Reviewed, UniProtKB/Swiss-Prot P11766 (ADHX_HUMAN)

Names and origin

Protein names

Recommended name:
    Alcohol dehydrogenase class-3
    EC=1.1.1.1
Alternative name(s):
    Alcohol dehydrogenase class-III
    Alcohol dehydrogenase 5
    Alcohol dehydrogenase class chi chain
    S-(hydroxymethyl)glutathione dehydrogenase
    EC=1.1.1.284
    Glutathione-dependent formaldehyde dehydrogenase
      Short name=GSH-FDH
      Short name=FALDH
      Short name=FDH
    EC=1.1.1.-

Gene names

Name:	ADH5
Synonyms:	ADHX, FDH

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 further processed into a mature form.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Class-III ADH is remarkably ineffective in oxidizing ethanol, but it readily catalyzes the oxidation of long-chain primary alcohols and the oxidation of S-(hydroxymethyl) glutathione.
Catalytic activity	An alcohol + NAD(+) = an aldehyde or ketone + NADH. S-(hydroxymethyl)glutathione + NAD(P)(+) = S-formylglutathione + NAD(P)H.
Cofactor	Binds 2 zinc ions per subunit.
Subunit structure	Homodimer.
Subcellular location	Cytoplasm.
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-III subfamily.

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 Ref.10 Traceable author statement. Source: ProtInc
Molecular function	S-(hydroxymethyl)glutathione dehydrogenase activity Ref.10 Traceable author statement. Source: UniProtKB electron carrier activity Ref.10 Traceable author statement. Source: UniProtKB fatty acid binding Ref.10 Traceable author statement. Source: ProtInc
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Molecule processing

Initiator methionine

1

1

Removed

Chain

2 – 374

373

Alcohol dehydrogenase class-3

Sites

Metal binding

45

1

Zinc 1; catalytic

Metal binding

67

1

Zinc 1; catalytic

Metal binding

97

1

Zinc 2

Metal binding

100

1

Zinc 2

Metal binding

103

1

Zinc 2

Metal binding

111

1

Zinc 2

Metal binding

174

1

Zinc 1; catalytic

Site

115

1

Important for FDH activity and activation by fatty acids

Amino acid modifications

Modified residue

2

1

N-acetylalanine

Natural variations

Natural variant

163

1

L → S

Natural variant

309

1

V → I

Experimental info

Mutagenesis

115

1

R → A or D: Loss of FDH activity and loss of activation by fatty acids

Sequence conflict

167

1

D → Y in AAA51597. Ref.2

Sequence conflict

246

1

F → L in AAA51597. Ref.2

Secondary structure

1

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374

Helix Strand Turn

Details...

Beta strand

6 – 13

8

Beta strand

21 – 27

7

Beta strand

34 – 43

10

Helix

46 – 53

8

Beta strand

61 – 63

3

Beta strand

68 – 76

9

Beta strand

88 – 91

4

Helix

101 – 104

4

Helix

115 – 119

5

Beta strand

129 – 132

4

Beta strand

135 – 138

4

Turn

141 – 143

3

Beta strand

146 – 153

8

Beta strand

156 – 159

4

Helix

166 – 169

4

Helix

170 – 173

4

Helix

175 – 184

10

Turn

185 – 187

3

Beta strand

194 – 198

5

Helix

202 – 213

12

Beta strand

217 – 222

6

Helix

226 – 228

3

Helix

229 – 234

6

Beta strand

238 – 241

4

Helix

243 – 245

3

Helix

250 – 257

8

Beta strand

262 – 267

6

Helix

272 – 280

9

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 – 336

13

Helix

343 – 345

3

Beta strand

346 – 351

6

Helix

352 – 354

3

Helix

355 – 362

8

Beta strand

363 – 366

4

Beta strand

369 – 373

5

Sequences

	Sequence		Length	Mass (Da)
	P11766-1 [UniParc]. Last modified January 23, 2007. Version 4. Checksum: F4F823B4A609C952	FASTA	374	39,724
	10 20 30 40 50 60 MANEVIKCKA AVAWEAGKPL SIEEIEVAPP KAHEVRIKII ATAVCHTDAY TLSGADPEGC 70 80 90 100 110 120 FPVILGHEGA GIVESVGEGV TKLKAGDTVI PLYIPQCGEC KFCLNPKTNL CQKIRVTQGK 130 140 150 160 170 180 GLMPDGTSRF TCKGKTILHY MGTSTFSEYT VVADISVAKI DPLAPLDKVC LLGCGISTGY 190 200 210 220 230 240 GAAVNTAKLE PGSVCAVFGL GGVGLAVIMG CKVAGASRII GVDINKDKFA RAKEFGATEC 250 260 270 280 290 300 INPQDFSKPI QEVLIEMTDG GVDYSFECIG NVKVMRAALE ACHKGWGVSV VVGVAASGEE 310 320 330 340 350 360 IATRPFQLVT GRTWKGTAFG GWKSVESVPK LVSEYMSKKI KVDEFVTHNL SFDEINKAFE 370 LMHSGKSIRT VVKI

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"cDNA sequence of human class III alcohol dehydrogenase." Sharma C.P., Fox E.A., Holmquist B., Joernvall H., Vallee B.L. Biochem. Biophys. Res. Commun. 164:631-637(1989) [PubMed: 2818582] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Cloning and comparative mapping of a human class III (chi) alcohol dehydrogenase cDNA." Giri P.R., Krug J.F., Kozak C., Moretti T., O'Brien S.J., Seuanez H.N., Goldman D. Biochem. Biophys. Res. Commun. 164:453-460(1989) [PubMed: 2679557] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"Cloning and characterization of the ADH5 gene encoding human alcohol dehydrogenase 5, formaldehyde dehydrogenase." Hur M.W., Edenberg H.J. Gene 121:305-311(1992) [PubMed: 1446828] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]	"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)." Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S., Neubert P., Kstrang K., Schatten R., Shen B., Henze S., Mar W., Korn B., Zuo D., Hu Y., LaBaer J. Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[5]	"Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[6]	"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., Rajkumar N., Downing T.K., Olson A.N., Nguyen C.P., Gildersleeve H., Cassidy C.M., Johnson E.J., Swanson J.E., McFarland I., Yool B., Park C., Nickerson D.A. Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS SER-163 AND ILE-309.
[7]	"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: B-cell.
[8]	"Class III human liver alcohol dehydrogenase: a novel structural type equidistantly related to the class I and class II enzymes." Kaiser R., Holmquist B., Hempel J., Vallee B.L., Joernvall H. Biochemistry 27:1132-1140(1988) [PubMed: 3365377] [Abstract] Cited for: PROTEIN SEQUENCE OF 2-374. Tissue: Liver.
[9]	"Role of arginine 115 in fatty acid activation and formaldehyde dehydrogenase activity of human class III alcohol dehydrogenase." Holmquist B., Moulis J.-M., Engeland K., Vallee B.L. Biochemistry 32:5139-5144(1993) [PubMed: 8494891] [Abstract] Cited for: PARTIAL PROTEIN SEQUENCE, MUTAGENESIS OF ARG-115.
[10]	"Mutation of Arg-115 of human class III alcohol dehydrogenase: a binding site required for formaldehyde dehydrogenase activity and fatty acid activation." Engeland K., Hoeoeg J.-O., Holmquist B., Estonius M., Joernvall H., Vallee B.L. Proc. Natl. Acad. Sci. U.S.A. 90:2491-2494(1993) [PubMed: 8460164] [Abstract] Cited for: MUTAGENESIS OF ARG-115.
[11]	"Structure of human chi chi alcohol dehydrogenase: a glutathione-dependent formaldehyde dehydrogenase." Yang Z.-N., Bosron W.F., Hurley T.D. J. Mol. Biol. 265:330-343(1997) [PubMed: 9018047] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS).
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

M30471 mRNA. Translation: AAA79018.1.
M29872 mRNA. Translation: AAA51597.1.
M81118 , M81112, M81113, M81114, M81115, M81116, M81117 Genomic DNA. Translation: AAA51596.1.
CR541689 mRNA. Translation: CAG46490.1.
BT019832 mRNA. Translation: AAV38635.1.
AY987960 Genomic DNA. Translation: AAX81412.1.
BC014665 mRNA. Translation: AAH14665.1.

PIR

DEHUC2. JH0789.

RefSeq

NP_000662.3.

UniGene

Hs.78989

3D structure databases

PDBMSD

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1M6H	X-ray	2.00	A/B	1-374	[»]
1M6W	X-ray	2.30	A/B	1-374	[»]
1MA0	X-ray	2.30	A/B	1-374	[»]
1MC5	X-ray	2.60	A/B	1-374	[»]
1MP0	X-ray	2.20	A/B	1-374	[»]
1TEH	X-ray	2.70	A/B	1-374	[»]
2FZE	X-ray	1.90	A/B	2-374	[»]
2FZW	X-ray	1.84	A/B	2-374	[»]

ModBase

Search...

PTM databases

PhosphoSite

P11766.

Polymorphism databases

NIEHS-SNPs

Search...

2-D gel databases

REPRODUCTION-2DPAGE

IPI00746777.

Genome annotation databases

Ensembl

ENSG00000197894. Homo sapiens. [Contig view]