ALDR_RAT
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 03-AUG-2022, entry version 168.
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}.
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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; P07943; -.
DR PRIDE; P07943; -.
DR GeneID; 24192; -.
DR KEGG; rno:24192; -.
DR UCSC; RGD:2092; rat.
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 OMA; HCRFVNM; -.
DR OrthoDB; 1016440at2759; -.
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 tissues.
DR Genevisible; P07943; RN.
DR GO; GO:0005829; C:cytosol; IDA: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: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:0072061; P:inner medullary collecting duct development; IDA: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:1901360; P:organic cyclic compound 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:0009414; P:response to water deprivation; IDA: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 Gene3D; 3.20.20.100; -; 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 Pfam; PF00248; Aldo_ket_red; 1.
DR PIRSF; PIRSF000097; AKR; 1.
DR PRINTS; PR00069; ALDKETRDTASE.
DR SUPFAM; SSF51430; SSF51430; 1.
DR PROSITE; PS00798; ALDOKETO_REDUCTASE_1; 1.
DR PROSITE; PS00062; ALDOKETO_REDUCTASE_2; 1.
DR PROSITE; PS00063; ALDOKETO_REDUCTASE_3; 1.
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
