ID ADH7_RAT Reviewed; 374 AA.
AC P41682; O55146;
DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT 15-JUL-1999, sequence version 2.
DT 08-NOV-2023, entry version 163.
DE RecName: Full=All-trans-retinol dehydrogenase [NAD(+)] ADH7 {ECO:0000305};
DE EC=1.1.1.105 {ECO:0000250|UniProtKB:P40394};
DE AltName: Full=Alcohol dehydrogenase class 4 mu/sigma chain;
DE EC=1.1.1.1 {ECO:0000250|UniProtKB:P40394};
DE AltName: Full=Alcohol dehydrogenase class IV mu/sigma chain;
DE AltName: Full=Omega-hydroxydecanoate dehydrogenase ADH7 {ECO:0000250|UniProtKB:P40394};
DE EC=1.1.1.66 {ECO:0000250|UniProtKB:P40394};
GN Name=Adh7;
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 PROTEIN SEQUENCE, AND ACETYLATION AT MET-1.
RC STRAIN=Sprague-Dawley; TISSUE=Stomach;
RX PubMed=8127901; DOI=10.1073/pnas.91.5.1893;
RA Pares X., Cederlund E., Moreno A., Hjelmqvist L., Farres J., Joernvall H.;
RT "Mammalian class IV alcohol dehydrogenase (stomach alcohol dehydrogenase):
RT structure, origin, and correlation with enzymology.";
RL Proc. Natl. Acad. Sci. U.S.A. 91:1893-1897(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Sprague-Dawley; TISSUE=Lung;
RX PubMed=10829036; DOI=10.1074/jbc.m910040199;
RA Crosas B., Allali-Hassani A., Martinez S.E., Martras S., Persson B.,
RA Jornvall H., Pares X., Farres J.;
RT "Molecular basis for differential substrate specificity in class IV alcohol
RT dehydrogenases: a conserved function in retinoid metabolism but not in
RT ethanol oxidation.";
RL J. Biol. Chem. 275:25180-25187(2000).
RN [3]
RP ACTIVITY REGULATION.
RX PubMed=9600267; DOI=10.1016/s0014-5793(98)00374-3;
RA Allali-Hassani A., Peralba J.M., Martras S., Farres J., Pares X.;
RT "Retinoids, omega-hydroxyfatty acids and cytotoxic aldehydes as
RT physiological substrates, and H2-receptor antagonists as pharmacological
RT inhibitors, of human class IV alcohol dehydrogenase.";
RL FEBS Lett. 426:362-366(1998).
CC -!- FUNCTION: Catalyzes the NAD-dependent oxidation of all-trans-retinol,
CC alcohol, aldehyde and omega-hydroxy fatty acids and their derivatives.
CC Oxidizes preferentially all trans-retinol, all-trans-4-hydroxyretinol,
CC 9-cis-retinol, 2-hexenol, and long chain omega-hydroxy fatty acids such
CC as juniperic acid. In vitro can also catalyzes the NADH-dependent
CC reduction of all-trans-retinal and aldehydes and their derivatives.
CC Reduces preferentially all trans-retinal, all-trans-4-oxoretinal and
CC hexanal. Catalyzes in the oxidative direction with higher efficiency.
CC Therefore may participate in retinoid metabolism, fatty acid omega-
CC oxidation, and elimination of cytotoxic aldehydes produced by lipid
CC peroxidation. {ECO:0000250|UniProtKB:P40394}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a primary alcohol + NAD(+) = an aldehyde + H(+) + NADH;
CC Xref=Rhea:RHEA:10736, ChEBI:CHEBI:15378, ChEBI:CHEBI:15734,
CC ChEBI:CHEBI:17478, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=1.1.1.1;
CC Evidence={ECO:0000250|UniProtKB:P40394};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:10737;
CC Evidence={ECO:0000250|UniProtKB:P40394};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:10738;
CC Evidence={ECO:0000250|UniProtKB:P40394};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=10-hydroxydecanoate + NAD(+) = 10-oxodecanoate + H(+) + NADH;
CC Xref=Rhea:RHEA:20880, ChEBI:CHEBI:11305, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:58022; EC=1.1.1.66;
CC Evidence={ECO:0000250|UniProtKB:P40394};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:20881;
CC Evidence={ECO:0000250|UniProtKB:P40394};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=all-trans-retinol + NAD(+) = all-trans-retinal + H(+) + NADH;
CC Xref=Rhea:RHEA:21284, ChEBI:CHEBI:15378, ChEBI:CHEBI:17336,
CC ChEBI:CHEBI:17898, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945;
CC EC=1.1.1.105; Evidence={ECO:0000250|UniProtKB:P40394};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:21285;
CC Evidence={ECO:0000250|UniProtKB:P40394};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=9-cis-retinol + NAD(+) = 9-cis-retinal + H(+) + NADH;
CC Xref=Rhea:RHEA:42052, ChEBI:CHEBI:15378, ChEBI:CHEBI:57540,
CC ChEBI:CHEBI:57945, ChEBI:CHEBI:78272, ChEBI:CHEBI:78273;
CC Evidence={ECO:0000250|UniProtKB:P40394};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:42053;
CC Evidence={ECO:0000250|UniProtKB:P40394};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=all-trans-3,4-didehydroretinol + NAD(+) = all-trans-3,4-
CC didehydroretinal + H(+) + NADH; Xref=Rhea:RHEA:55940,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:28537, ChEBI:CHEBI:57540,
CC ChEBI:CHEBI:57945, ChEBI:CHEBI:132246;
CC Evidence={ECO:0000250|UniProtKB:P40394};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:55941;
CC Evidence={ECO:0000250|UniProtKB:P40394};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=all-trans-4-hydroxyretinol + NAD(+) = all-trans-4-
CC hydroxyretinal + H(+) + NADH; Xref=Rhea:RHEA:55936,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945,
CC ChEBI:CHEBI:132259, ChEBI:CHEBI:139346;
CC Evidence={ECO:0000250|UniProtKB:P40394};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:55937;
CC Evidence={ECO:0000250|UniProtKB:P40394};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=all-trans-4-oxoretinol + NAD(+) = all-trans-4-oxoretinal +
CC H(+) + NADH; Xref=Rhea:RHEA:60632, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:44597, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945,
CC ChEBI:CHEBI:139347; Evidence={ECO:0000250|UniProtKB:P40394};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:60634;
CC Evidence={ECO:0000250|UniProtKB:P40394};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=12-hydroxydodecanoate + NAD(+) = 12-oxododecanoate + H(+) +
CC NADH; Xref=Rhea:RHEA:60980, ChEBI:CHEBI:15378, ChEBI:CHEBI:36204,
CC ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:144067;
CC Evidence={ECO:0000250|UniProtKB:P40394};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:60981;
CC Evidence={ECO:0000250|UniProtKB:P40394};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=16-hydroxyhexadecanoate + NAD(+) = 16-oxohexadecanoate + H(+)
CC + NADH; Xref=Rhea:RHEA:60984, ChEBI:CHEBI:15378, ChEBI:CHEBI:55329,
CC ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:144068;
CC Evidence={ECO:0000250|UniProtKB:P40394};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:60985;
CC Evidence={ECO:0000250|UniProtKB:P40394};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=hexan-1-ol + NAD(+) = H(+) + hexanal + NADH;
CC Xref=Rhea:RHEA:60972, ChEBI:CHEBI:15378, ChEBI:CHEBI:57540,
CC ChEBI:CHEBI:57945, ChEBI:CHEBI:87393, ChEBI:CHEBI:88528;
CC Evidence={ECO:0000250|UniProtKB:P40394};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:60973;
CC Evidence={ECO:0000250|UniProtKB:P40394};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:60974;
CC Evidence={ECO:0000250|UniProtKB:P40394};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(E)-hex-2-en-1-ol + NAD(+) = (E)-hex-2-enal + H(+) + NADH;
CC Xref=Rhea:RHEA:60988, ChEBI:CHEBI:15378, ChEBI:CHEBI:28913,
CC ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:141205;
CC Evidence={ECO:0000250|UniProtKB:P40394};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:60989;
CC Evidence={ECO:0000250|UniProtKB:P40394};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:60990;
CC Evidence={ECO:0000250|UniProtKB:P40394};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(E)-4-hydroxynon-2-en-1-ol + NAD(+) = (E)-4-hydroxynon-2-enal
CC + H(+) + NADH; Xref=Rhea:RHEA:60976, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:58968,
CC ChEBI:CHEBI:142617; Evidence={ECO:0000250|UniProtKB:P40394};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:60978;
CC Evidence={ECO:0000250|UniProtKB:P40394};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000250};
CC Note=Binds 2 Zn(2+) ions per subunit. {ECO:0000250};
CC -!- ACTIVITY REGULATION: Retinol oxidation is inhibited by the detergent
CC Tween 80. Ethanol inhibits both all-trans-retinol and 9-cis-retinol
CC oxidation. 13-cis-retinol is an effective competitive inhibitor of the
CC 9-cis-retinol oxidation. All-trans-retinoic acid is a powerful
CC inhibitor of all-trans-retinol oxidation. 13-cis-retinoic acid is a
CC powerful inhibitor of all-trans-retinol oxidation (By similarity).
CC Cimetidine and ranitidine inhibited ethanol oxidation (PubMed:9600267).
CC {ECO:0000250|UniProtKB:P40394, ECO:0000269|PubMed:9600267}.
CC -!- SUBUNIT: Homodimer.
CC -!- SUBCELLULAR LOCATION: Cytoplasm.
CC -!- TISSUE SPECIFICITY: Preferentially expressed in stomach.
CC -!- SIMILARITY: Belongs to the zinc-containing alcohol dehydrogenase
CC family. Class-IV subfamily. {ECO:0000305}.
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DR EMBL; X98746; CAA67297.1; -; mRNA.
DR PIR; A53142; A53142.
DR RefSeq; NP_599156.1; NM_134329.1.
DR AlphaFoldDB; P41682; -.
DR SMR; P41682; -.
DR STRING; 10116.ENSRNOP00000015870; -.
DR iPTMnet; P41682; -.
DR PhosphoSitePlus; P41682; -.
DR jPOST; P41682; -.
DR PaxDb; 10116-ENSRNOP00000015870; -.
DR GeneID; 171178; -.
DR KEGG; rno:171178; -.
DR AGR; RGD:621638; -.
DR CTD; 131; -.
DR RGD; 621638; Adh7.
DR eggNOG; KOG0022; Eukaryota.
DR InParanoid; P41682; -.
DR OrthoDB; 1077476at2759; -.
DR PhylomeDB; P41682; -.
DR Reactome; R-RNO-71384; Ethanol oxidation.
DR PRO; PR:P41682; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0004022; F:alcohol dehydrogenase (NAD+) activity; IDA:RGD.
DR GO; GO:0004024; F:alcohol dehydrogenase activity, zinc-dependent; ISO:RGD.
DR GO; GO:0004031; F:aldehyde oxidase activity; ISO:RGD.
DR GO; GO:0035276; F:ethanol binding; IDA:RGD.
DR GO; GO:0042802; F:identical protein binding; IPI:RGD.
DR GO; GO:0051287; F:NAD binding; IDA:RGD.
DR GO; GO:0004745; F:NAD-retinol dehydrogenase activity; ISS:UniProtKB.
DR GO; GO:0050153; F:omega-hydroxydecanoate dehydrogenase activity; IEA:UniProtKB-EC.
DR GO; GO:0048019; F:receptor antagonist activity; ISO:RGD.
DR GO; GO:0019841; F:retinol binding; IDA:RGD.
DR GO; GO:0008270; F:zinc ion binding; IDA:RGD.
DR GO; GO:0006068; P:ethanol catabolic process; ISO:RGD.
DR GO; GO:0006067; P:ethanol metabolic process; IDA:RGD.
DR GO; GO:0006069; P:ethanol oxidation; ISO:RGD.
DR GO; GO:0010430; P:fatty acid omega-oxidation; ISO:RGD.
DR GO; GO:0009617; P:response to bacterium; ISO:RGD.
DR GO; GO:0045471; P:response to ethanol; ISO:RGD.
DR GO; GO:0042573; P:retinoic acid metabolic process; ISO:RGD.
DR GO; GO:0001523; P:retinoid metabolic process; ISO:RGD.
DR GO; GO:0042572; P:retinol metabolic process; IDA:RGD.
DR CDD; cd08299; alcohol_DH_class_I_II_IV; 1.
DR Gene3D; 3.90.180.10; Medium-chain alcohol dehydrogenases, catalytic domain; 1.
DR Gene3D; 3.40.50.720; NAD(P)-binding Rossmann-like Domain; 1.
DR InterPro; IPR013149; ADH-like_C.
DR InterPro; IPR013154; ADH-like_N.
DR InterPro; IPR002328; ADH_Zn_CS.
DR InterPro; IPR011032; GroES-like_sf.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR020843; PKS_ER.
DR PANTHER; PTHR43880; ALCOHOL DEHYDROGENASE; 1.
DR PANTHER; PTHR43880:SF2; ALL-TRANS-RETINOL DEHYDROGENASE [NAD(+)] ADH7; 1.
DR Pfam; PF08240; ADH_N; 1.
DR Pfam; PF00107; ADH_zinc_N; 1.
DR SMART; SM00829; PKS_ER; 1.
DR SUPFAM; SSF50129; GroES-like; 2.
DR SUPFAM; SSF51735; NAD(P)-binding Rossmann-fold domains; 1.
DR PROSITE; PS00059; ADH_ZINC; 1.
PE 1: Evidence at protein level;
KW Acetylation; Cytoplasm; Direct protein sequencing; Lipid metabolism;
KW Metal-binding; NAD; Oxidoreductase; Reference proteome; Zinc.
FT CHAIN 1..374
FT /note="All-trans-retinol dehydrogenase [NAD(+)] ADH7"
FT /id="PRO_0000160696"
FT BINDING 47
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250"
FT BINDING 68
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250"
FT BINDING 98
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 101
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 104
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 112
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 174
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250"
FT BINDING 199..204
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250"
FT BINDING 223
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250"
FT BINDING 228
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250"
FT BINDING 292..294
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250"
FT BINDING 369
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0000305|PubMed:8127901"
FT CONFLICT 1..4
FT /note="MDTA -> SNRV (in Ref. 1; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 109
FT /note="G -> E (in Ref. 2; CAA67297)"
FT /evidence="ECO:0000305"
FT CONFLICT 208
FT /note="V -> I (in Ref. 1; AA sequence)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 374 AA; 40105 MW; DD745E7FCB01E452 CRC64;
MDTAGKVIKC KAAVLWGTNQ PFSIEDIEVA PPKAKEVRVK ILATGICGTD DHVIKGTMVS
KFPVIVGHEA VGIVESVGEE VTTVRPGDKV IPLFLPQCRE CNPCRNPEGN LCIRSDLTGR
GVLADGTTRF TCKGKPVQHF MNTSTFTEYT VLDESSVAKI DAEAPPEKAC LIGCGFSTGY
GAAVKTAKVS PGSTCAVFGL GGVGLSVVMG CKAAGASRII GIDINKDKFQ KALDVGATEC
INPRDFTKPI SEVLSDMTGN TVQYTFEVIG RLETMVDALS SCHMNYGTSV VVGAPPSAKM
LSYDPMLLFT GRTWKGCVFG GWKSRDDVPK LVTEFLEKKF DLGQLITHTL PFHNISEGFE
LLYSGQSIRT VLTF
//
