P11766 (ADHX_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Alcohol dehydrogenase class-3
EC=1.1.1.1

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

Gene names

Name:	ADH5
Synonyms:	ADHX, FDH

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › 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 Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	aging Inferred from electronic annotation. Source: Compara ethanol catabolic process Inferred from electronic annotation. Source: Compara ethanol oxidation Inferred from electronic annotation. Source: InterPro formaldehyde catabolic process Inferred from electronic annotation. Source: Compara peptidyl-cysteine S-nitrosylation Inferred from electronic annotation. Source: Compara positive regulation of blood pressure Inferred from electronic annotation. Source: Compara respiratory system process Inferred from electronic annotation. Source: Compara response to lipopolysaccharide Inferred from electronic annotation. Source: Compara response to nitrosative stress Inferred from electronic annotation. Source: Compara response to redox state Inferred from direct assay Ref.10. Source: UniProtKB retinoid metabolic process Inferred from electronic annotation. Source: Compara
Cellular_component	mitochondrion Inferred from electronic annotation. Source: Compara nucleus Inferred from electronic annotation. Source: Compara
Molecular_function	S-(hydroxymethyl)glutathione dehydrogenase activity Traceable author statement Ref.10. Source: UniProtKB alcohol dehydrogenase (NAD) activity Inferred from electronic annotation. Source: EC electron carrier activity Traceable author statement Ref.10. Source: UniProtKB fatty acid binding Inferred from direct assay Ref.10. Source: UniProtKB formaldehyde dehydrogenase activity Inferred from direct assay Ref.10. Source: UniProtKB nucleotide binding Inferred from electronic annotation. Source: InterPro zinc ion binding Inferred from direct assay PubMed 6375718. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed Ref.8

Chain

2 – 374

373

Alcohol dehydrogenase class-3

PRO_0000160759

Sites

Metal binding

45

1

Zinc 1; catalytic Ref.8

Metal binding

67

1

Zinc 1; catalytic Ref.8

Metal binding

97

1

Zinc 2 Ref.8

Metal binding

100

1

Zinc 2 Ref.8

Metal binding

103

1

Zinc 2 Ref.8

Metal binding

111

1

Zinc 2 Ref.8

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 By similarity

Natural variations

Natural variant

163

1

L → S. Ref.6
Corresponds to variant rs28730623 [ dbSNP | Ensembl ].

VAR_025823

Natural variant

309

1

V → I. Ref.6
Corresponds to variant rs28730628 [ dbSNP | Ensembl ].

VAR_025824

Natural variant

353

1

D → E.
Corresponds to variant rs16996593 [ dbSNP | Ensembl ].

VAR_048199

Experimental info

Mutagenesis

115

1

R → A or D: Loss of FDH activity and loss of activation by fatty acids. Ref.9 Ref.10

Sequence conflict

167

1

D → Y in AAA51597. Ref.2

Sequence conflict

246

1

F → L in AAA51597. Ref.2

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

374

Helix Strand Turn

Details...

Beta strand

6 – 13

8

Beta strand

21 – 27

7

Beta strand

34 – 43

10

Helix

46 – 52

7

Beta strand

61 – 63

3

Beta strand

68 – 76

9

Beta strand

88 – 91

4

Beta strand

98 – 100

3

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

Helix

154 – 156

3

Beta strand

157 – 159

3

Helix

166 – 169

4

Helix

170 – 173

4

Helix

175 – 184

10

Turn

185 – 187

3

Beta strand

194 – 198

5

Helix

202 – 214

13

Beta strand

217 – 222

6

Helix

226 – 228

3

Helix

229 – 235

7

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 – 363

9

Beta strand

368 – 373

6

Sequences

	Sequence		Length	Mass (Da)
	P11766 [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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 program 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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [Abstract] Cited for: MUTAGENESIS OF ARG-115.
[11]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[12]	"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] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS).
+	Additional computationally mapped references.

Web resources

NIEHS-SNPs

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

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.

IPI

IPI00746777.

PIR

DEHUC2. JH0789.

RefSeq

NP_000662.3. NM_000671.3.

UniGene

Hs.78989.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1M6H	X-ray	2.00	A/B	2-373	[»]
1M6W	X-ray	2.30	A/B	2-373	[»]
1MA0	X-ray	2.30	A/B	2-373	[»]
1MC5	X-ray	2.60	A/B	1-374	[»]
1MP0	X-ray	2.20	A/B	2-373	[»]
1TEH	X-ray	2.70	A/B	2-374	[»]
2FZE	X-ray	1.90	A/B	2-373	[»]
2FZW	X-ray	1.84	A/B	2-373	[»]
3QJ5	X-ray	1.90	A/B	2-374	[»]

ProteinModelPortal

P11766.

ModBase

Search...

Protein-protein interaction databases

IntAct

P11766. 7 interactions.

MINT

MINT-1374117.

STRING

9606.ENSP00000296412.

PTM databases

PhosphoSite

P11766.

Polymorphism databases

DMDM

113408.

2D gel databases

REPRODUCTION-2DPAGE

IPI00746777.

Proteomic databases

PaxDb

P11766.

PRIDE

P11766.

Protocols and materials databases

DNASU

128.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000296412; ENSP00000296412; ENSG00000197894.

GeneID

128.

KEGG

hsa:128.

UCSC

uc003hui.3. human.

Organism-specific databases

CTD

128.

GeneCards

GC04M099992.

HGNC

HGNC:253. ADH5.

HPA

HPA044578.

MIM

103710. gene.

neXtProt

NX_P11766.

PharmGKB

PA24574.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG1062.

HOGENOM

HOG000294674.

HOVERGEN

HBG000195.

InParanoid

P11766.

KO

K00121.

OMA

CGKIRAT.

OrthoDB

EOG4J6RR3.

PhylomeDB

P11766.

Enzyme and pathway databases

SABIO-RK

P11766.

Gene expression databases

ArrayExpress

P11766.

Bgee

P11766.

CleanEx

HS_ADH5.

Genevestigator

P11766.

GermOnline

ENSG00000197894. Homo sapiens.

Family and domain databases

Gene3D

3.40.50.720. 1 hit.

InterPro

IPR014183. ADH_3.
IPR013149. ADH_C.
IPR013154. ADH_GroES-like.
IPR002085. ADH_SF_Zn-type.
IPR002328. ADH_Zn_CS.
IPR011032. GroES-like.
IPR016040. NAD(P)-bd_dom.
[Graphical view]

PANTHER

PTHR11695. PTHR11695. 1 hit.

Pfam

PF08240. ADH_N. 1 hit.
PF00107. ADH_zinc_N. 1 hit.
[Graphical view]

SUPFAM

SSF50129. GroES_like. 2 hits.

TIGRFAMs

TIGR02818. adh_III_F_hyde. 1 hit.

PROSITE

PS00059. ADH_ZINC. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

P11766.

ChEMBL

CHEMBL4116.

ChiTaRS

ADH5. human.

DrugBank

DB00157. NADH.

EvolutionaryTrace

P11766.

GenomeRNAi

128.

NextBio

511.

SOURCE

Search...

Entry information

Entry name

ADHX_HUMAN

Accession

Primary (citable) accession number: P11766
Secondary accession number(s): Q6FHR2

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1989
Last sequence update:	January 23, 2007
Last modified:	May 1, 2013
This is version 155 of the entry and version 4 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.