AK1A1_MOUSE
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 03-AUG-2022, entry version 165.
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=1.1.1.33 {ECO:0000250|UniProtKB:P51635};
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, Pancreas,
RC 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(+) = 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 -!- 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}.
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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 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; Q9JII6; -.
DR PRIDE; Q9JII6; -.
DR ProteomicsDB; 296148; -.
DR Antibodypedia; 3338; 594 antibodies from 37 providers.
DR DNASU; 58810; -.
DR Ensembl; ENSMUST00000030455; ENSMUSP00000030455; ENSMUSG00000028692.
DR GeneID; 58810; -.
DR KEGG; mmu:58810; -.
DR UCSC; uc008uha.2; mouse.
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; WRHPDEP; -.
DR OrthoDB; 1016440at2759; -.
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 75 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 276 other tissues.
DR ExpressionAtlas; Q9JII6; baseline and differential.
DR Genevisible; Q9JII6; MM.
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: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; 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 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 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
