UniProtKB - P11766 (ADHX_HUMAN)
Protein
Alcohol dehydrogenase class-3
Gene
ADH5
Organism
Homo sapiens (Human)
Status
Functioni
Catalyzes the oxidation of long-chain primary alcohols and the oxidation of S-(hydroxymethyl) glutathione (PubMed:8460164). Also oxidizes long chain omega-hydroxy fatty acids, such as 20-HETE, producing both the intermediate aldehyde, 20-oxoarachidonate and the end product, a dicarboxylic acid, (5Z,8Z,11Z,14Z)-eicosatetraenedioate (PubMed:16081420). Class-III ADH is remarkably ineffective in oxidizing ethanol (PubMed:8460164).2 Publications
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.
Catalytic activityi
- EC:1.1.1.11 Publication
- EC:1.1.1.11 Publication
- EC:1.1.1.2841 Publication
- EC:1.1.1.2841 Publication
- 20-oxo-(5Z,8Z,11Z,14Z)-eicosatetraenoate + H2O + NAD+ = (5Z,8Z,11Z,14Z)-eicosatetraenedioate + 2 H+ + NADH1 PublicationThis reaction proceeds in the forward1 Publication direction.
- 20-hydroxy-(5Z,8Z,11Z,14Z)-eicosatetraenoate + NAD+ = 20-oxo-(5Z,8Z,11Z,14Z)-eicosatetraenoate + H+ + NADH1 PublicationThis reaction proceeds in the forward1 Publication direction.
Cofactori
Zn2+1 PublicationNote: Binds 2 Zn2+ ions per subunit.1 Publication
Kineticsi
- KM=21 µM for 20-HETE1 Publication
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Metal bindingi | 45 | Zinc 1; catalytic1 Publication | 1 | |
Metal bindingi | 67 | Zinc 1; catalytic1 Publication | 1 | |
Metal bindingi | 97 | Zinc 21 Publication | 1 | |
Metal bindingi | 100 | Zinc 21 Publication | 1 | |
Metal bindingi | 103 | Zinc 21 Publication | 1 | |
Metal bindingi | 111 | Zinc 21 Publication | 1 | |
Sitei | 115 | Important for FDH activity and activation by fatty acids2 Publications | 1 | |
Metal bindingi | 174 | Zinc 1; catalytic1 Publication | 1 |
GO - Molecular functioni
- alcohol dehydrogenase activity, zinc-dependent Source: GO_Central
- electron transfer activity Source: UniProtKB
- fatty acid binding Source: UniProtKB
- formaldehyde dehydrogenase activity Source: UniProtKB
- identical protein binding Source: Ensembl
- S-(hydroxymethyl)glutathione dehydrogenase activity Source: GO_Central
- zinc ion binding Source: UniProtKB
GO - Biological processi
- ethanol oxidation Source: Reactome
- fatty acid omega-oxidation Source: UniProtKB
- formaldehyde catabolic process Source: GO_Central
- peptidyl-cysteine S-nitrosylation Source: Ensembl
- positive regulation of blood pressure Source: Ensembl
- respiratory system process Source: Ensembl
- response to lipopolysaccharide Source: Ensembl
- response to nitrosative stress Source: Ensembl
- response to redox state Source: UniProtKB
- retinoid metabolic process Source: Ensembl
Keywordsi
Molecular function | Oxidoreductase |
Ligand | Metal-binding, NAD, Zinc |
Enzyme and pathway databases
BioCyci | MetaCyc:HS10601-MONOMER |
PathwayCommonsi | P11766 |
Reactomei | R-HSA-71384, Ethanol oxidation |
SABIO-RKi | P11766 |
Chemistry databases
SwissLipidsi | SLP:000000500 |
Names & Taxonomyi
Protein namesi | |
Gene namesi | |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
EuPathDBi | HostDB:ENSG00000197894.10 |
HGNCi | HGNC:253, ADH5 |
MIMi | 103710, gene |
neXtProti | NX_P11766 |
Subcellular locationi
Other locations
- Cytoplasm Curated
Cytosol
- cytosol Source: GO_Central
Extracellular region or secreted
- extracellular exosome Source: UniProtKB
Mitochondrion
- mitochondrion Source: Ensembl
Keywords - Cellular componenti
CytoplasmPathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 115 | R → A or D: Loss of FDH activity and loss of activation by fatty acids. 2 Publications | 1 |
Organism-specific databases
DisGeNETi | 128 |
OpenTargetsi | ENSG00000197894 |
PharmGKBi | PA24574 |
Miscellaneous databases
Pharosi | P11766, Tchem |
Chemistry databases
ChEMBLi | CHEMBL4116 |
DrugBanki | DB03704, 12-Hydroxydodecanoic Acid DB00898, Ethanol DB01020, Isosorbide mononitrate DB03017, Lauric acid DB00157, NADH DB12612, Ozanimod DB11077, Polyethylene glycol 400 DB04153, S-Hydroxymethyl Glutathione |
Polymorphism and mutation databases
BioMutai | ADH5 |
DMDMi | 113408 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Initiator methioninei | RemovedCombined sources1 Publication | |||
ChainiPRO_0000160759 | 2 – 374 | Alcohol dehydrogenase class-3Add BLAST | 373 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 2 | N-acetylalanineCombined sources | 1 | |
Modified residuei | 233 | N6-succinyllysineBy similarity | 1 | |
Modified residuei | 247 | PhosphoserineCombined sources | 1 | |
Modified residuei | 315 | N6-succinyllysineBy similarity | 1 | |
Modified residuei | 324 | PhosphoserineCombined sources | 1 | |
Modified residuei | 351 | PhosphoserineCombined sources | 1 |
Keywords - PTMi
Acetylation, PhosphoproteinProteomic databases
EPDi | P11766 |
jPOSTi | P11766 |
MassIVEi | P11766 |
PaxDbi | P11766 |
PeptideAtlasi | P11766 |
PRIDEi | P11766 |
ProteomicsDBi | 52803 |
2D gel databases
REPRODUCTION-2DPAGEi | IPI00746777 |
PTM databases
CarbonylDBi | P11766 |
iPTMneti | P11766 |
MetOSitei | P11766 |
PhosphoSitePlusi | P11766 |
SwissPalmi | P11766 |
Expressioni
Gene expression databases
Bgeei | ENSG00000197894, Expressed in lower esophagus and 247 other tissues |
ExpressionAtlasi | P11766, baseline and differential |
Genevisiblei | P11766, HS |
Organism-specific databases
HPAi | ENSG00000197894, Low tissue specificity |
Interactioni
Subunit structurei
Homodimer.
1 PublicationGO - Molecular functioni
- identical protein binding Source: Ensembl
Protein-protein interaction databases
BioGRIDi | 106640, 22 interactors |
IntActi | P11766, 9 interactors |
STRINGi | 9606.ENSP00000296412 |
Chemistry databases
BindingDBi | P11766 |
Miscellaneous databases
RNActi | P11766, protein |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
SMRi | P11766 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | P11766 |
Family & Domainsi
Sequence similaritiesi
Phylogenomic databases
eggNOGi | KOG0022, Eukaryota |
GeneTreei | ENSGT00940000155196 |
HOGENOMi | CLU_026673_14_0_1 |
InParanoidi | P11766 |
OMAi | ATHKGWG |
OrthoDBi | 664798at2759 |
PhylomeDBi | P11766 |
TreeFami | TF300429 |
Family and domain databases
CDDi | cd08300, alcohol_DH_class_III, 1 hit |
InterProi | View protein in InterPro IPR014183, ADH_3 IPR013149, ADH_C IPR013154, ADH_N IPR002328, ADH_Zn_CS IPR011032, GroES-like_sf IPR036291, NAD(P)-bd_dom_sf |
Pfami | View protein in Pfam PF08240, ADH_N, 1 hit PF00107, ADH_zinc_N, 1 hit |
SUPFAMi | SSF50129, SSF50129, 2 hits SSF51735, SSF51735, 1 hit |
TIGRFAMsi | TIGR02818, adh_III_F_hyde, 1 hit |
PROSITEi | View protein in PROSITE PS00059, ADH_ZINC, 1 hit |
(1+)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry has 1 described isoform and 4 potential isoforms that are computationally mapped.Show allAlign All
P11766-1 [UniParc]FASTAAdd to basket
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
Computationally mapped potential isoform sequencesi
There are 4 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketH0YAG8 | H0YAG8_HUMAN | Alcohol dehydrogenase class-3 | ADH5 | 262 | Annotation score: | ||
D6R9G2 | D6R9G2_HUMAN | Alcohol dehydrogenase class-3 | ADH5 | 95 | Annotation score: | ||
D6RFE4 | D6RFE4_HUMAN | Alcohol dehydrogenase class-3 | ADH5 | 115 | Annotation score: | ||
D6RAY0 | D6RAY0_HUMAN | Alcohol dehydrogenase class-3 | ADH5 | 56 | Annotation score: |
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 167 | D → Y in AAA51597 (PubMed:2679557).Curated | 1 | |
Sequence conflicti | 246 | F → L in AAA51597 (PubMed:2679557).Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_025823 | 163 | L → S1 PublicationCorresponds to variant dbSNP:rs28730623Ensembl. | 1 | |
Natural variantiVAR_025824 | 309 | V → I1 PublicationCorresponds to variant dbSNP:rs28730628Ensembl. | 1 | |
Natural variantiVAR_048199 | 353 | D → E. Corresponds to variant dbSNP:rs16996593Ensembl. | 1 |
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 |
CCDSi | CCDS47111.1 |
PIRi | JH0789, DEHUC2 |
RefSeqi | NP_000662.3, NM_000671.4 |
Genome annotation databases
Ensembli | ENST00000296412; ENSP00000296412; ENSG00000197894 |
GeneIDi | 128 |
KEGGi | hsa:128 |
Keywords - Coding sequence diversityi
PolymorphismSimilar proteinsi
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 |
CCDSi | CCDS47111.1 |
PIRi | JH0789, DEHUC2 |
RefSeqi | NP_000662.3, NM_000671.4 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
1M6H | X-ray | 2.00 | A/B | 2-374 | [»] | |
1M6W | X-ray | 2.30 | A/B | 2-374 | [»] | |
1MA0 | X-ray | 2.30 | A/B | 2-374 | [»] | |
1MC5 | X-ray | 2.60 | A/B | 1-374 | [»] | |
1MP0 | X-ray | 2.20 | A/B | 2-374 | [»] | |
1TEH | X-ray | 2.70 | A/B | 2-374 | [»] | |
2FZE | X-ray | 1.90 | A/B | 2-374 | [»] | |
2FZW | X-ray | 1.84 | A/B | 2-374 | [»] | |
3QJ5 | X-ray | 1.90 | A/B | 2-374 | [»] | |
SMRi | P11766 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 106640, 22 interactors |
IntActi | P11766, 9 interactors |
STRINGi | 9606.ENSP00000296412 |
Chemistry databases
BindingDBi | P11766 |
ChEMBLi | CHEMBL4116 |
DrugBanki | DB03704, 12-Hydroxydodecanoic Acid DB00898, Ethanol DB01020, Isosorbide mononitrate DB03017, Lauric acid DB00157, NADH DB12612, Ozanimod DB11077, Polyethylene glycol 400 DB04153, S-Hydroxymethyl Glutathione |
SwissLipidsi | SLP:000000500 |
PTM databases
CarbonylDBi | P11766 |
iPTMneti | P11766 |
MetOSitei | P11766 |
PhosphoSitePlusi | P11766 |
SwissPalmi | P11766 |
Polymorphism and mutation databases
BioMutai | ADH5 |
DMDMi | 113408 |
2D gel databases
REPRODUCTION-2DPAGEi | IPI00746777 |
Proteomic databases
EPDi | P11766 |
jPOSTi | P11766 |
MassIVEi | P11766 |
PaxDbi | P11766 |
PeptideAtlasi | P11766 |
PRIDEi | P11766 |
ProteomicsDBi | 52803 |
Protocols and materials databases
Antibodypediai | 25845, 410 antibodies |
DNASUi | 128 |
Genome annotation databases
Ensembli | ENST00000296412; ENSP00000296412; ENSG00000197894 |
GeneIDi | 128 |
KEGGi | hsa:128 |
Organism-specific databases
CTDi | 128 |
DisGeNETi | 128 |
EuPathDBi | HostDB:ENSG00000197894.10 |
GeneCardsi | ADH5 |
HGNCi | HGNC:253, ADH5 |
HPAi | ENSG00000197894, Low tissue specificity |
MIMi | 103710, gene |
neXtProti | NX_P11766 |
OpenTargetsi | ENSG00000197894 |
PharmGKBi | PA24574 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG0022, Eukaryota |
GeneTreei | ENSGT00940000155196 |
HOGENOMi | CLU_026673_14_0_1 |
InParanoidi | P11766 |
OMAi | ATHKGWG |
OrthoDBi | 664798at2759 |
PhylomeDBi | P11766 |
TreeFami | TF300429 |
Enzyme and pathway databases
BioCyci | MetaCyc:HS10601-MONOMER |
PathwayCommonsi | P11766 |
Reactomei | R-HSA-71384, Ethanol oxidation |
SABIO-RKi | P11766 |
Miscellaneous databases
BioGRID-ORCSi | 128, 108 hits in 847 CRISPR screens |
ChiTaRSi | ADH5, human |
EvolutionaryTracei | P11766 |
GeneWikii | ADH5 |
GenomeRNAii | 128 |
Pharosi | P11766, Tchem |
PROi | PR:P11766 |
RNActi | P11766, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000197894, Expressed in lower esophagus and 247 other tissues |
ExpressionAtlasi | P11766, baseline and differential |
Genevisiblei | P11766, HS |
Family and domain databases
CDDi | cd08300, alcohol_DH_class_III, 1 hit |
InterProi | View protein in InterPro IPR014183, ADH_3 IPR013149, ADH_C IPR013154, ADH_N IPR002328, ADH_Zn_CS IPR011032, GroES-like_sf IPR036291, NAD(P)-bd_dom_sf |
Pfami | View protein in Pfam PF08240, ADH_N, 1 hit PF00107, ADH_zinc_N, 1 hit |
SUPFAMi | SSF50129, SSF50129, 2 hits SSF51735, SSF51735, 1 hit |
TIGRFAMsi | TIGR02818, adh_III_F_hyde, 1 hit |
PROSITEi | View protein in PROSITE PS00059, ADH_ZINC, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | ADHX_HUMAN | |
Accessioni | P11766Primary (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: | December 2, 2020 | |
This is version 217 of the entry and version 4 of the sequence. See complete history. | ||
Entry statusi | 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. |
Miscellaneousi
Keywords - Technical termi
3D-structure, Direct protein sequencing, Reference proteomeDocuments
- Human chromosome 4
Human chromosome 4: entries, gene names and cross-references to MIM - 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 - Human entries with polymorphisms or disease mutations
List of human entries with polymorphisms or disease mutations