Full text data of AKR1A1
AKR1A1
(ALDR1, ALR)
[Confidence: low (only semi-automatic identification from reviews)]
Alcohol dehydrogenase [NADP(+)]; 1.1.1.2 (Aldehyde reductase; Aldo-keto reductase family 1 member A1)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Alcohol dehydrogenase [NADP(+)]; 1.1.1.2 (Aldehyde reductase; Aldo-keto reductase family 1 member A1)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
P14550
ID AK1A1_HUMAN Reviewed; 325 AA.
AC P14550; A8KAL8; D3DQ04; Q6IAZ4;
DT 01-JAN-1990, integrated into UniProtKB/Swiss-Prot.
read moreDT 23-JAN-2007, sequence version 3.
DT 22-JAN-2014, entry version 151.
DE RecName: Full=Alcohol dehydrogenase [NADP(+)];
DE EC=1.1.1.2;
DE AltName: Full=Aldehyde reductase;
DE AltName: Full=Aldo-keto reductase family 1 member A1;
GN Name=AKR1A1; Synonyms=ALDR1, ALR;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND PARTIAL PROTEIN SEQUENCE.
RC TISSUE=Liver;
RX PubMed=2498333;
RA Bohren K.M., Bullock B., Wermuth B., Gabbay K.H.;
RT "The aldo-keto reductase superfamily. cDNAs and deduced amino acid
RT sequences of human aldehyde and aldose reductases.";
RL J. Biol. Chem. 264:9547-9551(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=10393438;
RA Fujii J., Hamaoka R., Matsumoto A., Fujii T., Yamaguchi Y.,
RA Egashira M., Miyoshi O., Niikawa N., Taniguchi N.;
RT "The structural organization of the human aldehyde reductase gene,
RT AKR1A1, and mapping to chromosome 1p33-->p32.";
RL Cytogenet. Cell Genet. 84:230-232(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=10486210; DOI=10.1006/geno.1999.5915;
RA Barski O.A., Gabbay K.H., Bohren K.M.;
RT "Characterization of the human aldehyde reductase gene and promoter.";
RL Genomics 60:188-198(1999).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Uterus;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor
RT vector.";
RL Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D.,
RA Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A.,
RA Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F.,
RA McDonald L., Evans R., Phillips K., Atkinson A., Cooper R., Jones C.,
RA Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P.,
RA Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K.,
RA Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G.,
RA Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D.,
RA Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G.,
RA Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J.,
RA Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R.,
RA Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D.,
RA Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G.,
RA Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M.,
RA Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J.,
RA Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M.,
RA Loveland J., Lovell J., Lush M.J., Lyne R., Martin S.,
RA Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S.,
RA Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C.,
RA Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z.,
RA Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E.,
RA Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A.,
RA Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R.,
RA Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V.,
RA Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Colon, and Kidney;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [10]
RP PROTEIN SEQUENCE OF 2-325.
RC TISSUE=Liver;
RX PubMed=3615425;
RA Wermuth B., Omar A., Forster A., di Francesco C., Wolf M.,
RA von Wartburg J.-P., Bullock B., Gabbay K.H.;
RT "Primary structure of aldehyde reductase from human liver.";
RL Prog. Clin. Biol. Res. 232:297-307(1987).
RN [11]
RP MUTAGENESIS OF TYR-50; LYS-80; HIS-113; ILE-299 AND VAL-300.
RX PubMed=7669785; DOI=10.1021/bi00035a036;
RA Barski O.A., Gabbay K.H., Grimshaw C.E., Bohren K.M.;
RT "Mechanism of human aldehyde reductase: characterization of the active
RT site pocket.";
RL Biochemistry 34:11264-11275(1995).
RN [12]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=10510318; DOI=10.1042/0264-6021:3430487;
RA O'Connor T., Ireland L.S., Harrison D.J., Hayes J.D.;
RT "Major differences exist in the function and tissue-specific
RT expression of human aflatoxin B1 aldehyde reductase and the principal
RT human aldo-keto reductase AKR1 family members.";
RL Biochem. J. 343:487-504(1999).
RN [13]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=11306097; DOI=10.1016/S0009-2797(00)00237-4;
RA Palackal N.T., Burczynski M.E., Harvey R.G., Penning T.M.;
RT "Metabolic activation of polycyclic aromatic hydrocarbon trans-
RT dihydrodiols by ubiquitously expressed aldehyde reductase (AKR1A1).";
RL Chem. Biol. Interact. 130:815-824(2001).
RN [14]
RP FUNCTION, AND CHARACTERIZATION OF VARIANTS SER-52 AND ASP-55.
RX PubMed=18276838; DOI=10.1124/dmd.107.018895;
RA Bains O.S., Takahashi R.H., Pfeifer T.A., Grigliatti T.A., Reid R.E.,
RA Riggs K.W.;
RT "Two allelic variants of aldo-keto reductase 1A1 exhibit reduced in
RT vitro metabolism of daunorubicin.";
RL Drug Metab. Dispos. 36:904-910(2008).
RN [15]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, MASS SPECTROMETRY, AND
RP CLEAVAGE OF INITIATOR METHIONINE.
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [16]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [17]
RP X-RAY CRYSTALLOGRAPHY (2.48 ANGSTROMS).
RX PubMed=15299353; DOI=10.1107/S0907444994005275;
RA El-Kabbani O., Green N.C., Lin G., Carson M., Narayana S.V.L.,
RA Moore K.M., Flynn T.G., DeLucas L.J.;
RT "Structures of human and porcine aldehyde reductase: an enzyme
RT implicated in diabetic complications.";
RL Acta Crystallogr. D 50:859-868(1994).
CC -!- FUNCTION: Catalyzes the NADPH-dependent reduction of a variety of
CC aromatic and aliphatic aldehydes to their corresponding alcohols.
CC Catalyzes the reduction of mevaldate to mevalonic acid and of
CC glyceraldehyde to glycerol. Has broad substrate specificity. In
CC vitro substrates include succinic semialdehyde, 4-
CC nitrobenzaldehyde, 1,2-naphthoquinone, methylglyoxal, and D-
CC glucuronic acid. Plays a role in the activation of procarcinogens,
CC such as polycyclic aromatic hydrocarbon trans-dihydrodiols, and in
CC the metabolism of various xenobiotics and drugs, including the
CC anthracyclines doxorubicin (DOX) and daunorubicin (DAUN).
CC -!- CATALYTIC ACTIVITY: An alcohol + NADP(+) = an aldehyde + NADPH.
CC -!- SUBUNIT: Monomer (By similarity).
CC -!- TISSUE SPECIFICITY: Widely expressed. Highly expressed in kidney,
CC salivary gland and liver. Detected in trachea, stomach, brain,
CC lung, prostate, placenta, mammary gland, small intestine and lung.
CC -!- SIMILARITY: Belongs to the aldo/keto reductase family.
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DR EMBL; J04794; AAA51711.1; -; mRNA.
DR EMBL; AF036683; AAB92369.1; -; Genomic_DNA.
DR EMBL; AF036680; AAB92369.1; JOINED; Genomic_DNA.
DR EMBL; AF036681; AAB92369.1; JOINED; Genomic_DNA.
DR EMBL; AF036682; AAB92369.1; JOINED; Genomic_DNA.
DR EMBL; AF112485; AAF01260.1; -; Genomic_DNA.
DR EMBL; AF112484; AAF01260.1; JOINED; Genomic_DNA.
DR EMBL; AK293083; BAF85772.1; -; mRNA.
DR EMBL; CR457010; CAG33291.1; -; mRNA.
DR EMBL; BT007003; AAP35649.1; -; mRNA.
DR EMBL; AL355480; CAI22459.1; -; Genomic_DNA.
DR EMBL; CH471059; EAX06970.1; -; Genomic_DNA.
DR EMBL; CH471059; EAX06971.1; -; Genomic_DNA.
DR EMBL; CH471059; EAX06972.1; -; Genomic_DNA.
DR EMBL; CH471059; EAX06974.1; -; Genomic_DNA.
DR EMBL; BC000670; AAH00670.1; -; mRNA.
DR EMBL; BC005394; AAH05394.1; -; mRNA.
DR PIR; A33851; A33851.
DR RefSeq; NP_001189342.1; NM_001202413.1.
DR RefSeq; NP_001189343.1; NM_001202414.1.
DR RefSeq; NP_006057.1; NM_006066.3.
DR RefSeq; NP_697021.1; NM_153326.2.
DR UniGene; Hs.474584; -.
DR UniGene; Hs.721160; -.
DR PDB; 2ALR; X-ray; 2.48 A; A=2-325.
DR PDBsum; 2ALR; -.
DR ProteinModelPortal; P14550; -.
DR SMR; P14550; 2-325.
DR IntAct; P14550; 2.
DR MINT; MINT-5001699; -.
DR STRING; 9606.ENSP00000312606; -.
DR BindingDB; P14550; -.
DR ChEMBL; CHEMBL2246; -.
DR PhosphoSite; P14550; -.
DR DMDM; 113600; -.
DR REPRODUCTION-2DPAGE; IPI00220271; -.
DR REPRODUCTION-2DPAGE; P14550; -.
DR SWISS-2DPAGE; P14550; -.
DR UCD-2DPAGE; P14550; -.
DR PaxDb; P14550; -.
DR PeptideAtlas; P14550; -.
DR PRIDE; P14550; -.
DR DNASU; 10327; -.
DR Ensembl; ENST00000351829; ENSP00000312606; ENSG00000117448.
DR Ensembl; ENST00000372070; ENSP00000361140; ENSG00000117448.
DR GeneID; 10327; -.
DR KEGG; hsa:10327; -.
DR UCSC; uc001cod.3; human.
DR CTD; 10327; -.
DR GeneCards; GC01P046017; -.
DR HGNC; HGNC:380; AKR1A1.
DR HPA; CAB006246; -.
DR HPA; HPA017919; -.
DR HPA; HPA019649; -.
DR HPA; HPA027734; -.
DR MIM; 103830; gene.
DR neXtProt; NX_P14550; -.
DR PharmGKB; PA24674; -.
DR eggNOG; COG0656; -.
DR HOGENOM; HOG000250272; -.
DR HOVERGEN; HBG000020; -.
DR InParanoid; P14550; -.
DR KO; K00002; -.
DR OMA; WPYAFER; -.
DR OrthoDB; EOG70KGQF; -.
DR PhylomeDB; P14550; -.
DR SABIO-RK; P14550; -.
DR ChiTaRS; AKR1A1; human.
DR EvolutionaryTrace; P14550; -.
DR GeneWiki; Aldo-keto_reductase_family_1,_member_A1; -.
DR GenomeRNAi; 10327; -.
DR NextBio; 39151; -.
DR PRO; PR:P14550; -.
DR ArrayExpress; P14550; -.
DR Bgee; P14550; -.
DR CleanEx; HS_AKR1A1; -.
DR Genevestigator; P14550; -.
DR GO; GO:0016324; C:apical plasma membrane; IEA:Ensembl.
DR GO; GO:0005829; C:cytosol; IEA:Ensembl.
DR GO; GO:0004032; F:alditol:NADP+ 1-oxidoreductase activity; TAS:ProtInc.
DR GO; GO:0009055; F:electron carrier activity; TAS:UniProtKB.
DR GO; GO:0047939; F:L-glucuronate reductase activity; IEA:Ensembl.
DR GO; GO:0046185; P:aldehyde catabolic process; IEA:Ensembl.
DR GO; GO:0006081; P:cellular aldehyde metabolic process; TAS:ProtInc.
DR GO; GO:0042840; P:D-glucuronate catabolic process; IEA:Ensembl.
DR GO; GO:0006006; P:glucose metabolic process; TAS:ProtInc.
DR GO; GO:0019853; P:L-ascorbic acid biosynthetic process; IEA:Ensembl.
DR Gene3D; 3.20.20.100; -; 1.
DR InterPro; IPR001395; Aldo/ket_red.
DR InterPro; IPR018170; Aldo/ket_reductase_CS.
DR InterPro; IPR020471; Aldo/keto_reductase_subgr.
DR InterPro; IPR023210; NADP_OxRdtase_dom.
DR PANTHER; PTHR11732; PTHR11732; 1.
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; Complete proteome;
KW Direct protein sequencing; NADP; Oxidoreductase; Polymorphism;
KW Reference proteome.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 325 Alcohol dehydrogenase [NADP(+)].
FT /FTId=PRO_0000124617.
FT NP_BIND 211 273 NADP (By similarity).
FT ACT_SITE 50 50 Proton donor.
FT BINDING 113 113 Substrate.
FT SITE 80 80 Lowers pKa of active site Tyr.
FT MOD_RES 2 2 N-acetylalanine.
FT VARIANT 52 52 N -> S (reduced activity towards
FT daunorubicin; dbSNP:rs2229540).
FT /FTId=VAR_048212.
FT VARIANT 55 55 E -> D (reduced activity towards
FT daunorubicin; dbSNP:rs6690497).
FT /FTId=VAR_058909.
FT MUTAGEN 50 50 Y->F: Complete loss of enzymatic
FT activity.
FT MUTAGEN 50 50 Y->H: Complete loss of enzymatic
FT activity.
FT MUTAGEN 80 80 K->M: Complete loss of enzymatic
FT activity.
FT MUTAGEN 113 113 H->Q: Strong decrease in enzymatic
FT activity.
FT MUTAGEN 299 299 I->A: No change in enzymatic activity.
FT MUTAGEN 299 299 I->C: No change in enzymatic activity.
FT MUTAGEN 300 300 V->C: No change in enzymatic activity.
FT CONFLICT 305 305 V -> A (in Ref. 4; BAF85772).
FT STRAND 5 7
FT STRAND 13 17
FT HELIX 26 39
FT STRAND 43 45
FT HELIX 48 50
FT HELIX 53 63
FT STRAND 68 70
FT HELIX 72 74
FT STRAND 76 81
FT HELIX 83 85
FT HELIX 88 102
FT STRAND 107 113
FT STRAND 115 118
FT STRAND 120 122
FT HELIX 140 153
FT STRAND 155 163
FT HELIX 166 173
FT STRAND 182 186
FT HELIX 194 203
FT STRAND 206 210
FT HELIX 232 241
FT HELIX 245 255
FT HELIX 267 274
FT HELIX 283 290
FT STRAND 302 305
FT STRAND 308 313
FT STRAND 320 323
SQ SEQUENCE 325 AA; 36573 MW; F6B27517EB754E37 CRC64;
MAASCVLLHT GQKMPLIGLG TWKSEPGQVK AAVKYALSVG YRHIDCAAIY GNEPEIGEAL
KEDVGPGKAV PREELFVTSK LWNTKHHPED VEPALRKTLA DLQLEYLDLY LMHWPYAFER
GDNPFPKNAD GTICYDSTHY KETWKALEAL VAKGLVQALG LSNFNSRQID DILSVASVRP
AVLQVECHPY LAQNELIAHC QARGLEVTAY SPLGSSDRAW RDPDEPVLLE EPVVLALAEK
YGRSPAQILL RWQVQRKVIC IPKSITPSRI LQNIKVFDFT FSPEEMKQLN ALNKNWRYIV
PMLTVDGKRV PRDAGHPLYP FNDPY
//
ID AK1A1_HUMAN Reviewed; 325 AA.
AC P14550; A8KAL8; D3DQ04; Q6IAZ4;
DT 01-JAN-1990, integrated into UniProtKB/Swiss-Prot.
read moreDT 23-JAN-2007, sequence version 3.
DT 22-JAN-2014, entry version 151.
DE RecName: Full=Alcohol dehydrogenase [NADP(+)];
DE EC=1.1.1.2;
DE AltName: Full=Aldehyde reductase;
DE AltName: Full=Aldo-keto reductase family 1 member A1;
GN Name=AKR1A1; Synonyms=ALDR1, ALR;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND PARTIAL PROTEIN SEQUENCE.
RC TISSUE=Liver;
RX PubMed=2498333;
RA Bohren K.M., Bullock B., Wermuth B., Gabbay K.H.;
RT "The aldo-keto reductase superfamily. cDNAs and deduced amino acid
RT sequences of human aldehyde and aldose reductases.";
RL J. Biol. Chem. 264:9547-9551(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=10393438;
RA Fujii J., Hamaoka R., Matsumoto A., Fujii T., Yamaguchi Y.,
RA Egashira M., Miyoshi O., Niikawa N., Taniguchi N.;
RT "The structural organization of the human aldehyde reductase gene,
RT AKR1A1, and mapping to chromosome 1p33-->p32.";
RL Cytogenet. Cell Genet. 84:230-232(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=10486210; DOI=10.1006/geno.1999.5915;
RA Barski O.A., Gabbay K.H., Bohren K.M.;
RT "Characterization of the human aldehyde reductase gene and promoter.";
RL Genomics 60:188-198(1999).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Uterus;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor
RT vector.";
RL Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D.,
RA Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A.,
RA Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F.,
RA McDonald L., Evans R., Phillips K., Atkinson A., Cooper R., Jones C.,
RA Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P.,
RA Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K.,
RA Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G.,
RA Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D.,
RA Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G.,
RA Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J.,
RA Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R.,
RA Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D.,
RA Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G.,
RA Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M.,
RA Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J.,
RA Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M.,
RA Loveland J., Lovell J., Lush M.J., Lyne R., Martin S.,
RA Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S.,
RA Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C.,
RA Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z.,
RA Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E.,
RA Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A.,
RA Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R.,
RA Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V.,
RA Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Colon, and Kidney;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [10]
RP PROTEIN SEQUENCE OF 2-325.
RC TISSUE=Liver;
RX PubMed=3615425;
RA Wermuth B., Omar A., Forster A., di Francesco C., Wolf M.,
RA von Wartburg J.-P., Bullock B., Gabbay K.H.;
RT "Primary structure of aldehyde reductase from human liver.";
RL Prog. Clin. Biol. Res. 232:297-307(1987).
RN [11]
RP MUTAGENESIS OF TYR-50; LYS-80; HIS-113; ILE-299 AND VAL-300.
RX PubMed=7669785; DOI=10.1021/bi00035a036;
RA Barski O.A., Gabbay K.H., Grimshaw C.E., Bohren K.M.;
RT "Mechanism of human aldehyde reductase: characterization of the active
RT site pocket.";
RL Biochemistry 34:11264-11275(1995).
RN [12]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=10510318; DOI=10.1042/0264-6021:3430487;
RA O'Connor T., Ireland L.S., Harrison D.J., Hayes J.D.;
RT "Major differences exist in the function and tissue-specific
RT expression of human aflatoxin B1 aldehyde reductase and the principal
RT human aldo-keto reductase AKR1 family members.";
RL Biochem. J. 343:487-504(1999).
RN [13]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=11306097; DOI=10.1016/S0009-2797(00)00237-4;
RA Palackal N.T., Burczynski M.E., Harvey R.G., Penning T.M.;
RT "Metabolic activation of polycyclic aromatic hydrocarbon trans-
RT dihydrodiols by ubiquitously expressed aldehyde reductase (AKR1A1).";
RL Chem. Biol. Interact. 130:815-824(2001).
RN [14]
RP FUNCTION, AND CHARACTERIZATION OF VARIANTS SER-52 AND ASP-55.
RX PubMed=18276838; DOI=10.1124/dmd.107.018895;
RA Bains O.S., Takahashi R.H., Pfeifer T.A., Grigliatti T.A., Reid R.E.,
RA Riggs K.W.;
RT "Two allelic variants of aldo-keto reductase 1A1 exhibit reduced in
RT vitro metabolism of daunorubicin.";
RL Drug Metab. Dispos. 36:904-910(2008).
RN [15]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, MASS SPECTROMETRY, AND
RP CLEAVAGE OF INITIATOR METHIONINE.
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [16]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [17]
RP X-RAY CRYSTALLOGRAPHY (2.48 ANGSTROMS).
RX PubMed=15299353; DOI=10.1107/S0907444994005275;
RA El-Kabbani O., Green N.C., Lin G., Carson M., Narayana S.V.L.,
RA Moore K.M., Flynn T.G., DeLucas L.J.;
RT "Structures of human and porcine aldehyde reductase: an enzyme
RT implicated in diabetic complications.";
RL Acta Crystallogr. D 50:859-868(1994).
CC -!- FUNCTION: Catalyzes the NADPH-dependent reduction of a variety of
CC aromatic and aliphatic aldehydes to their corresponding alcohols.
CC Catalyzes the reduction of mevaldate to mevalonic acid and of
CC glyceraldehyde to glycerol. Has broad substrate specificity. In
CC vitro substrates include succinic semialdehyde, 4-
CC nitrobenzaldehyde, 1,2-naphthoquinone, methylglyoxal, and D-
CC glucuronic acid. Plays a role in the activation of procarcinogens,
CC such as polycyclic aromatic hydrocarbon trans-dihydrodiols, and in
CC the metabolism of various xenobiotics and drugs, including the
CC anthracyclines doxorubicin (DOX) and daunorubicin (DAUN).
CC -!- CATALYTIC ACTIVITY: An alcohol + NADP(+) = an aldehyde + NADPH.
CC -!- SUBUNIT: Monomer (By similarity).
CC -!- TISSUE SPECIFICITY: Widely expressed. Highly expressed in kidney,
CC salivary gland and liver. Detected in trachea, stomach, brain,
CC lung, prostate, placenta, mammary gland, small intestine and lung.
CC -!- SIMILARITY: Belongs to the aldo/keto reductase family.
CC -----------------------------------------------------------------------
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DR EMBL; J04794; AAA51711.1; -; mRNA.
DR EMBL; AF036683; AAB92369.1; -; Genomic_DNA.
DR EMBL; AF036680; AAB92369.1; JOINED; Genomic_DNA.
DR EMBL; AF036681; AAB92369.1; JOINED; Genomic_DNA.
DR EMBL; AF036682; AAB92369.1; JOINED; Genomic_DNA.
DR EMBL; AF112485; AAF01260.1; -; Genomic_DNA.
DR EMBL; AF112484; AAF01260.1; JOINED; Genomic_DNA.
DR EMBL; AK293083; BAF85772.1; -; mRNA.
DR EMBL; CR457010; CAG33291.1; -; mRNA.
DR EMBL; BT007003; AAP35649.1; -; mRNA.
DR EMBL; AL355480; CAI22459.1; -; Genomic_DNA.
DR EMBL; CH471059; EAX06970.1; -; Genomic_DNA.
DR EMBL; CH471059; EAX06971.1; -; Genomic_DNA.
DR EMBL; CH471059; EAX06972.1; -; Genomic_DNA.
DR EMBL; CH471059; EAX06974.1; -; Genomic_DNA.
DR EMBL; BC000670; AAH00670.1; -; mRNA.
DR EMBL; BC005394; AAH05394.1; -; mRNA.
DR PIR; A33851; A33851.
DR RefSeq; NP_001189342.1; NM_001202413.1.
DR RefSeq; NP_001189343.1; NM_001202414.1.
DR RefSeq; NP_006057.1; NM_006066.3.
DR RefSeq; NP_697021.1; NM_153326.2.
DR UniGene; Hs.474584; -.
DR UniGene; Hs.721160; -.
DR PDB; 2ALR; X-ray; 2.48 A; A=2-325.
DR PDBsum; 2ALR; -.
DR ProteinModelPortal; P14550; -.
DR SMR; P14550; 2-325.
DR IntAct; P14550; 2.
DR MINT; MINT-5001699; -.
DR STRING; 9606.ENSP00000312606; -.
DR BindingDB; P14550; -.
DR ChEMBL; CHEMBL2246; -.
DR PhosphoSite; P14550; -.
DR DMDM; 113600; -.
DR REPRODUCTION-2DPAGE; IPI00220271; -.
DR REPRODUCTION-2DPAGE; P14550; -.
DR SWISS-2DPAGE; P14550; -.
DR UCD-2DPAGE; P14550; -.
DR PaxDb; P14550; -.
DR PeptideAtlas; P14550; -.
DR PRIDE; P14550; -.
DR DNASU; 10327; -.
DR Ensembl; ENST00000351829; ENSP00000312606; ENSG00000117448.
DR Ensembl; ENST00000372070; ENSP00000361140; ENSG00000117448.
DR GeneID; 10327; -.
DR KEGG; hsa:10327; -.
DR UCSC; uc001cod.3; human.
DR CTD; 10327; -.
DR GeneCards; GC01P046017; -.
DR HGNC; HGNC:380; AKR1A1.
DR HPA; CAB006246; -.
DR HPA; HPA017919; -.
DR HPA; HPA019649; -.
DR HPA; HPA027734; -.
DR MIM; 103830; gene.
DR neXtProt; NX_P14550; -.
DR PharmGKB; PA24674; -.
DR eggNOG; COG0656; -.
DR HOGENOM; HOG000250272; -.
DR HOVERGEN; HBG000020; -.
DR InParanoid; P14550; -.
DR KO; K00002; -.
DR OMA; WPYAFER; -.
DR OrthoDB; EOG70KGQF; -.
DR PhylomeDB; P14550; -.
DR SABIO-RK; P14550; -.
DR ChiTaRS; AKR1A1; human.
DR EvolutionaryTrace; P14550; -.
DR GeneWiki; Aldo-keto_reductase_family_1,_member_A1; -.
DR GenomeRNAi; 10327; -.
DR NextBio; 39151; -.
DR PRO; PR:P14550; -.
DR ArrayExpress; P14550; -.
DR Bgee; P14550; -.
DR CleanEx; HS_AKR1A1; -.
DR Genevestigator; P14550; -.
DR GO; GO:0016324; C:apical plasma membrane; IEA:Ensembl.
DR GO; GO:0005829; C:cytosol; IEA:Ensembl.
DR GO; GO:0004032; F:alditol:NADP+ 1-oxidoreductase activity; TAS:ProtInc.
DR GO; GO:0009055; F:electron carrier activity; TAS:UniProtKB.
DR GO; GO:0047939; F:L-glucuronate reductase activity; IEA:Ensembl.
DR GO; GO:0046185; P:aldehyde catabolic process; IEA:Ensembl.
DR GO; GO:0006081; P:cellular aldehyde metabolic process; TAS:ProtInc.
DR GO; GO:0042840; P:D-glucuronate catabolic process; IEA:Ensembl.
DR GO; GO:0006006; P:glucose metabolic process; TAS:ProtInc.
DR GO; GO:0019853; P:L-ascorbic acid biosynthetic process; IEA:Ensembl.
DR Gene3D; 3.20.20.100; -; 1.
DR InterPro; IPR001395; Aldo/ket_red.
DR InterPro; IPR018170; Aldo/ket_reductase_CS.
DR InterPro; IPR020471; Aldo/keto_reductase_subgr.
DR InterPro; IPR023210; NADP_OxRdtase_dom.
DR PANTHER; PTHR11732; PTHR11732; 1.
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; Complete proteome;
KW Direct protein sequencing; NADP; Oxidoreductase; Polymorphism;
KW Reference proteome.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 325 Alcohol dehydrogenase [NADP(+)].
FT /FTId=PRO_0000124617.
FT NP_BIND 211 273 NADP (By similarity).
FT ACT_SITE 50 50 Proton donor.
FT BINDING 113 113 Substrate.
FT SITE 80 80 Lowers pKa of active site Tyr.
FT MOD_RES 2 2 N-acetylalanine.
FT VARIANT 52 52 N -> S (reduced activity towards
FT daunorubicin; dbSNP:rs2229540).
FT /FTId=VAR_048212.
FT VARIANT 55 55 E -> D (reduced activity towards
FT daunorubicin; dbSNP:rs6690497).
FT /FTId=VAR_058909.
FT MUTAGEN 50 50 Y->F: Complete loss of enzymatic
FT activity.
FT MUTAGEN 50 50 Y->H: Complete loss of enzymatic
FT activity.
FT MUTAGEN 80 80 K->M: Complete loss of enzymatic
FT activity.
FT MUTAGEN 113 113 H->Q: Strong decrease in enzymatic
FT activity.
FT MUTAGEN 299 299 I->A: No change in enzymatic activity.
FT MUTAGEN 299 299 I->C: No change in enzymatic activity.
FT MUTAGEN 300 300 V->C: No change in enzymatic activity.
FT CONFLICT 305 305 V -> A (in Ref. 4; BAF85772).
FT STRAND 5 7
FT STRAND 13 17
FT HELIX 26 39
FT STRAND 43 45
FT HELIX 48 50
FT HELIX 53 63
FT STRAND 68 70
FT HELIX 72 74
FT STRAND 76 81
FT HELIX 83 85
FT HELIX 88 102
FT STRAND 107 113
FT STRAND 115 118
FT STRAND 120 122
FT HELIX 140 153
FT STRAND 155 163
FT HELIX 166 173
FT STRAND 182 186
FT HELIX 194 203
FT STRAND 206 210
FT HELIX 232 241
FT HELIX 245 255
FT HELIX 267 274
FT HELIX 283 290
FT STRAND 302 305
FT STRAND 308 313
FT STRAND 320 323
SQ SEQUENCE 325 AA; 36573 MW; F6B27517EB754E37 CRC64;
MAASCVLLHT GQKMPLIGLG TWKSEPGQVK AAVKYALSVG YRHIDCAAIY GNEPEIGEAL
KEDVGPGKAV PREELFVTSK LWNTKHHPED VEPALRKTLA DLQLEYLDLY LMHWPYAFER
GDNPFPKNAD GTICYDSTHY KETWKALEAL VAKGLVQALG LSNFNSRQID DILSVASVRP
AVLQVECHPY LAQNELIAHC QARGLEVTAY SPLGSSDRAW RDPDEPVLLE EPVVLALAEK
YGRSPAQILL RWQVQRKVIC IPKSITPSRI LQNIKVFDFT FSPEEMKQLN ALNKNWRYIV
PMLTVDGKRV PRDAGHPLYP FNDPY
//
MIM
103830
*RECORD*
*FIELD* NO
103830
*FIELD* TI
*103830 ALDO-KETO REDUCTASE FAMILY 1, MEMBER A1; AKR1A1
;;ALDEHYDE REDUCTASE; ALR
*FIELD* TX
read more
DESCRIPTION
Aldehyde reductase (EC 1.1.1.2) and aldose reductase (EC 1.1.1.21;
103880) are monomeric NADPH-dependent oxidoreductases having wide
substrate specificities for carbonyl compounds (summary by Bohren et
al., 1989).
CLONING
Petrash et al. (1981) studied aldose reductase (AR), aldose reductase M
(ARM), and aldehyde reductase (ALR) in a variety of human tissues. Lens
aldose reductase is composed of a single subunit with molecular weight
35 kD, and liver aldehyde reductase is composed of a single subunit of
molecular weight 32 kD. Liver aldose reductase M is composed of 2
nonidentical subunits of molecular weights 35 kD and 42 kD. Lens has
only AR, liver has ARM and ALR, red cells have only ALR, while brain and
placenta have all 3 enzymes. Petrash et al. (1981) suggested that 3
loci--alpha, beta, and delta--code for these enzymes, and that AR is a
monomer of alpha polypeptide, ARM a dimer of alpha and beta subunits,
and ALR a monomer of delta polypeptide.
By screening a liver library with degenerate oligonucleotide primers
based on the protein sequence of liver aldehyde reductase, Bohren et al.
(1989) isolated aldehyde reductase cDNAs. The predicted protein contains
325 amino acids. Aldose reductase and aldehyde reductase share 3
homology domains and are 51% identical overall.
MAPPING
By fluorescence in situ hybridization, Fujii et al. (1999) mapped the
AKR1A1 gene to chromosome 1p33-p32.
*FIELD* RF
1. Bohren, K. M.; Bullock, B.; Wermuth, B.; Gabbay, K. H.: The aldo-keto
reductase superfamily: cDNAs and deduced amino acid sequences of human
aldehyde and aldose reductases. J. Biol. Chem. 264: 9547-9551, 1989.
2. Fujii, J.; Hamaoka, R.; Matsumoto, A.; Fujii, T.; Yamaguchi, Y.;
Egashira, M.; Miyoshi, O.; Niikawa, N.; Taniguchi, N.: The structural
organization of the human aldehyde reductase gene, AKR1A1, and mapping
to chromosome 1p33-p32. Cytogenet. Cell Genet. 84: 230-232, 1999.
3. Petrash, J. M.; Ansari, N. H.; Sadana, I.; Srivastava, S. K.:
Biochemical and genetic interrelationship between aldose reductase,
aldose reductase M and aldehyde reductase in human tissues. (Abstract) Am.
J. Hum. Genet. 33: 52A only, 1981.
*FIELD* CN
Carol A. Bocchini - updated: 4/30/2001
Rebekah S. Rasooly - updated: 7/20/1999
John A. Phillips, III - updated: 10/30/1997
*FIELD* CD
Victor A. McKusick: 6/4/1986
*FIELD* ED
carol: 05/22/2012
mgross: 2/4/2009
carol: 4/30/2001
terry: 4/30/2001
carol: 10/19/2000
mgross: 7/20/1999
jlewis: 6/25/1999
dholmes: 10/30/1997
dholmes: 10/17/1997
supermim: 3/16/1992
carol: 10/24/1990
supermim: 3/20/1990
carol: 12/13/1989
ddp: 10/27/1989
root: 10/26/1989
*RECORD*
*FIELD* NO
103830
*FIELD* TI
*103830 ALDO-KETO REDUCTASE FAMILY 1, MEMBER A1; AKR1A1
;;ALDEHYDE REDUCTASE; ALR
*FIELD* TX
read more
DESCRIPTION
Aldehyde reductase (EC 1.1.1.2) and aldose reductase (EC 1.1.1.21;
103880) are monomeric NADPH-dependent oxidoreductases having wide
substrate specificities for carbonyl compounds (summary by Bohren et
al., 1989).
CLONING
Petrash et al. (1981) studied aldose reductase (AR), aldose reductase M
(ARM), and aldehyde reductase (ALR) in a variety of human tissues. Lens
aldose reductase is composed of a single subunit with molecular weight
35 kD, and liver aldehyde reductase is composed of a single subunit of
molecular weight 32 kD. Liver aldose reductase M is composed of 2
nonidentical subunits of molecular weights 35 kD and 42 kD. Lens has
only AR, liver has ARM and ALR, red cells have only ALR, while brain and
placenta have all 3 enzymes. Petrash et al. (1981) suggested that 3
loci--alpha, beta, and delta--code for these enzymes, and that AR is a
monomer of alpha polypeptide, ARM a dimer of alpha and beta subunits,
and ALR a monomer of delta polypeptide.
By screening a liver library with degenerate oligonucleotide primers
based on the protein sequence of liver aldehyde reductase, Bohren et al.
(1989) isolated aldehyde reductase cDNAs. The predicted protein contains
325 amino acids. Aldose reductase and aldehyde reductase share 3
homology domains and are 51% identical overall.
MAPPING
By fluorescence in situ hybridization, Fujii et al. (1999) mapped the
AKR1A1 gene to chromosome 1p33-p32.
*FIELD* RF
1. Bohren, K. M.; Bullock, B.; Wermuth, B.; Gabbay, K. H.: The aldo-keto
reductase superfamily: cDNAs and deduced amino acid sequences of human
aldehyde and aldose reductases. J. Biol. Chem. 264: 9547-9551, 1989.
2. Fujii, J.; Hamaoka, R.; Matsumoto, A.; Fujii, T.; Yamaguchi, Y.;
Egashira, M.; Miyoshi, O.; Niikawa, N.; Taniguchi, N.: The structural
organization of the human aldehyde reductase gene, AKR1A1, and mapping
to chromosome 1p33-p32. Cytogenet. Cell Genet. 84: 230-232, 1999.
3. Petrash, J. M.; Ansari, N. H.; Sadana, I.; Srivastava, S. K.:
Biochemical and genetic interrelationship between aldose reductase,
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*FIELD* CN
Carol A. Bocchini - updated: 4/30/2001
Rebekah S. Rasooly - updated: 7/20/1999
John A. Phillips, III - updated: 10/30/1997
*FIELD* CD
Victor A. McKusick: 6/4/1986
*FIELD* ED
carol: 05/22/2012
mgross: 2/4/2009
carol: 4/30/2001
terry: 4/30/2001
carol: 10/19/2000
mgross: 7/20/1999
jlewis: 6/25/1999
dholmes: 10/30/1997
dholmes: 10/17/1997
supermim: 3/16/1992
carol: 10/24/1990
supermim: 3/20/1990
carol: 12/13/1989
ddp: 10/27/1989
root: 10/26/1989