ADHX_RAT
ID ADHX_RAT Reviewed; 374 AA.
AC P12711; Q5XIF8;
DT 01-OCT-1989, integrated into UniProtKB/Swiss-Prot.
DT 20-MAR-2007, sequence version 2.
DT 03-AUG-2022, entry version 162.
DE RecName: Full=Alcohol dehydrogenase class-3 {ECO:0000305};
DE EC=1.1.1.1 {ECO:0000250|UniProtKB:P11766};
DE AltName: Full=Alcohol dehydrogenase 2;
DE AltName: Full=Alcohol dehydrogenase 5;
DE AltName: Full=Alcohol dehydrogenase B2;
DE Short=ADH-B2;
DE AltName: Full=Alcohol dehydrogenase class-III;
DE AltName: Full=Glutathione-dependent formaldehyde dehydrogenase;
DE Short=FALDH;
DE Short=FDH;
DE Short=GSH-FDH;
DE EC=1.1.1.-;
DE AltName: Full=S-(hydroxymethyl)glutathione dehydrogenase;
DE EC=1.1.1.284 {ECO:0000250|UniProtKB:P11766};
GN Name=Adh5 {ECO:0000312|RGD:2292706}; Synonyms=Adh-2, Adh2;
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 [LARGE SCALE MRNA].
RC TISSUE=Heart;
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 [2]
RP PROTEIN SEQUENCE OF 2-374.
RC TISSUE=Liver;
RX PubMed=3278908; DOI=10.1111/j.1432-1033.1988.tb13857.x;
RA Julia P., Pares X., Joernvall H.;
RT "Rat liver alcohol dehydrogenase of class III. Primary structure,
RT functional consequences and relationships to other alcohol
RT dehydrogenases.";
RL Eur. J. Biochem. 172:73-83(1988).
RN [3]
RP PROTEIN SEQUENCE OF 2-7, AND ACETYLATION AT ALA-2.
RX PubMed=3653405; DOI=10.1016/0014-5793(87)80199-0;
RA Fairwell T., Julia P., Kaiser R., Holmquist B., Pares X., Vallee B.L.,
RA Joernvall H.;
RT "Acetylated N-terminal structures of class III alcohol dehydrogenases.
RT Differences among the three enzyme classes.";
RL FEBS Lett. 222:99-103(1987).
RN [4]
RP 3D-STRUCTURE MODELING.
RX PubMed=1888714; DOI=10.1016/0141-8130(91)90051-u;
RA Lapatto R.;
RT "Model for the structure of formaldehyde dehydrogenase based on alcohol
RT dehydrogenase.";
RL Int. J. Biol. Macromol. 13:73-76(1991).
CC -!- FUNCTION: Catalyzes the oxidation of long-chain primary alcohols and
CC the oxidation of S-(hydroxymethyl) glutathione. Also oxidizes long
CC chain 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. Class-III ADH
CC is remarkably ineffective in oxidizing ethanol.
CC {ECO:0000250|UniProtKB:P11766}.
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:P11766};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a secondary alcohol + NAD(+) = a ketone + H(+) + NADH;
CC Xref=Rhea:RHEA:10740, ChEBI:CHEBI:15378, ChEBI:CHEBI:17087,
CC ChEBI:CHEBI:35681, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=1.1.1.1;
CC Evidence={ECO:0000250|UniProtKB:P11766};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=NADP(+) + S-(hydroxymethyl)glutathione = H(+) + NADPH + S-
CC formylglutathione; Xref=Rhea:RHEA:19981, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:57688, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349,
CC ChEBI:CHEBI:58758; EC=1.1.1.284;
CC Evidence={ECO:0000250|UniProtKB:P11766};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=NAD(+) + S-(hydroxymethyl)glutathione = H(+) + NADH + S-
CC formylglutathione; Xref=Rhea:RHEA:19985, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:57540, ChEBI:CHEBI:57688, ChEBI:CHEBI:57945,
CC ChEBI:CHEBI:58758; EC=1.1.1.284;
CC Evidence={ECO:0000250|UniProtKB:P11766};
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:P11766};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39804;
CC Evidence={ECO:0000250|UniProtKB:P11766};
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:P11766};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39800;
CC Evidence={ECO:0000250|UniProtKB:P11766};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000250|UniProtKB:P11766};
CC Note=Binds 2 Zn(2+) ions per subunit. {ECO:0000250|UniProtKB:P11766};
CC -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:P11766}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the zinc-containing alcohol dehydrogenase
CC family. Class-III subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH83724.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; BC083724; AAH83724.1; ALT_INIT; mRNA.
DR PIR; S00331; DERTA.
DR RefSeq; NP_001119592.1; NM_001126120.1.
DR AlphaFoldDB; P12711; -.
DR SMR; P12711; -.
DR STRING; 10116.ENSRNOP00000017252; -.
DR BindingDB; P12711; -.
DR ChEMBL; CHEMBL4295715; -.
DR iPTMnet; P12711; -.
DR PhosphoSitePlus; P12711; -.
DR jPOST; P12711; -.
DR PaxDb; P12711; -.
DR PRIDE; P12711; -.
DR Ensembl; ENSRNOT00000017252; ENSRNOP00000017252; ENSRNOG00000046357.
DR GeneID; 100145871; -.
DR KEGG; rno:100145871; -.
DR CTD; 128; -.
DR RGD; 2292706; Adh5.
DR eggNOG; KOG0022; Eukaryota.
DR GeneTree; ENSGT00940000155196; -.
DR HOGENOM; CLU_026673_14_0_1; -.
DR InParanoid; P12711; -.
DR OrthoDB; 664798at2759; -.
DR Reactome; R-RNO-71384; Ethanol oxidation.
DR SABIO-RK; P12711; -.
DR PRO; PR:P12711; -.
DR Proteomes; UP000002494; Chromosome 2.
DR Bgee; ENSRNOG00000046357; Expressed in liver and 20 other tissues.
DR ExpressionAtlas; P12711; baseline and differential.
DR Genevisible; P12711; RN.
DR GO; GO:0005737; C:cytoplasm; IDA:RGD.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0005739; C:mitochondrion; ISO:RGD.
DR GO; GO:0005634; C:nucleus; IDA:RGD.
DR GO; GO:0004022; F:alcohol dehydrogenase (NAD+) activity; IDA:RGD.
DR GO; GO:0004024; F:alcohol dehydrogenase activity, zinc-dependent; IBA:GO_Central.
DR GO; GO:0005504; F:fatty acid binding; ISO:RGD.
DR GO; GO:0018467; F:formaldehyde dehydrogenase activity; ISO:RGD.
DR GO; GO:0042802; F:identical protein binding; ISO:RGD.
DR GO; GO:0051903; F:S-(hydroxymethyl)glutathione dehydrogenase activity; ISO:RGD.
DR GO; GO:0106322; F:S-(hydroxymethyl)glutathione dehydrogenase NAD activity; IEA:UniProtKB-EC.
DR GO; GO:0106321; F:S-(hydroxymethyl)glutathione dehydrogenase NADP activity; IEA:UniProtKB-EC.
DR GO; GO:0008270; F:zinc ion binding; ISO:RGD.
DR GO; GO:0007568; P:aging; IEP:RGD.
DR GO; GO:0006068; P:ethanol catabolic process; IDA:RGD.
DR GO; GO:0006069; P:ethanol oxidation; IEA:InterPro.
DR GO; GO:0010430; P:fatty acid omega-oxidation; ISS:UniProtKB.
DR GO; GO:0046294; P:formaldehyde catabolic process; ISO:RGD.
DR GO; GO:0018119; P:peptidyl-cysteine S-nitrosylation; ISO:RGD.
DR GO; GO:0045777; P:positive regulation of blood pressure; ISO:RGD.
DR GO; GO:0003016; P:respiratory system process; ISO:RGD.
DR GO; GO:0032496; P:response to lipopolysaccharide; ISO:RGD.
DR GO; GO:0051409; P:response to nitrosative stress; ISO:RGD.
DR GO; GO:0051775; P:response to redox state; ISO:RGD.
DR GO; GO:0001523; P:retinoid metabolic process; ISO:RGD.
DR CDD; cd08300; alcohol_DH_class_III; 1.
DR InterPro; IPR013149; ADH-like_C.
DR InterPro; IPR014183; ADH_3.
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 Pfam; PF08240; ADH_N; 1.
DR Pfam; PF00107; ADH_zinc_N; 1.
DR SUPFAM; SSF50129; SSF50129; 2.
DR SUPFAM; SSF51735; SSF51735; 1.
DR TIGRFAMs; TIGR02818; adh_III_F_hyde; 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; Phosphoprotein; Reference proteome;
KW Zinc.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:3278908,
FT ECO:0000269|PubMed:3653405"
FT CHAIN 2..374
FT /note="Alcohol dehydrogenase class-3"
FT /id="PRO_0000160762"
FT BINDING 45
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:P11766"
FT BINDING 67
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:P11766"
FT BINDING 97
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P11766"
FT BINDING 100
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P11766"
FT BINDING 103
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P11766"
FT BINDING 111
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P11766"
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|UniProtKB:P11766"
FT SITE 115
FT /note="Important for FDH activity and activation by fatty
FT acids"
FT /evidence="ECO:0000250|UniProtKB:P11766"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000269|PubMed:3278908,
FT ECO:0000269|PubMed:3653405"
FT MOD_RES 233
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:P28474"
FT MOD_RES 247
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P11766"
FT MOD_RES 315
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:P28474"
FT MOD_RES 324
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P11766"
FT MOD_RES 351
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P11766"
FT CONFLICT 374
FT /note="M -> L (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 374 AA; 39576 MW; D97A768DEED84C96 CRC64;
MANQVIRCKA AVAWEAGKPL SIEEIEVAPP QAHEVRIKII ATAVCHTDAY TLSGADPEGC
FPVILGHEGA GIVESVGEGV TKLKAGDTVI PLYIPQCGEC KFCLNPKTNL CQKIRVTQGK
GLMPDGTSRF TCKGKPILHF MGTSTFSEYT VVADISVAKI DPSAPLDKVC LLGCGISTGY
GAAVNTAKVE PGSTCAVFGL GGVGLAVIMG CKVAGASRII GIDINKDKFA KAKEFGATEC
INPQDFSKSI QEVLIEMTDG GVDFSFECIG NVKVMRSALE AAHKGWGVSV VVGVAASGEE
ISTRPFQLVT GRTWKGTAFG GWKSVESVPK LVSEYMSKKI KVDEFVTGNL SFDQINKAFD
LMHSGNSIRT VLKM
