Reviewed, UniProtKB/Swiss-Prot P40394 (ADH7_HUMAN)

Names and origin

Protein names

Recommended name:
    Alcohol dehydrogenase class 4 mu/sigma chain
    EC=1.1.1.1
Alternative name(s):
    Alcohol dehydrogenase class IV mu/sigma chain
    Retinol dehydrogenase
    Gastric alcohol dehydrogenase

Gene names

Name:

ADH7

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	374 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Could function in retinol oxidation for the synthesis of retinoic acid, a hormone important for cellular differentiation. Medium-chain (octanol) and aromatic (m-nitrobenzaldehyde) compounds are the best substrates. Ethanol is not a good substrate but at the high ethanol concentrations reached in the digestive tract, it plays a role in the ethanol oxidation and contributes to the first pass ethanol metabolism.
Catalytic activity	An alcohol + NAD(+) = an aldehyde or ketone + NADH.
Cofactor	Binds 2 zinc ions per subunit.
Subunit structure	Homodimer.
Subcellular location	Cytoplasm.
Tissue specificity	Preferentially expressed in stomach.
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. Class-IV subfamily.

Ontologies

Keywords
Cellular component	Cytoplasm
Coding sequence diversity	Polymorphism
Ligand	Metal-binding NAD Zinc
Molecular function	Oxidoreductase
Technical term	3D-structure Direct protein sequencing
Gene Ontology (GO)
Biological process	ethanol oxidation Ref.5 Inferred from direct assay. Source: UniProtKB fatty acid omega-oxidation Inferred from direct assay. Source: UniProtKB oxidation reduction Ref.5 Inferred from direct assay. Source: UniProtKB response to ethanol Inferred from direct assay. Source: UniProtKB retinoid metabolic process Inferred from direct assay. Source: UniProtKB
Cellular component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	alcohol dehydrogenase activity, zinc-dependent Ref.5 Inferred from direct assay. Source: UniProtKB aldehyde oxidase activity Inferred from direct assay. Source: UniProtKB ethanol binding Ref.9 Inferred from direct assay. Source: UniProtKB receptor antagonist activity Inferred from direct assay. Source: UniProtKB retinol binding Ref.9 Inferred from direct assay. Source: UniProtKB retinol dehydrogenase activity Ref.5 Inferred from direct assay. Source: UniProtKB zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 374

374

Alcohol dehydrogenase class 4 mu/sigma chain

PRO_0000160691

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

174

1

Zinc 1; catalytic

Natural variations

Natural variant

80

1

G → A: dbSNP rs1573496.

VAR_024364

Experimental info

Sequence conflict

20

1

Q → R AA sequence Ref.8

Sequence conflict

71

1

T → R AA sequence Ref.8

Sequence conflict

98

1

C → V in AAB38424. Ref.6

Sequence conflict

138 – 139

2

HH → GR AA sequence Ref.8

Sequence conflict

148 – 149

2

EY → VI in AAB38424. Ref.6

Sequence conflict

157

1

V → E in AAB38424. Ref.6

Sequence conflict

205

1

L → V in AAB38424. Ref.6

Secondary structure

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374

Helix Strand Turn

Details...

Beta strand

8 – 17

10

Beta strand

23 – 29

7

Beta strand

36 – 45

10

Helix

48 – 55

8

Beta strand

62 – 64

3

Beta strand

69 – 77

9

Beta strand

89 – 92

4

Beta strand

99 – 101

3

Helix

102 – 105

4

Beta strand

130 – 138

9

Turn

141 – 143

3

Beta strand

146 – 153

8

Helix

154 – 156

3

Beta strand

157 – 159

3

Helix

166 – 169

4

Helix

170 – 173

4

Helix

175 – 184

10

Beta strand

194 – 198

5

Helix

202 – 213

12

Beta strand

217 – 222

6

Helix

226 – 228

3

Helix

229 – 235

7

Beta strand

238 – 241

4

Helix

243 – 245

3

Helix

250 – 258

9

Beta strand

264 – 267

4

Helix

272 – 279

8

Turn

284 – 286

3

Beta strand

288 – 291

4

Beta strand

301 – 303

3

Helix

306 – 309

4

Beta strand

313 – 316

4

Helix

319 – 321

3

Helix

324 – 335

12

Turn

336 – 338

3

Helix

343 – 345

3

Beta strand

346 – 351

6

Helix

352 – 354

3

Helix

355 – 363

9

Beta strand

368 – 373

6

Sequences

	Sequence		Length	Mass (Da)
	P40394-1 [UniParc]. Last modified February 1, 1995. Version 1. Checksum: 1D785CD022CBD387	FASTA	374	40,006
	10 20 30 40 50 60 MGTAGKVIKC KAAVLWEQKQ PFSIEEIEVA PPKTKEVRIK ILATGICRTD DHVIKGTMVS 70 80 90 100 110 120 KFPVIVGHEA TGIVESIGEG VTTVKPGDKV IPLFLPQCRE CNACRNPDGN LCIRSDITGR 130 140 150 160 170 180 GVLADGTTRF TCKGKPVHHF MNTSTFTEYT VVDESSVAKI DDAAPPEKVC LIGCGFSTGY 190 200 210 220 230 240 GAAVKTGKVK PGSTCVVFGL GGVGLSVIMG CKSAGASRII GIDLNKDKFE KAMAVGATEC 250 260 270 280 290 300 ISPKDSTKPI SEVLSEMTGN NVGYTFEVIG HLETMIDALA SCHMNYGTSV VVGVPPSAKM 310 320 330 340 350 360 LTYDPMLLFT GRTWKGCVFG GLKSRDDVPK LVTEFLAKKF DLDQLITHVL PFKKISEGFE 370 LLNSGQSIRT VLTF

References

[1]	"The complete structure of human class IV alcohol dehydrogenase (retinol dehydrogenase) determined from the ADH7 gene." Satre M.A., Zgombic-Knight M., Duester G. J. Biol. Chem. 269:15606-15612(1994) [PubMed: 8195208] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Stomach.
[2]	"Genomic structure and expression of the ADH7 gene encoding human class IV alcohol dehydrogenase, the form most efficient for retinol metabolism in vitro." Zgombic-Knight M., Foglio M.H., Duester G. J. Biol. Chem. 270:4305-4311(1995) [PubMed: 7876191] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	"Alcohol dehydrogenase of class IV (sigma sigma-ADH) from human stomach. cDNA sequence and structure/function relationships." Farres J., Moreno A., Crosas B., Peralba J.M., Allali-Hassani A., Hjelmqvist L., Joernvall H., Pares X. Eur. J. Biochem. 224:549-557(1994) [PubMed: 7925371] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Stomach.
[4]	"Molecular characterization of a class IV human alcohol dehydrogenase gene (ADH7)." Yokoyama S., Matsuo Y., Ramsbotham R., Yokoyama R. FEBS Lett. 351:411-415(1994) [PubMed: 8082805] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], ZINC-BINDING SITES. Tissue: Stomach.
[5]	"Expression and kinetic characterization of recombinant human stomach alcohol dehydrogenase. Active-site amino acid sequence explains substrate specificity compared with liver isozymes." Kedishvili N.Y., Bosron W.F., Stone C.L., Hurley T.D., Peggs C.F., Thomasson H.R., Popov K.M., Carr L.G., Edenberg H.J., Li T.K. J. Biol. Chem. 270:3625-3630(1995) [PubMed: 7876099] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Stomach.
[6]	"Molecular cloning and chromosomal localization of the ADH7 gene encoding human class IV (sigma) ADH." Yokoyama H., Baraona E., Lieber C.S. Genomics 31:243-245(1996) [PubMed: 8824810] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Tissue: Foreskin.
[7]	"Human stomach class IV alcohol dehydrogenase: molecular genetic analysis." Cheung B., Anderson J.K., Holmes R.S., Beacham I.R. Alcohol. Clin. Exp. Res. 19:185-186(1995) [PubMed: 7771649] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 227-299. Tissue: Stomach.
[8]	"Class IV alcohol dehydrogenase (the gastric enzyme). Structural analysis of human sigma sigma-ADH reveals class IV to be variable and confirms the presence of a fifth mammalian alcohol dehydrogenase class." Pares X., Cederlund E., Moreno A., Saubi N., Hoeoeg J.-O., Joernvall H. FEBS Lett. 303:69-72(1992) [PubMed: 1592118] [Abstract] Cited for: PROTEIN SEQUENCE OF 12-21; 41-46; 62-80; 85-111; 135-142 AND 169-174.
[9]	"X-ray structure of human class IV sigmasigma alcohol dehydrogenase. Structural basis for substrate specificity." Xie P., Parsons S.H., Speckhard D.C., Bosron W.F., Hurley T.D. J. Biol. Chem. 272:18558-18563(1997) [PubMed: 9228021] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS).
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

L33179 mRNA. Translation: AAA59211.1.
U16293 , U16286, U16287, U16288, U16289, U16290, U16291, U16292 Genomic DNA. Translation: AAC51351.1.
X76342 mRNA. Translation: CAA53961.1.
X76342 mRNA. Translation: CAA53960.1. Different initiation.
U07821 mRNA. Translation: AAA19002.1.
U09623 mRNA. Translation: AAA82165.1.
L47166 Genomic DNA. Translation: AAB38424.1.
S77168 mRNA. Translation: AAB34478.1.

PIR

DEHUAS. A55878.

UniGene

Hs.389

3D structure databases

PDBMSD

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1AGN	X-ray	3.00	A/B/C/D	2-374	[»]
1D1S	X-ray	2.50	A/B/C/D	2-374	[»]
1D1T	X-ray	2.40	A/B/C/D	2-374	[»]

ModBase

Search...

Genome annotation databases

Ensembl

ENSG00000196344. Homo sapiens. [Contig view]

NMPDR

fig|9606.3.peg.24458.

Organism-specific databases

H-InvDB

HIX0031505.

HGNC

HGNC:256. ADH7.

MIM

600086. gene.

PharmGKB

PA24577.

GenAtlas

Search...

GeneCards

Search...

Phylogenomic databases

HOGENOM

P40394.

HOVERGEN

P40394.

Enzyme and pathway databases

Reactome

REACT_2063. Metabolism of xenobiotics.

Gene expression databases

ArrayExpress

P40394.

CleanEx

HS_ADH7.

GermOnline

ENSG00000196344. Homo sapiens.

Family and domain databases