AK1A1_BOVIN
ID AK1A1_BOVIN Reviewed; 325 AA.
AC Q3ZCJ2;
DT 15-MAY-2007, integrated into UniProtKB/Swiss-Prot.
DT 27-SEP-2005, sequence version 1.
DT 03-AUG-2022, entry version 114.
DE RecName: Full=Aldo-keto reductase family 1 member A1;
DE EC=1.1.1.2 {ECO:0000250|UniProtKB:P14550};
DE EC=1.1.1.33 {ECO:0000250|UniProtKB:P14550};
DE EC=1.1.1.372 {ECO:0000250|UniProtKB:P14550};
DE EC=1.1.1.54 {ECO:0000250|UniProtKB:P14550};
DE AltName: Full=Alcohol dehydrogenase [NADP(+)];
DE AltName: Full=Aldehyde reductase;
DE AltName: Full=Glucuronate reductase {ECO:0000250|UniProtKB:P51635};
DE EC=1.1.1.19 {ECO:0000250|UniProtKB:P51635};
DE AltName: Full=Glucuronolactone reductase {ECO:0000250|UniProtKB:P51635};
DE EC=1.1.1.20 {ECO:0000250|UniProtKB:P51635};
GN Name=AKR1A1;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Crossbred X Angus; TISSUE=Ileum;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (AUG-2005) to the EMBL/GenBank/DDBJ databases.
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, monosaccharides and bile acids, with a
CC preference for negatively charged substrates, such as glucuronate and
CC succinic semialdehyde (By similarity). Plays an important role in
CC ascorbic acid biosynthesis by catalyzing the reduction of D-glucuronic
CC acid and D-glucurono-gamma-lactone (By similarity). Functions as a
CC detoxifiying enzyme by reducing a range of toxic aldehydes. Reduces
CC methylglyoxal and 3-deoxyglucosone, which are present at elevated
CC levels under hyperglycemic conditions and are cytotoxic. Involved also
CC in the detoxification of lipid-derived aldehydes like acrolein (By
CC similarity). Plays a role in the activation of procarcinogens, such as
CC polycyclic aromatic hydrocarbon trans-dihydrodiols, and in the
CC metabolism of various xenobiotics and drugs (By similarity). Displays
CC no reductase activity towards retinoids (By similarity).
CC {ECO:0000250|UniProtKB:P14550, ECO:0000250|UniProtKB:P50578,
CC ECO:0000250|UniProtKB:P51635}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a primary alcohol + NADP(+) = an aldehyde + H(+) + NADPH;
CC Xref=Rhea:RHEA:15937, ChEBI:CHEBI:15378, ChEBI:CHEBI:15734,
CC ChEBI:CHEBI:17478, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; EC=1.1.1.2;
CC Evidence={ECO:0000250|UniProtKB:P51635};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=L-gulonate + NADP(+) = aldehydo-D-glucuronate + H(+) + NADPH;
CC Xref=Rhea:RHEA:14909, ChEBI:CHEBI:13115, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:57783, ChEBI:CHEBI:58349, ChEBI:CHEBI:142686;
CC EC=1.1.1.19; Evidence={ECO:0000250|UniProtKB:P51635};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=L-gulono-1,4-lactone + NADP(+) = D-glucurono-3,6-lactone +
CC H(+) + NADPH; Xref=Rhea:RHEA:18925, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:17587, ChEBI:CHEBI:18268, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:58349; EC=1.1.1.20;
CC Evidence={ECO:0000250|UniProtKB:P51635};
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:P51635};
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:P51635};
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:P51635};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=hydroxyacetone + NADP(+) = H(+) + methylglyoxal + NADPH;
CC Xref=Rhea:RHEA:27986, ChEBI:CHEBI:15378, ChEBI:CHEBI:17158,
CC ChEBI:CHEBI:27957, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349;
CC Evidence={ECO:0000250|UniProtKB:P51635};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3-deoxyfructose + NADP(+) = 3-deoxyglucosone + H(+) + NADPH;
CC Xref=Rhea:RHEA:58668, ChEBI:CHEBI:15378, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:58349, ChEBI:CHEBI:60777, ChEBI:CHEBI:142685;
CC Evidence={ECO:0000250|UniProtKB:P51635};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(R)-mevalonate + NADP(+) = H(+) + mevaldate + NADPH;
CC Xref=Rhea:RHEA:20193, ChEBI:CHEBI:15378, ChEBI:CHEBI:36464,
CC ChEBI:CHEBI:57783, ChEBI:CHEBI:58219, ChEBI:CHEBI:58349; EC=1.1.1.33;
CC Evidence={ECO:0000250|UniProtKB:P51635};
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:P51635};
CC -!- SUBUNIT: Monomer. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol
CC {ECO:0000250|UniProtKB:Q9JII6}. Apical cell membrane
CC {ECO:0000250|UniProtKB:Q9JII6}.
CC -!- SIMILARITY: Belongs to the aldo/keto reductase family. {ECO:0000305}.
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DR EMBL; BC102166; AAI02167.1; -; mRNA.
DR RefSeq; NP_001069981.1; NM_001076513.2.
DR AlphaFoldDB; Q3ZCJ2; -.
DR SMR; Q3ZCJ2; -.
DR STRING; 9913.ENSBTAP00000000630; -.
DR BindingDB; Q3ZCJ2; -.
DR PaxDb; Q3ZCJ2; -.
DR PeptideAtlas; Q3ZCJ2; -.
DR PRIDE; Q3ZCJ2; -.
DR Ensembl; ENSBTAT00000000630; ENSBTAP00000000630; ENSBTAG00000000497.
DR GeneID; 618607; -.
DR KEGG; bta:618607; -.
DR CTD; 10327; -.
DR VEuPathDB; HostDB:ENSBTAG00000000497; -.
DR VGNC; VGNC:25795; AKR1A1.
DR eggNOG; KOG1577; Eukaryota.
DR GeneTree; ENSGT00940000156539; -.
DR HOGENOM; CLU_023205_0_0_1; -.
DR InParanoid; Q3ZCJ2; -.
DR OMA; WRHPDEP; -.
DR OrthoDB; 1016440at2759; -.
DR TreeFam; TF106492; -.
DR Reactome; R-BTA-156590; Glutathione conjugation.
DR Reactome; R-BTA-5661270; Formation of xylulose-5-phosphate.
DR SABIO-RK; Q3ZCJ2; -.
DR Proteomes; UP000009136; Chromosome 3.
DR Bgee; ENSBTAG00000000497; Expressed in cortex of kidney and 106 other tissues.
DR GO; GO:0016324; C:apical plasma membrane; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0045202; C:synapse; IEA:Ensembl.
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:0047941; F:glucuronolactone reductase activity; ISS:UniProtKB.
DR GO; GO:0047956; F:glycerol dehydrogenase [NADP+] activity; IEA:RHEA.
DR GO; GO:0047939; F:L-glucuronate reductase activity; ISS:UniProtKB.
DR GO; GO:1990002; F:methylglyoxal reductase (NADPH-dependent, acetol producing); IEA:RHEA.
DR GO; GO:0019726; F:mevaldate reductase (NADPH) activity; IEA:UniProtKB-EC.
DR GO; GO:0016657; F:oxidoreductase activity, acting on NAD(P)H, nitrogenous group as acceptor; IEA:Ensembl.
DR GO; GO:0046185; P:aldehyde catabolic process; IEA:Ensembl.
DR GO; GO:0110095; P:cellular detoxification of aldehyde; ISS:UniProtKB.
DR GO; GO:0042840; P:D-glucuronate catabolic process; ISS:UniProtKB.
DR GO; GO:0044597; P:daunorubicin metabolic process; IEA:Ensembl.
DR GO; GO:0044598; P:doxorubicin metabolic process; IEA:Ensembl.
DR GO; GO:0019853; P:L-ascorbic acid biosynthetic process; ISS:UniProtKB.
DR GO; GO:0006629; P:lipid metabolic process; IEA:UniProtKB-KW.
DR CDD; cd19106; AKR_AKR1A1-4; 1.
DR Gene3D; 3.20.20.100; -; 1.
DR InterPro; IPR020471; AKR.
DR InterPro; IPR044481; AKR1A.
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; Cell membrane; Cytoplasm; Lipid metabolism; Membrane; NADP;
KW Oxidoreductase; Phosphoprotein; Reference proteome.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:P14550"
FT CHAIN 2..325
FT /note="Aldo-keto reductase family 1 member A1"
FT /id="PRO_0000287129"
FT ACT_SITE 50
FT /note="Proton donor"
FT BINDING 113
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P14550"
FT BINDING 211..273
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT SITE 80
FT /note="Lowers pKa of active site Tyr"
FT /evidence="ECO:0000250|UniProtKB:P14550"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000250|UniProtKB:P14550"
FT MOD_RES 4
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P51635"
FT MOD_RES 38
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P14550"
FT MOD_RES 127
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9JII6"
FT MOD_RES 127
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9JII6"
FT MOD_RES 211
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P14550"
SQ SEQUENCE 325 AA; 36617 MW; 66584EFE75C03036 CRC64;
MAASCILLHT GQKMPLIGLG TWKSDPGQVK AAIKYALSVG YRHIDCAAIY GNETEIGEAL
KENVGPGKLV PREELFVTSK LWNTKHHPED VEPALRKTLA DLQLEYLDLY LMHWPYAFER
GDSPFPKNAD GTIRYDSTHY KETWRALEAL VAKGLVRALG LSNFNSRQID DVLSVASVRP
AVLQVECHPY LAQNELIAHC QARNLEVTAY SPLGSSDRAW RDPEEPVLLK EPVVLALAEK
HGRSPAQILL RWQVQRKVSC IPKSVTPSRI LENIQVFDFT FSPEEMKQLD ALNKNLRFIV
PMLTVDGKRV PRDAGHPLYP FNDPY
