Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

P11766 (ADHX_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified March 19, 2014. Version 164. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
OrganismHomo sapiens (Human) [Reference proteome]
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.

Ontologies

Keywords
   Cellular componentCytoplasm
   Coding sequence diversityPolymorphism
   LigandMetal-binding
NAD
Zinc
   Molecular functionOxidoreductase
   PTMAcetylation
Phosphoprotein
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processaging

Inferred from electronic annotation. Source: Ensembl

ethanol catabolic process

Inferred from electronic annotation. Source: Ensembl

ethanol oxidation

Inferred from electronic annotation. Source: InterPro

formaldehyde catabolic process

Inferred from electronic annotation. Source: Ensembl

peptidyl-cysteine S-nitrosylation

Inferred from electronic annotation. Source: Ensembl

positive regulation of blood pressure

Inferred from electronic annotation. Source: Ensembl

respiratory system process

Inferred from electronic annotation. Source: Ensembl

response to lipopolysaccharide

Inferred from electronic annotation. Source: Ensembl

response to nitrosative stress

Inferred from electronic annotation. Source: Ensembl

response to redox state

Inferred from direct assay Ref.10. Source: UniProtKB

retinoid metabolic process

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentextracellular vesicular exosome

Inferred from direct assay PubMed 19056867. Source: UniProt

mitochondrion

Inferred from electronic annotation. Source: Ensembl

nucleus

Inferred from electronic annotation. Source: Ensembl

   Molecular_functionS-(hydroxymethyl)glutathione dehydrogenase activity

Traceable author statement Ref.10. Source: UniProtKB

alcohol dehydrogenase (NAD) activity

Inferred from electronic annotation. Source: UniProtKB-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

zinc ion binding

Inferred from direct assay PubMed 6375718. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed Ref.8 Ref.11
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 Ref.11
Modified residue2331N6-succinyllysine By similarity
Modified residue2471Phosphoserine By similarity
Modified residue3151N6-succinyllysine By similarity

Natural variations

Natural variant1631L → S. Ref.6
Corresponds to variant rs28730623 [ dbSNP | Ensembl ].
VAR_025823
Natural variant3091V → I. Ref.6
Corresponds to variant rs28730628 [ dbSNP | Ensembl ].
VAR_025824
Natural variant3531D → E.
Corresponds to variant rs16996593 [ dbSNP | Ensembl ].
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 [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] [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]"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.
Anal. Chem. 81:4493-4501(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS], CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS].
[12]"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].
[13]"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

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
PIRDEHUC2. JH0789.
RefSeqNP_000662.3. NM_000671.4.
UniGeneHs.78989.

3D structure databases

PDBe
RCSB PDB
PDBj
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[»]
3QJ5X-ray1.90A/B2-374[»]
ProteinModelPortalP11766.
SMRP11766. Positions 2-374.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid106640. 15 interactions.
IntActP11766. 8 interactions.
MINTMINT-1374117.
STRING9606.ENSP00000296412.

Chemistry

BindingDBP11766.
ChEMBLCHEMBL4116.
DrugBankDB00157. NADH.

PTM databases

PhosphoSiteP11766.

Polymorphism databases

DMDM113408.

2D gel databases

REPRODUCTION-2DPAGEIPI00746777.

Proteomic databases

PaxDbP11766.
PRIDEP11766.

Protocols and materials databases

DNASU128.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000296412; ENSP00000296412; ENSG00000197894.
GeneID128.
KEGGhsa:128.
UCSCuc003hui.3. human.

Organism-specific databases

CTD128.
GeneCardsGC04M099992.
HGNCHGNC:253. ADH5.
HPAHPA044578.
MIM103710. gene.
neXtProtNX_P11766.
PharmGKBPA24574.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG1062.
HOGENOMHOG000294674.
HOVERGENHBG000195.
InParanoidP11766.
KOK00121.
OMAAWKSGAP.
OrthoDBEOG72NRQ6.
PhylomeDBP11766.
TreeFamTF300429.

Enzyme and pathway databases

SABIO-RKP11766.

Gene expression databases

ArrayExpressP11766.
BgeeP11766.
CleanExHS_ADH5.
GenevestigatorP11766.

Family and domain databases

Gene3D3.40.50.720. 1 hit.
3.90.180.10. 1 hit.
InterProIPR014183. 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]
PANTHERPTHR11695. PTHR11695. 1 hit.
PfamPF08240. ADH_N. 1 hit.
PF00107. ADH_zinc_N. 1 hit.
[Graphical view]
SUPFAMSSF50129. SSF50129. 2 hits.
TIGRFAMsTIGR02818. adh_III_F_hyde. 1 hit.
PROSITEPS00059. ADH_ZINC. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSADH5. human.
EvolutionaryTraceP11766.
GeneWikiADH5.
GenomeRNAi128.
NextBio511.
PROP11766.
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: March 19, 2014
This is version 164 of the entry and version 4 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

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

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 4

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