ID   ADH2_ENTH1              Reviewed;         870 AA.
AC   Q24803; A0A175JQB7; C4M2R2; Q27649;
DT   01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT   22-FEB-2023, sequence version 2.
DT   27-MAR-2024, entry version 110.
DE   RecName: Full=Aldehyde-alcohol dehydrogenase 2 {ECO:0000305};
DE   Includes:
DE     RecName: Full=Alcohol dehydrogenase {ECO:0000303|PubMed:7935603, ECO:0000303|PubMed:7980441};
DE              Short=ADH {ECO:0000303|PubMed:7935603, ECO:0000303|PubMed:7980441};
DE              EC=1.1.1.1 {ECO:0000269|PubMed:7935603, ECO:0000269|PubMed:7980441};
DE   Includes:
DE     RecName: Full=Acetaldehyde dehydrogenase {ECO:0000303|PubMed:7935603, ECO:0000303|PubMed:7980441};
DE              Short=ACDH {ECO:0000303|PubMed:7980441};
DE              EC=1.2.1.10 {ECO:0000269|PubMed:7935603, ECO:0000269|PubMed:7980441};
GN   Name=ADH2; ORFNames=EHI_160940 {ECO:0000312|EMBL:EAL50431.2};
OS   Entamoeba histolytica (strain ATCC 30459 / HM-1:IMSS / ABRM).
OC   Eukaryota; Amoebozoa; Evosea; Archamoebae; Mastigamoebida; Entamoebidae;
OC   Entamoeba.
OX   NCBI_TaxID=294381 {ECO:0000312|EMBL:EAL50431.2};
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 377-395 AND 860-870,
RP   FUNCTION, AND CATALYTIC ACTIVITY.
RC   STRAIN=ATCC 30459 / HM-1:IMSS / ABRM;
RX   PubMed=7935603; DOI=10.1016/0166-6851(93)00020-a;
RA   Yang W., Li E., Kairong T., Stanley S.L. Jr.;
RT   "Entamoeba histolytica has an alcohol dehydrogenase homologous to the
RT   multifunctional adhE gene product of Escherichia coli.";
RL   Mol. Biochem. Parasitol. 64:253-260(1994).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY,
RP   BIOPHYSICOCHEMICAL PROPERTIES, AND SUBUNIT.
RC   STRAIN=ATCC 30459 / HM-1:IMSS / ABRM;
RX   PubMed=7980441; DOI=10.1042/bj3030743;
RA   Bruchhaus I., Tannich E.;
RT   "Purification and molecular characterization of the NAD(+)-dependent
RT   acetaldehyde/alcohol dehydrogenase from Entamoeba histolytica.";
RL   Biochem. J. 303:743-748(1994).
RN   [3] {ECO:0000312|EMBL:EAL50431.2}
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 30459 / HM-1:IMSS / ABRM {ECO:0000312|EMBL:EAL50431.2};
RX   PubMed=15729342; DOI=10.1038/nature03291;
RA   Loftus B.J., Anderson I., Davies R., Alsmark U.C., Samuelson J., Amedeo P.,
RA   Roncaglia P., Berriman M., Hirt R.P., Mann B.J., Nozaki T., Suh B., Pop M.,
RA   Duchene M., Ackers J., Tannich E., Leippe M., Hofer M., Bruchhaus I.,
RA   Willhoeft U., Bhattacharya A., Chillingworth T., Churcher C.M., Hance Z.,
RA   Harris B., Harris D., Jagels K., Moule S., Mungall K.L., Ormond D.,
RA   Squares R., Whitehead S., Quail M.A., Rabbinowitsch E., Norbertczak H.,
RA   Price C., Wang Z., Guillen N., Gilchrist C., Stroup S.E., Bhattacharya S.,
RA   Lohia A., Foster P.G., Sicheritz-Ponten T., Weber C., Singh U.,
RA   Mukherjee C., El-Sayed N.M.A., Petri W.A., Clark C.G., Embley T.M.,
RA   Barrell B.G., Fraser C.M., Hall N.;
RT   "The genome of the protist parasite Entamoeba histolytica.";
RL   Nature 433:865-868(2005).
CC   -!- FUNCTION: This enzyme has two NAD(+)-dependent activities: ADH and
CC       ACDH. May be a critical enzyme in the fermentative pathway.
CC       {ECO:0000269|PubMed:7935603, ECO:0000269|PubMed:7980441}.
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:0000269|PubMed:7935603, ECO:0000269|PubMed:7980441};
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:0000269|PubMed:7935603, ECO:0000269|PubMed:7980441};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=acetaldehyde + CoA + NAD(+) = acetyl-CoA + H(+) + NADH;
CC         Xref=Rhea:RHEA:23288, ChEBI:CHEBI:15343, ChEBI:CHEBI:15378,
CC         ChEBI:CHEBI:57287, ChEBI:CHEBI:57288, ChEBI:CHEBI:57540,
CC         ChEBI:CHEBI:57945; EC=1.2.1.10; Evidence={ECO:0000269|PubMed:7935603,
CC         ECO:0000269|PubMed:7980441};
CC   -!- COFACTOR:
CC       Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000250};
CC       Name=Fe(2+); Xref=ChEBI:CHEBI:29033; Evidence={ECO:0000250};
CC       Note=Zinc or iron. {ECO:0000250};
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=80 mM for ethanol {ECO:0000269|PubMed:7980441};
CC         KM=0.15 mM for acetaldehyde {ECO:0000269|PubMed:7980441};
CC         KM=0.015 mM for acetyl-CoA {ECO:0000269|PubMed:7980441};
CC         KM=0.15 mM for NAD(+) (for ADH activity)
CC         {ECO:0000269|PubMed:7980441};
CC         KM=0.05 mM for NADH (for ADH activity) {ECO:0000269|PubMed:7980441};
CC         KM=0.18 mM for NADH (for ACDH activity) {ECO:0000269|PubMed:7980441};
CC   -!- SUBUNIT: Seems to form a rod shaped homomer composed of at least 20
CC       identical subunits. {ECO:0000269|PubMed:7980441}.
CC   -!- SIMILARITY: In the N-terminal section; belongs to the aldehyde
CC       dehydrogenase family. {ECO:0000305}.
CC   -!- SIMILARITY: In the C-terminal section; belongs to the iron-containing
CC       alcohol dehydrogenase family. {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=CAA54388.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={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   EMBL; U04863; AAA81906.1; -; mRNA.
DR   EMBL; X77132; CAA54388.1; ALT_INIT; mRNA.
DR   EMBL; DS571228; EAL50431.2; -; Genomic_DNA.
DR   PIR; S53319; S53319.
DR   RefSeq; XP_655817.2; XM_650725.2.
DR   AlphaFoldDB; Q24803; -.
DR   SMR; Q24803; -.
DR   STRING; 5759.C4M2R2; -.
DR   MoonProt; Q24803; -.
DR   EnsemblProtists; GAT95573; GAT95573; CL6EHI_160940.
DR   EnsemblProtists; rna_EHI_160940-1; rna_EHI_160940-1; EHI_160940.
DR   GeneID; 3410145; -.
DR   KEGG; ehi:EHI_160940; -.
DR   VEuPathDB; AmoebaDB:EHI5A_157720; -.
DR   VEuPathDB; AmoebaDB:EHI7A_198850; -.
DR   VEuPathDB; AmoebaDB:EHI8A_086570; -.
DR   VEuPathDB; AmoebaDB:EHI_160940; -.
DR   VEuPathDB; AmoebaDB:KM1_283380; -.
DR   eggNOG; KOG3857; Eukaryota.
DR   HOGENOM; CLU_007207_1_0_1; -.
DR   OMA; DQCTAAN; -.
DR   OrthoDB; 5479153at2759; -.
DR   Proteomes; UP000001926; Partially assembled WGS sequence.
DR   GO; GO:0008774; F:acetaldehyde dehydrogenase (acetylating) activity; IDA:CAFA.
DR   GO; GO:0004022; F:alcohol dehydrogenase (NAD+) activity; IDA:CAFA.
DR   GO; GO:0005518; F:collagen binding; IDA:CAFA.
DR   GO; GO:0001968; F:fibronectin binding; IDA:CAFA.
DR   GO; GO:0043236; F:laminin binding; IDA:CAFA.
DR   GO; GO:0046872; F:metal ion binding; IEA:InterPro.
DR   GO; GO:0006066; P:alcohol metabolic process; IEA:InterPro.
DR   GO; GO:0015976; P:carbon utilization; IEA:InterPro.
DR   CDD; cd08178; AAD_C; 1.
DR   CDD; cd07122; ALDH_F20_ACDH; 1.
DR   Gene3D; 3.40.50.1970; -; 1.
DR   Gene3D; 1.20.1090.10; Dehydroquinate synthase-like - alpha domain; 1.
DR   InterPro; IPR034789; AAD_C.
DR   InterPro; IPR001670; ADH_Fe/GldA.
DR   InterPro; IPR018211; ADH_Fe_CS.
DR   InterPro; IPR039697; Alcohol_dehydrogenase_Fe.
DR   InterPro; IPR016161; Ald_DH/histidinol_DH.
DR   InterPro; IPR016163; Ald_DH_C.
DR   InterPro; IPR016162; Ald_DH_N.
DR   InterPro; IPR015590; Aldehyde_DH_dom.
DR   InterPro; IPR012079; Bifunc_Ald-ADH.
DR   PANTHER; PTHR11496; ALCOHOL DEHYDROGENASE; 1.
DR   PANTHER; PTHR11496:SF83; HYDROXYACID-OXOACID TRANSHYDROGENASE, MITOCHONDRIAL; 1.
DR   Pfam; PF00171; Aldedh; 1.
DR   Pfam; PF00465; Fe-ADH; 1.
DR   PIRSF; PIRSF000111; ALDH_ADH; 1.
DR   SUPFAM; SSF53720; ALDH-like; 1.
DR   SUPFAM; SSF56796; Dehydroquinate synthase-like; 1.
DR   PROSITE; PS00913; ADH_IRON_1; 1.
DR   PROSITE; PS00060; ADH_IRON_2; 1.
PE   1: Evidence at protein level;
KW   Direct protein sequencing; Iron; Multifunctional enzyme; NAD;
KW   Oxidoreductase; Reference proteome.
FT   CHAIN           1..870
FT                   /note="Aldehyde-alcohol dehydrogenase 2"
FT                   /id="PRO_0000087835"
FT   ACT_SITE        252
FT                   /evidence="ECO:0000250"
FT   BINDING         431..436
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /evidence="ECO:0000255"
FT   CONFLICT        18
FT                   /note="A -> R (in Ref. 1; AAA81906)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        165
FT                   /note="S -> A (in Ref. 2; CAA54388 and 1; AAA81906)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        380
FT                   /note="R -> E (in Ref. 1; AA sequence)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        382
FT                   /note="H -> Q (in Ref. 1; AA sequence)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        387..388
FT                   /note="HS -> NP (in Ref. 1; AA sequence)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        482
FT                   /note="A -> R (in Ref. 2; CAA54388)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        534
FT                   /note="T -> I (in Ref. 2; CAA54388)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        566
FT                   /note="W -> R (in Ref. 2; CAA54388)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        739
FT                   /note="A -> G (in Ref. 2; CAA54388)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        821
FT                   /note="Q -> K (in Ref. 1; AAA81906)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   870 AA;  95590 MW;  E416AF26AC71F902 CRC64;
     MSTQQTMTVD EHINQLVAKA QVALKEYLKP EYTQEKIDYI VKKASVAALD QHCALAAAAV
     EETGRGIFED KATKNIFACE HVTHEMRHAK TVGIINVDPL YGITEIAEPV GVVCGVTPVT
     NPTSTAIFKS LISIKTRNPI VFSFHPSALK CSIMAAKIVR DAAISAGAPE NCIQWIEFGG
     IEASNKLMNH PGVATILATG GNAMVKAAYS SGKPALGVGA GNVPTYIEKT CNIKQAANDV
     VMSKSFDNGM ICASEQAAII DKEIYDQVVE EMKTLGAYFI NEEEKAKLEK FMFGVNAYSA
     DVNNARLNPK CPGMSPQWFA EQVGIKVPED CNIICAVCKE VGPNEPLTRE KLSPVLAILK
     AENTQDGIDK AEAMVEFNGR GHSAAIHSND KAVVEKYALT MKACRILHNT PSSQGGIGSI
     YNYIWPSFTL GCGSYGGNSV SANVTYHNLL NIKRLADRRN NLQWFRVPPK IFFEPHSIRY
     LAELKELSKI FIVSDRMMYK LGYVDRVMDV LKRRSNEVEI EIFIDVEPDP SIQTVQKGLA
     VMNTFGPDNI IAIGGGSAMD AAKIMWLLYE HPEADFFAMK QKFIDLRKRA FKFPTMGKKA
     RLICIPTTSG TGSEVTPFAV ISDHETGKKY PLADYSLTPS VAIVDPMFTM SLPKRAIADT
     GLDVLVHATE AYVSVMANEY TDGLAREAVK LVFENLLKSY NGDLEAREKM HNAATIAGMA
     FASAFLGMDH SMAHKVGAAF HLPHGRCVAV LLPHVIRYNG QKPRKLAMWP KYNFYKADQR
     YMELAQMVGL KCNTPAEGVE AFAKACEELM KATETITGFK QANIDEAAWM SKVPEMALLA
     FEDQCSPANP RVPMVKDMEK ILKAAYYPIA
//