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Protein

Alcohol dehydrogenase class-3

Gene

ADH5

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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 activityi

An alcohol + NAD+ = an aldehyde or ketone + NADH.
S-(hydroxymethyl)glutathione + NAD(P)+ = S-formylglutathione + NAD(P)H.

Cofactori

Zn2+1 PublicationNote: Binds 2 Zn2+ ions per subunit.1 Publication

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi45 – 451Zinc 1; catalytic1 Publication
Metal bindingi67 – 671Zinc 1; catalytic1 Publication
Metal bindingi97 – 971Zinc 21 Publication
Metal bindingi100 – 1001Zinc 21 Publication
Metal bindingi103 – 1031Zinc 21 Publication
Metal bindingi111 – 1111Zinc 21 Publication
Sitei115 – 1151Important for FDH activity and activation by fatty acids
Metal bindingi174 – 1741Zinc 1; catalytic

GO - Molecular functioni

  • alcohol dehydrogenase (NAD) activity Source: UniProtKB-EC
  • electron carrier activity Source: UniProtKB
  • fatty acid binding Source: UniProtKB
  • formaldehyde dehydrogenase activity Source: UniProtKB
  • S-(hydroxymethyl)glutathione dehydrogenase activity Source: UniProtKB
  • zinc ion binding Source: UniProtKB

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Oxidoreductase

Keywords - Ligandi

Metal-binding, NAD, Zinc

Enzyme and pathway databases

SABIO-RKP11766.

Names & Taxonomyi

Protein namesi
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 (EC:1.1.1.-)
Short name:
FALDH
Short name:
FDH
Short name:
GSH-FDH
S-(hydroxymethyl)glutathione dehydrogenase (EC:1.1.1.284)
Gene namesi
Name:ADH5Imported
Synonyms:ADHX, FDH
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 4

Organism-specific databases

HGNCiHGNC:253. ADH5.

Subcellular locationi

GO - Cellular componenti

  • extracellular exosome Source: UniProtKB
  • mitochondrion Source: Ensembl
  • nucleus Source: Ensembl
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi115 – 1151R → A or D: Loss of FDH activity and loss of activation by fatty acids. 2 Publications

Organism-specific databases

PharmGKBiPA24574.

Polymorphism and mutation databases

DMDMi113408.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methioninei1 – 11Removed2 Publications
Chaini2 – 374373Alcohol dehydrogenase class-3PRO_0000160759Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei2 – 21N-acetylalanine1 Publication
Modified residuei233 – 2331N6-succinyllysineBy similarity
Modified residuei247 – 2471Phosphoserine1 Publication
Modified residuei315 – 3151N6-succinyllysineBy similarity

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

MaxQBiP11766.
PaxDbiP11766.
PRIDEiP11766.

2D gel databases

REPRODUCTION-2DPAGEIPI00746777.

PTM databases

PhosphoSiteiP11766.

Expressioni

Gene expression databases

BgeeiP11766.
CleanExiHS_ADH5.
ExpressionAtlasiP11766. baseline and differential.
GenevestigatoriP11766.

Organism-specific databases

HPAiHPA044578.

Interactioni

Subunit structurei

Homodimer.

Protein-protein interaction databases

BioGridi106640. 15 interactions.
IntActiP11766. 8 interactions.
MINTiMINT-1374117.
STRINGi9606.ENSP00000296412.

Structurei

Secondary structure

1
374
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi6 – 138Combined sources
Beta strandi21 – 277Combined sources
Beta strandi34 – 4310Combined sources
Helixi46 – 527Combined sources
Beta strandi61 – 633Combined sources
Beta strandi68 – 769Combined sources
Beta strandi88 – 914Combined sources
Beta strandi98 – 1003Combined sources
Helixi101 – 1044Combined sources
Helixi115 – 1195Combined sources
Beta strandi129 – 1324Combined sources
Beta strandi135 – 1384Combined sources
Turni141 – 1433Combined sources
Beta strandi146 – 1538Combined sources
Helixi154 – 1563Combined sources
Beta strandi157 – 1593Combined sources
Helixi166 – 1694Combined sources
Helixi170 – 1734Combined sources
Helixi175 – 18410Combined sources
Turni185 – 1873Combined sources
Beta strandi194 – 1985Combined sources
Helixi202 – 21413Combined sources
Beta strandi217 – 2226Combined sources
Helixi226 – 2283Combined sources
Helixi229 – 2357Combined sources
Beta strandi238 – 2414Combined sources
Helixi243 – 2453Combined sources
Helixi250 – 2578Combined sources
Beta strandi262 – 2676Combined sources
Helixi272 – 2809Combined sources
Turni284 – 2863Combined sources
Beta strandi288 – 2914Combined sources
Beta strandi301 – 3033Combined sources
Helixi306 – 3094Combined sources
Beta strandi313 – 3164Combined sources
Helixi319 – 3213Combined sources
Helixi324 – 33613Combined sources
Helixi343 – 3453Combined sources
Beta strandi346 – 3516Combined sources
Helixi352 – 3543Combined sources
Helixi355 – 3639Combined sources
Beta strandi368 – 3736Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1M6HX-ray2.00A/B2-374[»]
1M6WX-ray2.30A/B2-374[»]
1MA0X-ray2.30A/B2-374[»]
1MC5X-ray2.60A/B1-374[»]
1MP0X-ray2.20A/B2-374[»]
1TEHX-ray2.70A/B2-374[»]
2FZEX-ray1.90A/B2-374[»]
2FZWX-ray1.84A/B2-374[»]
3QJ5X-ray1.90A/B2-374[»]
ProteinModelPortaliP11766.
SMRiP11766. Positions 2-374.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP11766.

Family & Domainsi

Sequence similaritiesi

Phylogenomic databases

eggNOGiCOG1062.
HOGENOMiHOG000294674.
HOVERGENiHBG000195.
InParanoidiP11766.
KOiK00121.
OMAiWKSVESI.
OrthoDBiEOG72NRQ6.
PhylomeDBiP11766.
TreeFamiTF300429.

Family and domain databases

Gene3Di3.40.50.720. 1 hit.
3.90.180.10. 1 hit.
InterProiIPR014183. 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]
PANTHERiPTHR11695. PTHR11695. 1 hit.
PfamiPF08240. ADH_N. 1 hit.
PF00107. ADH_zinc_N. 1 hit.
[Graphical view]
SUPFAMiSSF50129. SSF50129. 2 hits.
TIGRFAMsiTIGR02818. adh_III_F_hyde. 1 hit.
PROSITEiPS00059. ADH_ZINC. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P11766-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MANEVIKCKA AVAWEAGKPL SIEEIEVAPP KAHEVRIKII ATAVCHTDAY
60 70 80 90 100
TLSGADPEGC FPVILGHEGA GIVESVGEGV TKLKAGDTVI PLYIPQCGEC
110 120 130 140 150
KFCLNPKTNL CQKIRVTQGK GLMPDGTSRF TCKGKTILHY MGTSTFSEYT
160 170 180 190 200
VVADISVAKI DPLAPLDKVC LLGCGISTGY GAAVNTAKLE PGSVCAVFGL
210 220 230 240 250
GGVGLAVIMG CKVAGASRII GVDINKDKFA RAKEFGATEC INPQDFSKPI
260 270 280 290 300
QEVLIEMTDG GVDYSFECIG NVKVMRAALE ACHKGWGVSV VVGVAASGEE
310 320 330 340 350
IATRPFQLVT GRTWKGTAFG GWKSVESVPK LVSEYMSKKI KVDEFVTHNL
360 370
SFDEINKAFE LMHSGKSIRT VVKI
Length:374
Mass (Da):39,724
Last modified:January 23, 2007 - v4
Checksum:iF4F823B4A609C952
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti167 – 1671D → Y in AAA51597 (PubMed:2679557).Curated
Sequence conflicti246 – 2461F → L in AAA51597 (PubMed:2679557).Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti163 – 1631L → S.1 Publication
Corresponds to variant rs28730623 [ dbSNP | Ensembl ].
VAR_025823
Natural varianti309 – 3091V → I.1 Publication
Corresponds to variant rs28730628 [ dbSNP | Ensembl ].
VAR_025824
Natural varianti353 – 3531D → E.
Corresponds to variant rs16996593 [ dbSNP | Ensembl ].
VAR_048199

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS47111.1.
PIRiJH0789. DEHUC2.
RefSeqiNP_000662.3. NM_000671.4.
UniGeneiHs.78989.

Genome annotation databases

EnsembliENST00000296412; ENSP00000296412; ENSG00000197894.
GeneIDi128.
KEGGihsa:128.
UCSCiuc003hui.3. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Web resourcesi

NIEHS-SNPs

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS47111.1.
PIRiJH0789. DEHUC2.
RefSeqiNP_000662.3. NM_000671.4.
UniGeneiHs.78989.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1M6HX-ray2.00A/B2-374[»]
1M6WX-ray2.30A/B2-374[»]
1MA0X-ray2.30A/B2-374[»]
1MC5X-ray2.60A/B1-374[»]
1MP0X-ray2.20A/B2-374[»]
1TEHX-ray2.70A/B2-374[»]
2FZEX-ray1.90A/B2-374[»]
2FZWX-ray1.84A/B2-374[»]
3QJ5X-ray1.90A/B2-374[»]
ProteinModelPortaliP11766.
SMRiP11766. Positions 2-374.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi106640. 15 interactions.
IntActiP11766. 8 interactions.
MINTiMINT-1374117.
STRINGi9606.ENSP00000296412.

Chemistry

ChEMBLiCHEMBL4116.

PTM databases

PhosphoSiteiP11766.

Polymorphism and mutation databases

DMDMi113408.

2D gel databases

REPRODUCTION-2DPAGEIPI00746777.

Proteomic databases

MaxQBiP11766.
PaxDbiP11766.
PRIDEiP11766.

Protocols and materials databases

DNASUi128.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000296412; ENSP00000296412; ENSG00000197894.
GeneIDi128.
KEGGihsa:128.
UCSCiuc003hui.3. human.

Organism-specific databases

CTDi128.
GeneCardsiGC04M099992.
HGNCiHGNC:253. ADH5.
HPAiHPA044578.
MIMi103710. gene.
neXtProtiNX_P11766.
PharmGKBiPA24574.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiCOG1062.
HOGENOMiHOG000294674.
HOVERGENiHBG000195.
InParanoidiP11766.
KOiK00121.
OMAiWKSVESI.
OrthoDBiEOG72NRQ6.
PhylomeDBiP11766.
TreeFamiTF300429.

Enzyme and pathway databases

SABIO-RKP11766.

Miscellaneous databases

ChiTaRSiADH5. human.
EvolutionaryTraceiP11766.
GeneWikiiADH5.
GenomeRNAii128.
NextBioi511.
PROiP11766.
SOURCEiSearch...

Gene expression databases

BgeeiP11766.
CleanExiHS_ADH5.
ExpressionAtlasiP11766. baseline and differential.
GenevestigatoriP11766.

Family and domain databases

Gene3Di3.40.50.720. 1 hit.
3.90.180.10. 1 hit.
InterProiIPR014183. 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]
PANTHERiPTHR11695. PTHR11695. 1 hit.
PfamiPF08240. ADH_N. 1 hit.
PF00107. ADH_zinc_N. 1 hit.
[Graphical view]
SUPFAMiSSF50129. SSF50129. 2 hits.
TIGRFAMsiTIGR02818. adh_III_F_hyde. 1 hit.
PROSITEiPS00059. ADH_ZINC. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. 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, COFACTOR.
    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. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  13. "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome."
    Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., Ye M., Zou H.
    J. Proteomics 96:253-262(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-247, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Liver.
  14. "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).

Entry informationi

Entry nameiADHX_HUMAN
AccessioniPrimary (citable) accession number: P11766
Secondary accession number(s): Q6FHR2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1989
Last sequence update: January 23, 2007
Last modified: May 27, 2015
This is version 174 of the entry and version 4 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

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.

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 4
    Human chromosome 4: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.