Alcohol dehydrogenase class-3 - Homo sapiens (Human)

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Reviewed, UniProtKB/Swiss-Prot P11766 (ADHX_HUMAN)

Last modified June 16, 2009. Version 112. History...

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Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents

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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

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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.

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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.

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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 Inferred from electronic annotation. Source: InterPro oxidation reduction Inferred from electronic annotation. Source: UniProtKB-KW response to redox state Ref.10 Inferred from direct assay. Source: UniProtKB
Molecular function	S-(hydroxymethyl)glutathione dehydrogenase activity Ref.10 Traceable author statement. Source: UniProtKB alcohol dehydrogenase activity Inferred from electronic annotation. Source: EC electron carrier activity Ref.10 Traceable author statement. Source: UniProtKB fatty acid binding Ref.10 Inferred from direct assay. Source: UniProtKB formaldehyde dehydrogenase activity Ref.10 Inferred from direct assay. Source: UniProtKB zinc ion binding Inferred from direct assay. Source: UniProtKB
Complete GO annotation...

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Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

Removed Ref.8

Chain

2 – 374

373

Alcohol dehydrogenase class-3

PRO_0000160759

Sites

Metal binding

Zinc 1; catalytic Ref.8

Metal binding

Zinc 1; catalytic Ref.8

Metal binding

Zinc 2 Ref.8

Metal binding

100

Zinc 2 Ref.8

Metal binding

103

Zinc 2 Ref.8

Metal binding

111

Zinc 2 Ref.8

Metal binding

174

Zinc 1; catalytic

Site

115

Important for FDH activity and activation by fatty acids

Amino acid modifications

Modified residue

N-acetylalanine Ref.8

Natural variations

Natural variant

163

L → S: dbSNP rs28730623. Ref.6

VAR_025823

Natural variant

309

V → I Ref.6

VAR_025824

Natural variant

353

D → E: dbSNP rs16996593.

VAR_048199

Experimental info

Mutagenesis

115

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

Sequence conflict

167

D → Y in AAA51597. Ref.2

Sequence conflict

246

F → L in AAA51597. Ref.2

Secondary structure

374

Helix Strand Turn

Details...

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Sequences

Sequence

Length

Mass (Da)

Tools

P11766-1 [UniParc].

Last modified January 23, 2007. Version 4.
Checksum: F4F823B4A609C952
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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

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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 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: 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]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[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: 9018047] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS).
+	Additional computationally mapped references.

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Web resources

NIEHS-SNPs

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Cross-references

Sequence databases

M30471 mRNA. Translation: AAA79018.1.
M29872 mRNA. Translation: AAA51597.1.
M81118

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.

UniGene

Hs.78989

3D structure databases

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	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

P11766. 1 interaction.

PTM databases

PhosphoSite

P11766.

2-D gel databases

REPRODUCTION-2DPAGE

IPI00746777.

Proteomic databases

PRIDE

P11766.

Genome annotation databases

Ensembl

ENSG00000197894. Homo sapiens. [Contig view]

GeneID

128.

KEGG

hsa:128.

Organism-specific databases

GeneCards

GC04M100238.
GC06M066606.

H-InvDB

HIX0004394.
HIX0033392.

HGNC

HGNC:253. ADH5.

MIM

103710. gene.

PharmGKB

PA24574.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

P11766.

HOVERGEN

P11766.

Enzyme and pathway databases

BRENDA

1.1.1.1. 247.
1.1.1.284. 247.

Gene expression databases

ArrayExpress

P11766.

Bgee

P11766.

CleanEx

HS_ADH5.

GermOnline

ENSG00000197894. Homo sapiens.

Family and domain databases

InterPro

IPR014183. ADH_3.
IPR013154. ADH_GroES-like.
IPR002085. ADH_SF_Zn.
IPR013149. ADH_Zn-bd.
IPR002328. ADH_Zn_CS.
[Graphical view]

PANTHER

PTHR11695. ADH_Sf_Zn. 1 hit.

Pfam

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

TIGRFAMs

TIGR02818. adh_III_F_hyde. 1 hit.

PROSITE

PS00059. ADH_ZINC. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

DrugBank

DB00157. NADH.

NextBio

511.

SOURCE

Search...

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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:	June 16, 2009
This is version 112 of the entry and version 4 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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