CASP9
Caspase-9
Also known as: APAF-3, CASP9_HUMAN, ICE-LAP6, MCH6, PPP1R56
Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene
Protein identityUniProt · HPA
- UniProt accession
- P55211
- Gene
- CASP9
- Ensembl
- ENSG00000132906
- Chromosome
- 1
- Canonical length
- 416 aa
- Protein class
- Cancer-related genes, Enzymes, Predicted intracellular proteins
- Subcellular location
- Mitochondria
OverviewNCBI Gene
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]
Canonical amino-acid sequenceUniProt
416 residues, UniProt reviewed canonical sequence.
>P55211|CASP9
1 MDEADRRLLR RCRLRLVEEL QVDQLWDALL SRELFRPHMI EDIQRAGSGS RRDQARQLII
61 DLETRGSQAL PLFISCLEDT GQDMLASFLR TNRQAAKLSK PTLENLTPVV LRPEIRKPEV
121 LRPETPRPVD IGSGGFGDVG ALESLRGNAD LAYILSMEPC GHCLIINNVN FCRESGLRTR
181 TGSNIDCEKL RRRFSSLHFM VEVKGDLTAK KMVLALLELA QQDHGALDCC VVVILSHGCQ
241 ASHLQFPGAV YGTDGCPVSV EKIVNIFNGT SCPSLGGKPK LFFIQACGGE QKDHGFEVAS
301 TSPEDESPGS NPEPDATPFQ EGLRTFDQLD AISSLPTPSD IFVSYSTFPG FVSWRDPKSG
361 SWYVETLDDI FEQWAHSEDL QSLLLRVANA VSVKGIYKQM PGCFNFLRKK LFFKTSLocalizationUniProt · AlphaFold · HPA
Whether an antibody against CASP9 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.
- Antibody reachability
- Intracellular
- Secreted
- No
- Transmembrane segments
- 0
- Mean surface accessibility (rSASA)
- 0.32
- Highest tissue expression
- 52 nTPM
Expression across tissuesHPA
Tissue
- ovary: 52 nTPM
- adrenal gland: 49 nTPM
- pancreas: 36 nTPM
- pituitary gland: 33 nTPM
- thyroid gland: 27 nTPM
- testis: 27 nTPM
Single-cell type
- somatotrophs: 91 nCPM
- neutrophils: 88 nCPM
- monocytes: 76 nCPM
- cdc: 70 nCPM
- lactotrophs: 68 nCPM
- esophageal apical cells: 64 nCPM
Immune cell
- eosinophil: 55 nTPM
- basophil: 55 nTPM
- neutrophil: 37 nTPM
- naive B-cell: 30 nTPM
- NK-cell: 29 nTPM
- myeloid DC: 25 nTPM
Brain region
- white matter: 24 nTPM
- cerebellum: 21 nTPM
- medulla oblongata: 21 nTPM
- thalamus: 19 nTPM
- midbrain: 19 nTPM
- cerebral cortex: 19 nTPM
Genetic constraint and essentialitygnomAD · DepMap
Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.
- gnomAD LOEUF (loss-of-function intolerance)
- 0.97
- gnomAD pLI
- 0
- gnomAD missense Z
- 0.03
- DepMap mean gene effect
- -0.02
- DepMap dependency class
- selective
Cancer expressionTCGA
Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).
OntologyGO
Biological processes
- apoptotic process
- cellular response to dexamethasone stimulus
- cellular response to UV
- DNA damage response
- epithelial cell apoptotic process
- fibroblast apoptotic process
- glial cell apoptotic process
- intrinsic apoptotic signaling pathway
- intrinsic apoptotic signaling pathway in response to DNA damage
- kidney development
- leukocyte apoptotic process
- neuron apoptotic process
- platelet formation
- positive regulation of apoptotic process
- positive regulation of execution phase of apoptosis
- positive regulation of neuron apoptotic process
- protein maturation
- protein processing
- response to anesthetic
- response to cobalt ion
- response to estradiol
- response to ethanol
- response to hypoxia
- response to ischemia
- response to lipopolysaccharide
- signal transduction in response to DNA damage
- response to indole-3-methanol
Molecular functions
- cysteine-type endopeptidase activity
- enzyme activator activity
- identical protein binding
- peptidase activity
- protein kinase binding
Cellular components
Protein domainsUniProt · Pfam · InterPro
- Peptidase C14, p20 domain
- CARD domain
- Peptidase C14, caspase non-catalytic subunit p10
- Peptidase C14 family
- Death-like domain superfamily
- Peptidase C14, caspase domain
- Peptidase C14A, caspase catalytic domain
- Peptidase family C14A, His active site
- Caspase-like domain superfamily
- Peptidase family C14A, cysteine active site
- Caspase recruitment domain
- Caspase domain
- CASP9, CARD domain
KeywordsUniProt
InteractionsUniProt · HPA
Protein binding partners of CASP9 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.
Antibody and autoantibody relevanceSeroatlas analysis
Seroatlas reads CASP9 as an antibody target. Whether an autoantibody or antibody against CASP9 could matter depends on whether native CASP9 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.
CASP9 is annotated as predominantly intracellular. Intracellular proteins are common autoantibody markers, becoming visible to the immune system after cell injury or altered processing, but are usually markers of disease rather than direct drivers.
Annotation status
The present source text does not explicitly label CASP9 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.
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