ID   AK1A1_MOUSE             Reviewed;         325 AA.
AC   Q9JII6; Q9CQI5; Q9CQT8; Q9CT53; Q9D012; Q9D016; Q9D0I7; Q9D0P3;
DT   30-AUG-2002, integrated into UniProtKB/Swiss-Prot.
DT   23-JAN-2007, sequence version 3.
DT   27-MAR-2024, entry version 174.
DE   RecName: Full=Aldo-keto reductase family 1 member A1;
DE            EC=1.1.1.2 {ECO:0000269|PubMed:15769935, ECO:0000269|PubMed:20410296};
DE            EC=1.1.1.372 {ECO:0000269|PubMed:22820017};
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;
DE            EC=1.1.1.19 {ECO:0000269|PubMed:15769935, ECO:0000269|PubMed:20410296};
DE   AltName: Full=Glucuronolactone reductase {ECO:0000250|UniProtKB:P51635};
DE            EC=1.1.1.20 {ECO:0000250|UniProtKB:P51635};
GN   Name=Akr1a1; Synonyms=Akr1a4 {ECO:0000303|PubMed:10842086};
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RC   TISSUE=Embryo;
RX   PubMed=10842086; DOI=10.1016/s0925-4773(00)00293-8;
RA   Allan D., Lohnes D.;
RT   "Cloning and developmental expression of mouse aldehyde reductase
RT   (AKR1A4).";
RL   Mech. Dev. 94:271-275(2000).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=C57BL/6J; TISSUE=Cerebellum, Embryo, and Tongue;
RX   PubMed=16141072; DOI=10.1126/science.1112014;
RA   Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA   Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA   Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA   Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA   Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA   Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA   Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA   Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA   Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA   Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA   Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA   Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA   Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA   Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA   Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA   Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA   Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA   Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA   Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA   Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA   Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA   Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA   Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA   Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA   Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA   van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA   Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA   Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA   Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA   Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA   Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA   Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA   Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA   Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT   "The transcriptional landscape of the mammalian genome.";
RL   Science 309:1559-1563(2005).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=FVB/N; TISSUE=Mammary gland;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [4]
RP   PROTEIN SEQUENCE OF 2-13 AND 244-251, CLEAVAGE OF INITIATOR METHIONINE,
RP   ACETYLATION AT THR-2, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC   STRAIN=C57BL/6J; TISSUE=Liver;
RA   Bienvenut W.V.;
RL   Submitted (JUL-2005) to UniProtKB.
RN   [5]
RP   PROTEIN SEQUENCE OF 204-218; 222-240 AND 313-325, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY.
RC   TISSUE=Hippocampus;
RA   Lubec G., Klug S.;
RL   Submitted (MAR-2007) to UniProtKB.
RN   [6]
RP   INDUCTION.
RX   PubMed=11533224; DOI=10.1101/lm.39401;
RA   Stork O., Stork S., Pape H.-C., Obata K.;
RT   "Identification of genes expressed in the amygdala during the formation of
RT   fear memory.";
RL   Learn. Memory 8:209-219(2001).
RN   [7]
RP   TISSUE SPECIFICITY, SUBCELLULAR LOCATION, CATALYTIC ACTIVITY, AND FUNCTION.
RX   PubMed=15769935; DOI=10.1152/ajprenal.00411.2004;
RA   Barski O.A., Papusha V.Z., Ivanova M.M., Rudman D.M., Finegold M.J.;
RT   "Developmental expression and function of aldehyde reductase in proximal
RT   tubules of the kidney.";
RL   Am. J. Physiol. 289:F200-F207(2005).
RN   [8]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung,
RC   Pancreas, Spleen, and Testis;
RX   PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA   Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA   Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT   "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL   Cell 143:1174-1189(2010).
RN   [9]
RP   DISRUPTION PHENOTYPE, CATALYTIC ACTIVITY, FUNCTION, AND BIOPHYSICOCHEMICAL
RP   PROPERTIES.
RX   PubMed=20410296; DOI=10.1074/jbc.m110.110247;
RA   Gabbay K.H., Bohren K.M., Morello R., Bertin T., Liu J., Vogel P.;
RT   "Ascorbate synthesis pathway: dual role of ascorbate in bone homeostasis.";
RL   J. Biol. Chem. 285:19510-19520(2010).
RN   [10]
RP   DISRUPTION PHENOTYPE, FUNCTION, AND CATALYTIC ACTIVITY.
RX   PubMed=22820017; DOI=10.1016/j.bbagen.2012.07.003;
RA   Takahashi M., Miyata S., Fujii J., Inai Y., Ueyama S., Araki M., Soga T.,
RA   Fujinawa R., Nishitani C., Ariki S., Shimizu T., Abe T., Ihara Y.,
RA   Nishikimi M., Kozutsumi Y., Taniguchi N., Kuroki Y.;
RT   "In vivo role of aldehyde reductase.";
RL   Biochim. Biophys. Acta 1820:1787-1796(2012).
RN   [11]
RP   ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-127, SUCCINYLATION [LARGE SCALE
RP   ANALYSIS] AT LYS-127 AND LYS-145, AND IDENTIFICATION BY MASS SPECTROMETRY
RP   [LARGE SCALE ANALYSIS].
RC   TISSUE=Embryonic fibroblast, and Liver;
RX   PubMed=23806337; DOI=10.1016/j.molcel.2013.06.001;
RA   Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y.,
RA   Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.;
RT   "SIRT5-mediated lysine desuccinylation impacts diverse metabolic
RT   pathways.";
RL   Mol. Cell 50:919-930(2013).
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) (PubMed:22820017,
CC       PubMed:15769935, PubMed:20410296). Plays an important role in ascorbic
CC       acid biosynthesis by catalyzing the reduction of D-glucuronic acid and
CC       D-glucurono-gamma-lactone (PubMed:20410296, PubMed:15769935,
CC       PubMed:22820017). Functions as a detoxifiying enzyme by reducing a
CC       range of toxic aldehydes. Reduces methylglyoxal and 3-deoxyglucosone,
CC       which are present at elevated levels under hyperglycemic conditions and
CC       are cytotoxic (By similarity). Involved in the detoxification of lipid-
CC       derived aldehydes like acrolein (By similarity). Plays a role in the
CC       activation of procarcinogens, such as polycyclic aromatic hydrocarbon
CC       trans-dihydrodiols, and in the metabolism of various xenobiotics and
CC       drugs (By similarity). Displays no reductase activity towards retinoids
CC       (By similarity). {ECO:0000250|UniProtKB:P14550,
CC       ECO:0000250|UniProtKB:P50578, ECO:0000250|UniProtKB:P51635,
CC       ECO:0000269|PubMed:15769935, ECO:0000269|PubMed:20410296,
CC       ECO:0000269|PubMed:22820017}.
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:0000269|PubMed:20410296};
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:0000269|PubMed:15769935,
CC         ECO:0000269|PubMed:20410296, ECO:0000269|PubMed:22820017};
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:0000269|PubMed:22820017};
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:0000269|PubMed:22820017};
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:0000269|PubMed:22820017};
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(+) = (R)-mevaldate + H(+) + NADPH;
CC         Xref=Rhea:RHEA:20193, ChEBI:CHEBI:15378, ChEBI:CHEBI:36464,
CC         ChEBI:CHEBI:57783, ChEBI:CHEBI:58349, ChEBI:CHEBI:195523;
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   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=5 mM for D-glucuronate {ECO:0000269|PubMed:20410296};
CC   -!- SUBUNIT: Monomer. {ECO:0000250}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:15769935}.
CC       Apical cell membrane {ECO:0000269|PubMed:15769935}.
CC   -!- TISSUE SPECIFICITY: Widely expressed. {ECO:0000269|PubMed:10842086,
CC       ECO:0000269|PubMed:15769935}.
CC   -!- DEVELOPMENTAL STAGE: Detected at high levels in several tissues
CC       including neural ectoderm, gut endoderm, somites, branchial arches,
CC       otic vesicles, limb buds and tail bud. {ECO:0000269|PubMed:10842086}.
CC   -!- INDUCTION: Fear memory increases expression 7-fold.
CC       {ECO:0000269|PubMed:11533224}.
CC   -!- DISRUPTION PHENOTYPE: Deficient mice develop and grow normally but
CC       suffer severe osteopenia and spontaneous fractures with stresses that
CC       increase ascorbic acid requirements, such as pregnancy or castration
CC       (PubMed:20410296). Deficient mice exhibit reduced asorbic acid and D,L-
CC       glyceraldehyde levels. The activities of glucuronate reductase and
CC       glucuronolactone reductase, which are involved in ascorbic acid
CC       biosynthesis, are suppressed in AKR1A knockout mice (PubMed:22820017,
CC       PubMed:20410296). {ECO:0000269|PubMed:20410296,
CC       ECO:0000269|PubMed:22820017}.
CC   -!- SIMILARITY: Belongs to the aldo/keto reductase family. {ECO:0000305}.
CC   ---------------------------------------------------------------------------
CC   Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC   Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC   ---------------------------------------------------------------------------
DR   EMBL; AF225564; AAF67111.1; -; mRNA.
DR   EMBL; AK011906; BAB27907.1; -; mRNA.
DR   EMBL; AK009462; BAB26303.1; -; mRNA.
DR   EMBL; AK011321; BAB27543.1; -; mRNA.
DR   EMBL; AK011794; BAB27846.1; -; mRNA.
DR   EMBL; AK011908; BAB27909.1; -; mRNA.
DR   EMBL; AK011918; BAB27915.1; -; mRNA.
DR   EMBL; AK011856; BAB27883.1; -; mRNA.
DR   EMBL; AK011667; BAB27767.1; -; mRNA.
DR   EMBL; AK011388; BAB27586.1; -; mRNA.
DR   EMBL; AK011157; BAB27437.1; -; mRNA.
DR   EMBL; AK011209; BAB27469.1; -; mRNA.
DR   EMBL; AK005162; BAB23853.1; -; mRNA.
DR   EMBL; AK011221; -; NOT_ANNOTATED_CDS; mRNA.
DR   EMBL; BC039926; AAH39926.1; -; mRNA.
DR   CCDS; CCDS18514.1; -.
DR   RefSeq; NP_067448.1; NM_021473.3.
DR   PDB; 4GAC; X-ray; 1.64 A; A/B=2-325.
DR   PDBsum; 4GAC; -.
DR   AlphaFoldDB; Q9JII6; -.
DR   SMR; Q9JII6; -.
DR   IntAct; Q9JII6; 2.
DR   STRING; 10090.ENSMUSP00000030455; -.
DR   GlyGen; Q9JII6; 1 site, 1 O-linked glycan (1 site).
DR   iPTMnet; Q9JII6; -.
DR   PhosphoSitePlus; Q9JII6; -.
DR   SwissPalm; Q9JII6; -.
DR   REPRODUCTION-2DPAGE; IPI00466128; -.
DR   REPRODUCTION-2DPAGE; Q9JII6; -.
DR   CPTAC; non-CPTAC-3762; -.
DR   EPD; Q9JII6; -.
DR   jPOST; Q9JII6; -.
DR   MaxQB; Q9JII6; -.
DR   PaxDb; 10090-ENSMUSP00000030455; -.
DR   ProteomicsDB; 296148; -.
DR   Pumba; Q9JII6; -.
DR   Antibodypedia; 3338; 654 antibodies from 37 providers.
DR   DNASU; 58810; -.
DR   Ensembl; ENSMUST00000030455.15; ENSMUSP00000030455.9; ENSMUSG00000028692.15.
DR   GeneID; 58810; -.
DR   KEGG; mmu:58810; -.
DR   UCSC; uc008uha.2; mouse.
DR   AGR; MGI:1929955; -.
DR   CTD; 10327; -.
DR   MGI; MGI:1929955; Akr1a1.
DR   VEuPathDB; HostDB:ENSMUSG00000028692; -.
DR   eggNOG; KOG1577; Eukaryota.
DR   GeneTree; ENSGT00940000156539; -.
DR   HOGENOM; CLU_023205_0_0_1; -.
DR   InParanoid; Q9JII6; -.
DR   OMA; MVNQIFL; -.
DR   OrthoDB; 890110at2759; -.
DR   PhylomeDB; Q9JII6; -.
DR   TreeFam; TF106492; -.
DR   BRENDA; 1.1.1.2; 3474.
DR   Reactome; R-MMU-156590; Glutathione conjugation.
DR   Reactome; R-MMU-5661270; Formation of xylulose-5-phosphate.
DR   SABIO-RK; Q9JII6; -.
DR   BioGRID-ORCS; 58810; 1 hit in 80 CRISPR screens.
DR   ChiTaRS; Akr1a1; mouse.
DR   PRO; PR:Q9JII6; -.
DR   Proteomes; UP000000589; Chromosome 4.
DR   RNAct; Q9JII6; Protein.
DR   Bgee; ENSMUSG00000028692; Expressed in metanephric mesenchyme and 280 other cell types or tissues.
DR   ExpressionAtlas; Q9JII6; baseline and differential.
DR   GO; GO:0016324; C:apical plasma membrane; IDA:MGI.
DR   GO; GO:0005829; C:cytosol; IDA:MGI.
DR   GO; GO:0045202; C:synapse; IDA:SynGO.
DR   GO; GO:0008106; F:alcohol dehydrogenase (NADP+) activity; NAS:UniProtKB.
DR   GO; GO:0004032; F:alditol:NADP+ 1-oxidoreductase activity; IDA:MGI.
DR   GO; GO:0047655; F:allyl-alcohol dehydrogenase activity; IEA:UniProtKB-EC.
DR   GO; GO:0047941; F:glucuronolactone reductase activity; IDA:UniProtKB.
DR   GO; GO:0047956; F:glycerol dehydrogenase [NADP+] activity; IEA:RHEA.
DR   GO; GO:0047939; F:L-glucuronate reductase activity; IDA:MGI.
DR   GO; GO:1990002; F:methylglyoxal reductase (NADPH-dependent, acetol producing); IEA:RHEA.
DR   GO; GO:0016657; F:oxidoreductase activity, acting on NAD(P)H, nitrogenous group as acceptor; IMP:MGI.
DR   GO; GO:0046185; P:aldehyde catabolic process; IDA:MGI.
DR   GO; GO:0110095; P:cellular detoxification of aldehyde; IMP:UniProtKB.
DR   GO; GO:0042840; P:D-glucuronate catabolic process; IDA:MGI.
DR   GO; GO:0044597; P:daunorubicin metabolic process; ISO:MGI.
DR   GO; GO:0044598; P:doxorubicin metabolic process; ISO:MGI.
DR   GO; GO:0019640; P:glucuronate catabolic process to xylulose 5-phosphate; IDA:MGI.
DR   GO; GO:0019853; P:L-ascorbic acid biosynthetic process; IDA:MGI.
DR   GO; GO:0006629; P:lipid metabolic process; IEA:UniProtKB-KW.
DR   GO; GO:0043066; P:negative regulation of apoptotic process; ISO:MGI.
DR   CDD; cd19106; AKR_AKR1A1-4; 1.
DR   Gene3D; 3.20.20.100; NADP-dependent oxidoreductase domain; 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   PANTHER; PTHR11732:SF544; ALDO-KETO REDUCTASE FAMILY 1 MEMBER A1; 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; Q9JII6; MM.
PE   1: Evidence at protein level;
KW   3D-structure; Acetylation; Cell membrane; Cytoplasm;
KW   Direct protein sequencing; Lipid metabolism; Membrane; NADP;
KW   Oxidoreductase; Phosphoprotein; Reference proteome.
FT   INIT_MET        1
FT                   /note="Removed"
FT                   /evidence="ECO:0000269|Ref.4"
FT   CHAIN           2..325
FT                   /note="Aldo-keto reductase family 1 member A1"
FT                   /id="PRO_0000124618"
FT   ACT_SITE        50
FT                   /note="Proton donor"
FT                   /evidence="ECO:0000250|UniProtKB:P14550"
FT   BINDING         11..20
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000255"
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-acetylthreonine"
FT                   /evidence="ECO:0000269|Ref.4"
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:0007744|PubMed:23806337"
FT   MOD_RES         127
FT                   /note="N6-succinyllysine; alternate"
FT                   /evidence="ECO:0007744|PubMed:23806337"
FT   MOD_RES         145
FT                   /note="N6-succinyllysine"
FT                   /evidence="ECO:0007744|PubMed:23806337"
FT   MOD_RES         211
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P14550"
FT   CONFLICT        54
FT                   /note="T -> A (in Ref. 2; BAB27586)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        60
FT                   /note="L -> P (in Ref. 2; BAB27915)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        95
FT                   /note="L -> I (in Ref. 2; BAB27883/BAB27767)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        120
FT                   /note="R -> L (in Ref. 2; BAB27909)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        284
FT                   /note="E -> G (in Ref. 2; BAB27437)"
FT                   /evidence="ECO:0000305"
FT   STRAND          5..7
FT                   /evidence="ECO:0007829|PDB:4GAC"
FT   STRAND          13..17
FT                   /evidence="ECO:0007829|PDB:4GAC"
FT   HELIX           26..38
FT                   /evidence="ECO:0007829|PDB:4GAC"
FT   STRAND          43..45
FT                   /evidence="ECO:0007829|PDB:4GAC"
FT   HELIX           48..50
FT                   /evidence="ECO:0007829|PDB:4GAC"
FT   HELIX           53..63
FT                   /evidence="ECO:0007829|PDB:4GAC"
FT   STRAND          68..70
FT                   /evidence="ECO:0007829|PDB:4GAC"
FT   HELIX           72..74
FT                   /evidence="ECO:0007829|PDB:4GAC"
FT   STRAND          76..81
FT                   /evidence="ECO:0007829|PDB:4GAC"
FT   HELIX           83..85
FT                   /evidence="ECO:0007829|PDB:4GAC"
FT   HELIX           88..102
FT                   /evidence="ECO:0007829|PDB:4GAC"
FT   STRAND          107..113
FT                   /evidence="ECO:0007829|PDB:4GAC"
FT   STRAND          115..118
FT                   /evidence="ECO:0007829|PDB:4GAC"
FT   STRAND          120..122
FT                   /evidence="ECO:0007829|PDB:4GAC"
FT   HELIX           140..152
FT                   /evidence="ECO:0007829|PDB:4GAC"
FT   STRAND          155..157
FT                   /evidence="ECO:0007829|PDB:4GAC"
FT   STRAND          159..163
FT                   /evidence="ECO:0007829|PDB:4GAC"
FT   HELIX           166..175
FT                   /evidence="ECO:0007829|PDB:4GAC"
FT   STRAND          182..186
FT                   /evidence="ECO:0007829|PDB:4GAC"
FT   HELIX           194..202
FT                   /evidence="ECO:0007829|PDB:4GAC"
FT   STRAND          206..211
FT                   /evidence="ECO:0007829|PDB:4GAC"
FT   HELIX           216..221
FT                   /evidence="ECO:0007829|PDB:4GAC"
FT   HELIX           228..230
FT                   /evidence="ECO:0007829|PDB:4GAC"
FT   HELIX           232..241
FT                   /evidence="ECO:0007829|PDB:4GAC"
FT   HELIX           245..255
FT                   /evidence="ECO:0007829|PDB:4GAC"
FT   HELIX           267..273
FT                   /evidence="ECO:0007829|PDB:4GAC"
FT   HELIX           283..290
FT                   /evidence="ECO:0007829|PDB:4GAC"
FT   STRAND          302..305
FT                   /evidence="ECO:0007829|PDB:4GAC"
FT   STRAND          308..313
FT                   /evidence="ECO:0007829|PDB:4GAC"
SQ   SEQUENCE   325 AA;  36587 MW;  0097939061DA34CB CRC64;
     MTASSVLLHT GQKMPLIGLG TWKSEPGQVK AAIKHALSAG YRHIDCASVY GNETEIGEAL
     KESVGSGKAV PREELFVTSK LWNTKHHPED VEPALRKTLA DLQLEYLDLY LMHWPYAFER
     GDNPFPKNAD GTVRYDSTHY KETWKALEVL VAKGLVKALG LSNFNSRQID DVLSVASVRP
     AVLQVECHPY LAQNELIAHC HARGLEVTAY SPLGSSDRAW RHPDEPVLLE EPVVLALAEK
     HGRSPAQILL RWQVQRKVIC IPKSINPSRI LQNIQVFDFT FSPEEMKQLD ALNKNWRYIV
     PMITVDGKRV PRDAGHPLYP FNDPY
//