ADH6_HUMAN
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 03-AUG-2022, entry version 180.
DE RecName: Full=Alcohol dehydrogenase 6;
DE EC=1.1.1.1;
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].
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 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 -!- 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 -!- 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 -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000250};
CC Note=Binds 2 Zn(2+) ions per subunit. {ECO:0000250};
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.
CC -!- MISCELLANEOUS: There are 7 different ADH's isozymes in human: three
CC belongs 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 -!- SIMILARITY: Belongs to the zinc-containing alcohol dehydrogenase
CC family. Class-V subfamily. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/adh6/";
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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_000672.3. [P28332-1]
DR RefSeq; NP_001095940.1; NM_001102470.1. [P28332-2]
DR AlphaFoldDB; P28332; -.
DR SMR; P28332; -.
DR BioGRID; 106642; 10.
DR IntAct; P28332; 9.
DR STRING; 9606.ENSP00000378359; -.
DR ChEMBL; CHEMBL2096668; -.
DR DrugBank; DB01048; Abacavir.
DR DrugBank; DB00898; Ethanol.
DR DrugBank; DB00157; NADH.
DR GlyGen; P28332; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P28332; -.
DR PhosphoSitePlus; P28332; -.
DR BioMuta; ADH6; -.
DR DMDM; 254763246; -.
DR EPD; P28332; -.
DR jPOST; P28332; -.
DR MassIVE; P28332; -.
DR MaxQB; P28332; -.
DR PaxDb; P28332; -.
DR PeptideAtlas; P28332; -.
DR PRIDE; P28332; -.
DR ProteomicsDB; 54474; -. [P28332-1]
DR ProteomicsDB; 54475; -. [P28332-2]
DR Antibodypedia; 14841; 166 antibodies from 28 providers.
DR DNASU; 130; -.
DR Ensembl; ENST00000237653.11; ENSP00000237653.7; ENSG00000172955.17. [P28332-1]
DR Ensembl; ENST00000394899.6; ENSP00000378359.2; ENSG00000172955.17. [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 CTD; 130; -.
DR DisGeNET; 130; -.
DR GeneCards; ADH6; -.
DR HGNC; HGNC:255; ADH6.
DR HPA; ENSG00000172955; Tissue enriched (liver).
DR MIM; 103735; gene.
DR neXtProt; NX_P28332; -.
DR OpenTargets; ENSG00000172955; -.
DR PharmGKB; PA24576; -.
DR VEuPathDB; HostDB:ENSG00000172955; -.
DR eggNOG; KOG0022; Eukaryota.
DR GeneTree; ENSGT00940000163645; -.
DR HOGENOM; CLU_026673_14_0_1; -.
DR InParanoid; P28332; -.
DR OMA; SCHESHG; -.
DR OrthoDB; 664798at2759; -.
DR PhylomeDB; P28332; -.
DR TreeFam; TF300429; -.
DR PathwayCommons; P28332; -.
DR Reactome; R-HSA-71384; Ethanol oxidation.
DR SignaLink; P28332; -.
DR BioGRID-ORCS; 130; 12 hits in 1066 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 112 other tissues.
DR ExpressionAtlas; P28332; baseline and differential.
DR Genevisible; P28332; HS.
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:0004024; F:alcohol dehydrogenase activity, zinc-dependent; IBA:GO_Central.
DR GO; GO:0004745; F:NAD-retinol dehydrogenase activity; IBA:GO_Central.
DR GO; GO:0008270; F:zinc ion binding; IBA:GO_Central.
DR GO; GO:0006069; P:ethanol oxidation; IDA:UniProtKB.
DR GO; GO:0045471; P:response to ethanol; IDA:UniProtKB.
DR GO; GO:0042573; P:retinoic acid metabolic process; IBA:GO_Central.
DR GO; GO:0042572; P:retinol metabolic process; IBA:GO_Central.
DR InterPro; IPR013149; ADH-like_C.
DR InterPro; IPR028633; ADH6.
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 InterPro; IPR020843; PKS_ER.
DR PANTHER; PTHR43880:SF20; PTHR43880:SF20; 1.
DR Pfam; PF08240; ADH_N; 1.
DR Pfam; PF00107; ADH_zinc_N; 1.
DR SMART; SM00829; PKS_ER; 1.
DR SUPFAM; SSF50129; SSF50129; 2.
DR SUPFAM; SSF51735; SSF51735; 1.
DR PROSITE; PS00059; ADH_ZINC; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cytoplasm; Metal-binding; NAD; Oxidoreductase;
KW Phosphoprotein; 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"
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"
FT BINDING 99
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 102
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 105
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 113
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
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"
FT BINDING 200..205
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250"
FT BINDING 224
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250"
FT BINDING 229
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250"
FT BINDING 293..295
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250"
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
