Details of the Target

General Information of Target

Target ID LDTP08567
Target Name Hydroxyacid-oxoacid transhydrogenase, mitochondrial (ADHFE1)
Gene Name ADHFE1
Gene ID 137872
Synonyms
Hydroxyacid-oxoacid transhydrogenase, mitochondrial; HOT; EC 1.1.99.24; Alcohol dehydrogenase iron-containing protein 1; ADHFe1; Fe-containing alcohol dehydrogenase
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Sequence
MAAAARARVAYLLRQLQRAACQCPTHSHTYSQAPGLSPSGKTTDYAFEMAVSNIRYGAAV
TKEVGMDLKNMGAKNVCLMTDKNLSKLPPVQVAMDSLVKNGIPFTVYDNVRVEPTDSSFM
EAIEFAQKGAFDAYVAVGGGSTMDTCKAANLYASSPHSDFLDYVSAPIGKGKPVSVPLKP
LIAVPTTSGTGSETTGVAIFDYEHLKVKIGITSRAIKPTLGLIDPLHTLHMPARVVANSG
FDVLCHALESYTTLPYHLRSPCPSNPITRPAYQGSNPISDIWAIHALRIVAKYLKRAVRN
PDDLEARSHMHLASAFAGIGFGNAGVHLCHGMSYPISGLVKMYKAKDYNVDHPLVPHGLS
VVLTSPAVFTFTAQMFPERHLEMAEILGADTRTARIQDAGLVLADTLRKFLFDLDVDDGL
AAVGYSKADIPALVKGTLPQERVTKLAPCPQSEEDLAALFEASMKLY
Target Bioclass
Enzyme
Family
Iron-containing alcohol dehydrogenase family, Hydroxyacid-oxoacid transhydrogenase subfamily
Subcellular location
Mitochondrion
Function
Catalyzes the cofactor-independent reversible oxidation of gamma-hydroxybutyrate (GHB) to succinic semialdehyde (SSA) coupled to reduction of 2-ketoglutarate (2-KG) to D-2-hydroxyglutarate (D-2-HG). D,L-3-hydroxyisobutyrate and L-3-hydroxybutyrate (L-3-OHB) are also substrates for HOT with 10-fold lower activities.
Uniprot ID
Q8IWW8
Ensemble ID
ENST00000396623.8
HGNC ID
HGNC:16354
ChEMBL ID
CHEMBL4947

Target Site Mutations in Different Cell Lines

Cell line Mutation details Probe for labeling this protein in this cell
LS180 SNV: p.P266H .
MFE319 SNV: p.K128R; p.A233V .
MOLT4 SNV: p.A133V .
NB4 SNV: p.V434L .
NCIH1048 SNV: p.R14M .
RKO SNV: p.D280V .
SW403 SNV: p.R234Q .

Probe(s) Labeling This Target

ABPP Probe
Click To Hide/Show 1 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
BTD
 Probe Info  		C77(2.40)  LDD1699  [1]

Competitor(s) Related to This Target

Competitor ID Name Cell line Binding Site(Ratio) Interaction ID Ref
 LDCM0548  1-(4-(Benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-2-nitroethan-1-one MDA-MB-231 C77(0.30)  LDD2142  [1]
 LDCM0520  AKOS000195272 MDA-MB-231 C77(0.86)  LDD2113  [1]
 LDCM0509  N-(4-bromo-3,5-dimethylphenyl)-2-nitroacetamide MDA-MB-231 C77(1.27)  LDD2102  [1]
 LDCM0504  Nucleophilic fragment 15a MDA-MB-231 C77(0.70)  LDD2097  [1]
 LDCM0507  Nucleophilic fragment 16b MDA-MB-231 C77(0.26)  LDD2100  [1]
 LDCM0515  Nucleophilic fragment 20b MDA-MB-231 C77(0.52)  LDD2108  [1]
 LDCM0522  Nucleophilic fragment 24a MDA-MB-231 C77(0.45)  LDD2115  [1]
 LDCM0533  Nucleophilic fragment 29b MDA-MB-231 C77(0.53)  LDD2126  [1]
 LDCM0551  Nucleophilic fragment 5b MDA-MB-231 C77(0.37)  LDD2145  [1]
 LDCM0554  Nucleophilic fragment 7a MDA-MB-231 C77(0.45)  LDD2148  [1]

The Interaction Atlas With This Target

The Drug(s) Related To This Target

Approved
Click To Hide/Show 1 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
Sodium Oxybate . DB09072

References

1 Nucleophilic covalent ligand discovery for the cysteine redoxome. Nat Chem Biol. 2023 Nov;19(11):1309-1319. doi: 10.1038/s41589-023-01330-5. Epub 2023 May 29.
Mass spectrometry data entry: PXD039908 , PXD029761