ID   AK1CD_MESAU             Reviewed;         322 AA.
AC   P82809;
DT   17-JAN-2003, integrated into UniProtKB/Swiss-Prot.
DT   01-MAR-2001, sequence version 1.
DT   02-SEP-2026, entry version 84.
DE   RecName: Full=Aldo-keto reductase family 1 member C13;
DE            EC=1.1.1.-;
DE   AltName: Full=Morphine 6-dehydrogenase;
DE            EC=1.1.1.218;
GN   Name=AKR1C13;
OS   Mesocricetus auratus (Golden hamster).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea;
OC   Cricetidae; Cricetinae; Mesocricetus.
OX   NCBI_TaxID=10036;
RN   [1]
RP   PROTEIN SEQUENCE, AND CHARACTERIZATION.
RC   TISSUE=Liver;
RX   PubMed=10666297; DOI=10.1006/abbi.1999.1450;
RA   Todaka T., Yamano S., Toki S.;
RT   "Purification and characterization of NAD-dependent morphine 6-
RT   dehydrogenase from hamster liver cytosol, a new member of the aldo-keto
RT   reductase superfamily.";
RL   Arch. Biochem. Biophys. 374:189-197(2000).
CC   -!- FUNCTION: Catalyzes the dehydrogenation of morphine to morphinone. The
CC       enzyme also exhibits significant activity for a variety of cyclic and
CC       alicyclic alcohols. In addition to xenobiotics, the enzyme catalyzes
CC       the dehydrogenation of 17-beta-hydroxysteroids with much higher
CC       affinities than morphine. Uses both NAD and NADP, but the activity is
CC       much greater with NAD than with NADP.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=morphine + NAD(+) = morphinone + NADH + H(+);
CC         Xref=Rhea:RHEA:14317, ChEBI:CHEBI:15378, ChEBI:CHEBI:57540,
CC         ChEBI:CHEBI:57728, ChEBI:CHEBI:57945, ChEBI:CHEBI:58097;
CC         EC=1.1.1.218;
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=morphine + NADP(+) = morphinone + NADPH + H(+);
CC         Xref=Rhea:RHEA:14321, ChEBI:CHEBI:15378, ChEBI:CHEBI:57728,
CC         ChEBI:CHEBI:57783, ChEBI:CHEBI:58097, ChEBI:CHEBI:58349;
CC         EC=1.1.1.218;
CC   -!- ACTIVITY REGULATION: Strongly inhibited by sulfhydryl reagents and
CC       ketamine, but not by pyrazole, barbital and indomethacine.
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       pH dependence:
CC         Optimum pH is 9.3 with NAD as the cofactor.;
CC   -!- SUBUNIT: Monomer.
CC   -!- PTM: The N-terminus is blocked.
CC   -!- SIMILARITY: Belongs to the aldo/keto reductase family. {ECO:0000305}.
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DR   STRING; 10036.ENSMAUP00000013732; -.
DR   eggNOG; KOG1577; Eukaryota.
DR   Proteomes; UP000886700; Unplaced.
DR   GO; GO:0050109; F:morphine 6-dehydrogenase activity; IEA:UniProtKB-EC.
DR   CDD; cd19108; AKR_AKR1C1-35; 1.
DR   FunFam; 3.20.20.100:FF:000003; Aldo-keto reductase family 1 member C3; 1.
DR   Gene3D; 3.20.20.100; NADP-dependent oxidoreductase domain; 1.
DR   InterPro; IPR020471; AKR.
DR   InterPro; IPR044482; AKR1C.
DR   InterPro; IPR018170; Aldo/ket_reductase_CS.
DR   InterPro; IPR036812; NAD(P)_OxRdtase_dom_sf.
DR   InterPro; IPR023210; NADP_OxRdtase_dom.
DR   PANTHER; PTHR11732; ALDO/KETO REDUCTASE; 1.
DR   Pfam; PF00248; Aldo_ket_red; 1.
DR   PIRSF; PIRSF000097; AKR; 1.
DR   PRINTS; PR00069; ALDKETRDTASE.
DR   SUPFAM; SSF51430; NAD(P)-linked oxidoreductase; 1.
DR   PROSITE; PS00798; ALDOKETO_REDUCTASE_1; 1.
DR   PROSITE; PS00062; ALDOKETO_REDUCTASE_2; 1.
PE   1: Evidence at protein level;
KW   Alkaloid metabolism; Direct protein sequencing; NAD; NADP; Oxidoreductase;
KW   Reference proteome.
FT   CHAIN           1..322
FT                   /note="Aldo-keto reductase family 1 member C13"
FT                   /id="PRO_0000124643"
FT   ACT_SITE        55
FT                   /note="Proton donor"
FT                   /evidence="ECO:0000250"
FT   BINDING         20..24
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /evidence="ECO:0000250"
FT   BINDING         50
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /evidence="ECO:0000250"
FT   BINDING         117
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
FT   BINDING         166..167
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /evidence="ECO:0000250"
FT   BINDING         190
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /evidence="ECO:0000250"
FT   BINDING         216..224
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /evidence="ECO:0000250"
FT   BINDING         270..280
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /evidence="ECO:0000250"
FT   SITE            84
FT                   /note="Lowers pKa of active site Tyr"
FT                   /evidence="ECO:0000250"
SQ   SEQUENCE   322 AA;  36507 MW;  0CFC67A8E37D2685 CRC64;
     XXXXXXXXXX XDGHCIPALG FGTYKPIEVP KSKAMEAANL AIGVGYRHID TAYAYQIEEE
     IGQAIQSNIK AGIVKREDMF ITTKLWCTCF QPELVRPSLE KXXXKLQLEH VDLFIMHYPV
     PMKAGDNDFP LDEQGKLLLD TVDFCATWEA LEKXXDAGLV KSIGVSNFNM RQLERILNKP
     GLKYKPVCNQ VECHVYNNQS KLLDYCKSKD IVLVAFGALG TQRYKEWVDQ DSPVLLNDPV
     LCGGAKXXXR SPALIALRYL VQRGVVPLAQ SFYESEMKEN LQVFEFQLSP EDMKILDGLN
     KNFRYLPAQF FADHPEYPFS EE
//