ID   FRMA_ECOLI              Reviewed;         369 AA.
AC   P25437; P75696; Q2MC68; Q47533;
DT   01-MAY-1992, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1997, sequence version 3.
DT   02-SEP-2026, entry version 193.
DE   RecName: Full=S-(hydroxymethyl)glutathione dehydrogenase;
DE            EC=1.1.1.284 {ECO:0000269|PubMed:1731906};
DE   AltName: Full=Alcohol dehydrogenase class-3;
DE            EC=1.1.1.1 {ECO:0000269|PubMed:1731906};
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.- {ECO:0000269|PubMed:1731906};
GN   Name=frmA; Synonyms=adhC; OrderedLocusNames=b0356, JW0347;
OS   Escherichia coli (strain K12).
OC   Bacteria; Pseudomonadati; Pseudomonadota; Gammaproteobacteria;
OC   Enterobacterales; Enterobacteriaceae; Escherichia.
OX   NCBI_TaxID=83333;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   STRAIN=K12;
RA   Nashimoto H., Saito N.;
RL   Submitted (MAY-1996) to the EMBL/GenBank/DDBJ databases.
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA   Ito K., Matsumoto K., Tsuru D., Yoshimoto T.;
RL   Submitted (SEP-1997) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=K12 / MG1655 / ATCC 47076;
RA   Chung E., Allen E., Araujo R., Aparicio A.M., Davis K., Duncan M.,
RA   Federspiel N., Hyman R., Kalman S., Komp C., Kurdi O., Lew H., Lin D.,
RA   Namath A., Oefner P., Roberts D., Schramm S., Davis R.W.;
RT   "Sequence of minutes 4-25 of Escherichia coli.";
RL   Submitted (JAN-1997) to the EMBL/GenBank/DDBJ databases.
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=K12 / MG1655 / ATCC 47076;
RX   PubMed=9278503; DOI=10.1126/science.277.5331.1453;
RA   Blattner F.R., Plunkett G. III, Bloch C.A., Perna N.T., Burland V.,
RA   Riley M., Collado-Vides J., Glasner J.D., Rode C.K., Mayhew G.F.,
RA   Gregor J., Davis N.W., Kirkpatrick H.A., Goeden M.A., Rose D.J., Mau B.,
RA   Shao Y.;
RT   "The complete genome sequence of Escherichia coli K-12.";
RL   Science 277:1453-1462(1997).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=K12 / W3110 / ATCC 27325 / DSM 5911;
RX   PubMed=16738553; DOI=10.1038/msb4100049;
RA   Hayashi K., Morooka N., Yamamoto Y., Fujita K., Isono K., Choi S.,
RA   Ohtsubo E., Baba T., Wanner B.L., Mori H., Horiuchi T.;
RT   "Highly accurate genome sequences of Escherichia coli K-12 strains MG1655
RT   and W3110.";
RL   Mol. Syst. Biol. 2:E1-E5(2006).
RN   [6]
RP   PROTEIN SEQUENCE OF 1-47, FUNCTION, CATALYTIC ACTIVITY, COFACTOR,
RP   SUBCELLULAR LOCATION, AND SUBUNIT.
RX   PubMed=1731906; DOI=10.1021/bi00117a025;
RA   Gutheil W.G., Holmquist B., Vallee B.L.;
RT   "Purification, characterization, and partial sequence of the glutathione-
RT   dependent formaldehyde dehydrogenase from Escherichia coli: a class III
RT   alcohol dehydrogenase.";
RL   Biochemistry 31:475-481(1992).
RN   [7]
RP   PARTIAL PROTEIN SEQUENCE, FUNCTION, AND CATALYTIC ACTIVITY.
RX   PubMed=11260719; DOI=10.1038/35068596;
RA   Liu L., Hausladen A., Zeng M., Que L., Heitman J., Stamler J.S.;
RT   "A metabolic enzyme for S-nitrosothiol conserved from bacteria to humans.";
RL   Nature 410:490-494(2001).
RN   [8]
RP   INDUCTION.
RC   STRAIN=K12 / MG1655 / ATCC 47076;
RX   PubMed=15466022; DOI=10.1128/jb.186.20.6714-6720.2004;
RA   Herring C.D., Blattner F.R.;
RT   "Global transcriptional effects of a suppressor tRNA and the inactivation
RT   of the regulator frmR.";
RL   J. Bacteriol. 186:6714-6720(2004).
CC   -!- FUNCTION: Has high formaldehyde dehydrogenase activity in the presence
CC       of glutathione and catalyzes the oxidation of normal alcohols in a
CC       reaction that is not GSH-dependent (PubMed:1731906). In addition,
CC       hemithiolacetals other than those formed from GSH, including omega-
CC       thiol fatty acids, also are substrates (PubMed:1731906). Also acts as a
CC       S-nitroso-glutathione reductase by catalyzing the NADH-dependent
CC       reduction of S-nitrosoglutathione (PubMed:11260719).
CC       {ECO:0000269|PubMed:11260719, ECO:0000269|PubMed:1731906}.
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:0000269|PubMed:1731906};
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:0000269|PubMed:1731906};
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:0000269|PubMed:1731906};
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:0000269|PubMed:1731906};
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:0000269|PubMed:11260719};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:78372;
CC         Evidence={ECO:0000269|PubMed:11260719};
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:0000269|PubMed:1731906}.
CC   -!- INTERACTION:
CC       P25437; P25437: frmA; NbExp=3; IntAct=EBI-556478, EBI-556478;
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:1731906}.
CC   -!- INDUCTION: Induced by formaldehyde and repressed by FrmR.
CC       {ECO:0000269|PubMed:15466022}.
CC   -!- SIMILARITY: Belongs to the zinc-containing alcohol dehydrogenase
CC       family. Class-III subfamily. {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=AAB18081.1; Type=Frameshift; Evidence={ECO:0000305};
CC       Sequence=BAA12834.1; Type=Frameshift; Evidence={ECO:0000305};
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DR   EMBL; D85613; BAA12834.1; ALT_FRAME; Genomic_DNA.
DR   EMBL; D38504; BAA22412.1; -; Genomic_DNA.
DR   EMBL; U73857; AAB18081.1; ALT_FRAME; Genomic_DNA.
DR   EMBL; U00096; AAC73459.1; -; Genomic_DNA.
DR   EMBL; AP009048; BAE76138.1; -; Genomic_DNA.
DR   PIR; D64763; D64763.
DR   RefSeq; NP_414890.1; NC_000913.3.
DR   RefSeq; WP_000842106.1; NZ_CP009789.1.
DR   AlphaFoldDB; P25437; -.
DR   SMR; P25437; -.
DR   BioGRID; 4261803; 21.
DR   BioGRID; 849385; 3.
DR   DIP; DIP-2901N; -.
DR   FunCoup; P25437; 800.
DR   IntAct; P25437; 8.
DR   STRING; 511145.b0356; -.
DR   jPOST; P25437; -.
DR   PaxDb; 511145-b0356; -.
DR   EnsemblBacteria; AAC73459; AAC73459; b0356.
DR   GeneID; 944988; -.
DR   KEGG; ecj:JW0347; -.
DR   KEGG; eco:b0356; -.
DR   PATRIC; fig|1411691.4.peg.1922; -.
DR   EchoBASE; EB4303; -.
DR   eggNOG; COG1062; Bacteria.
DR   HOGENOM; CLU_026673_14_0_6; -.
DR   InParanoid; P25437; -.
DR   OMA; IKGRSEM; -.
DR   OrthoDB; 9770544at2; -.
DR   PhylomeDB; P25437; -.
DR   BioCyc; EcoCyc:ADHC-MONOMER; -.
DR   BioCyc; MetaCyc:ADHC-MONOMER; -.
DR   PRO; PR:P25437; -.
DR   Proteomes; UP000000625; Chromosome.
DR   GO; GO:0005737; C:cytoplasm; IDA:EcoliWiki.
DR   GO; GO:0005829; C:cytosol; IDA:EcoCyc.
DR   GO; GO:0004022; F:alcohol dehydrogenase (NAD+) activity; EXP:UniProtKB.
DR   GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR   GO; GO:0106322; F:S-(hydroxymethyl)glutathione dehydrogenase (NAD+) activity; EXP:UniProtKB.
DR   GO; GO:0106321; F:S-(hydroxymethyl)glutathione dehydrogenase (NADP+) activity; EXP:UniProtKB.
DR   GO; GO:0051903; F:S-(hydroxymethyl)glutathione dehydrogenase [NAD(P)+] activity; IDA:EcoliWiki.
DR   GO; GO:0080007; F:S-nitrosoglutathione reductase (NADH) activity; EXP:UniProtKB.
DR   GO; GO:0008270; F:zinc ion binding; IDA:EcoliWiki.
DR   GO; GO:0046294; P:formaldehyde catabolic process; IMP:EcoliWiki.
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   Cytoplasm; Direct protein sequencing; Metal-binding; NAD; Oxidoreductase;
KW   Reference proteome; Zinc.
FT   CHAIN           1..369
FT                   /note="S-(hydroxymethyl)glutathione dehydrogenase"
FT                   /id="PRO_0000160775"
FT   BINDING         40
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         62
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         92
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000250|UniProtKB:P11766"
FT   BINDING         95
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000250|UniProtKB:P11766"
FT   BINDING         98
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000250|UniProtKB:P11766"
FT   BINDING         106
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000250|UniProtKB:P11766"
FT   BINDING         169
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   CONFLICT        41
FT                   /note="H -> E (in Ref. 6; AA sequence)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        46
FT                   /note="T -> G (in Ref. 6; AA sequence)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   369 AA;  39359 MW;  35B59078F8173521 CRC64;
     MKSRAAVAFA PGKPLEIVEI DVAPPKKGEV LIKVTHTGVC HTDAFTLSGD DPEGVFPVVL
     GHEGAGVVVE VGEGVTSVKP GDHVIPLYTA ECGECEFCRS GKTNLCVAVR ETQGKGLMPD
     GTTRFSYNGQ PLYHYMGCST FSEYTVVAEV SLAKINPEAN HEHVCLLGCG VTTGIGAVHN
     TAKVQPGDSV AVFGLGAIGL AVVQGARQAK AGRIIAIDTN PKKFDLARRF GATDCINPND
     YDKPIKDVLL DINKWGIDHT FECIGNVNVM RAALESAHRG WGQSVIIGVA VAGQEISTRP
     FQLVTGRVWK GSAFGGVKGR SQLPGMVEDA MKGDIDLEPF VTHTMSLDEI NDAFDLMHEG
     KSIRTVIRY
//