Target Information

Target General Information

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Target ID

T09770 (Former ID: TTDI02473)

Target Name

Gastric alcohol dehydrogenase (ADH7)

Synonyms

Alcohol dehydrogenase class IV mu/sigma chain; Alcohol dehydrogenase class 4 mu/sigma chain; ADH7

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Gene Name

ADH7

Target Type

Literature-reported target

[1]

Function

Could function in retinol oxidation for the synthesis of retinoic acid, a hormone important for cellular differentiation. Medium-chain (octanol) and aromatic (m-nitrobenzaldehyde) compounds are the best substrates. Ethanol is not a good substrate but at the high ethanol concentrations reached in the digestive tract, it plays a role in the ethanol oxidation and contributes to the first pass ethanol metabolism.

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BioChemical Class

Short-chain dehydrogenases reductase

UniProt ID

ADH7_HUMAN

EC Number

EC 1.1.1.1

Sequence

MFAEIQIQDKDRMGTAGKVIKCKAAVLWEQKQPFSIEEIEVAPPKTKEVRIKILATGICR
TDDHVIKGTMVSKFPVIVGHEATGIVESIGEGVTTVKPGDKVIPLFLPQCRECNACRNPD
GNLCIRSDITGRGVLADGTTRFTCKGKPVHHFMNTSTFTEYTVVDESSVAKIDDAAPPEK
VCLIGCGFSTGYGAAVKTGKVKPGSTCVVFGLGGVGLSVIMGCKSAGASRIIGIDLNKDK
FEKAMAVGATECISPKDSTKPISEVLSEMTGNNVGYTFEVIGHLETMIDALASCHMNYGT
SVVVGVPPSAKMLTYDPMLLFTGRTWKGCVFGGLKSRDDVPKLVTEFLAKKFDLDQLITH
VLPFKKISEGFELLNSGQSIRTVLTF

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3D Structure

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PDB

Cell-based Target Expression Variations

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Cell-based Target Expression Variations

Cell-based Target Expression Variations Info

Drug Binding Sites of Target

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Ligand Name: Nicotinamide-Adenine-Dinucleotide

Ligand Info

Structure Description

MUTANT OF HUMAN SIGMA ALCOHOL DEHYDROGENASE WITH LEUCINE AT POSITION 141

PDB:1D1T

Method

X-ray diffraction

Resolution

2.40 Å

Mutation

Yes

[2]

PDB Sequence

GTAGKVIKCK

¹⁰

AAVLWEQKQP

²⁰

FSIEEIEVAP

³⁰

PKTKEVRIKI

⁴⁰

LATGICRTDD

⁵⁰

HVIKGTMVSK

⁶⁰

FPVIVGHEAT

⁷⁰

GIVESIGEGV

⁸⁰

TTVKPGDKVI

⁹⁰

PLFLPQCREC

¹⁰⁰

NACRNPDGNL

¹¹⁰

CIRSDITGRG

¹²¹

VLADGTTRFT

¹³¹

CKGKPVHHFL

¹⁴¹

NTSTFTEYTV

¹⁵¹

VDESSVAKID

¹⁶¹

DAAPPEKVCL

¹⁷¹

IGCGFSTGYG

¹⁸¹

AAVKTGKVKP

¹⁹¹

GSTCVVFGLG

²⁰¹

GVGLSVIMGC

²¹¹

KSAGASRIIG

²²¹

IDLNKDKFEK

²³¹

AMAVGATECI

²⁴¹

SPKDSTKPIS

²⁵¹

EVLSEMTGNN

²⁶¹

VGYTFEVIGH

²⁷¹

LETMIDALAS

²⁸¹

CHMNYGTSVV

²⁹¹

VGVPPSAKML

³⁰¹

TYDPMLLFTG

³¹¹

RTWKGCVFGG

³²¹

LKSRDDVPKL

³³¹

VTEFLAKKFD

³⁴¹

LDQLITHVLP

³⁵¹

FKKISEGFEL

³⁶¹

LNSGQSIRTV

³⁷¹

LTF

Residue

Distance (Å)

CYS46

3.937

ARG47

2.989

THR48

2.700

HIS51

2.774

PHE93

4.432

CYS174

3.412

GLY175

4.763

THR178

3.031

GLY199

3.765

LEU200

3.736

GLY201

3.244

GLY202

3.042

VAL203

2.792

GLY204

4.330

ILE222

4.095

ASP223

2.421

LEU224

3.508

Residue

Distance (Å)

ASN225

4.186

LYS228

3.208

PRO243

4.448

VAL268

3.629

ILE269

3.083

GLY270

3.670

HIS271

3.580

THR274

3.987

VAL292

2.839

GLY293

3.490

VAL294

3.019

CYS317

2.894

VAL318

3.807

PHE319

2.888

GLY320

4.606

LEU362

3.892

ARG369

3.197

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Different Human System Profiles of Target	Top
Human Similarity Proteins of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target. A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs (Brief Bioinform, 21: 649-662, 2020). Human Tissue Distribution of target is determined from a proteomics study that quantified more than 12,000 genes across 32 normal human tissues. Tissue Specificity (TS) score was used to define the enrichment of target across tissues. The distribution of targets among different tissues or organs need to be taken into consideration when assessing the target druggability, as it is generally accepted that the wider the target distribution, the greater the concern over potential adverse effects (Nat Rev Drug Discov, 20: 64-81, 2021). Human Pathway Affiliation of target is determined by the life-essential pathways provided on KEGG database. The target-affiliated pathways were defined based on the following two criteria (a) the pathways of the studied target should be life-essential for both healthy individuals and patients, and (b) the studied target should occupy an upstream position in the pathways and therefore had the ability to regulate biological function. Targets involved in a fewer pathways have greater likelihood to be successfully developed, while those associated with more human pathways increase the chance of undesirable interferences with other human processes (Pharmacol Rev, 58: 259-279, 2006). Biological Network Descriptors of target is determined based on a human protein-protein interactions (PPI) network consisting of 9,309 proteins and 52,713 PPIs, which were with a high confidence score of ≥ 0.95 collected from STRING database. The network properties of targets based on protein-protein interactions (PPIs) have been widely adopted for the assessment of target’s druggability. Proteins with high node degree tend to have a high impact on network function through multiple interactions, while proteins with high betweenness centrality are regarded to be central for communication in interaction networks and regulate the flow of signaling information (Front Pharmacol, 9, 1245, 2018; Curr Opin Struct Biol. 44:134-142, 2017). Human Similarity Proteins Human Tissue Distribution Human Pathway Affiliation Biological Network Descriptors

Different Human System Profiles of Target

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Human Similarity Proteins of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target.

A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs (Brief Bioinform, 21: 649-662, 2020).

Human Tissue Distribution of target is determined from a proteomics study that quantified more than 12,000 genes across 32 normal human tissues. Tissue Specificity (TS) score was used to define the enrichment of target across tissues.

The distribution of targets among different tissues or organs need to be taken into consideration when assessing the target druggability, as it is generally accepted that the wider the target distribution, the greater the concern over potential adverse effects (Nat Rev Drug Discov, 20: 64-81, 2021).

Human Pathway Affiliation of target is determined by the life-essential pathways provided on KEGG database. The target-affiliated pathways were defined based on the following two criteria (a) the pathways of the studied target should be life-essential for both healthy individuals and patients, and (b) the studied target should occupy an upstream position in the pathways and therefore had the ability to regulate biological function.

Targets involved in a fewer pathways have greater likelihood to be successfully developed, while those associated with more human pathways increase the chance of undesirable interferences with other human processes (Pharmacol Rev, 58: 259-279, 2006).

Biological Network Descriptors of target is determined based on a human protein-protein interactions (PPI) network consisting of 9,309 proteins and 52,713 PPIs, which were with a high confidence score of ≥ 0.95 collected from STRING database.

The network properties of targets based on protein-protein interactions (PPIs) have been widely adopted for the assessment of target’s druggability. Proteins with high node degree tend to have a high impact on network function through multiple interactions, while proteins with high betweenness centrality are regarded to be central for communication in interaction networks and regulate the flow of signaling information (Front Pharmacol, 9, 1245, 2018; Curr Opin Struct Biol. 44:134-142, 2017).

Human Similarity Proteins

Human Tissue Distribution

Human Pathway Affiliation

Biological Network Descriptors

There is no similarity protein (E value < 0.005) for this target


Note: If a protein has TS (tissue specficity) scores at least in one tissue >= 2.5, this protein is called tissue-enriched (including tissue-enriched-but-not-specific and tissue-specific). In the plots, the vertical lines are at thresholds 2.5 and 4.

KEGG Pathway	Pathway ID	Affiliated Target
Glycolysis / Gluconeogenesis	hsa00010	Affiliated Target
Class: Metabolism => Carbohydrate metabolism	Pathway Hierarchy
Fatty acid degradation	hsa00071	Affiliated Target
Class: Metabolism => Lipid metabolism	Pathway Hierarchy
Tyrosine metabolism	hsa00350	Affiliated Target
Class: Metabolism => Amino acid metabolism	Pathway Hierarchy
Pyruvate metabolism	hsa00620	Affiliated Target
Class: Metabolism => Carbohydrate metabolism	Pathway Hierarchy
Retinol metabolism	hsa00830	Affiliated Target
Class: Metabolism => Metabolism of cofactors and vitamins	Pathway Hierarchy
Metabolism of xenobiotics by cytochrome P450	hsa00980	Affiliated Target
Class: Metabolism => Xenobiotics biodegradation and metabolism	Pathway Hierarchy
Drug metabolism - cytochrome P450	hsa00982	Affiliated Target
Class: Metabolism => Xenobiotics biodegradation and metabolism	Pathway Hierarchy
Click to Show/Hide the Information of Affiliated Human Pathways

Degree	1	Degree centrality	1.07E-04	Betweenness centrality	0.00E+00
Closeness centrality	1.55E-01	Radiality	1.22E+01	Clustering coefficient	0.00E+00
Neighborhood connectivity	1.60E+01	Topological coefficient	1.00E+00	Eccentricity	12
Download	Click to Download the Full PPI Network of This Target

Chemical Structure based Activity Landscape of Target

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Target Poor or Non Binders

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Target Poor or Non Binders

Target Poor or Non Binders Info

References

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REF 1

Retinol dehydrogenase 13 deficiency diminishes carbon tetrachloride-induced liver fibrosis in mice. Toxicol Lett. 2017 Jan 4;265:17-22.

REF 2

Methionine-141 directly influences the binding of 4-methylpyrazole in human sigma sigma alcohol dehydrogenase. Protein Sci. 1999 Dec;8(12):2639-44.

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