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   24-JAN-2024, entry version 155.
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.ENSSSCP00000064633; -.
DR   BindingDB; P80276; -.
DR   ChEMBL; CHEMBL4559; -.
DR   DrugCentral; P80276; -.
DR   iPTMnet; P80276; -.
DR   PaxDb; 9823-ENSSSCP00000017525; -.
DR   PeptideAtlas; 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; 890110at2759; -.
DR   TreeFam; TF106492; -.
DR   SABIO-RK; P80276; -.
DR   EvolutionaryTrace; P80276; -.
DR   PRO; PR:P80276; -.
DR   Proteomes; UP000008227; Unplaced.
DR   Proteomes; UP000314985; Unplaced.
DR   Proteomes; UP000694570; Unplaced.
DR   Proteomes; UP000694571; Unplaced.
DR   Proteomes; UP000694720; Unplaced.
DR   Proteomes; UP000694722; Unplaced.
DR   Proteomes; UP000694723; Unplaced.
DR   Proteomes; UP000694724; Unplaced.
DR   Proteomes; UP000694725; Unplaced.
DR   Proteomes; UP000694726; Unplaced.
DR   Proteomes; UP000694727; Unplaced.
DR   Proteomes; UP000694728; Unplaced.
DR   GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR   GO; GO:0004032; F:alditol:NADP+ 1-oxidoreductase activity; IBA:GO_Central.
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   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; P80276; SS.
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
//