ARK73_RAT
ID ARK73_RAT Reviewed; 327 AA.
AC P38918; Q5EBB7; Q68FZ3; Q9QX16;
DT 01-FEB-1995, integrated into UniProtKB/Swiss-Prot.
DT 15-DEC-2003, sequence version 2.
DT 03-AUG-2022, entry version 156.
DE RecName: Full=Aflatoxin B1 aldehyde reductase member 3;
DE Short=AFB1-AR;
DE EC=1.-.-.-;
DE AltName: Full=Aflatoxin B1 aldehyde reductase member 1;
DE Short=rAFAR1;
GN Name=Akr7a3; Synonyms=Afar, Akr7a1;
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 [MRNA].
RC STRAIN=Fischer 344; TISSUE=Liver;
RX PubMed=8234296; DOI=10.1073/pnas.90.21.10350;
RA Ellis E.M., Judah D.J., Neal G.E., Hayes J.D.;
RT "An ethoxyquin-inducible aldehyde reductase from rat liver that metabolizes
RT aflatoxin B1 defines a subfamily of aldo-keto reductases.";
RL Proc. Natl. Acad. Sci. U.S.A. 90:10350-10354(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND CHARACTERIZATION.
RC STRAIN=Fischer 344; TISSUE=Liver;
RX PubMed=10383892; DOI=10.1093/carcin/20.7.1215;
RA Knight L.P., Primiano T., Groopman J.D., Kensler T.W., Sutter T.R.;
RT "cDNA cloning, expression and activity of a second human aflatoxin B1-
RT metabolizing member of the aldo-keto reductase superfamily, AKR7A3.";
RL Carcinogenesis 20:1215-1223(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=Fischer 344;
RX PubMed=12727802; DOI=10.1093/carcin/bgg016;
RA Ellis E.M., Slattery C.M., Hayes J.D.;
RT "Characterization of the rat aflatoxin B1 aldehyde reductase gene, AKR7A1.
RT Structure and chromosomal localization of AKR7A1 as well as identification
RT of antioxidant response elements in the gene promoter.";
RL Carcinogenesis 24:727-737(2003).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=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 project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP PROTEIN SEQUENCE OF 6-17; 89-97; 156-184; 232-246 AND 250-274.
RC TISSUE=Liver;
RA Raymackers J., Anderson L.;
RL Submitted (NOV-1994) to UniProtKB.
RN [6]
RP PARTIAL PROTEIN SEQUENCE.
RX PubMed=8395332;
RA Hayes J.D., Judah D.J., Neal G.E.;
RT "Resistance to aflatoxin B1 is associated with the expression of a novel
RT aldo-keto reductase which has catalytic activity towards a cytotoxic
RT aldehyde-containing metabolite of the toxin.";
RL Cancer Res. 53:3887-3894(1993).
RN [7]
RP FUNCTION, AND SUBUNIT.
RX PubMed=12071861; DOI=10.1042/bj20020342;
RA Kelly V.P., Sherratt P.J., Crouch D.H., Hayes J.D.;
RT "Novel homodimeric and heterodimeric rat gamma-hydroxybutyrate synthases
RT that associate with the Golgi apparatus define a distinct subclass of aldo-
RT keto reductase 7 family proteins.";
RL Biochem. J. 366:847-861(2002).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-2, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
RN [9]
RP X-RAY CRYSTALLOGRAPHY (1.38 ANGSTROMS) IN COMPLEX WITH NADP AND CITRATE,
RP AND SUBUNIT.
RX PubMed=11839745; DOI=10.1074/jbc.m110808200;
RA Kozma E., Brown E., Ellis E.M., Lapthorn A.J.;
RT "The crystal structure of rat liver AKR7A1. A dimeric member of the aldo-
RT keto reductase superfamily.";
RL J. Biol. Chem. 277:16285-16293(2002).
CC -!- FUNCTION: Can reduce the dialdehyde protein-binding form of aflatoxin
CC B1 (AFB1) to the non-binding AFB1 dialcohol. Probably involved in
CC protection of liver against the toxic and carcinogenic effects of AFB1,
CC a potent hepatocarcinogen. {ECO:0000269|PubMed:12071861}.
CC -!- SUBUNIT: Homodimer. Heterodimer with AKR7A2.
CC {ECO:0000269|PubMed:11839745, ECO:0000269|PubMed:12071861}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm.
CC -!- INDUCTION: By the phenolic antioxidant ethoxyquin.
CC -!- MISCELLANEOUS: With succinic semialdehyde or 4-nitrobenzaldehyde as
CC substrate, it exhibits a substantially greater specific activity with
CC NADPH than with NADH Conversely, it has a 3-fold higher activity
CC towards 2-carboxybenzaldehyde with NADH than with NADPH.
CC -!- SIMILARITY: Belongs to the aldo/keto reductase family. Aldo/keto
CC reductase 2 subfamily. {ECO:0000305}.
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DR EMBL; X74673; CAA52740.1; -; mRNA.
DR EMBL; AF045464; AAD02413.1; -; mRNA.
DR EMBL; AY230497; AAO48423.1; -; Genomic_DNA.
DR EMBL; AY230491; AAO48423.1; JOINED; Genomic_DNA.
DR EMBL; AY230492; AAO48423.1; JOINED; Genomic_DNA.
DR EMBL; AY230493; AAO48423.1; JOINED; Genomic_DNA.
DR EMBL; AY230494; AAO48423.1; JOINED; Genomic_DNA.
DR EMBL; AY230495; AAO48423.1; JOINED; Genomic_DNA.
DR EMBL; AY230496; AAO48423.1; JOINED; Genomic_DNA.
DR EMBL; BC078872; AAH78872.2; -; mRNA.
DR EMBL; BC089811; AAH89811.1; -; mRNA.
DR PIR; A48804; A48804.
DR RefSeq; NP_037347.1; NM_013215.1.
DR PDB; 1GVE; X-ray; 1.38 A; A/B=1-327.
DR PDBsum; 1GVE; -.
DR AlphaFoldDB; P38918; -.
DR SMR; P38918; -.
DR STRING; 10116.ENSRNOP00000024160; -.
DR ChEMBL; CHEMBL2697; -.
DR iPTMnet; P38918; -.
DR PhosphoSitePlus; P38918; -.
DR PaxDb; P38918; -.
DR PRIDE; P38918; -.
DR GeneID; 26760; -.
DR KEGG; rno:26760; -.
DR UCSC; RGD:628635; rat.
DR CTD; 22977; -.
DR RGD; 628635; Akr7a3.
DR VEuPathDB; HostDB:ENSRNOG00000017899; -.
DR eggNOG; ENOG502QU2T; Eukaryota.
DR HOGENOM; CLU_023205_1_1_1; -.
DR InParanoid; P38918; -.
DR OMA; TELIPCC; -.
DR OrthoDB; 1226539at2759; -.
DR PhylomeDB; P38918; -.
DR TreeFam; TF329173; -.
DR Reactome; R-RNO-5423646; Aflatoxin activation and detoxification.
DR SABIO-RK; P38918; -.
DR EvolutionaryTrace; P38918; -.
DR PRO; PR:P38918; -.
DR Proteomes; UP000002494; Chromosome 5.
DR Bgee; ENSRNOG00000017899; Expressed in adult mammalian kidney and 18 other tissues.
DR Genevisible; P38918; RN.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; IEA:Ensembl.
DR GO; GO:0005794; C:Golgi apparatus; IEA:Ensembl.
DR GO; GO:0004033; F:aldo-keto reductase (NADP) activity; IDA:RGD.
DR GO; GO:0042802; F:identical protein binding; ISO:RGD.
DR GO; GO:0046223; P:aflatoxin catabolic process; IMP:RGD.
DR GO; GO:0046222; P:aflatoxin metabolic process; IDA:RGD.
DR Gene3D; 3.20.20.100; -; 1.
DR InterPro; IPR020471; AKR.
DR InterPro; IPR023210; NADP_OxRdtase_dom.
DR InterPro; IPR036812; NADP_OxRdtase_dom_sf.
DR Pfam; PF00248; Aldo_ket_red; 1.
DR PRINTS; PR00069; ALDKETRDTASE.
DR SUPFAM; SSF51430; SSF51430; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cytoplasm; Detoxification; Direct protein sequencing; NAD;
KW NADP; Oxidoreductase; Phosphoprotein; Reference proteome.
FT CHAIN 1..327
FT /note="Aflatoxin B1 aldehyde reductase member 3"
FT /id="PRO_0000070374"
FT ACT_SITE 45
FT /note="Proton donor"
FT BINDING 40
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:11839745"
FT BINDING 109
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:11839745"
FT BINDING 139..140
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:11839745"
FT BINDING 165
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:11839745"
FT BINDING 194..204
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:11839745"
FT BINDING 218
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:11839745"
FT BINDING 228
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:11839745"
FT BINDING 231
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:11839745"
FT BINDING 286..294
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:11839745"
FT BINDING 327
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:11839745"
FT SITE 73
FT /note="Lowers pKa of active site Tyr"
FT /evidence="ECO:0000250"
FT MOD_RES 2
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT CONFLICT 126..127
FT /note="QL -> HV (in Ref. 1; CAA52740)"
FT /evidence="ECO:0000305"
FT STRAND 7..11
FT /evidence="ECO:0007829|PDB:1GVE"
FT TURN 16..18
FT /evidence="ECO:0007829|PDB:1GVE"
FT HELIX 21..33
FT /evidence="ECO:0007829|PDB:1GVE"
FT STRAND 38..40
FT /evidence="ECO:0007829|PDB:1GVE"
FT HELIX 45..48
FT /evidence="ECO:0007829|PDB:1GVE"
FT HELIX 49..54
FT /evidence="ECO:0007829|PDB:1GVE"
FT STRAND 68..74
FT /evidence="ECO:0007829|PDB:1GVE"
FT HELIX 84..97
FT /evidence="ECO:0007829|PDB:1GVE"
FT STRAND 103..108
FT /evidence="ECO:0007829|PDB:1GVE"
FT HELIX 117..129
FT /evidence="ECO:0007829|PDB:1GVE"
FT STRAND 132..140
FT /evidence="ECO:0007829|PDB:1GVE"
FT HELIX 143..156
FT /evidence="ECO:0007829|PDB:1GVE"
FT STRAND 161..167
FT /evidence="ECO:0007829|PDB:1GVE"
FT HELIX 174..176
FT /evidence="ECO:0007829|PDB:1GVE"
FT HELIX 179..186
FT /evidence="ECO:0007829|PDB:1GVE"
FT STRAND 189..193
FT /evidence="ECO:0007829|PDB:1GVE"
FT HELIX 197..202
FT /evidence="ECO:0007829|PDB:1GVE"
FT HELIX 207..211
FT /evidence="ECO:0007829|PDB:1GVE"
FT STRAND 216..221
FT /evidence="ECO:0007829|PDB:1GVE"
FT HELIX 225..232
FT /evidence="ECO:0007829|PDB:1GVE"
FT HELIX 235..252
FT /evidence="ECO:0007829|PDB:1GVE"
FT HELIX 259..269
FT /evidence="ECO:0007829|PDB:1GVE"
FT HELIX 275..277
FT /evidence="ECO:0007829|PDB:1GVE"
FT STRAND 280..283
FT /evidence="ECO:0007829|PDB:1GVE"
FT HELIX 288..297
FT /evidence="ECO:0007829|PDB:1GVE"
FT HELIX 305..318
FT /evidence="ECO:0007829|PDB:1GVE"
FT HELIX 319..321
FT /evidence="ECO:0007829|PDB:1GVE"
SQ SEQUENCE 327 AA; 36747 MW; F0C908C014DF672D CRC64;
MSQARPATVL GAMEMGRRMD VTSSSASVRA FLQRGHTEID TAFVYANGQS ETILGDLGLG
LGRSGCKVKI ATKAAPMFGK TLKPADVRFQ LETSLKRLQC PRVDLFYLHF PDHGTPIEET
LQACHQLHQE GKFVELGLSN YVSWEVAEIC TLCKKNGWIM PTVYQGMYNA ITRQVETELF
PCLRHFGLRF YAFNPLAGGL LTGRYKYQDK DGKNPESRFF GNPFSQLYMD RYWKEEHFNG
IALVEKALKT TYGPTAPSMI SAAVRWMYHH SQLKGTQGDA VILGMSSLEQ LEQNLALVEE
GPLEPAVVDA FDQAWNLVAH ECPNYFR
