ARK72_RAT
ID ARK72_RAT Reviewed; 367 AA.
AC Q8CG45; Q6P765; Q8K435; Q9JM82;
DT 15-DEC-2003, integrated into UniProtKB/Swiss-Prot.
DT 15-DEC-2003, sequence version 2.
DT 03-AUG-2022, entry version 137.
DE RecName: Full=Aflatoxin B1 aldehyde reductase member 2;
DE Short=rAFAR2;
DE EC=1.1.1.n11;
DE AltName: Full=Succinic semialdehyde reductase;
DE Short=SSA reductase;
GN Name=Akr7a2; Synonyms=Afar2, Aiar;
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], PROTEIN SEQUENCE OF 4-14 AND 33-44, FUNCTION,
RP SUBUNIT, AND SUBCELLULAR LOCATION.
RC STRAIN=Fischer 344; TISSUE=Liver;
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 11-367.
RC TISSUE=Prostate;
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 [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 11-367.
RX PubMed=12879023; DOI=10.1038/sj.onc.1206684;
RA Praml C., Savelyeva L., Schwab M.;
RT "Aflatoxin B1 aldehyde reductase (AFAR) genes cluster at 1p35-1p36.1 in a
RT region frequently altered in human tumour cells.";
RL Oncogene 22:4765-4773(2003).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 12-367.
RC STRAIN=Sprague-Dawley;
RX PubMed=10965890; DOI=10.1210/endo.141.9.7685;
RA Nishi N., Shoji H., Miyanaka H., Nakamura T.;
RT "Androgen-regulated expression of a novel member of the aldo-keto reductase
RT superfamily in regrowing rat prostate.";
RL Endocrinology 141:3194-3199(2000).
RN [5]
RP PROTEIN SEQUENCE OF 230-244; 259-269 AND 306-317, AND IDENTIFICATION BY
RP MASS SPECTROMETRY.
RC STRAIN=Sprague-Dawley; TISSUE=Spinal cord;
RA Lubec G., Afjehi-Sadat L.;
RL Submitted (NOV-2006) to UniProtKB.
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-263, AND IDENTIFICATION BY
RP MASS 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).
CC -!- FUNCTION: Catalyzes the NADPH-dependent reduction of succinic
CC semialdehyde to gamma-hydroxybutyrate. May have an important role in
CC producing the neuromodulator gamma-hydroxybutyrate (GHB). Has broad
CC substrate specificity. Can reduce the dialdehyde protein-binding form
CC of aflatoxin B1 (AFB1) to the non-binding AFB1 dialcohol. Acts as a 2-
CC carboxybenzaldehyde reductase. {ECO:0000269|PubMed:12071861}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=4-hydroxybutanoate + NADP(+) = H(+) + NADPH + succinate
CC semialdehyde; Xref=Rhea:RHEA:26381, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:16724, ChEBI:CHEBI:57706, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:58349; EC=1.1.1.n11;
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC Note=Has a low KM for succinic semialdehyde.;
CC -!- SUBUNIT: Homodimer. Heterodimer with AKR7A1.
CC {ECO:0000269|PubMed:12071861}.
CC -!- SUBCELLULAR LOCATION: Golgi apparatus, Golgi stack
CC {ECO:0000269|PubMed:12071861}. Cytoplasm {ECO:0000269|PubMed:12071861}.
CC Note=Its association with the Golgi stack may facilitate secretion of
CC GHB.
CC -!- MISCELLANEOUS: With 4-nitrobenzaldehyde as substrate, it exhibits a
CC substantially greater specific activity with NADPH than with NADH.
CC Conversely, it has a 1.8-fold higher activity towards succinic
CC semialdehyde with NADH than with NADPH.
CC -!- SIMILARITY: Belongs to the aldo/keto reductase family. Aldo/keto
CC reductase 2 subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH61816.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=BAA90396.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=CAC81080.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AF503514; AAN03824.1; -; mRNA.
DR EMBL; BC061816; AAH61816.1; ALT_INIT; mRNA.
DR EMBL; AJ271883; CAC81080.1; ALT_INIT; mRNA.
DR EMBL; AB037424; BAA90396.1; ALT_INIT; mRNA.
DR RefSeq; NP_599234.1; NM_134407.1.
DR AlphaFoldDB; Q8CG45; -.
DR SMR; Q8CG45; -.
DR BioGRID; 251255; 1.
DR STRING; 10116.ENSRNOP00000024063; -.
DR iPTMnet; Q8CG45; -.
DR PhosphoSitePlus; Q8CG45; -.
DR jPOST; Q8CG45; -.
DR PaxDb; Q8CG45; -.
DR PRIDE; Q8CG45; -.
DR GeneID; 171445; -.
DR KEGG; rno:171445; -.
DR UCSC; RGD:620311; rat.
DR CTD; 8574; -.
DR RGD; 620311; Akr7a2.
DR eggNOG; ENOG502QU2T; Eukaryota.
DR InParanoid; Q8CG45; -.
DR OrthoDB; 1226539at2759; -.
DR PhylomeDB; Q8CG45; -.
DR TreeFam; TF329173; -.
DR Reactome; R-RNO-5423646; Aflatoxin activation and detoxification.
DR SABIO-RK; Q8CG45; -.
DR PRO; PR:Q8CG45; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0005737; C:cytoplasm; IDA:RGD.
DR GO; GO:0005794; C:Golgi apparatus; IDA:RGD.
DR GO; GO:0005795; C:Golgi stack; IEA:UniProtKB-SubCell.
DR GO; GO:0005635; C:nuclear envelope; IDA:RGD.
DR GO; GO:0004032; F:alditol:NADP+ 1-oxidoreductase activity; IDA:RGD.
DR GO; GO:0004033; F:aldo-keto reductase (NADP) activity; IBA:GO_Central.
DR GO; GO:0019119; F:phenanthrene-9,10-epoxide hydrolase activity; ISO:RGD.
DR GO; GO:0044597; P:daunorubicin metabolic process; ISO:RGD.
DR GO; GO:0044598; P:doxorubicin metabolic process; ISO:RGD.
DR GO; GO:0006629; P:lipid metabolic process; IEA:UniProtKB-KW.
DR Gene3D; 3.20.20.100; -; 1.
DR InterPro; IPR023210; NADP_OxRdtase_dom.
DR InterPro; IPR036812; NADP_OxRdtase_dom_sf.
DR Pfam; PF00248; Aldo_ket_red; 1.
DR SUPFAM; SSF51430; SSF51430; 1.
PE 1: Evidence at protein level;
KW Acetylation; Cytoplasm; Direct protein sequencing; Golgi apparatus;
KW Lipid metabolism; NADP; Oxidoreductase; Phosphoprotein; Reference proteome.
FT CHAIN 1..367
FT /note="Aflatoxin B1 aldehyde reductase member 2"
FT /id="PRO_0000070377"
FT REGION 27..46
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 85
FT /note="Proton donor"
FT /evidence="ECO:0000250"
FT BINDING 80
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 149
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 179..180
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 205
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 234..244
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 258
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 268
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 271
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 326..334
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 367
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT SITE 113
FT /note="Lowers pKa of active site Tyr"
FT /evidence="ECO:0000250"
FT MOD_RES 40
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8CG76"
FT MOD_RES 48
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q8CG76"
FT MOD_RES 136
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q8CG76"
FT MOD_RES 244
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q8CG76"
FT MOD_RES 263
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT CONFLICT 136
FT /note="K -> N (in Ref. 1; AAN03824)"
FT /evidence="ECO:0000305"
FT CONFLICT 295
FT /note="S -> D (in Ref. 1; AAN03824)"
FT /evidence="ECO:0000305"
FT CONFLICT 299..300
FT /note="MT -> ND (in Ref. 3; CAC81080)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 367 AA; 40675 MW; AA27A3FBB454FEC5 CRC64;
MLRAVSRAVS RAAVRCAWRS GPSVARPLAM SRSPAPRAVS GAPLRPGTVL GTMEMGRRMD
ASASAATVRA FLERGLNELD TAFMYCDGQS ESILGSLGLG LGSGDCTVKI ATKANPWDGK
SLKPDSVRSQ LETSLKRLQC PRVDLFYLHA PDHGTPIVET LQACQQLHQE GKFVELGLSN
YASWEVAEIY TLCKSNGWIL PTVYQGMYNA TTRQVETELL PCLRYFGLRF YAYNPLAGGL
LTGKYRYEDK DGKQPEGRFF GNSWSETYRN RFWKEHHFEA IALVEKALKT TYGTSAPSMT
SAALRWMYHH SQLQGTRGDA VILGMSSLEQ LEQNLAATEE GPLEPAVVEA FNQAWNVVAH
ECPNYFR
