ALDR_RABIT
ID ALDR_RABIT Reviewed; 316 AA.
AC P15122;
DT 01-APR-1990, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 122.
DE RecName: Full=Aldo-keto reductase family 1 member B1;
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;
DE EC=1.1.1.21 {ECO:0000250|UniProtKB:P15121};
GN Name=AKR1B1;
OS Oryctolagus cuniculus (Rabbit).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Lagomorpha; Leporidae; Oryctolagus.
OX NCBI_TaxID=9986;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
RC TISSUE=Spleen;
RX PubMed=7938022; DOI=10.1073/pnas.91.22.10742;
RA Ferraris J.D., Williams C.K., Martin B.M., Burg M.B., Garcia-Perez A.;
RT "Cloning, genomic organization, and osmotic response of the aldose
RT reductase gene.";
RL Proc. Natl. Acad. Sci. U.S.A. 91:10742-10746(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 15-316.
RC TISSUE=Kidney;
RX PubMed=2506183; DOI=10.1016/s0021-9258(19)84779-8;
RA Garcia-Perez A., Martin B., Murphy H.R., Uchida S., Murer H.,
RA Cowley B.D. Jr., Handler J.S., Burg M.B.;
RT "Molecular cloning of cDNA coding for kidney aldose reductase. Regulation
RT of specific mRNA accumulation by NaCl-mediated osmotic stress.";
RL J. Biol. Chem. 264:16815-16821(1989).
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; U13694; AAB60687.1; -; Genomic_DNA.
DR EMBL; U13689; AAB60687.1; JOINED; Genomic_DNA.
DR EMBL; U13690; AAB60687.1; JOINED; Genomic_DNA.
DR EMBL; U13691; AAB60687.1; JOINED; Genomic_DNA.
DR EMBL; U13692; AAB60687.1; JOINED; Genomic_DNA.
DR EMBL; U13693; AAB60687.1; JOINED; Genomic_DNA.
DR EMBL; M32818; AAA31160.1; -; mRNA.
DR EMBL; U12316; AAA50833.1; -; mRNA.
DR EMBL; J05048; AAA31157.1; -; mRNA.
DR PIR; A34406; A34406.
DR RefSeq; NP_001075756.1; NM_001082287.1.
DR AlphaFoldDB; P15122; -.
DR SMR; P15122; -.
DR ChEMBL; CHEMBL3567; -.
DR PRIDE; P15122; -.
DR GeneID; 100009122; -.
DR KEGG; ocu:100009122; -.
DR CTD; 231; -.
DR InParanoid; P15122; -.
DR OrthoDB; 1016440at2759; -.
DR SABIO-RK; P15122; -.
DR Proteomes; UP000001811; Unplaced.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0004032; F:alditol:NADP+ 1-oxidoreductase activity; IEA:UniProtKB-EC.
DR GO; GO:0047655; F:allyl-alcohol dehydrogenase activity; IEA:UniProtKB-EC.
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:0001523; P:retinoid metabolic process; ISS:UniProtKB.
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 2: Evidence at transcript level;
KW Acetylation; Cytoplasm; Lipid metabolism; NADP; Oxidoreductase;
KW 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_0000124626"
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 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; 35763 MW; E52C078822BC2DFB CRC64;
MATHLVLYNG AKMPILGLGT WKSPPGQVTE AVKTAIDLGY RHIDCAHVYQ NENEVGVALQ
EKLKEQVVKR EELFIVSKLW CTSHDKSLVK GACQKTLNDL KLDYLDLYLI HWPTGFKHGS
EYFPLDAAGN VIPSDTDFLD TWEAMEGLVD EGLVKSIGVS NFNHLQIERI LNKPGLKYKP
AVNQIECHPY LTQEKLIQYC HSKGIVVTAY SPLGSPDRPW AKPEDPSLLE DPRIKAIADK
HKKTTAQVLI RFPMQRNLVV IPKSVTPARI AENFQVFDFE LSSEDMTTLL SYNRNWRVCA
LVSCASHKDY PFHAEF
