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Reviewed, UniProtKB/Swiss-Prot P11766 (ADHX_HUMAN)

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

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents

Names and origin

Protein namesRecommended 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
OrganismHomo sapiens (Human)
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length374 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence 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.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed Ref.8
Chain2 – 374373Alcohol dehydrogenase class-3
PRO_0000160759

Sites

Metal binding451Zinc 1; catalytic Ref.8
Metal binding671Zinc 1; catalytic Ref.8
Metal binding971Zinc 2 Ref.8
Metal binding1001Zinc 2 Ref.8
Metal binding1031Zinc 2 Ref.8
Metal binding1111Zinc 2 Ref.8
Metal binding1741Zinc 1; catalytic
Site1151Important for FDH activity and activation by fatty acids

Amino acid modifications

Modified residue21N-acetylalanine Ref.8

Natural variations

Natural variant1631L → S: dbSNP rs28730623. Ref.6
VAR_025823
Natural variant3091V → I Ref.6
VAR_025824
Natural variant3531D → E: dbSNP rs16996593.
VAR_048199

Experimental info

Mutagenesis1151R → A or D: Loss of FDH activity and loss of activation by fatty acids. Ref.9 Ref.10
Sequence conflict1671D → Y in AAA51597. Ref.2
Sequence conflict2461F → L in AAA51597. Ref.2

Secondary structure

............................................................................ 374
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P11766-1 [UniParc].

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

FASTA37439,724
        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 

« Hide

References

« Hide '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.

Web resources

Cross-references

Sequence databases

M30471 mRNA. Translation: AAA79018.1.
M29872 mRNA. Translation: AAA51597.1.
M81118 expand/collapse EMBL AC list , 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.
IPIIPI00746777.
PIRDEHUC2. JH0789.
RefSeqNP_000662.3.
UniGeneHs.78989

3D structure databases

EntryMethodResolution (Å)ChainPositionsPDBsum
1M6HX-ray2.00A/B2-373[»]
1M6WX-ray2.30A/B2-373[»]
1MA0X-ray2.30A/B2-373[»]
1MC5X-ray2.60A/B1-374[»]
1MP0X-ray2.20A/B2-373[»]
1TEHX-ray2.70A/B2-374[»]
2FZEX-ray1.90A/B2-373[»]
2FZWX-ray1.84A/B2-373[»]
ModBaseSearch...

Protein-protein interaction databases

IntActP11766. 1 interaction.

PTM databases

PhosphoSiteP11766.

2-D gel databases

REPRODUCTION-2DPAGEIPI00746777.

Proteomic databases

PRIDEP11766.

Genome annotation databases

EnsemblENSG00000197894. Homo sapiens. [Contig view]
GeneID128.
KEGGhsa:128.

Organism-specific databases

GeneCardsGC04M100238.
GC06M066606.
H-InvDBHIX0004394.
HIX0033392.
HGNCHGNC:253. ADH5.
MIM103710. gene.
PharmGKBPA24574.
GenAtlasSearch...

Phylogenomic databases

HOGENOMP11766.
HOVERGENP11766.

Enzyme and pathway databases

BRENDA1.1.1.1. 247.
1.1.1.284. 247.

Gene expression databases

ArrayExpressP11766.
BgeeP11766.
CleanExHS_ADH5.
GermOnlineENSG00000197894. Homo sapiens.

Family and domain databases

InterProIPR014183. ADH_3.
IPR013154. ADH_GroES-like.
IPR002085. ADH_SF_Zn.
IPR013149. ADH_Zn-bd.
IPR002328. ADH_Zn_CS.
[Graphical view]
PANTHERPTHR11695. ADH_Sf_Zn. 1 hit.
PfamPF08240. ADH_N. 1 hit.
PF00107. ADH_zinc_N. 1 hit.
[Graphical view]
TIGRFAMsTIGR02818. adh_III_F_hyde. 1 hit.
PROSITEPS00059. ADH_ZINC. 1 hit.
[Graphical view]
ProtoNetSearch...

Other Resources

DrugBankDB00157. NADH.
NextBio511.
SOURCESearch...

Entry information

Entry nameADHX_HUMAN
AccessionPrimary (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 statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)

Relevant documents

Human chromosome 4

Human chromosome 4: entries, gene names and cross-references to MIM

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families

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