ID   ADH6_HUMAN              Reviewed;         368 AA.
AC   P28332; A0A0A0MS56; B3KS45; Q58F53;
DT   01-DEC-1992, integrated into UniProtKB/Swiss-Prot.
DT   12-SEP-2018, sequence version 3.
DT   02-SEP-2026, entry version 199.
DE   RecName: Full=Alcohol dehydrogenase 6;
DE            EC=1.1.1.1 {ECO:0000269|PubMed:1755855};
GN   Name=ADH6;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND TISSUE SPECIFICITY.
RC   TISSUE=Liver;
RX   PubMed=1881901; DOI=10.1073/pnas.88.17.7610;
RA   Yasunami M., Chen C.-S., Yoshida A.;
RT   "A human alcohol dehydrogenase gene (ADH6) encoding an additional class of
RT   isozyme.";
RL   Proc. Natl. Acad. Sci. U.S.A. 88:7610-7614(1991).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC   TISSUE=Small intestine;
RX   PubMed=14702039; DOI=10.1038/ng1285;
RA   Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA   Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA   Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA   Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA   Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA   Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA   Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA   Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA   Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA   Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA   Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA   Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA   Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA   Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA   Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA   Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA   Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA   Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA   Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA   Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA   Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA   Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA   Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA   Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA   Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA   Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA   Isogai T., Sugano S.;
RT   "Complete sequencing and characterization of 21,243 full-length human
RT   cDNAs.";
RL   Nat. Genet. 36:40-45(2004).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS GLY-102 AND VAL-114.
RG   NIEHS SNPs program;
RL   Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases.
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=15815621; DOI=10.1038/nature03466;
RA   Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA   Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA   Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA   Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA   Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA   Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA   Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA   Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA   Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA   McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA   Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA   Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA   Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA   Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA   Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA   Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA   Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA   Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA   Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA   Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA   Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA   Wilson R.K.;
RT   "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT   4.";
RL   Nature 434:724-731(2005).
RN   [5]
RP   FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, AND BIOPHYSICOCHEMICAL
RP   PROPERTIES.
RX   PubMed=1755855; DOI=10.1016/0006-291x(91)91253-9;
RA   Chen C.S., Yoshida A.;
RT   "Enzymatic properties of the protein encoded by newly cloned human alcohol
RT   dehydrogenase ADH6 gene.";
RL   Biochem. Biophys. Res. Commun. 181:743-747(1991).
RN   [6]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-23, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Liver;
RX   PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA   Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA   Ye M., Zou H.;
RT   "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT   phosphoproteome.";
RL   J. Proteomics 96:253-262(2014).
CC   -!- FUNCTION: Alcohol dehydrogenase (PubMed:1755855). Catalyzes the NAD-
CC       dependent oxidation of primary alcohols to the corresponding aldehydes
CC       (PubMed:1755855). Oxidizes secondary alcohols to the corresponding
CC       ketones (By similarity). {ECO:0000250|UniProtKB:P07327,
CC       ECO:0000269|PubMed:1755855}.
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:1755855};
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:P07327};
CC   -!- COFACTOR:
CC       Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC         Evidence={ECO:0000250|UniProtKB:P07327};
CC       Note=Binds 2 Zn(2+) ions per subunit. {ECO:0000250|UniProtKB:P07327};
CC   -!- ACTIVITY REGULATION: Inhibited partially by pyrazole (10 mM) in the
CC       reaction mixture containing 100 mM ethanol at pH 10.0.
CC       {ECO:0000269|PubMed:1755855}.
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=28 mM for ethanol (at pH 10.0 and 25 degrees Celsius)
CC         {ECO:0000269|PubMed:1755855};
CC         KM=3.2 mM for 1-propanol (at pH 10.0 and 25 degrees Celsius)
CC         {ECO:0000269|PubMed:1755855};
CC         KM=0.12 mM for benzyl alcohol (at pH 10.0 and 25 degrees Celsius)
CC         {ECO:0000269|PubMed:1755855};
CC       pH dependence:
CC         Optimum pH is 10.0. {ECO:0000269|PubMed:1755855};
CC   -!- SUBUNIT: Dimer. {ECO:0000250|UniProtKB:P41681}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=P28332-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=P28332-2; Sequence=VSP_037702;
CC   -!- TISSUE SPECIFICITY: Stomach and liver. {ECO:0000269|PubMed:1881901}.
CC   -!- MISCELLANEOUS: There are 7 different ADH's isozymes in human: three
CC       belong to class-I: alpha, beta, and gamma, one to class-II: pi, one to
CC       class-III: chi, one to class-IV: ADH7 and one to class-V: ADH6.
CC   -!- MISCELLANEOUS: Isoelectric point (pH(I)) is 8.6.
CC       {ECO:0000269|PubMed:1755855}.
CC   -!- SIMILARITY: Belongs to the zinc-containing alcohol dehydrogenase
CC       family. Class-V subfamily. {ECO:0000305}.
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DR   EMBL; M84402; AAA35509.1; -; Genomic_DNA.
DR   EMBL; M84403; AAA35509.1; JOINED; Genomic_DNA.
DR   EMBL; M84404; AAA35509.1; JOINED; Genomic_DNA.
DR   EMBL; M84405; AAA35509.1; JOINED; Genomic_DNA.
DR   EMBL; M84406; AAA35509.1; JOINED; Genomic_DNA.
DR   EMBL; M84407; AAA35509.1; JOINED; Genomic_DNA.
DR   EMBL; M84408; AAA35509.1; JOINED; Genomic_DNA.
DR   EMBL; M84409; AAA35509.1; JOINED; Genomic_DNA.
DR   EMBL; AK092768; BAG52607.1; -; mRNA.
DR   EMBL; AY962311; AAX44051.1; -; Genomic_DNA.
DR   EMBL; AP002026; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; KF457794; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   CCDS; CCDS3647.1; -. [P28332-1]
DR   CCDS; CCDS43255.1; -. [P28332-2]
DR   PIR; A41274; DEHUA6.
DR   RefSeq; NP_000663.1; NM_000672.4. [P28332-1]
DR   RefSeq; NP_001095940.1; NM_001102470.2. [P28332-2]
DR   AlphaFoldDB; P28332; -.
DR   SMR; P28332; -.
DR   BioGRID; 106642; 11.
DR   FunCoup; P28332; 247.
DR   IntAct; P28332; 9.
DR   NDEx; IQUERY-CP-ADH6; 1 NDEx IQuery Curated Pathway.
DR   STRING; 9606.ENSP00000378359; -.
DR   ChEMBL; CHEMBL2096668; -.
DR   DrugBank; DB01048; Abacavir.
DR   DrugBank; DB00898; Ethanol.
DR   DrugBank; DB00157; NADH.
DR   GlyGen; P28332; 2 sites, 1 O-linked glycan (1 site).
DR   iPTMnet; P28332; -.
DR   PhosphoSitePlus; P28332; -.
DR   BioMuta; ADH6; -.
DR   DMDM; 254763246; -.
DR   jPOST; P28332; -.
DR   MassIVE; P28332; -.
DR   PaxDb; 9606-ENSP00000378359; -.
DR   PeptideAtlas; P28332; -.
DR   ProteomicsDB; 54474; -. [P28332-1]
DR   ProteomicsDB; 54475; -. [P28332-2]
DR   Antibodypedia; 14841; 161 antibodies from 27 providers.
DR   DNASU; 130; -.
DR   Ensembl; ENST00000237653.11; ENSP00000237653.7; ENSG00000172955.18. [P28332-1]
DR   Ensembl; ENST00000394899.6; ENSP00000378359.2; ENSG00000172955.18. [P28332-2]
DR   GeneID; 130; -.
DR   KEGG; hsa:130; -.
DR   MANE-Select; ENST00000394899.6; ENSP00000378359.2; NM_001102470.2; NP_001095940.1. [P28332-2]
DR   UCSC; uc003hup.5; human. [P28332-1]
DR   AGR; HGNC:255; -.
DR   ClinPGx; PA24576; -.
DR   CTD; 130; -.
DR   DisGeNET; 130; -.
DR   GeneCards; ADH6; -.
DR   HGNC; HGNC:255; ADH6.
DR   HPA; ENSG00000172955; Tissue enriched (liver).
DR   MIM; 103735; gene.
DR   OpenTargets; ENSG00000172955; -.
DR   VEuPathDB; HostDB:ENSG00000172955; -.
DR   eggNOG; KOG0022; Eukaryota.
DR   GeneTree; ENSGT00940000163645; -.
DR   HOGENOM; CLU_026673_14_0_1; -.
DR   InParanoid; P28332; -.
DR   OMA; QVNEGYQ; -.
DR   OrthoDB; 417550at2759; -.
DR   PAN-GO; P28332; 5 GO annotations based on evolutionary models.
DR   PhylomeDB; P28332; -.
DR   PathwayCommons; P28332; -.
DR   Reactome; R-HSA-71384; Ethanol oxidation.
DR   SignaLink; P28332; -.
DR   Agora; ENSG00000172955; -.
DR   BioGRID-ORCS; 130; 14 hits in 1150 CRISPR screens.
DR   GeneWiki; ADH6; -.
DR   GenomeRNAi; 130; -.
DR   Pharos; P28332; Tbio.
DR   PRO; PR:P28332; -.
DR   Proteomes; UP000005640; Chromosome 4.
DR   RNAct; P28332; protein.
DR   Bgee; ENSG00000172955; Expressed in right lobe of liver and 113 other cell types or tissues.
DR   ExpressionAtlas; P28332; baseline and differential.
DR   GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR   GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR   GO; GO:0004022; F:alcohol dehydrogenase (NAD+) activity; IDA:UniProtKB.
DR   GO; GO:0004745; F:all-trans-retinol dehydrogenase (NAD+) activity; IBA:GO_Central.
DR   GO; GO:0008270; F:zinc ion binding; IBA:GO_Central.
DR   GO; GO:0042573; P:retinoic acid metabolic process; IBA:GO_Central.
DR   GO; GO:0042572; P:retinol metabolic process; IBA:GO_Central.
DR   CDD; cd08299; alcohol_DH_class_I_II_IV; 1.
DR   FunFam; 3.90.180.10:FF:000007; Alcohol dehydrogenase 6; 1.
DR   FunFam; 3.40.50.720:FF:000003; 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; IPR002328; ADH_Zn_CS.
DR   InterPro; IPR020843; ER.
DR   InterPro; IPR011032; GroES-like_sf.
DR   InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR   PANTHER; PTHR43880; ALCOHOL DEHYDROGENASE; 1.
DR   PANTHER; PTHR43880:SF20; ALCOHOL DEHYDROGENASE 6; 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   Alternative splicing; Cytoplasm; Metal-binding; NAD; Oxidoreductase;
KW   Phosphoprotein; Proteomics identification; Reference proteome; Zinc.
FT   CHAIN           1..368
FT                   /note="Alcohol dehydrogenase 6"
FT                   /id="PRO_0000160687"
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:P07327"
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:P07327"
FT   BINDING         99
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000250|UniProtKB:P07327"
FT   BINDING         102
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000250|UniProtKB:P07327"
FT   BINDING         105
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000250|UniProtKB:P07327"
FT   BINDING         113
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000250|UniProtKB:P07327"
FT   BINDING         175
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000250|UniProtKB:P07327"
FT   BINDING         200..205
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /evidence="ECO:0000250|UniProtKB:P07327"
FT   BINDING         224
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /evidence="ECO:0000250|UniProtKB:P07327"
FT   BINDING         229
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /evidence="ECO:0000250|UniProtKB:P07327"
FT   BINDING         293..295
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /evidence="ECO:0000250|UniProtKB:P07327"
FT   MOD_RES         23
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:24275569"
FT   VAR_SEQ         368
FT                   /note="W -> CIRCILLL (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:14702039"
FT                   /id="VSP_037702"
FT   VARIANT         102
FT                   /note="C -> G (in dbSNP:rs28720152)"
FT                   /evidence="ECO:0000269|Ref.3"
FT                   /id="VAR_022655"
FT   VARIANT         114
FT                   /note="I -> V (in dbSNP:rs28720153)"
FT                   /evidence="ECO:0000269|Ref.3"
FT                   /id="VAR_022656"
FT   VARIANT         151
FT                   /note="T -> P (in dbSNP:rs34582580)"
FT                   /id="VAR_048198"
FT   CONFLICT        266
FT                   /note="C -> R (in Ref. 2; BAG52607)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   368 AA;  39073 MW;  EC8E81E9571E6241 CRC64;
     MSTTGQVIRC KAAILWKPGA PFSIEEVEVA PPKAKEVRIK VVATGLCGTE MKVLGSKHLD
     LLYPTILGHE GAGIVESIGE GVSTVKPGDK VITLFLPQCG ECTSCLNSEG NFCIQFKQSK
     TQLMSDGTSR FTCKGKSIYH FGNTSTFCEY TVIKEISVAK IDAVAPLEKV CLISCGFSTG
     FGAAINTAKV TPGSTCAVFG LGGVGLSVVM GCKAAGAARI IGVDVNKEKF KKAQELGATE
     CLNPQDLKKP IQEVLFDMTD AGIDFCFEAI GNLDVLAAAL ASCNESYGVC VVVGVLPASV
     QLKISGQLFF SGRSLKGSVF GGWKSRQHIP KLVADYMAEK LNLDPLITHT LNLDKINEAV
     ELMKTGKW
//