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 02-SEP-2026, entry version 171. 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 catalyze 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 + NADH + H(+); 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 + NADH + H(+); 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 + NADH + H(+); 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 + NADH + H(+); 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 + NADH + H(+); 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 + NADH + H(+); 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 NADH + H(+); 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 + NADH + CC H(+); 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 + NADH CC + H(+); 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(+) = hexanal + NADH + H(+); 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 + NADH + H(+); 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 + NADH + H(+); 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}. 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; X98746; CAA67297.1; -; mRNA. DR PIR; A53142; A53142. DR RefSeq; NP_599156.2; NM_134329.2. DR AlphaFoldDB; P41682; -. DR SMR; P41682; -. DR FunCoup; P41682; 132. DR STRING; 10116.ENSRNOP00000015870; -. DR iPTMnet; P41682; -. DR PhosphoSitePlus; 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 PhylomeDB; P41682; -. DR Reactome; R-RNO-211935; Fatty acids. DR Reactome; R-RNO-71384; Ethanol oxidation. DR PRO; PR:P41682; -. DR Proteomes; UP000002494; Unplaced. DR GO; GO:0005829; C:cytosol; ISO:RGD. DR GO; GO:0004022; F:alcohol dehydrogenase (NAD+) activity; IDA:RGD. DR GO; GO:0004031; F:aldehyde oxidase activity; ISO:RGD. DR GO; GO:0004745; F:all-trans-retinol dehydrogenase (NAD+) activity; ISS:UniProtKB. 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:0050153; F:omega-hydroxydecanoate dehydrogenase activity; ISS:UniProtKB. 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: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 FunFam; 3.90.180.10:FF:000007; Alcohol dehydrogenase 6; 1. DR FunFam; 3.40.50.720:FF:001857; Alcohol dehydrogenase class 4 mu/sigma chain; 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; IPR020843; ER. DR InterPro; IPR011032; GroES-like_sf. DR InterPro; IPR036291; NAD(P)-bd_dom_sf. 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 //