Tchem CASP9 Caspase-9

Protein Classes

PANTHER Classes

Protein / Hydrolase / Protease / Cysteine Protease / Caspase-9

Protein / Enzyme Modulator / Protease Inhibitor / Caspase-9

DTO Classes

Protein / Enzyme / Protease / Cysteine Protease / Caspase-9

Protein Summary

Description

Involved in the activation cascade of caspases responsible for apoptosis execution. Binding of caspase-9 to Apaf-1 leads to activation of the protease which then cleaves and activates caspase-3. Promotes DNA damage-induced apoptosis in a ABL1/c-Abl-dependent manner. Proteolytically cleaves poly(ADP-ribose) polymerase (PARP). Isoform 2 lacks activity is an dominant-negative inhibitor of caspase-9. This gene encodes a member of the cysteine-aspartic acid protease (caspase) family. Sequential activation of caspases plays a central role in the execution-phase of cell apoptosis. Caspases exist as inactive proenzymes which undergo proteolytic processing at conserved aspartic residues to produce two subunits, large and small, that dimerize to form the active enzyme. This protein can undergo autoproteolytic processing and activation by the apoptosome, a protein complex of cytochrome c and the apoptotic peptidase activating factor 1; this step is thought to be one of the earliest in the caspase activation cascade. This protein is thought to play a central role in apoptosis and to be a tumor suppressor. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2013]

Uniprot Accession IDs

• P55211
• B4E1A3
• O95348
• Q53Y70
• Q5JRU9
• Q5UGI1
• Q92852
• Q9BQ62
• Q9UEQ3
• Q9UIJ8
• CASP-9

Gene Name

• CASP9

Ensembl ID

• ENST00000333868
• ENSP00000330237
• ENSG00000132906
• ENST00000348549
• ENSP00000255256
• ENST00000375890
• ENSP00000365051

Symbol

• MCH6
• MCH6
• APAF3
• APAF-3
• PPP1R56
• ICE-LAP6

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
chemical	1
kinase	0.99
protein domain	0.99
hub protein	0.95
biological process	0.92

Related Tools

Target Illumination GWAS Analytics (TIGA)

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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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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: 3592.87   (req: < 5)

Gene RIFs: 227   (req: <= 3)

Antibodies: 1672   (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: 3592.87   (req: >= 5)

Gene RIFs: 227   (req: > 3)

Antibodies: 1672   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 29

Tchem

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

Active Ligands: 13

Tclin

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

Active Drug: 0

Active Ligands (13)

Explore Active Ligands

1 – 10 of 13

CHEMBL23226

CASP9Tchem Enzyme

IC50 : 8.3

CHEMBL237310

CASP9Tchem Enzyme

IC50 : 8.22

CHEMBL2324339

CASP9Tchem Enzyme

IC50 : 6.1

CHEMBL1325945

CASP9Tchem Enzyme

AC50 : 6.67

CHEMBL180263

CASP9Tchem Enzyme

IC50 : 7.52

CHEMBL2324341

CASP9Tchem Enzyme

IC50 : 6

CHEMBL1463659

CASP9Tchem Enzyme

AC50 : 6.5

CHEMBL185356

CASP9Tchem Enzyme

IC50 : 8.05

CHEMBL90307

CASP9Tchem Enzyme

IC50 : 6.64

CHEMBL3906811

CASP9Tchem Enzyme

IC50 : 6.52

GWAS Traits (4)

• Explore on Target Illumination GWAS Analytics (TIGA)

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5

1 – 4 of 4

GWAS Trait	EFO ID	Study Count	SNP Count	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
creatinine measurement	EFO_0004518	1	1	1		27.4
glomerular filtration rate	EFO_0005208	1	1	1		27.4
alcoholic pancreatitis	EFO_1002013	1	1	0	1.6	25.8
urate measurement	EFO_0004531	1	1	1		18.3

• Explore on Target Illumination GWAS Analytics (TIGA)

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1 – 4 of 4

GWAS Trait	EFO ID	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
creatinine measurement	EFO_0004518	1		27.4
glomerular filtration rate	EFO_0005208	1		27.4
alcoholic pancreatitis	EFO_1002013	0	1.6	25.8
urate measurement	EFO_0004531	1		18.3

Reset Zoom  Beta Count   Odds Ratio

Orthologs (10)

1 – 5 of 10

Species	Name	Source ID	Gene ID	OMA	EggNOG	Inparanoid
Macaque	caspase 9		694544
Mouse	caspase 9	MGI:1277950	12371
Rat	caspase 9	RGD:61867	58918
Dog	caspase 9		487432
Horse	caspase 9	VGNC:50673	100054331

Species	Name	OMA	EggNOG	Inparanoid
Macaque	caspase 9
Mouse	caspase 9
Rat	caspase 9
Dog	caspase 9
Horse	caspase 9

Protein Structure (10 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-P55211-F1-model_v1

AlphaFold Structures Developed by DeepMind and EMBL-EBI

1 – 5 of 10

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 (107)

Reactome (25)

KEGG (31)

PathwayCommons (17)

WikiPathways (34)

AKT phosphorylates targets in the cytosol (R-HSA-198323)

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Find Similar Targets

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Data Source	Name	Explore in Pharos	Explore in Source
Reactome	AKT phosphorylates targets in the cytosol	14 targets	R-HSA-198323
Reactome	Activation of caspases through apoptosome-mediated cleavage	6 targets	R-HSA-111459
Reactome	Apoptosis	177 targets	R-HSA-109581
Reactome	Apoptotic factor-mediated response	16 targets	R-HSA-111471
Reactome	Caspase activation via Dependence Receptors in the absence of ligand	10 targets	R-HSA-418889

Name	Explore in Pharos	Explore in Source
AKT phosphorylates targets in the cytosol	14 targets	R-HSA-198323
Activation of caspases through apoptosome-mediated cleavage	6 targets	R-HSA-111459
Apoptosis	177 targets	R-HSA-109581
Apoptotic factor-mediated response	16 targets	R-HSA-111471
Caspase activation via Dependence Receptors in the absence of ligand	10 targets	R-HSA-418889

Gene Ontology Terms (35)

Functions (8)

Components (6)

Processes (21)

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Items per page:

10

1 – 8 of 8

GO Term	Evidence	Assigned by
cysteine-type endopeptidase activity	Inferred from Direct Assay (IDA)	UniProtKB
peptidase activity	Inferred from Direct Assay (IDA)	BHF-UCL
protein kinase binding	Inferred from Direct Assay (IDA)	UniProtKB
SH3 domain binding	Inferred from Direct Assay (IDA)	UniProtKB
identical protein binding	Inferred from Physical Interaction (IPI)	IntAct
cysteine-type endopeptidase activity involved in apoptotic signaling pathway	Inferred from Mutant Phenotype (IMP)	UniProtKB
cysteine-type endopeptidase activity involved in apoptotic process	Inferred from Biological aspect of Ancestor (IBA)	GO_Central
enzyme activator activity	Traceable Author Statement (TAS)	ProtInc

Protein-Protein Interactions (283)

Explore Interacting Targets

1 – 10 of 283

• See Interactions on String-DB

BIRC8

Tchem

Novelty: 0.05142518

p_int: 0.916097331

p_wrong: 0.083902669

Score: 0.965

Data Source: BioPlex,STRINGDB

XIAP

Tchem

Family: Enzyme

Novelty: 0.00062268

Score: 0.999

Data Source: Reactome,STRINGDB

APAF1

Tbio

Family: Enzyme

Novelty: 0.00107622

Score: 0.999

Data Source: Reactome,STRINGDB

CYCS

Tchem

Novelty: 0.00014004

Score: 0.998

Data Source: Reactome,STRINGDB

AKT1

Tchem

Family: Kinase

Novelty: 0.00003185

Score: 0.994

Data Source: Reactome,STRINGDB

CASP8

Tchem

Family: Enzyme

Novelty: 0.00024321

Score: 0.994

Data Source: STRINGDB

CASP2

Tchem

Family: Enzyme

Novelty: 0.00189892

Score: 0.994

Data Source: STRINGDB

DIABLO

Tbio

Novelty: 0.0007851

Score: 0.989

Data Source: Reactome,STRINGDB

BIRC2

Tchem

Novelty: 0.00199701

Score: 0.987

Data Source: STRINGDB

BIRC3

Tchem

Novelty: 0.00189613

Score: 0.986

Data Source: STRINGDB

Publication Statistics

PubMed Score  3592.87

PubMed score by year

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PubTator Score  3273.28

PubTator score by year

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Amino Acid Sequence

Residue Counts

Protein Sequence

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UniProt Keyword Find Similar Targets

3D-structure
Alternative splicing
Apoptosis
Complete proteome
Hydrolase
Phosphoprotein
Polymorphism
Protease
Reference proteome
Thiol protease

GWAS Trait Find Similar Targets

alcoholic pancreatitis
creatinine measurement
glomerular filtration rate
urate measurement

MGI Phenotype Find Similar Targets

cardiovascular system phenotype
cellular phenotype
craniofacial phenotype
embryo phenotype
endocrine/exocrine gland phenotype
growth/size/body region phenotype
hematopoietic system phenotype
immune system phenotype
mortality/aging
nervous system phenotype