ADHX_HORSE
ID ADHX_HORSE Reviewed; 374 AA.
AC P19854;
DT 01-FEB-1991, integrated into UniProtKB/Swiss-Prot.
DT 03-APR-2007, sequence version 2.
DT 03-AUG-2022, entry version 128.
DE RecName: Full=Alcohol dehydrogenase class-3 {ECO:0000250|UniProtKB:P11766};
DE EC=1.1.1.1 {ECO:0000250|UniProtKB:P11766};
DE AltName: Full=Alcohol dehydrogenase 5;
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:0000250|UniProtKB:P11766};
OS Equus caballus (Horse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Perissodactyla; Equidae; Equus.
OX NCBI_TaxID=9796;
RN [1]
RP PROTEIN SEQUENCE OF 2-374, AND ACETYLATION AT SER-2.
RX PubMed=2690942; DOI=10.1021/bi00447a024;
RA Kaiser R., Holmquist B., Vallee B.L., Joernvall H.;
RT "Characteristics of mammalian class III alcohol dehydrogenases, an enzyme
RT less variable than the traditional liver enzyme of class I.";
RL Biochemistry 28:8432-8438(1989).
RN [2]
RP PROTEIN SEQUENCE OF 2-7, AND ACETYLATION AT SER-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).
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 ---------------------------------------------------------------------------
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 PIR; A33419; A33419.
DR PIR; S02617; S02617.
DR AlphaFoldDB; P19854; -.
DR SMR; P19854; -.
DR STRING; 9796.ENSECAP00000027421; -.
DR iPTMnet; P19854; -.
DR PeptideAtlas; P19854; -.
DR PRIDE; P19854; -.
DR InParanoid; P19854; -.
DR Proteomes; UP000002281; Unplaced.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0004022; F:alcohol dehydrogenase (NAD+) activity; IEA:UniProtKB-EC.
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; IEA:InterPro.
DR GO; GO:0006069; P:ethanol oxidation; IEA:InterPro.
DR GO; GO:0010430; P:fatty acid omega-oxidation; ISS:UniProtKB.
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:2690942,
FT ECO:0000269|PubMed:3653405"
FT CHAIN 2..374
FT /note="Alcohol dehydrogenase class-3"
FT /id="PRO_0000160758"
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-acetylserine"
FT /evidence="ECO:0000269|PubMed:2690942,
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"
SQ SEQUENCE 374 AA; 39572 MW; 190D38896ED9D094 CRC64;
MSAEVIKCKA AVAWEAGKPV SIEEVEVAPP KAHEVRIKII ATAVCHTDAY TLSGADPEGS
FPVILGHEGA GIVESVGEGV TKLKAGDTVI PLYIPQCGEC KFCLNPQTNL CQKIRTTQGK
GLMPDGTSRF TCKGKTILHY MGTSTFSEYT VVADISVAKI DPLAPLDKVC LLGCGVSTGY
GAAVNTAKVE PGSTCAIFGL GGVGLAVIMG CKVAGASRII GVDINKDKFA KAKEFGASEC
INPQDFSKPI QEVLIEMTDG GVDYSFECIG NVKVMRAALE ACHKGWGVSV VVGVAASGEE
IATRPFQLVT GRTWKGTAFG GWKSVESIPK LVSEYMSKKI KVDEFVTHSL SFDQINEAFE
LMHAGKSIRT VVKL
