ALD1_RAT
ID ALD1_RAT Reviewed; 316 AA.
AC Q5RJP0;
DT 25-JAN-2012, integrated into UniProtKB/Swiss-Prot.
DT 21-DEC-2004, sequence version 1.
DT 03-AUG-2022, entry version 116.
DE RecName: Full=Aldo-keto reductase family 1 member B7;
DE EC=1.1.1.21 {ECO:0000269|PubMed:21048316, ECO:0000269|PubMed:21168333};
DE AltName: Full=Aldehyde reductase;
DE AltName: Full=Aldose reductase-like protein AKR1B14 {ECO:0000303|PubMed:21048316};
DE AltName: Full=Aldose reductase-related protein 1;
GN Name=Akr1b7; Synonyms=Akr1b14;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway;
RX PubMed=15057822; DOI=10.1038/nature02426;
RA Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA Mockrin S., Collins F.S.;
RT "Genome sequence of the Brown Norway rat yields insights into mammalian
RT evolution.";
RL Nature 428:493-521(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway;
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Ovary;
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 FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND ACTIVITY
RP REGULATION.
RX PubMed=21048316; DOI=10.1248/bpb.33.1886;
RA Endo S., Matsunaga T., Fujita A., Tajima K., El-Kabbani O., Hara A.;
RT "Rat aldose reductase-like protein (AKR1B14) efficiently reduces the lipid
RT peroxidation product 4-oxo-2-nonenal.";
RL Biol. Pharm. Bull. 33:1886-1890(2010).
RN [5]
RP X-RAY CRYSTALLOGRAPHY (1.86 ANGSTROMS) IN COMPLEX WITH NADP, CATALYTIC
RP ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND MUTAGENESIS OF HIS-269.
RX PubMed=21168333; DOI=10.1016/j.bmcl.2010.11.086;
RA Sundaram K., Dhagat U., Endo S., Chung R., Matsunaga T., Hara A.,
RA El-Kabbani O.;
RT "Structure of rat aldose reductase-like protein AKR1B14 holoenzyme: Probing
RT the role of His269 in coenzyme binding by site-directed mutagenesis.";
RL Bioorg. Med. Chem. Lett. 21:801-804(2011).
CC -!- FUNCTION: Reduces a broad range of aliphatic and aromatic aldehydes to
CC the corresponding alcohols (PubMed:21048316). Reduces prostaglandins
CC (By similarity). May play a role in the metabolism of xenobiotic
CC aromatic aldehydes. {ECO:0000250|UniProtKB:P21300,
CC ECO:0000269|PubMed:21048316}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=an alditol + NADP(+) = an aldose + H(+) + NADPH;
CC Xref=Rhea:RHEA:12789, Rhea:RHEA-COMP:9554, Rhea:RHEA-COMP:9555,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15693, ChEBI:CHEBI:17522,
CC ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; EC=1.1.1.21;
CC Evidence={ECO:0000269|PubMed:21048316, ECO:0000269|PubMed:21168333};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=NADP(+) + prostaglandin F2alpha = H(+) + NADPH + prostaglandin
CC H2; Xref=Rhea:RHEA:45312, ChEBI:CHEBI:15378, ChEBI:CHEBI:57404,
CC ChEBI:CHEBI:57405, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349;
CC Evidence={ECO:0000250|UniProtKB:P21300};
CC -!- ACTIVITY REGULATION: Inhibited by tolrestat and epalrestat.
CC {ECO:0000269|PubMed:21048316}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=1.5 uM for NADPH {ECO:0000269|PubMed:21048316,
CC ECO:0000269|PubMed:21168333};
CC KM=220 uM for NADH {ECO:0000269|PubMed:21048316,
CC ECO:0000269|PubMed:21168333};
CC KM=0.16 uM for 4-oxo-2-nonenal {ECO:0000269|PubMed:21048316,
CC ECO:0000269|PubMed:21168333};
CC KM=37 uM for geraniol {ECO:0000269|PubMed:21048316,
CC ECO:0000269|PubMed:21168333};
CC KM=1.5 uM for 4-nitrobenzaldehyde {ECO:0000269|PubMed:21048316,
CC ECO:0000269|PubMed:21168333};
CC pH dependence:
CC Optimum pH is 6.5-7. {ECO:0000269|PubMed:21048316,
CC ECO:0000269|PubMed:21168333};
CC -!- SUBUNIT: Monomer. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}.
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; CH473959; EDM15308.1; -; Genomic_DNA.
DR EMBL; BC086563; AAH86563.1; -; mRNA.
DR RefSeq; NP_446233.2; NM_053781.2.
DR PDB; 3O3R; X-ray; 1.86 A; A/B=1-316.
DR PDB; 3QKZ; X-ray; 1.87 A; A/B=1-316.
DR PDBsum; 3O3R; -.
DR PDBsum; 3QKZ; -.
DR AlphaFoldDB; Q5RJP0; -.
DR SMR; Q5RJP0; -.
DR STRING; 10116.ENSRNOP00000013423; -.
DR BindingDB; Q5RJP0; -.
DR ChEMBL; CHEMBL3421523; -.
DR DrugCentral; Q5RJP0; -.
DR iPTMnet; Q5RJP0; -.
DR PhosphoSitePlus; Q5RJP0; -.
DR jPOST; Q5RJP0; -.
DR PaxDb; Q5RJP0; -.
DR PRIDE; Q5RJP0; -.
DR Ensembl; ENSRNOT00000013423; ENSRNOP00000013423; ENSRNOG00000009875.
DR GeneID; 116463; -.
DR KEGG; rno:116463; -.
DR UCSC; RGD:620257; rat.
DR CTD; 11997; -.
DR RGD; 620257; Akr1b7.
DR eggNOG; KOG1577; Eukaryota.
DR GeneTree; ENSGT00940000154773; -.
DR HOGENOM; CLU_023205_0_0_1; -.
DR InParanoid; Q5RJP0; -.
DR OMA; NTFHEKS; -.
DR OrthoDB; 1016440at2759; -.
DR PhylomeDB; Q5RJP0; -.
DR TreeFam; TF106492; -.
DR Reactome; R-RNO-193144; Estrogen biosynthesis.
DR Reactome; R-RNO-975634; Retinoid metabolism and transport.
DR EvolutionaryTrace; Q5RJP0; -.
DR PRO; PR:Q5RJP0; -.
DR Proteomes; UP000002494; Chromosome 4.
DR Proteomes; UP000234681; Chromosome 4.
DR Bgee; ENSRNOG00000009875; Expressed in ovary and 8 other tissues.
DR Genevisible; Q5RJP0; RN.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0005739; C:mitochondrion; IBA:GO_Central.
DR GO; GO:0004032; F:alditol:NADP+ 1-oxidoreductase activity; IBA:GO_Central.
DR GO; GO:0004033; F:aldo-keto reductase (NADP) activity; TAS:RGD.
DR GO; GO:0036130; F:prostaglandin H2 endoperoxidase reductase activity; IEA:RHEA.
DR Gene3D; 3.20.20.100; -; 1.
DR InterPro; IPR020471; AKR.
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 1: Evidence at protein level;
KW 3D-structure; Cytoplasm; NADP; Oxidoreductase; Reference proteome.
FT CHAIN 1..316
FT /note="Aldo-keto reductase family 1 member B7"
FT /id="PRO_0000415351"
FT ACT_SITE 49
FT /note="Proton donor"
FT /evidence="ECO:0000250"
FT BINDING 20..21
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:21168333"
FT BINDING 44
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:21168333"
FT BINDING 160..161
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:21168333"
FT BINDING 184
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:21168333"
FT BINDING 210..215
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:21168333"
FT BINDING 263..269
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:21168333"
FT BINDING 273
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:21168333"
FT SITE 78
FT /note="Lowers pKa of active site Tyr"
FT /evidence="ECO:0000250"
FT MUTAGEN 269
FT /note="H->F,R: Reduced affinity for NADP."
FT /evidence="ECO:0000269|PubMed:21168333"
FT MUTAGEN 269
FT /note="H->M: Strongly reduced affinity for NADP."
FT /evidence="ECO:0000269|PubMed:21168333"
FT STRAND 4..6
FT /evidence="ECO:0007829|PDB:3O3R"
FT STRAND 12..19
FT /evidence="ECO:0007829|PDB:3O3R"
FT HELIX 27..37
FT /evidence="ECO:0007829|PDB:3O3R"
FT STRAND 42..44
FT /evidence="ECO:0007829|PDB:3O3R"
FT HELIX 47..49
FT /evidence="ECO:0007829|PDB:3O3R"
FT HELIX 52..64
FT /evidence="ECO:0007829|PDB:3O3R"
FT HELIX 70..72
FT /evidence="ECO:0007829|PDB:3O3R"
FT STRAND 74..79
FT /evidence="ECO:0007829|PDB:3O3R"
FT HELIX 81..83
FT /evidence="ECO:0007829|PDB:3O3R"
FT HELIX 86..100
FT /evidence="ECO:0007829|PDB:3O3R"
FT STRAND 105..111
FT /evidence="ECO:0007829|PDB:3O3R"
FT HELIX 138..150
FT /evidence="ECO:0007829|PDB:3O3R"
FT STRAND 153..161
FT /evidence="ECO:0007829|PDB:3O3R"
FT HELIX 164..171
FT /evidence="ECO:0007829|PDB:3O3R"
FT STRAND 182..186
FT /evidence="ECO:0007829|PDB:3O3R"
FT HELIX 194..201
FT /evidence="ECO:0007829|PDB:3O3R"
FT TURN 202..204
FT /evidence="ECO:0007829|PDB:3O3R"
FT STRAND 206..210
FT /evidence="ECO:0007829|PDB:3O3R"
FT HELIX 228..230
FT /evidence="ECO:0007829|PDB:3QKZ"
FT HELIX 232..241
FT /evidence="ECO:0007829|PDB:3O3R"
FT HELIX 245..254
FT /evidence="ECO:0007829|PDB:3O3R"
FT TURN 255..257
FT /evidence="ECO:0007829|PDB:3O3R"
FT HELIX 267..273
FT /evidence="ECO:0007829|PDB:3O3R"
FT HELIX 283..290
FT /evidence="ECO:0007829|PDB:3O3R"
FT HELIX 302..304
FT /evidence="ECO:0007829|PDB:3O3R"
FT HELIX 311..313
FT /evidence="ECO:0007829|PDB:3O3R"
SQ SEQUENCE 316 AA; 36122 MW; E5733ADA0ED5FF21 CRC64;
MTTFVKLRTK AKMPLVGLGT WKSPPGQVKE AVKAAIDAGY RHFDCAYVYQ NESEVGEAIQ
EKIKEKAVRR EDLFIVSKLW STFFEKSLMK EAFQKTLSDL KLDYLDLYLI HWPQGLQAGK
EFLPKDSQGK VLMSKSTFLD AWEGMEELVD QGLVKALGVS NFNHFQIERL LNKPGLKHKP
VTNQVECHPY LTQEKLIQYC HSKGIAVIAY SPLGSPDRPY AKPEDPVVLE IPKIKEIAAK
HKKTIAQVLI RFHVQRNVAV IPKSVTLSHI KENIQVFDFQ LSEEDMAAIL SLNRNWRACG
LFVTSDEEDF PFHEEY
