AK1A1_PONAB
ID AK1A1_PONAB Reviewed; 325 AA.
AC Q5R5D5;
DT 22-SEP-2009, integrated into UniProtKB/Swiss-Prot.
DT 21-DEC-2004, sequence version 1.
DT 03-AUG-2022, entry version 72.
DE RecName: Full=Aldo-keto reductase family 1 member A1;
DE EC=1.1.1.2 {ECO:0000250|UniProtKB:P51635};
DE EC=1.1.1.33 {ECO:0000250|UniProtKB:P51635};
DE EC=1.1.1.372 {ECO:0000250|UniProtKB:P51635};
DE EC=1.1.1.54 {ECO:0000250|UniProtKB:P51635};
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;
DE EC=1.1.1.20 {ECO:0000250|UniProtKB:P51635};
GN Name=AKR1A1;
OS Pongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Pongo.
OX NCBI_TaxID=9601;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Kidney;
RG The German cDNA consortium;
RL Submitted (NOV-2004) 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). Functions as a detoxifiying
CC enzyme by reducing a range of toxic aldehydes. Reduces methylglyoxal
CC and 3-deoxyglucosone, which are present at elevated levels under
CC hyperglycemic conditions and are cytotoxic. Involved also in the
CC 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; CR860927; CAH93031.1; -; mRNA.
DR RefSeq; NP_001126792.1; NM_001133320.1.
DR AlphaFoldDB; Q5R5D5; -.
DR SMR; Q5R5D5; -.
DR STRING; 9601.ENSPPYP00000001636; -.
DR GeneID; 100173796; -.
DR KEGG; pon:100173796; -.
DR CTD; 10327; -.
DR eggNOG; KOG1577; Eukaryota.
DR InParanoid; Q5R5D5; -.
DR OrthoDB; 1016440at2759; -.
DR Proteomes; UP000001595; Unplaced.
DR GO; GO:0016324; C:apical plasma membrane; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0008106; F:alcohol dehydrogenase (NADP+) activity; IEA:UniProtKB-EC.
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:0046185; P:aldehyde catabolic process; IEA:InterPro.
DR GO; GO:0110095; P:cellular detoxification of aldehyde; 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_0000384150"
FT ACT_SITE 50
FT /note="Proton donor"
FT /evidence="ECO:0000250|UniProtKB:P14550"
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 145
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9JII6"
FT MOD_RES 211
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P14550"
SQ SEQUENCE 325 AA; 36390 MW; 11FD0210C3B99455 CRC64;
MAASCVLLHT GQKMPLIGLG TWKSEPGQVK AAVKYALSVG YRHIDCAAIY GNEPEIGEAL
KEDVGPGKAV PREELFVTSK LWNTKHHPED VEPALQKTLA DLQLEYLDLY LMHWPYAFER
GDNPFPKNAD GTICYDSTHY KETWKALEAL VAKGLVRALG LSNFNSRQID DILSVASVRP
AVLQVECHPY LAQNELIAHC QARGLAVTAY SPLGSSDRAW RDPDEPVLLE EPVVLALAEK
YGGSPAQILL RWQVQRKVIC IPKSITPSRI LQNIKVFDFT FSPEEMKQLN ALNKNWRHIV
PMLTVDGKRV PRDAGHPLYP FNDPY
