ADH4_RAT
ID ADH4_RAT Reviewed; 377 AA.
AC Q64563;
DT 29-MAR-2004, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 132.
DE RecName: Full=All-trans-retinol dehydrogenase [NAD(+)] ADH4 {ECO:0000305};
DE EC=1.1.1.105 {ECO:0000250|UniProtKB:P08319};
DE AltName: Full=ADH2;
DE AltName: Full=Alcohol dehydrogenase 4;
DE AltName: Full=Alcohol dehydrogenase class II;
DE Short=Alcohol dehydrogenase II;
GN Name=Adh4 {ECO:0000312|RGD:71028};
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=Sprague-Dawley; TISSUE=Liver;
RX PubMed=7635195; DOI=10.1016/0014-5793(95)00707-g;
RA Hoeoeg J.-O.;
RT "Cloning and characterization of a novel rat alcohol dehydrogenase of class
RT II type.";
RL FEBS Lett. 368:445-448(1995).
CC -!- FUNCTION: Catalyzes the NAD-dependent oxidation of either all-trans-
CC retinol or 9-cis-retinol (By similarity). Also oxidizes long chain
CC omega-hydroxy fatty acids, such as 20-HETE, producing both the
CC intermediate aldehyde, 20-oxoarachidonate and the end product, a
CC dicarboxylic acid, (5Z,8Z,11Z,14Z)-eicosatetraenedioate (By
CC similarity). Also catalyzes the reduction of benzoquinones (By
CC similarity). {ECO:0000250|UniProtKB:P08319,
CC ECO:0000250|UniProtKB:Q9QYY9}.
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:P08319};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:21285;
CC Evidence={ECO:0000250|UniProtKB:P08319};
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:P08319};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:42053;
CC Evidence={ECO:0000250|UniProtKB:P08319};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=20-oxo-(5Z,8Z,11Z,14Z)-eicosatetraenoate + H2O + NAD(+) =
CC (5Z,8Z,11Z,14Z)-eicosatetraenedioate + 2 H(+) + NADH;
CC Xref=Rhea:RHEA:39803, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:76645,
CC ChEBI:CHEBI:76647; Evidence={ECO:0000250|UniProtKB:Q9QYY9};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39804;
CC Evidence={ECO:0000250|UniProtKB:Q9QYY9};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=20-hydroxy-(5Z,8Z,11Z,14Z)-eicosatetraenoate + NAD(+) = 20-
CC oxo-(5Z,8Z,11Z,14Z)-eicosatetraenoate + H(+) + NADH;
CC Xref=Rhea:RHEA:39799, ChEBI:CHEBI:15378, ChEBI:CHEBI:57540,
CC ChEBI:CHEBI:57945, ChEBI:CHEBI:76624, ChEBI:CHEBI:76645;
CC Evidence={ECO:0000250|UniProtKB:Q9QYY9};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39800;
CC Evidence={ECO:0000250|UniProtKB:Q9QYY9};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1,4-benzoquinone + H(+) + NADH = hydroquinone + NAD(+);
CC Xref=Rhea:RHEA:60660, ChEBI:CHEBI:15378, ChEBI:CHEBI:16509,
CC ChEBI:CHEBI:17594, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945;
CC Evidence={ECO:0000250|UniProtKB:P08319};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:60661;
CC Evidence={ECO:0000250|UniProtKB:P08319};
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: Oxidation of 20-HETE is inhibited by low
CC concentrations of N-heptylformamide. Oxidation of 20-HETE is a
CC decreased by 55-65% by either all-trans-retinol or all-trans-retinoic
CC acid. Strongly inhibited by omega-hydroxy fatty acids.
CC {ECO:0000250|UniProtKB:Q9QYY9}.
CC -!- SUBUNIT: Dimer.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Liver specific.
CC -!- MISCELLANEOUS: Has much lower enzymatic activity towards alcohols and
CC aldehydes compared to human class II ADH. Strongly inhibited by omega-
CC hydroxy fatty acids.
CC -!- SIMILARITY: Belongs to the zinc-containing alcohol dehydrogenase
CC family. Class-II subfamily. {ECO:0000305}.
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DR EMBL; X90710; CAA62241.1; -; mRNA.
DR PIR; S66286; S66286.
DR AlphaFoldDB; Q64563; -.
DR SMR; Q64563; -.
DR STRING; 10116.ENSRNOP00000016891; -.
DR CarbonylDB; Q64563; -.
DR PaxDb; Q64563; -.
DR PRIDE; Q64563; -.
DR RGD; 71028; Adh4.
DR eggNOG; KOG0022; Eukaryota.
DR InParanoid; Q64563; -.
DR Reactome; R-RNO-5365859; RA biosynthesis pathway.
DR Reactome; R-RNO-71384; Ethanol oxidation.
DR PRO; PR:Q64563; -.
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:0004032; F:alditol:NADP+ 1-oxidoreductase activity; ISO:RGD.
DR GO; GO:0005503; F:all-trans retinal binding; ISO:RGD.
DR GO; GO:0019115; F:benzaldehyde dehydrogenase [NAD(P)+] activity; ISO:RGD.
DR GO; GO:0035276; F:ethanol binding; IDA:RGD.
DR GO; GO:0051287; F:NAD binding; IDA:RGD.
DR GO; GO:0004745; F:NAD-retinol dehydrogenase activity; ISS:UniProtKB.
DR GO; GO:0003960; F:NADPH:quinone reductase activity; ISO:RGD.
DR GO; GO:0016620; F:oxidoreductase activity, acting on the aldehyde or oxo group of donors, NAD or NADP as acceptor; ISO:RGD.
DR GO; GO:0019841; F:retinol binding; ISO:RGD.
DR GO; GO:0051903; F:S-(hydroxymethyl)glutathione dehydrogenase activity; IBA:GO_Central.
DR GO; GO:0008270; F:zinc ion binding; ISO:RGD.
DR GO; GO:0007568; P:aging; IEP:RGD.
DR GO; GO:0046164; P:alcohol catabolic process; ISO:RGD.
DR GO; GO:0006066; P:alcohol metabolic process; ISO:RGD.
DR GO; GO:0006081; P:cellular aldehyde metabolic process; ISO:RGD.
DR GO; GO:0006067; P:ethanol metabolic process; ISO:RGD.
DR GO; GO:0006069; P:ethanol oxidation; IDA:RGD.
DR GO; GO:0010430; P:fatty acid omega-oxidation; ISS:UniProtKB.
DR GO; GO:0046294; P:formaldehyde catabolic process; IBA:GO_Central.
DR GO; GO:0042698; P:ovulation cycle; IEP:RGD.
DR GO; GO:1901661; P:quinone metabolic process; ISO:RGD.
DR GO; GO:0001523; P:retinoid metabolic process; ISO:RGD.
DR GO; GO:0042572; P:retinol metabolic process; ISS:UniProtKB.
DR InterPro; IPR013149; ADH-like_C.
DR InterPro; IPR013154; ADH_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 InterPro; IPR028632; Zinc_ADH_II.
DR PANTHER; PTHR43880:SF14; PTHR43880:SF14; 1.
DR Pfam; PF08240; ADH_N; 1.
DR Pfam; PF00107; ADH_zinc_N; 1.
DR SMART; SM00829; PKS_ER; 1.
DR SUPFAM; SSF50129; SSF50129; 2.
DR SUPFAM; SSF51735; SSF51735; 1.
DR PROSITE; PS00059; ADH_ZINC; 1.
PE 2: Evidence at transcript level;
KW Cytoplasm; Lipid metabolism; Metal-binding; NAD; Oxidoreductase;
KW Reference proteome; Zinc.
FT CHAIN 1..377
FT /note="All-trans-retinol dehydrogenase [NAD(+)] ADH4"
FT /id="PRO_0000160683"
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 48..49
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
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 179
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250"
FT BINDING 204..209
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 233
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250"
FT BINDING 297..299
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250"
FT BINDING 320..322
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250"
FT BINDING 372
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250"
SQ SEQUENCE 377 AA; 40277 MW; 9944E04A86868CBF CRC64;
MGTQGKVITC KAAIAWKTDS PLCIEEIEVS PPKAHEVRIK VIATCVCPTD INATNPKKKA
LFPVVLGHEC AGIVESVGPG VTNFKPGDKV IPFFAPQCKK CKLCLSPLTN LCGKLRNFKY
PTIDQELMED RTSRFTSKER SIYHFMGVSS FSQYTVVSEA NLARVDDEAN LERVCLIGCG
FTSGYGAAIN TAKVTPGSAC AVFGLGCVGL SAVIGCKIAG ASRIIAIDIN SEKFPKAKAL
GATDCLNPRD LDKPVQDVIT ELTGGGVDFS LDCAGTAQTL KAAVDCTVVG WGSCTVVGAK
VDEMNISTVD MILGRSVKGT FFGGWKSVDS VPNLVTDYKN KKFDLDLLVT HALPFDKIND
AIDLMNQGKS IRTILTF
