AK1A1_CRIGR
ID AK1A1_CRIGR Reviewed; 324 AA.
AC O70473;
DT 28-FEB-2003, integrated into UniProtKB/Swiss-Prot.
DT 13-FEB-2019, sequence version 2.
DT 03-AUG-2022, entry version 88.
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 {ECO:0000250|UniProtKB:P51635};
DE EC=1.1.1.20 {ECO:0000250|UniProtKB:P51635};
GN Name=AKR1A1; Synonyms=ALR;
OS Cricetulus griseus (Chinese hamster) (Cricetulus barabensis griseus).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea;
OC Cricetidae; Cricetinae; Cricetulus.
OX NCBI_TaxID=10029;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=21804562; DOI=10.1038/nbt.1932;
RA Xu X., Nagarajan H., Lewis N.E., Pan S., Cai Z., Liu X., Chen W., Xie M.,
RA Wang W., Hammond S., Andersen M.R., Neff N., Passarelli B., Koh W.,
RA Fan H.C., Wang J., Gui Y., Lee K.H., Betenbaugh M.J., Quake S.R.,
RA Famili I., Palsson B.O., Wang J.;
RT "The genomic sequence of the Chinese hamster ovary (CHO)-K1 cell line.";
RL Nat. Biotechnol. 29:735-741(2011).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 15-242.
RA Hyndman D.J., Flynn T.G.;
RT "Partial sequence of Chinese hamster aldehyde reductase.";
RL Submitted (APR-1998) 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 by
CC catalyzing the reduction of D-glucuronic acid and D-glucurono-gamma-
CC lactone. Functions as a detoxifiying enzyme by reducing a range of
CC toxic aldehydes. Reduces methylglyoxal and 3-deoxyglucosone, which are
CC present at elevated levels under hyperglycemic conditions and are
CC cytotoxic. Involved also in the detoxification of lipid-derived
CC aldehydes like acrolein (By similarity). Plays a role in the activation
CC of procarcinogens, such as polycyclic aromatic hydrocarbon trans-
CC dihydrodiols, and in the metabolism of various xenobiotics and drugs
CC (By similarity). Displays no reductase activity towards retinoids (By
CC similarity). {ECO:0000250|UniProtKB:P14550,
CC ECO:0000250|UniProtKB:P50578, 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:P14550};
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 -!- 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; JH000068; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AF060820; AAC15760.1; -; mRNA.
DR RefSeq; XP_003497420.1; XM_003497372.3.
DR AlphaFoldDB; O70473; -.
DR SMR; O70473; -.
DR STRING; 10029.XP_007620230.1; -.
DR Ensembl; ENSCGRT00001030375; ENSCGRP00001026129; ENSCGRG00001023544.
DR GeneID; 100689106; -.
DR KEGG; cge:100689106; -.
DR CTD; 10327; -.
DR eggNOG; KOG1577; Eukaryota.
DR GeneTree; ENSGT00940000156539; -.
DR OMA; WRHPDEP; -.
DR Proteomes; UP000001075; Unassembled WGS sequence.
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; IEA:Ensembl.
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; IEA:Ensembl.
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; IEA:Ensembl.
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.
PE 2: Evidence at transcript level;
KW Acetylation; Cell membrane; Cytoplasm; Lipid metabolism; Membrane; NADP;
KW Oxidoreductase; Phosphoprotein; Reference proteome.
FT CHAIN 1..324
FT /note="Aldo-keto reductase family 1 member A1"
FT /id="PRO_0000124616"
FT ACT_SITE 49
FT /note="Proton donor"
FT /evidence="ECO:0000250|UniProtKB:P14550"
FT BINDING 20..22
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:O60218"
FT BINDING 44
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:O60218"
FT BINDING 112
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P14550"
FT BINDING 161..162
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:O60218"
FT BINDING 183
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:O60218"
FT BINDING 209..216
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:O60218"
FT BINDING 260..272
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:O60218"
FT SITE 79
FT /note="Lowers pKa of active site Tyr"
FT /evidence="ECO:0000250|UniProtKB:P14550"
FT MOD_RES 3
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P51635"
FT MOD_RES 37
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P14550"
FT MOD_RES 126
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9JII6"
FT MOD_RES 126
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9JII6"
FT MOD_RES 144
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9JII6"
FT MOD_RES 210
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P14550"
SQ SEQUENCE 324 AA; 36510 MW; 35B0A9A0D00D6545 CRC64;
MASCVLLHTG QKMPLIGLGT WKSNPGQVKA AIKYALSVGY RHIDCAAVYG NEIEIGEALK
ENVGPGKAVP REELFVTSKL WNTKHHPEDV EAALRKTLAD LQLEYLDLYL MHWPYAFERG
DNPFPKNDDG TIRYDSTHYK ETWKALEALV AKGLVKALGL SNFNSRQIDD ILSVASVRPA
VLQVECHPYL AQNELIAHCQ ARGLEVTAYS PLGSSDRAWR HPDEPVLLEE PVVLALAEKH
GRSPAQILLR WQVQRKVVCI PKSITPSRIL QNIQVFDFTF SPEEMKQLDA LNKHWRYIVP
MITVDGKSVP RDAGHPLYPF NDPY
