ALDR_PIG
ID ALDR_PIG Reviewed; 316 AA.
AC P80276;
DT 01-FEB-1994, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 2.
DT 03-AUG-2022, entry version 148.
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; Synonyms=ALR2;
OS Sus scrofa (Pig).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Suina; Suidae; Sus.
OX NCBI_TaxID=9823;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Brain;
RX PubMed=8493902; DOI=10.1007/978-1-4615-2904-0_28;
RA Kubiseski T.J., Green N.C., Flynn T.G.;
RT "Location of an essential arginine residue in the primary structure of pig
RT aldose reductase.";
RL Adv. Exp. Med. Biol. 328:259-265(1993).
RN [2]
RP PROTEIN SEQUENCE OF 2-316, ACETYLATION AT ALA-2, AND MASS SPECTROMETRY.
RC TISSUE=Lens;
RX PubMed=8281941; DOI=10.1111/j.1432-1033.1993.tb18445.x;
RA Jaquinod M., Potier N., Klarskov K., Reymann J.-M., Sorokine O.,
RA Kieffer S., Barth P., Andriantomanga V., Biellmann J.-F.,
RA van Dorsselaer A.;
RT "Sequence of pig lens aldose reductase and electrospray mass spectrometry
RT of non-covalent and covalent complexes.";
RL Eur. J. Biochem. 218:893-903(1993).
RN [3]
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS).
RX PubMed=1734286; DOI=10.1038/355469a0;
RA Rondeau J.-M., Tete-Favier F., Podjarny A., Reymann J.-M., Barth P.,
RA Biellmann J.-F., Moras D.;
RT "Novel NADPH-binding domain revealed by the crystal structure of aldose
RT reductase.";
RL Nature 355:469-472(1992).
RN [4]
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS).
RX PubMed=9195881; DOI=10.1016/s0969-2126(97)00216-5;
RA Urzhumtsev A., Tete-Favier F., Mitschler A., Barbanton J., Barth P.,
RA Urzhumtseva L., Biellmann J.-F., Podjarny A.D., Moras D.;
RT "A 'specificity' pocket inferred from the crystal structures of the
RT complexes of aldose reductase with the pharmaceutically important
RT inhibitors tolrestat and sorbinil.";
RL Structure 5:601-612(1997).
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 -!- MASS SPECTROMETRY: Mass=35778; Mass_error=3; Method=Electrospray;
CC Evidence={ECO:0000269|PubMed:8281941};
CC -!- SIMILARITY: Belongs to the aldo/keto reductase family. {ECO:0000305}.
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DR EMBL; L14950; AAA30989.1; -; mRNA.
DR EMBL; U46065; AAC48515.1; -; mRNA.
DR PIR; A59021; A59021.
DR RefSeq; NP_001001539.1; NM_001001539.2.
DR PDB; 1AH0; X-ray; 2.30 A; A=2-316.
DR PDB; 1AH3; X-ray; 2.30 A; A=2-316.
DR PDB; 1AH4; X-ray; 2.00 A; A=2-316.
DR PDB; 1DLA; X-ray; 3.00 A; A/B/C/D=3-316.
DR PDB; 1EKO; X-ray; 2.20 A; A=2-316.
DR PDBsum; 1AH0; -.
DR PDBsum; 1AH3; -.
DR PDBsum; 1AH4; -.
DR PDBsum; 1DLA; -.
DR PDBsum; 1EKO; -.
DR AlphaFoldDB; P80276; -.
DR SMR; P80276; -.
DR STRING; 9823.ENSSSCP00000017525; -.
DR BindingDB; P80276; -.
DR ChEMBL; CHEMBL4559; -.
DR DrugCentral; P80276; -.
DR iPTMnet; P80276; -.
DR PaxDb; P80276; -.
DR PeptideAtlas; P80276; -.
DR PRIDE; P80276; -.
DR GeneID; 396816; -.
DR KEGG; ssc:396816; -.
DR CTD; 231; -.
DR eggNOG; KOG1577; Eukaryota.
DR HOGENOM; CLU_023205_0_0_1; -.
DR InParanoid; P80276; -.
DR OrthoDB; 1016440at2759; -.
DR TreeFam; TF106492; -.
DR SABIO-RK; P80276; -.
DR EvolutionaryTrace; P80276; -.
DR PRO; PR:P80276; -.
DR Proteomes; UP000008227; Unplaced.
DR Proteomes; UP000314985; Unplaced.
DR Genevisible; P80276; SS.
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 1: Evidence at protein level;
KW 3D-structure; Acetylation; Cytoplasm; Direct protein sequencing;
KW Lipid metabolism; NADP; Oxidoreductase; Phosphoprotein; Reference proteome.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:8281941"
FT CHAIN 2..316
FT /note="Aldo-keto reductase family 1 member B1"
FT /id="PRO_0000124625"
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 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:0000269|PubMed:8281941"
FT MOD_RES 3
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P07943"
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"
FT CONFLICT 99
FT /note="D -> N (in Ref. 1; AAA30989/AAC48515)"
FT /evidence="ECO:0000305"
FT STRAND 4..6
FT /evidence="ECO:0007829|PDB:1AH4"
FT STRAND 12..16
FT /evidence="ECO:0007829|PDB:1AH4"
FT HELIX 25..38
FT /evidence="ECO:0007829|PDB:1AH4"
FT STRAND 42..44
FT /evidence="ECO:0007829|PDB:1AH4"
FT HELIX 47..49
FT /evidence="ECO:0007829|PDB:1AH4"
FT HELIX 52..64
FT /evidence="ECO:0007829|PDB:1AH4"
FT HELIX 70..72
FT /evidence="ECO:0007829|PDB:1AH4"
FT STRAND 74..79
FT /evidence="ECO:0007829|PDB:1AH4"
FT HELIX 81..83
FT /evidence="ECO:0007829|PDB:1AH4"
FT HELIX 86..88
FT /evidence="ECO:0007829|PDB:1AH4"
FT HELIX 89..100
FT /evidence="ECO:0007829|PDB:1AH4"
FT STRAND 105..110
FT /evidence="ECO:0007829|PDB:1AH4"
FT STRAND 118..120
FT /evidence="ECO:0007829|PDB:1EKO"
FT STRAND 129..131
FT /evidence="ECO:0007829|PDB:1AH4"
FT HELIX 138..150
FT /evidence="ECO:0007829|PDB:1AH4"
FT STRAND 153..155
FT /evidence="ECO:0007829|PDB:1AH4"
FT STRAND 157..161
FT /evidence="ECO:0007829|PDB:1AH4"
FT HELIX 164..171
FT /evidence="ECO:0007829|PDB:1AH4"
FT STRAND 181..186
FT /evidence="ECO:0007829|PDB:1AH4"
FT HELIX 194..203
FT /evidence="ECO:0007829|PDB:1AH4"
FT STRAND 206..210
FT /evidence="ECO:0007829|PDB:1AH4"
FT STRAND 223..225
FT /evidence="ECO:0007829|PDB:1AH0"
FT HELIX 228..230
FT /evidence="ECO:0007829|PDB:1AH4"
FT HELIX 232..241
FT /evidence="ECO:0007829|PDB:1AH4"
FT HELIX 245..255
FT /evidence="ECO:0007829|PDB:1AH4"
FT HELIX 267..272
FT /evidence="ECO:0007829|PDB:1AH4"
FT TURN 273..278
FT /evidence="ECO:0007829|PDB:1AH4"
FT HELIX 283..290
FT /evidence="ECO:0007829|PDB:1AH4"
FT HELIX 302..304
FT /evidence="ECO:0007829|PDB:1AH4"
FT HELIX 311..313
FT /evidence="ECO:0007829|PDB:1AH4"
SQ SEQUENCE 316 AA; 35868 MW; 7218B663AC1B4E92 CRC64;
MASHLVLYTG AKMPILGLGT WKSPPGKVTE AVKVAIDLGY RHIDCAHVYQ NENEVGLGLQ
EKLQGQVVKR EDLFIVSKLW CTDHEKNLVK GACQTTLRDL KLDYLDLYLI HWPTGFKPGK
DPFPLDGDGN VVPDESDFVE TWEAMEELVD EGLVKAIGVS NFNHLQVEKI LNKPGLKYKP
AVNQIEVHPY LTQEKLIEYC KSKGIVVTAY SPLGSPDRPW AKPEDPSLLE DPRIKAIAAK
YNKTTAQVLI RFPMQRNLIV IPKSVTPERI AENFQVFDFE LSPEDMNTLL SYNRNWRVCA
LMSCASHKDY PFHEEY
