Tclin IDH1 Isocitrate dehydrogenase [NADP] cytoplasmic

Protein Summary

Description

Isocitrate dehydrogenases catalyze the oxidative decarboxylation of isocitrate to 2-oxoglutarate. These enzymes belong to two distinct subclasses, one of which utilizes NAD(+) as the electron acceptor and the other NADP(+). Five isocitrate dehydrogenases have been reported: three NAD(+)-dependent isocitrate dehydrogenases, which localize to the mitochondrial matrix, and two NADP(+)-dependent isocitrate dehydrogenases, one of which is mitochondrial and the other predominantly cytosolic. Each NADP(+)-dependent isozyme is a homodimer. The protein encoded by this gene is the NADP(+)-dependent isocitrate dehydrogenase found in the cytoplasm and peroxisomes. It contains the PTS-1 peroxisomal targeting signal sequence. The presence of this enzyme in peroxisomes suggests roles in the regeneration of NADPH for intraperoxisomal reductions, such as the conversion of 2, 4-dienoyl-CoAs to 3-enoyl-CoAs, as well as in peroxisomal reactions that consume 2-oxoglutarate, namely the alpha-hydroxylation of phytanic acid. The cytoplasmic enzyme serves a significant role in cytoplasmic NADPH production. Alternatively spliced transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Sep 2013]

Uniprot Accession IDs

• O75874
• Q567U4
• Q6FHQ6
• Q7Z3V0
• Q93090
• Q9NTJ9
• Q9UKW8
• IDH

Gene Name

• IDH1

Ensembl ID

• ENST00000345146
• ENSP00000260985
• ENSG00000138413
• ENST00000415913
• ENSP00000390265
• ENST00000446179
• ENSP00000410513

Symbol

• PICD
• IDH
• IDP
• IDCD
• IDPC
• PICD
• HEL-216
• HEL-S-26

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
biological term	1
transcription factor perturbation	0.99
disease perturbation	0.93
kinase perturbation	0.91
transcription factor binding site profile	0.87

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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: 2261.54   (req: < 5)

Gene RIFs: 585   (req: <= 3)

Antibodies: 843   (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: 2261.54   (req: >= 5)

Gene RIFs: 585   (req: > 3)

Antibodies: 843   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 23

Tchem

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

Active Ligands: 706

Tclin

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

Active Drug: 1

Approved Drugs (1)

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1 – 1 of 1

ivosidenib

IDH1Tclin Enzyme

INHIBITOR IC50 : 7.14874165

Active Ligands (706)

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1 – 10 of 706

CHEMBL3925569

IDH1Tclin Enzyme

IC50 : 6

CHEMBL3682008

IDH1Tclin Enzyme

IC50 : 6

CHEMBL3682029

IDH1Tclin Enzyme

IC50 : 6

CHEMBL3897491

IDH1Tclin Enzyme

IC50 : 6

CHEMBL3985642

IDH1Tclin Enzyme

IC50 : 6

CHEMBL3985326

IDH1Tclin Enzyme

IC50 : 6.01

CHEMBL3920526

IDH1Tclin Enzyme

IC50 : 6.01

CHEMBL3893404

IDH1Tclin Enzyme

IC50 : 6.02

CHEMBL3955798

IDH1Tclin Enzyme

IC50 : 6.02

CHEMBL3343458

IDH1Tclin Enzyme

Ki : 6.02

Orthologs (15)

1 – 5 of 15

Species	Name	Source ID	Gene ID	OMA	EggNOG	Inparanoid
Chimp	isocitrate dehydrogenase (NADP(+)) 1, cytosolic	VGNC:1968	460113
Macaque	isocitrate dehydrogenase (NADP(+)) 1, cytosolic		710019
Mouse	isocitrate dehydrogenase 1 (NADP+), soluble	MGI:96413	15926
Rat	isocitrate dehydrogenase (NADP(+)) 1, cytosolic	RGD:2862	24479
Dog	isocitrate dehydrogenase (NADP(+)) 1, cytosolic		478889

Species	Name	OMA	EggNOG	Inparanoid
Chimp	isocitrate dehydrogenase (NADP(+)) 1, cytosolic
Macaque	isocitrate dehydrogenase (NADP(+)) 1, cytosolic
Mouse	isocitrate dehydrogenase 1 (NADP+), soluble
Rat	isocitrate dehydrogenase (NADP(+)) 1, cytosolic
Dog	isocitrate dehydrogenase (NADP(+)) 1, cytosolic

Protein Structure (36 Structures, 1 AlphaFold Model)

Representation

  axes   backbone   ball+stick   cartoon   rocket   rope   spacefill

Color Scheme

  target   atomindex   bfactor   chainname   electrostatic   element   hydrophobicity   resname   sstruc

Click on a row in the table to change the structure displayed.
More information can be found at RCSB PDB

AF-O75874-F1-model_v1

AlphaFold Structures Developed by DeepMind and EMBL-EBI

1 – 5 of 36

PDB Structure Id	Ligand	Method	Resolution (Å)	Residues	Fraction of Total Protein	Pub Year	Title

PDB Structure Id	Fraction of Total Protein	Resolution	Pub Year

Pathways (30)

Reactome (12)

KEGG (8)

WikiPathways (10)

Abnormal conversion of 2-oxoglutarate to 2-hydroxyglutarate (R-HSA-2978092)

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5

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Data Source	Name	Explore in Pharos	Explore in Source
Reactome	Abnormal conversion of 2-oxoglutarate to 2-hydroxyglutarate	1 targets	R-HSA-2978092
Reactome	Disease	1105 targets	R-HSA-1643685
Reactome	Diseases of metabolism	103 targets	R-HSA-5668914
Reactome	Immune System	2246 targets	R-HSA-168256
Reactome	Innate Immune System	1188 targets	R-HSA-168249

Name	Explore in Pharos	Explore in Source
Abnormal conversion of 2-oxoglutarate to 2-hydroxyglutarate	1 targets	R-HSA-2978092
Disease	1105 targets	R-HSA-1643685
Diseases of metabolism	103 targets	R-HSA-5668914
Immune System	2246 targets	R-HSA-168256
Innate Immune System	1188 targets	R-HSA-168249

Gene Ontology Terms (33)

Functions (9)

Components (10)

Processes (14)

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Items per page:

10

1 – 9 of 9

GO Term	Evidence	Assigned by
(R)-2-hydroxyglutarate dehydrogenase activity	Inferred from Experiment (EXP)	Reactome
isocitrate dehydrogenase (NADP+) activity	Inferred from Direct Assay (IDA)	UniProtKB
magnesium ion binding	Inferred from Direct Assay (IDA)	UniProtKB
identical protein binding	Inferred from Physical Interaction (IPI)	IntAct
protein homodimerization activity	Inferred from Physical Interaction (IPI)	UniProtKB
signaling receptor binding	Inferred from Physical Interaction (IPI)	UniProtKB
cadherin binding	Inferred from High Throughput Direct Assay (HDA)	BHF-UCL
NAD binding	Inferred from Electronic Annotation (IEA)	InterPro
NADP binding	Inferred from Electronic Annotation (IEA)	Ensembl

Protein-Protein Interactions (376)

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1 – 10 of 376

• See Interactions on String-DB

IDH3B

Tbio

Family: Enzyme

Novelty: 0.04326765

Score: 0.995

Data Source: STRINGDB

IDH3G

Tbio

Family: Enzyme

Novelty: 0.04861242

Score: 0.995

Data Source: STRINGDB

IDH3A

Tbio

Family: Enzyme

Novelty: 0.02027198

Score: 0.989

Data Source: STRINGDB

OGDH

Tbio

Family: Enzyme

Novelty: 0.00674601

Score: 0.987

Data Source: STRINGDB

ACO2

Tbio

Family: Enzyme

Novelty: 0.00276725

Score: 0.979

Data Source: STRINGDB

IDH2

Tclin

Family: Enzyme

Novelty: 0.00131782

Score: 0.976

Data Source: STRINGDB

ACO1

Tbio

Family: Enzyme

Novelty: 0.00194023

Score: 0.971

Data Source: STRINGDB

PGM1

Tbio

Family: Enzyme

Novelty: 0.00163947

Score: 0.964

Data Source: STRINGDB

HSD17B4

Tbio

Novelty: 0.00547499

Score: 0.957

Data Source: STRINGDB

CAT

Tbio

Family: Enzyme

Novelty: 0.00181888

Score: 0.951

Data Source: STRINGDB

Publication Statistics

PubMed Score  2261.54

PubMed score by year

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PubTator Score  1729.94

PubTator score by year

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Amino Acid Sequence

Residue Counts

Protein Sequence

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3D-structure
Acetylation
Complete proteome
Cytoplasm
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Glyoxylate bypass
Magnesium
Manganese
Metal-binding
NADP

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growth/size/body region phenotype
hematopoietic system phenotype
homeostasis/metabolism phenotype
immune system phenotype
mortality/aging
respiratory system phenotype
skeleton phenotype