Reviewed, UniProtKB/Swiss-Prot P00325 (ADH1B_HUMAN)

Names and origin

Protein names

Recommended name:
    Alcohol dehydrogenase 1B
    EC=1.1.1.1
Alternative name(s):
    Alcohol dehydrogenase subunit beta

Gene names

Name:	ADH1B
Synonyms:	ADH2

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	375 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

General annotation (Comments)

Catalytic activity	An alcohol + NAD(+) = an aldehyde or ketone + NADH.
Cofactor	Binds 2 zinc ions per subunit.
Subunit structure	Dimer of identical or non-identical chains of three types; alpha, beta and gamma.
Subcellular location	Cytoplasm.
Polymorphism	Three alleles are known: ADH1B*1 (ADH2*1) corresponding to variant beta-1, ADH1B*2 (ADH2*2) corresponding to variant beta-2, ADH1B*3 (ADH2*3) corresponding to variant beta-3. The sequence shown is that of allele ADH1B*1. The ADH1B*2 allele frequency in orientals is approximately 75%, whereas it is less than 5% in most Caucasian populations.
Miscellaneous	There are 7 different ADH's isozymes in human: three belongs to class-I: alpha, beta, and gamma, one to class-II: pi, one to class-III: chi, one to class-IV: ADH7 and one to class-V: ADH6.
Sequence similarities	Belongs to the zinc-containing alcohol dehydrogenase family.

Ontologies

Keywords
Cellular component	Cytoplasm
Coding sequence diversity	Polymorphism
Ligand	Metal-binding NAD Zinc
Molecular function	Oxidoreductase
PTM	Acetylation
Technical term	3D-structure Direct protein sequencing
Gene Ontology (GO)
Biological process	ethanol oxidation Traceable author statement. Source: ProtInc
Molecular function	alcohol dehydrogenase activity, zinc-dependent Traceable author statement. Source: ProtInc electron carrier activity Traceable author statement. Source: UniProtKB zinc ion binding Inferred from direct assay. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Molecule processing

Initiator methionine

1

1

Removed

Chain

2 – 375

374

Alcohol dehydrogenase 1B

Sites

Metal binding

47

1

Zinc 1; catalytic

Metal binding

68

1

Zinc 1; catalytic

Metal binding

98

1

Zinc 2

Metal binding

101

1

Zinc 2

Metal binding

104

1

Zinc 2

Metal binding

112

1

Zinc 2

Metal binding

175

1

Zinc 1; catalytic

Amino acid modifications

Modified residue

2

1

N-acetylserine

Natural variations

Natural variant

48

1

R → H in beta-2; allele ADH1B*2; common in Asian populations; associated with a lower risk of alcoholism.

Natural variant

57

1

N → K: dbSNP rs1041969.

Natural variant

60

1

T → S: dbSNP rs6413413.

Natural variant

370

1

R → C in beta-3/Indianapolis; allele ADH1B*3; decreased NAD(H) binding.

Experimental info

Sequence conflict

8

1

I → M in AAA51592. Ref.13

Sequence conflict

130

1

Missing AA sequence Ref.12

Sequence conflict

166

1

P → K in AAA51592. Ref.13

Sequence conflict

190

1

V → VV in CAA33487. Ref.8

Sequence conflict

230

1

F → K in AAA51884. Ref.1

Sequence conflict

235

1

E → V in AAA51592. Ref.13

Secondary structure

1

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375

Helix Strand Turn

Details...

Beta strand

8 – 15

8

Beta strand

23 – 29

7

Beta strand

36 – 45

10

Helix

48 – 54

7

Beta strand

62 – 65

4

Beta strand

69 – 77

9

Beta strand

89 – 92

4

Beta strand

99 – 101

3

Helix

102 – 105

4

Beta strand

116 – 119

4

Beta strand

131 – 133

3

Beta strand

136 – 139

4

Turn

142 – 144

3

Beta strand

147 – 154

8

Helix

155 – 157

3

Beta strand

158 – 160

3

Turn

167 – 169

3

Helix

170 – 174

5

Helix

176 – 185

10

Turn

186 – 188

3

Beta strand

195 – 199

5

Helix

203 – 215

13

Beta strand

218 – 223

6

Helix

227 – 229

3

Helix

230 – 236

7

Beta strand

239 – 242

4

Helix

244 – 246

3

Helix

251 – 258

8

Beta strand

263 – 268

6

Helix

273 – 281

9

Turn

285 – 287

3

Beta strand

289 – 292

4

Beta strand

302 – 304

3

Helix

307 – 310

4

Beta strand

314 – 317

4

Helix

320 – 322

3

Helix

325 – 337

13

Turn

344 – 346

3

Beta strand

347 – 352

6

Helix

353 – 355

3

Helix

356 – 364

9

Beta strand

369 – 374

6

Sequences

	Sequence		Length	Mass (Da)
	P00325-1 [UniParc]. Last modified January 23, 2007. Version 2. Checksum: 6962B9A0F967673B	FASTA	375	39,855
	10 20 30 40 50 60 MSTAGKVIKC KAAVLWEVKK PFSIEDVEVA PPKAYEVRIK MVAVGICRTD DHVVSGNLVT 70 80 90 100 110 120 PLPVILGHEA AGIVESVGEG VTTVKPGDKV IPLFTPQCGK CRVCKNPESN YCLKNDLGNP 130 140 150 160 170 180 RGTLQDGTRR FTCRGKPIHH FLGTSTFSQY TVVDENAVAK IDAASPLEKV CLIGCGFSTG 190 200 210 220 230 240 YGSAVNVAKV TPGSTCAVFG LGGVGLSAVM GCKAAGAARI IAVDINKDKF AKAKELGATE 250 260 270 280 290 300 CINPQDYKKP IQEVLKEMTD GGVDFSFEVI GRLDTMMASL LCCHEACGTS VIVGVPPASQ 310 320 330 340 350 360 NLSINPMLLL TGRTWKGAVY GGFKSKEGIP KLVADFMAKK FSLDALITHV LPFEKINEGF 370 DLLHSGKSIR TVLTF

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning of a full-length cDNA for human alcohol dehydrogenase." Ikuta T., Fujiyoshi T., Kurachi K., Yoshida A. Proc. Natl. Acad. Sci. U.S.A. 82:2703-2707(1985) [PubMed: 2986130] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	Erratum Ikuta T., Fujiyoshi T., Kurachi K., Yoshida A. Proc. Natl. Acad. Sci. U.S.A. 82:5578-5578(1985)
[3]	"cDNA clones coding for the beta-subunit of human liver alcohol dehydrogenase have differently sized 3'-non-coding regions." Heden L.-O., Hoeoeg J.-O., Larsson K., Lake M., Lagerholm E., Holmgren A., Vallee B.L., Joernvall H., von Bahr-Lindstroem H. FEBS Lett. 194:327-332(1986) [PubMed: 3000832] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]	"Molecular analysis of the human class I alcohol dehydrogenase gene family and nucleotide sequence of the gene encoding the beta subunit." Duester G., Smith M., Bilanchone V., Hatfield G.W. J. Biol. Chem. 261:2027-2033(1986) [PubMed: 2935533] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[5]	"Three human alcohol dehydrogenase subunits: cDNA structure and molecular and evolutionary divergence." Ikuta T., Szeto S., Yoshida A. Proc. Natl. Acad. Sci. U.S.A. 83:634-638(1986) [PubMed: 2935875] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[6]	"Molecular characterization of cDNA clones encoding the human alcohol dehydrogenase beta 1 and the evolutionary relationship to the other class I subunits alpha and gamma." Yokoyama S., Yokoyama R., Rotwein P. Jpn. J. Genet. 62:241-256(1987) Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[7]	"Nucleotide sequence of the ADH2(3) gene encoding the human alcohol dehydrogenase beta 3 subunit." Carr L.G., Xu Y., Ho W.H., Edenberg H.J. Alcohol. Clin. Exp. Res. 13:594-596(1989) [PubMed: 2679216] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS HIS-48; LYS-57 AND CYS-370. Tissue: Liver.
[8]	"The genes for human alcohol dehydrogenases beta 1 and beta 2 differ by only one nucleotide." Matsuo Y., Yokoyama R., Yokoyama S. Eur. J. Biochem. 183:317-320(1989) [PubMed: 2547609] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT HIS-48.
[9]	Polin L., Hey-Chi H. Submitted (MAY-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT HIS-48. Tissue: Liver.
[10]	"NIEHS-SNPs, environmental genome project, NIEHS ES15478, Department of Genome Sciences, Seattle, WA (URL: http://egp.gs.washington.edu)." Livingston R.J., Rieder M.J., Shaffer T., Bertucci C., Baier C.N., Rajkumar N., Willa H.T., Daniels M., Downing T.K., Stanaway I.B., Nguyen C.P., Gildersleeve H., Cassidy C.M., Johnson E.J., Swanson J.E., McFarland I., Yool B., Park C., Nickerson D.A. Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS HIS-48; SER-60 AND CYS-370.
[11]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Testis.
[12]	"Human liver alcohol dehydrogenase. 1. The primary structure of the beta 1 beta 1 isoenzyme." Hempel J., Buhler R., Kaiser R., Holmquist B., de Zalenski C., von Wartburg J.-P., Vallee B.L., Joernvall H. Eur. J. Biochem. 145:437-445(1984) [PubMed: 6391920] [Abstract] Cited for: PROTEIN SEQUENCE OF 2-375.
[13]	"Genotyping of human alcohol dehydrogenases at the ADH2 and ADH3 loci following DNA sequence amplification." Xu Y.L., Carr L.G., Bosron W.F., Li T.K., Edenberg H.J. Genomics 2:209-214(1988) [PubMed: 3397059] [Abstract] Cited for: PARTIAL NUCLEOTIDE SEQUENCE [MRNA], VARIANT LYS-57.
[14]	Osier M., Speed W.C., Seaman M.I., Kidd K.K. Submitted (JAN-1998) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 41-86.
[15]	"Human liver alcohol dehydrogenase: amino acid substitution in the beta 2 beta 2 Oriental isozyme explains functional properties, establishes an active site structure, and parallels mutational exchanges in the yeast enzyme." Joernvall H., Hempel J., Vallee B.L., Bosron W.F., Li T.-K. Proc. Natl. Acad. Sci. U.S.A. 81:3024-3028(1984) [PubMed: 6374651] [Abstract] Cited for: VARIANT HIS-48.
[16]	"The human beta 3 alcohol dehydrogenase subunit differs from beta 1 by a Cys for Arg-369 substitution which decreases NAD(H) binding." Burnell J.C., Carr L.G., Dwulet F.E., Edenberg H.J., Li T.-K., Bosron W.F. Biochem. Biophys. Res. Commun. 146:1127-1133(1987) [PubMed: 3619918] [Abstract] Cited for: VARIANT CYS-370.
[17]	"Structure of human beta 1 beta 1 alcohol dehydrogenase: catalytic effects of non-active-site substitutions." Hurley T.D., Bosron W.F., Hamilton J.A., Amzel L.M. Proc. Natl. Acad. Sci. U.S.A. 88:8149-8153(1991) [PubMed: 1896463] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS).
[18]	"Structures of three human beta alcohol dehydrogenase variants. Correlations with their functional differences." Hurley T.D., Bosron W.F., Stone C.L., Amzel L.M. J. Mol. Biol. 239:415-429(1994) [PubMed: 8201622] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.45 ANGSTROMS).
[19]	"X-ray structure of human beta3beta3 alcohol dehydrogenase. The contribution of ionic interactions to coenzyme binding." Davis G.J., Bosron W.F., Stone C.L., Owusu-Dekyi K., Hurley T.D. J. Biol. Chem. 271:17057-17061(1996) [PubMed: 8663387] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS).
[20]	"Three-dimensional structures of the three human class I alcohol dehydrogenases." Niederhut M.S., Gibbons B.J., Perez-Miller S., Hurley T.D. Protein Sci. 10:697-706(2001) [PubMed: 11274460] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS).
[21]	"Genetic polymorphism of alcohol dehydrogenase in Europeans: the ADH2*2 allele decreases the risk for alcoholism and is associated with ADH3*1." Borras E., Coutelle C., Rosell A., Fernandez-Muixi F., Broch M., Crosas B., Hjelmqvist L., Lorenzo A., Gutierrez C., Santos M., Szczepanek M., Heilig M., Quattrocchi P., Farres J., Vidal F., Richart C., Mach T., Bogdal J. , Jornvall H., Seitz H.K., Couzigou P., Pares X. Hepatology 31:984-989(2000) [PubMed: 10733556] [Abstract] Cited for: ASSOCIATION OF VARIANT HIS-48 WITH LOWER RISK OF ALCOHOLISM.
+	Additional computationally mapped references.

Cross-references

Sequence databases