ID ADHX_MYXGL Reviewed; 376 AA. AC P80360; DT 01-FEB-1995, integrated into UniProtKB/Swiss-Prot. DT 01-FEB-1995, sequence version 1. DT 02-SEP-2026, entry version 118. DE RecName: Full=Alcohol dehydrogenase class-3; DE EC=1.1.1.1 {ECO:0000250|UniProtKB:P11766}; 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}; OS Myxine glutinosa (Atlantic hagfish). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Cyclostomata; Myxini; OC Myxiniformes; Myxinidae; Myxininae; Myxine. OX NCBI_TaxID=7769; RN [1] RP PROTEIN SEQUENCE, TISSUE SPECIFICITY, AND ACETYLATION AT SER-1. RC TISSUE=Liver; RX PubMed=7957198; DOI=10.1111/j.1432-1033.1994.1081b.x; RA Danielsson O., Shafqat J., Estonius M., Joernvall H.; RT "Alcohol dehydrogenase class III contrasted to class I. Characterization of RT the cyclostome enzyme, the existence of multiple forms as for the human RT enzyme, and distant cross-species hybridization."; RL Eur. J. Biochem. 225:1081-1088(1994). RN [2] RP PARTIAL PROTEIN SEQUENCE, AND ACETYLATION AT SER-1. RX PubMed=7607314; DOI=10.1016/0014-5793(95)00572-q; RA Hjelmqvist L., Hackett M., Shafqat J., Danielsson O., Iida J., RA Hendrickson R.C., Michel H., Shabanowitz J., Hunt D.F., Joernvall H.; RT "Multiplicity of N-terminal structures of medium-chain alcohol RT dehydrogenases. Mass-spectrometric analysis of plant, lower vertebrate and RT higher vertebrate class I, II, and III forms of the enzyme."; RL FEBS Lett. 367:237-240(1995). CC -!- FUNCTION: Class-III ADH is remarkably ineffective in oxidizing ethanol, CC but it readily catalyzes the oxidation of long-chain primary alcohols CC and the oxidation of S-(hydroxymethyl) glutathione. Also acts as a S- CC nitroso-glutathione reductase by catalyzing the NADH-dependent CC reduction of S-nitrosoglutathione, thereby regulating protein S- CC nitrosylation (By similarity). {ECO:0000250|UniProtKB:P11766, CC ECO:0000250|UniProtKB:P28474}. 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:P11766}; CC -!- CATALYTIC ACTIVITY: CC Reaction=a secondary alcohol + NAD(+) = a ketone + NADH + H(+); 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=S-(hydroxymethyl)glutathione + NADP(+) = S-formylglutathione + CC NADPH + H(+); 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=S-(hydroxymethyl)glutathione + NAD(+) = S-formylglutathione + CC NADH + H(+); 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=S-nitrosoglutathione + NADH + H(+) = S- CC (hydroxysulfenamide)glutathione + NAD(+); Xref=Rhea:RHEA:78371, CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, CC ChEBI:CHEBI:145544, ChEBI:CHEBI:229723; CC Evidence={ECO:0000250|UniProtKB:P28474}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:78372; CC Evidence={ECO:0000250|UniProtKB:P28474}; 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 -!- TISSUE SPECIFICITY: Liver and gut. {ECO:0000269|PubMed:7957198}. 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; S51187; S51187. DR AlphaFoldDB; P80360; -. DR SMR; P80360; -. DR iPTMnet; P80360; -. DR GO; GO:0005829; C:cytosol; IEA:TreeGrafter. DR GO; GO:0004022; F:alcohol dehydrogenase (NAD+) activity; ISS:UniProtKB. DR GO; GO:0106322; F:S-(hydroxymethyl)glutathione dehydrogenase (NAD+) activity; ISS:UniProtKB. DR GO; GO:0106321; F:S-(hydroxymethyl)glutathione dehydrogenase (NADP+) activity; ISS:UniProtKB. DR GO; GO:0080007; F:S-nitrosoglutathione reductase (NADH) activity; ISS:UniProtKB. DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro. DR GO; GO:0046294; P:formaldehyde catabolic process; IEA:InterPro. DR CDD; cd08300; alcohol_DH_class_III; 1. DR FunFam; 3.40.50.720:FF:000003; S-(hydroxymethyl)glutathione dehydrogenase; 1. DR FunFam; 3.90.180.10:FF:000001; S-(hydroxymethyl)glutathione dehydrogenase; 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; IPR014183; ADH_3. 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 NCBIfam; TIGR02818; adh_III_F_hyde; 1. DR PANTHER; PTHR43880; ALCOHOL DEHYDROGENASE; 1. DR PANTHER; PTHR43880:SF12; ALCOHOL DEHYDROGENASE CLASS-3; 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; Metal-binding; NAD; KW Oxidoreductase; Zinc. FT CHAIN 1..376 FT /note="Alcohol dehydrogenase class-3" FT /id="PRO_0000160765" 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|UniProtKB:P11766" FT BINDING 69 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 99 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000250|UniProtKB:P11766" FT BINDING 102 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000250|UniProtKB:P11766" FT BINDING 105 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000250|UniProtKB:P11766" FT BINDING 113 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000250|UniProtKB:P11766" FT BINDING 176 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 117 FT /note="Important for FDH activity and activation by fatty FT acids" FT /evidence="ECO:0000250|UniProtKB:P11766" FT MOD_RES 1 FT /note="N-acetylserine" FT /evidence="ECO:0000269|PubMed:7607314, FT ECO:0000269|PubMed:7957198" SQ SEQUENCE 376 AA; 39747 MW; FFD20C195FF67B5F CRC64; SKMDGQVIHC KAAVAWEAKK PLSLEEIEVA PPKAHEVRMK VLATAVCHTD AYTLSGVDPE GSFPVVLGHE GAGIVESVGE GVTKFKPGDS VIPLYIPQCG ECKFCLNPKT NLCQKIRVTQ GKGMMPDGTS RLTCRGKSLY HFMGASTFSE YAVVADISLC RVAPEAPPDR VCLLGCGVST GYGAPLNTAK VEPGSTCAIF GLGAVGLAAI MGCRVAGASR IIAIDRNPDK FEKARIFGAT DCVVPDASDK PISQVLGEMT DGGLDYTFEC VGNVGIMRAA LESCHKGWGV SVILGVAGGG QEISTRPFQL VTGRTWKGAA FGGWKSVESV PKLVDDYMAG KIMVDEFVSH SLPFDSINEA FDLMHAGKSI RTVLQL //