChEBI:CHEBI:17522, CC ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; EC=1.1.1.21; CC Evidence={ECO:0000250|UniProtKB:P15121}; CC -!- CATALYTIC ACTIVITY: CC Reaction=all-trans-retinol + NADP(+) = all-trans-retinal + H(+) + CC NADPH; Xref=Rhea:RHEA:25033, ChEBI:CHEBI:15378, ChEBI:CHEBI:17336, CC ChEBI:CHEBI:17898, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; CC EC=1.1.1.300; Evidence={ECO:0000250|UniProtKB:P15121}; CC -!- CATALYTIC ACTIVITY: CC Reaction=9-cis-retinol + NADP(+) = 9-cis-retinal + H(+) + NADPH; CC Xref=Rhea:RHEA:54916, ChEBI:CHEBI:15378, ChEBI:CHEBI:57783, CC ChEBI:CHEBI:58349, ChEBI:CHEBI:78272, ChEBI:CHEBI:78273; CC Evidence={ECO:0000250|UniProtKB:P15121}; CC -!- CATALYTIC ACTIVITY: CC Reaction=13-cis-retinol + NADP(+) = 13-cis-retinal + H(+) + NADPH; CC Xref=Rhea:RHEA:54920, ChEBI:CHEBI:15378, ChEBI:CHEBI:45479, CC ChEBI:CHEBI:45487, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; CC Evidence={ECO:0000250|UniProtKB:P15121}; CC -!- CATALYTIC ACTIVITY: CC Reaction=glycerol + NADP(+) = D-glyceraldehyde + H(+) + NADPH; CC Xref=Rhea:RHEA:23592, ChEBI:CHEBI:15378, ChEBI:CHEBI:17378, CC ChEBI:CHEBI:17754, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; CC EC=1.1.1.372; Evidence={ECO:0000250|UniProtKB:P15121}; CC -!- CATALYTIC ACTIVITY: CC Reaction=glycerol + NADP(+) = H(+) + L-glyceraldehyde + NADPH; CC Xref=Rhea:RHEA:38111, ChEBI:CHEBI:15378, ChEBI:CHEBI:17754, CC ChEBI:CHEBI:27975, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; CC EC=1.1.1.372; Evidence={ECO:0000250|UniProtKB:P15121}; CC -!- CATALYTIC ACTIVITY: CC Reaction=NADP(+) + prenol = 3-methyl-2-butenal + H(+) + NADPH; CC Xref=Rhea:RHEA:58420, ChEBI:CHEBI:15378, ChEBI:CHEBI:15825, CC ChEBI:CHEBI:16019, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; CC Evidence={ECO:0000250|UniProtKB:P15121}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(E)-hex-2-en-1-ol + NADP(+) = (E)-hex-2-enal + H(+) + NADPH; CC Xref=Rhea:RHEA:58424, ChEBI:CHEBI:15378, ChEBI:CHEBI:28913, CC ChEBI:CHEBI:57783, ChEBI:CHEBI:58349, ChEBI:CHEBI:141205; CC Evidence={ECO:0000250|UniProtKB:P15121}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(E,E)-2,4-hexadien-1-ol + NADP(+) = (E,E)-2,4-hexadienal + CC H(+) + NADPH; Xref=Rhea:RHEA:58428, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:57783, ChEBI:CHEBI:58349, ChEBI:CHEBI:82334, CC ChEBI:CHEBI:142625; Evidence={ECO:0000250|UniProtKB:P15121}; CC -!- CATALYTIC ACTIVITY: CC Reaction=a 4-hydroxynonen-1-ol + NADP(+) = a 4-hydroxynonenal + H(+) + CC NADPH; Xref=Rhea:RHEA:58336, ChEBI:CHEBI:15378, ChEBI:CHEBI:57783, CC ChEBI:CHEBI:58349, ChEBI:CHEBI:142593, ChEBI:CHEBI:142606; CC Evidence={ECO:0000250|UniProtKB:P15121}; CC -!- CATALYTIC ACTIVITY: CC Reaction=NADP(+) + prostaglandin F2alpha = H(+) + NADPH + prostaglandin CC H2; Xref=Rhea:RHEA:45312, ChEBI:CHEBI:15378, ChEBI:CHEBI:57404, CC ChEBI:CHEBI:57405, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; CC Evidence={ECO:0000250|UniProtKB:P15121}; CC -!- CATALYTIC ACTIVITY: CC Reaction=allyl alcohol + NADP(+) = acrolein + H(+) + NADPH; CC Xref=Rhea:RHEA:12168, ChEBI:CHEBI:15368, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:16605, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; EC=1.1.1.54; CC Evidence={ECO:0000250|UniProtKB:P15121}; CC -!- CATALYTIC ACTIVITY: CC Reaction=NADP(+) + pyridine 3-methanol = H(+) + NADPH + pyridine-3- CC carbaldehyde; Xref=Rhea:RHEA:58776, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:28345, ChEBI:CHEBI:45213, ChEBI:CHEBI:57783, CC ChEBI:CHEBI:58349; Evidence={ECO:0000250|UniProtKB:P15121}; CC -!- CATALYTIC ACTIVITY: CC Reaction=1-hexadecanoyl-2-(5-oxopentanoyl)-sn-glycero-3-phosphocholine CC + H(+) + NADPH = 1-hexadecanoyl-2-(5-hydroxypentanoyl)-sn-glycero-3- CC phosphocholine + NADP(+); Xref=Rhea:RHEA:58512, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:57783, ChEBI:CHEBI:58349, ChEBI:CHEBI:77890, CC ChEBI:CHEBI:142747; Evidence={ECO:0000250|UniProtKB:P15121}; CC -!- CATALYTIC ACTIVITY: CC Reaction=1-hexadecanoyl-2-(7-oxoheptanoyl)-sn-glycero-3-phosphocholine CC + H(+) + NADPH = 1-hexadecanoyl-2-(7-hydroxyheptanoyl)-sn-glycero-3- CC phosphocholine + NADP(+); Xref=Rhea:RHEA:58752, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:57783, ChEBI:CHEBI:58349, ChEBI:CHEBI:134601, CC ChEBI:CHEBI:142748; Evidence={ECO:0000250|UniProtKB:P15121}; CC -!- CATALYTIC ACTIVITY: CC Reaction=1-hexadecanoyl-2-(9-oxononanoyl)-sn-glycero-3-phosphocholine + CC H(+) + NADPH = 1-hexadecanoyl-2-(9-hydroxynonanoyl)-sn-glycero-3- CC phosphocholine + NADP(+); Xref=Rhea:RHEA:58592, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:57783, ChEBI:CHEBI:58349, ChEBI:CHEBI:61042, CC ChEBI:CHEBI:142749; Evidence={ECO:0000250|UniProtKB:P15121}; CC -!- CATALYTIC ACTIVITY: CC Reaction=1-hexadecanoyl-2-(5-oxopentanoyl)-sn-glycero-3- CC phosphoethanolamine + H(+) + NADPH = 1-hexadecanoyl-2-(5- CC hydroxypentanoyl)-sn-glycero-3-phosphoethanolamine + NADP(+); CC Xref=Rhea:RHEA:58756, ChEBI:CHEBI:15378, ChEBI:CHEBI:57783, CC ChEBI:CHEBI:58349, ChEBI:CHEBI:142750, ChEBI:CHEBI:142751; CC Evidence={ECO:0000250|UniProtKB:P15121}; CC -!- SUBUNIT: Monomer. {ECO:0000250|UniProtKB:P15121}. CC -!- SUBCELLULAR LOCATION: Cytoplasm. CC -!- SIMILARITY: Belongs to the aldo/keto reductase family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; X05884; CAA29308.1; -; mRNA. DR EMBL; M60322; AAA40721.1; -; Genomic_DNA. DR EMBL; BC062034; AAH62034.1; -; mRNA. DR PIR; A60603; A60603. DR RefSeq; NP_036630.1; NM_012498.1. DR AlphaFoldDB; P07943; -. DR SMR; P07943; -. DR BioGRID; 246382; 2. DR STRING; 10116.ENSRNOP00000012879; -. DR BindingDB; P07943; -. DR ChEMBL; CHEMBL2622; -. DR DrugCentral; P07943; -. DR iPTMnet; P07943; -. DR PhosphoSitePlus; P07943; -. DR SwissPalm; P07943; -. DR jPOST; P07943; -. DR PaxDb; 10116-ENSRNOP00000012879; -. DR GeneID; 24192; -. DR KEGG; rno:24192; -. DR UCSC; RGD:2092; rat. DR AGR; RGD:2092; -. DR CTD; 231; -. DR RGD; 2092; Akr1b1. DR VEuPathDB; HostDB:ENSRNOG00000009513; -. DR eggNOG; KOG1577; Eukaryota. DR HOGENOM; CLU_023205_0_0_1; -. DR InParanoid; P07943; -. DR OrthoDB; 890110at2759; -. DR PhylomeDB; P07943; -. DR TreeFam; TF106492; -. DR BRENDA; 1.1.1.2; 5301. DR BRENDA; 1.1.1.21; 5301. DR Reactome; R-RNO-196108; Pregnenolone biosynthesis. DR Reactome; R-RNO-5652227; Fructose biosynthesis. DR SABIO-RK; P07943; -. DR PRO; PR:P07943; -. DR Proteomes; UP000002494; Chromosome 4. DR Bgee; ENSRNOG00000009513; Expressed in ovary and 19 other cell types or tissues. DR GO; GO:0005829; C:cytosol; ISO:RGD. DR GO; GO:0005615; C:extracellular space; IDA:RGD. DR GO; GO:0042629; C:mast cell granule; IDA:RGD. DR GO; GO:0033010; C:paranodal junction; IDA:RGD. DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:RGD. DR GO; GO:0032838; C:plasma membrane bounded cell projection cytoplasm; IDA:RGD. DR GO; GO:0043220; C:Schmidt-Lanterman incisure; IDA:RGD. DR GO; GO:0097454; C:Schwann cell microvillus; IDA:RGD. DR GO; GO:0004032; F:alditol:NADP+ 1-oxidoreductase activity; IDA:RGD. DR GO; GO:0047655; F:allyl-alcohol dehydrogenase activity; IEA:UniProtKB-EC. DR GO; GO:0018505; F:cis-1,2-dihydro-1,2-dihydroxynaphthalene dehydrogenase activity; IDA:RGD. DR GO; GO:0043795; F:glyceraldehyde oxidoreductase activity; ISO:RGD. DR GO; GO:0047956; F:glycerol dehydrogenase [NADP+] activity; IEA:RHEA. DR GO; GO:0047939; F:L-glucuronate reductase activity; ISO:RGD. DR GO; GO:0052650; F:NADP-retinol dehydrogenase activity; IEA:UniProtKB-EC. DR GO; GO:0036130; F:prostaglandin H2 endoperoxidase reductase activity; IEA:RHEA. DR GO; GO:0001758; F:retinal dehydrogenase activity; ISS:UniProtKB. DR GO; GO:0071475; P:cellular hyperosmotic salinity response; ISO:RGD. DR GO; GO:0097238; P:cellular response to methylglyoxal; IDA:RGD. DR GO; GO:1901653; P:cellular response to peptide; IEP:RGD. DR GO; GO:0044597; P:daunorubicin metabolic process; ISO:RGD. DR GO; GO:0044598; P:doxorubicin metabolic process; ISO:RGD. DR GO; GO:0002070; P:epithelial cell maturation; ISO:RGD. DR GO; GO:0046370; P:fructose biosynthetic process; ISO:RGD. DR GO; GO:0072061; P:inner medullary collecting duct development; IDA:RGD. DR GO; GO:0019853; P:L-ascorbic acid biosynthetic process; ISO:RGD. DR GO; GO:0060135; P:maternal process involved in female pregnancy; IEP:RGD. DR GO; GO:0072205; P:metanephric collecting duct development; ISO:RGD. DR GO; GO:0005996; P:monosaccharide metabolic process; IDA:RGD. DR GO; GO:0043066; P:negative regulation of apoptotic process; ISO:RGD. DR GO; GO:0042415; P:norepinephrine metabolic process; IDA:RGD. DR GO; GO:0046427; P:positive regulation of receptor signaling pathway via JAK-STAT; IMP:RGD. DR GO; GO:0048661; P:positive regulation of smooth muscle cell proliferation; IMP:RGD. DR GO; GO:0035809; P:regulation of urine volume; ISO:RGD. DR GO; GO:0003091; P:renal water homeostasis; ISO:RGD. DR GO; GO:0010033; P:response to organic substance; IDA:RGD. DR GO; GO:0097066; P:response to thyroid hormone; IEP:RGD. DR GO; GO:0001523; P:retinoid metabolic process; ISS:UniProtKB. DR GO; GO:0006061; P:sorbitol biosynthetic process; IMP:RGD. DR GO; GO:0031098; P:stress-activated protein kinase signaling cascade; IMP:RGD. DR GO; GO:0001894; P:tissue homeostasis; IMP:RGD. DR CDD; cd19107; AKR_AKR1B1-19; 1. DR Gene3D; 3.20.20.100; NADP-dependent oxidoreductase domain; 1. DR InterPro; IPR020471; AKR. DR InterPro; IPR018170; Aldo/ket_reductase_CS. DR InterPro; IPR023210; NADP_OxRdtase_dom. DR InterPro; IPR036812; NADP_OxRdtase_dom_sf. DR PANTHER; PTHR11732:SF294; ALDO-KETO REDUCTASE FAMILY 1 MEMBER B1; 1. DR PANTHER; PTHR11732; ALDO/KETO REDUCTASE; 1. DR Pfam; PF00248; Aldo_ket_red; 1. DR PIRSF; PIRSF000097; AKR; 1. DR PRINTS; PR00069; ALDKETRDTASE. DR SUPFAM; SSF51430; NAD(P)-linked oxidoreductase; 1. DR PROSITE; PS00798; ALDOKETO_REDUCTASE_1; 1. DR PROSITE; PS00062; ALDOKETO_REDUCTASE_2; 1. DR PROSITE; PS00063; ALDOKETO_REDUCTASE_3; 1. DR Genevisible; P07943; RN. PE 1: Evidence at protein level; KW Acetylation; Cytoplasm; Direct protein sequencing; Lipid metabolism; NADP; KW Oxidoreductase; Phosphoprotein; Reference proteome. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0000250|UniProtKB:P16116" FT CHAIN 2..316 FT /note="Aldo-keto reductase family 1 member B1" FT /id="PRO_0000124627" FT ACT_SITE 49 FT /note="Proton donor" FT /evidence="ECO:0000250|UniProtKB:P15121" FT BINDING 10..19 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000255" FT BINDING 111 FT /ligand="substrate" FT /evidence="ECO:0000250" FT BINDING 211..273 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000250|UniProtKB:P15121" FT SITE 78 FT /note="Lowers pKa of active site Tyr" FT /evidence="ECO:0000250" FT MOD_RES 2 FT /note="N-acetylalanine" FT /evidence="ECO:0000250|UniProtKB:P16116" FT MOD_RES 3 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:22673903" FT MOD_RES 95 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:P15121" FT MOD_RES 222 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:P15121" FT MOD_RES 263 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:P15121" SQ SEQUENCE 316 AA; 35797 MW; D6D07843B6850002 CRC64; MASHLELNNG TKMPTLGLGT WKSPPGQVTE AVKVAIDMGY RHIDCAQVYQ NEKEVGVALQ EKLKEQVVKR QDLFIVSKLW CTFHDQSMVK GACQKTLSDL QLDYLDLYLI HWPTGFKPGP DYFPLDASGN VIPSDTDFVD TWTAMEQLVD EGLVKAIGVS NFNPLQIERI LNKPGLKYKP AVNQIECHPY LTQEKLIEYC HCKGIVVTAY SPLGSPDRPW AKPEDPSLLE DPRIKEIAAK YNKTTAQVLI RFPIQRNLVV IPKSVTPARI AENFKVFDFE LSNEDMATLL SYNRNWRVCA LMSCAKHKDY PFHAEV //