Tbio DLD Dihydrolipoyl dehydrogenase, mitochondrial

Protein Summary

Description

Lipoamide dehydrogenase is a component of the glycine cleavage system as well as an E3 component of three alpha-ketoacid dehydrogenase complexes (pyruvate-, alpha-ketoglutarate-, and branched-chain amino acid-dehydrogenase complex) (PubMed:15712224, PubMed:16442803, PubMed:16770810, PubMed:17404228, PubMed:20160912, PubMed:20385101). The 2-oxoglutarate dehydrogenase complex is mainly active in the mitochondrion (PubMed:29211711). A fraction of the 2-oxoglutarate dehydrogenase complex also localizes in the nucleus and is required for lysine succinylation of histones: associates with KAT2A on chromatin and provides succinyl-CoA to histone succinyltransferase KAT2A (PubMed:29211711). In monomeric form may have additional moonlighting function as serine protease (PubMed:17404228). Involved in the hyperactivation of spermatazoa during capacitation and in the spermatazoal acrosome reaction (By similarity). This gene encodes a member of the class-I pyridine nucleotide-disulfide oxidoreductase family. The encoded protein has been identified as a moonlighting protein based on its ability to perform mechanistically distinct functions. In homodimeric form, the encoded protein functions as a dehydrogenase and is found in several multi-enzyme complexes that regulate energy metabolism. However, as a monomer, this protein can function as a protease. Mutations in this gene have been identified in patients with E3-deficient maple syrup urine disease and lipoamide dehydrogenase deficiency. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2014]

Uniprot Accession IDs

• P09622
• B2R5X0
• B4DHG0
• B4DT69
• Q14131
• Q14167
• Q59EV8
• Q8WTS4

Gene Name

• DLD

Ensembl ID

• ENST00000205402
• ENSP00000205402
• ENSG00000091140
• ENST00000417551
• ENSP00000390667
• ENST00000437604
• ENSP00000387542

Symbol

• GCSL
• LAD
• PHE3
• E3
• LAD
• DLDD
• DLDH
• GCSL
• PHE3

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
interacting protein	0.99
virus perturbation	0.94
disease perturbation	0.93
protein domain	0.92
molecular function	0.86

Protein Classes

PANTHER Classes

Protein / Oxidoreductase / Reductase / Dihydrolipoyl Dehydrogenase, Mitochondrial

Protein / Oxidoreductase / Oxidase / Dihydrolipoyl Dehydrogenase, Mitochondrial

Protein / Oxidoreductase / Dehydrogenase / Dihydrolipoyl Dehydrogenase, Mitochondrial

DTO Classes

Protein / Enzyme / Oxidoreductase / Dehydrogenase / Dihydrolipoyl Dehydrogenase, Mitochondrial

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 467.66   (req: < 5)

Gene RIFs: 25   (req: <= 3)

Antibodies: 448   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 467.66   (req: >= 5)

Gene RIFs: 25   (req: > 3)

Antibodies: 448   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 17

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligand: 0

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0

Protein Sequence and Structure

Residue Counts

Protein Sequence

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Expression Data (0 Tissues)

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No expression data found

Related Tools

Target Illumination GWAS Analytics (TIGA)

TIGA scores and ranks GWAS discovered associations according to the quantity and quality of the evidence supporting the association.

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GENEVA

GENEVA (GENe Expression Variance Analysis) allows you to identify RNA-sequencing datasets from the Gene Expression Omnibus (GEO) that contain conditions modulating a gene or a gene signature.

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GlyGen

GlyGen is a data integration and dissemination project for carbohydrate and glycoconjugate related data.

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ARCHS4

ARCHS4 provides access to gene-function predictions based on RNA-seq co-expression, and gene expression levels across cell and tissues.

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Approved Drugs (0)

No approved drugs found

Active Ligands (0)

No active ligands found

Protein-Protein Interactions (247)

Explore Interacting Targets

1 – 10 of 247

• See Interactions on String-DB

OGDHL

Tbio

Family:  Enzyme

Novelty:  0.05079572

p_int:  1

Score:  0.987

Data Source:  BioPlex,STRINGDB

PDHX

Tbio

Family:  Enzyme

Novelty:  0.00946631

p_int:  0.999998313

p_ni:  0.000001687

Score:  0.999

Data Source:  BioPlex,Reactome,STRINGDB

DBT

Tbio

Family:  Enzyme

Novelty:  0.0070589

p_int:  0.999992693

p_ni:  0.000007305

p_wrong:  2e-9

Score:  0.997

Data Source:  BioPlex,Reactome,STRINGDB

MRPS36

Tdark

Novelty:  0.23031933

p_int:  0.999800686

p_ni:  0.000199314

Score:  0.649

Data Source:  BioPlex,STRINGDB

SLX4IP

Tbio

Novelty:  0.25359409

p_int:  0.999761271

p_ni:  0.000238724

p_wrong:  5e-9

Score:  0.159

Data Source:  BioPlex,STRINGDB

BTRC

Tbio

Novelty:  0.00293475

p_int:  0.999721753

p_ni:  0.000278247

Data Source:  BioPlex

DLST

Tbio

Family:  Enzyme

Novelty:  0.01516932

p_int:  0.999605395

p_ni:  0.000394605

Score:  0.999

Data Source:  BioPlex,Reactome,STRINGDB

SIAH1

Tbio

Family:  Enzyme

Novelty:  0.00831224

p_int:  0.999396481

p_ni:  0.000603519

Score:  0.59

Data Source:  BioPlex,STRINGDB

FBXW11

Tbio

Novelty:  0.0715377

p_int:  0.998932939

p_ni:  0.001067061

Data Source:  BioPlex

FMC1

Tbio

Novelty:  0.06702205

p_int:  0.998489121

p_ni:  0.000975379

p_wrong:  0.000535499

Score:  0.185

Data Source:  BioPlex,STRINGDB

Nearest Tclin Targets (1)

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Downstream (1)

1 – 1 of 1

IDH2

Tclin

Family:  Enzyme

KEGG Distance:  2

Common Pathways:  3

1: Citrate cycle (TCA cycle)

2: Carbon metabolism

3: Metabolic pathways

Pathways (34)

Reactome (14)

KEGG (11)

PathwayCommons (4)

WikiPathways (5)

Branched-chain amino acid catabolism (R-HSA-70895)

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Items per page:

5

1 – 5 of 14

Data Source	Name	Explore in Pharos	Explore in Source
Reactome	Branched-chain amino acid catabolism	19 targets	R-HSA-70895
Reactome	Citric acid cycle (TCA cycle)	22 targets	R-HSA-71403
Reactome	Glycine degradation	4 targets	R-HSA-6783984
Reactome	Glyoxylate metabolism and glycine degradation	31 targets	R-HSA-389661
Reactome	Lysine catabolism	12 targets	R-HSA-71064

Name	Explore in Pharos	Explore in Source
Branched-chain amino acid catabolism	19 targets	R-HSA-70895
Citric acid cycle (TCA cycle)	22 targets	R-HSA-71403
Glycine degradation	4 targets	R-HSA-6783984
Glyoxylate metabolism and glycine degradation	31 targets	R-HSA-389661
Lysine catabolism	12 targets	R-HSA-71064

Viral Interactions (0)

No viral interactions found

Gene Ontology Terms (26)

Functions (5)

Components (9)

Processes (12)

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Items per page:

10

1 – 5 of 5

GO Term	Evidence	Assigned by
dihydrolipoyl dehydrogenase activity	Inferred from Direct Assay (IDA)	UniProtKB
electron transfer activity	Inferred from Electronic Annotation (IEA)	InterPro
flavin adenine dinucleotide binding	Inferred from Electronic Annotation (IEA)	Ensembl
lipoamide binding	Inferred from Electronic Annotation (IEA)	Ensembl
NAD binding	Inferred from Electronic Annotation (IEA)	Ensembl

Disease Associations ()

No disease associations found

GWAS Traits (6)

• Explore on Target Illumination GWAS Analytics (TIGA)

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5

1 – 5 of 6

GWAS Trait	EFO ID	Study Count	SNP Count	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
BMI-adjusted waist-hip ratio	EFO_0007788	6	9	10		93.4
ulcerative colitis	EFO_0000729	4	3	0	1.1	79.3
waist-hip ratio	EFO_0004343	4	8	8		79.3
waist circumference	EFO_0004342	1	5	5		74
BMI-adjusted waist circumference	EFO_0007789	1	5	5		60.2

• Explore on Target Illumination GWAS Analytics (TIGA)

Items per page:

5

1 – 5 of 6

GWAS Trait	EFO ID	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
BMI-adjusted waist-hip ratio	EFO_0007788	10		93.4
ulcerative colitis	EFO_0000729	0	1.1	79.3
waist-hip ratio	EFO_0004343	8		79.3
waist circumference	EFO_0004342	5		74
BMI-adjusted waist circumference	EFO_0007789	5		60.2

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UniProt Keyword Find Similar Targets

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3D-structure
Acetylation
Alternative splicing
Cell projection
Cilium
Complete proteome
Cytoplasmic vesicle
Disease mutation
Disulfide bond
FAD

GWAS Trait Find Similar Targets

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BMI-adjusted waist circumference
BMI-adjusted waist-hip ratio
inflammatory bowel disease
ulcerative colitis
waist circumference
waist-hip ratio

MGI Phenotype Find Similar Targets

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embryo phenotype
growth/size/body region phenotype
mortality/aging

IDG Resources

No IDG generated resources found

Orthologs (17)

1 – 5 of 17

Species	Name	Source ID	Gene ID	OMA	EggNOG	Inparanoid
Chimp	dihydrolipoamide dehydrogenase	VGNC:13647	463861
Macaque	dihydrolipoamide dehydrogenase		700494
Mouse	dihydrolipoamide dehydrogenase	MGI:107450	13382
Rat	dihydrolipoamide dehydrogenase	RGD:735073	298942
Dog	dihydrolipoamide dehydrogenase	VGNC:39976	403978

Species	Name	OMA	EggNOG	Inparanoid
Chimp	dihydrolipoamide dehydrogenase
Macaque	dihydrolipoamide dehydrogenase
Mouse	dihydrolipoamide dehydrogenase
Rat	dihydrolipoamide dehydrogenase
Dog	dihydrolipoamide dehydrogenase

Publication Statistics

PubMed Score 467.66

PubMed score by year

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PubTator Score 535.17

PubTator score by year

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Related Publications

Text Mined References (51)

GeneRif Annotations (25)

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PMID	Year	Title