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This gene encodes a protein that is 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 composed of a prodomain and a large and small protease subunit. Activation of caspases requires proteolytic processing at conserved internal aspartic residues to generate a heterodimeric enzyme consisting of the large and small subunits. This caspase is able to cleave and activate its own precursor protein, as well as caspase 1 precursor. When overexpressed, this gene induces cell apoptosis. Alternative splicing results in transcript variants encoding distinct isoforms. [provided by RefSeq, Jul 2008]
CASP4 (Caspase 4) is a Protein Coding gene. Diseases associated with CASP4 include Cystinosis and Cardiomyopathy, Familial Hypertrophic, 1. Among its related pathways are Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signaling pathways and Apoptosis Modulation and Signaling. Gene Ontology (GO) annotations related to this gene include cysteine-type endopeptidase activity and cysteine-type endopeptidase activity involved in execution phase of apoptosis. An important paralog of this gene is CASP5.
Caspases (cysteinyl aspartate proteases) are involved in the signaling pathways of apoptosis, necrosis and inflammation. These enzymes can be divided into initiators and effectors. The initiator isoforms are activated by, and interact with, upstream adaptor molecules.
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0004197 | cysteine-type endopeptidase activity | IEA,IDA | 16920334 |
GO:0005515 | protein binding | IPI | 30692621 |
GO:0008233 | peptidase activity | IEA | -- |
GO:0008234 | cysteine-type peptidase activity | IEA | -- |
GO:0016787 | hydrolase activity | IEA | -- |
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0005576 | extracellular region | IEA | -- |
GO:0005737 | cytoplasm | IBA | 21873635 |
GO:0005739 | mitochondrion | IDA | 15123740 |
GO:0005783 | endoplasmic reticulum | IDA | 15123740 |
GO:0005789 | endoplasmic reticulum membrane | IEA | -- |
SuperPathway | Contained pathways | ||
---|---|---|---|
1 | p53 Signaling |
.46
|
p53 Signaling
.46
|
2 | TRAF Pathway |
TNF Superfamily Pathway
.42
|
14-3-3 Induced Apoptosis
.33
|
3 | Ceramide Pathway |
Ceramide Pathway
.32
|
TNF-Induced Apoptosis Implicating Sphingolipids
.32
|
4 | Innate Immune System |
.61
|
|
5 | Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signaling pathways |
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0002376 | immune system process | IEA | -- |
GO:0006508 | proteolysis | IEA | -- |
GO:0006915 | NOT apoptotic process | IBA | 21873635 |
GO:0006919 | NOT activation of cysteine-type endopeptidase activity involved in apoptotic process | IBA | 21873635 |
GO:0006954 | inflammatory response | IEA | -- |
Name | Status | Disease Links | Group | Role | Mechanism of Action | Clinical Trials |
---|---|---|---|---|---|---|
Cisplatin | Approved | Pharma | Inhibits DNA synthesis,chemotherapy drug, Potent pro-apoptotic anticancer agent; activates caspase-3, Platinum | 3412 | ||
Incadronic acid | Experimental | Pharma | Target, activator | 0 | ||
Tasisulam | Investigational | Pharma | 0 | |||
Apoptosis Activator 2 | Pharma | Indoledione caspase activator, cell-permeable, Promotes apoptosome formation and activates caspase-9/caspase-3 pathway. Selectively induces tumor cell apoptosis | 0 | |||
PETCM | Pharma | Activator | Caspase-3 activator, Activator of caspase-3 | 0 |
Name | Synonyms | Role | CAS Number | PubChem IDs | PubMed IDs | |
---|---|---|---|---|---|---|
PAC 1 |
|
315183-21-2 |
|
|
Compound | Action | Cas Number |
---|---|---|
Apoptosis Activator 2 | Promotes apoptosome formation and activates caspase-9/caspase-3 pathway. Selectively induces tumor cell apoptosis | 79183-19-0 |
Cisplatin | Potent pro-apoptotic anticancer agent; activates caspase-3 | 15663-27-1 |
PAC 1 | Activator of procaspase-3; pro-apoptotic | 315183-21-2 |
PETCM | Activator of caspase-3 | 10129-56-3 |
Compound | Action | Cas Number |
---|---|---|
Apoptosis Activator 2 | Indoledione caspase activator, cell-permeable | 79183-19-0 |
Cisplatin | Inhibits DNA synthesis,chemotherapy drug | 15663-27-1 |
Tasisulam | 519055-62-0 |
ExUns: | 1 | ^ | 2 | ^ | 3 | ^ | 4a | · | 4b | ^ | 5 | ^ | 6 | ^ | 7a | · | 7b | ^ | 8 | ^ | 9 | ^ | 10 |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
SP1: | - | ||||||||||||||||||||||
SP2: | |||||||||||||||||||||||
SP3: | - | - | - | ||||||||||||||||||||
SP4: |
This gene was present in the common ancestor of animals.
Organism | Taxonomy | Gene | Similarity | Type | Details |
---|---|---|---|---|---|
Chimpanzee (Pan troglodytes) |
Mammalia | CASP4 30 31 |
|
OneToOne | |
Cow (Bos Taurus) |
Mammalia | CASP4 30 |
|
||
CASP13 31 |
|
OneToMany | |||
Mouse (Mus musculus) |
Mammalia | Casp4 30 17 31 |
|
OneToMany | |
Rat (Rattus norvegicus) |
Mammalia | Casp4 30 |
|
||
Dog (Canis familiaris) |
Mammalia | CASP4 31 |
|
OneToMany | |
Platypus (Ornithorhynchus anatinus) |
Mammalia | -- 31 |
|
OneToMany | |
Chicken (Gallus gallus) |
Aves | -- 31 |
|
OneToMany | |
Lizard (Anolis carolinensis) |
Reptilia | -- 31 |
|
OneToMany | |
Zebrafish (Danio rerio) |
Actinopterygii | caspbl 31 |
|
ManyToMany | |
Fruit Fly (Drosophila melanogaster) |
Insecta | Nc 31 |
|
ManyToMany | |
Dredd 31 |
|
ManyToMany | |||
Worm (Caenorhabditis elegans) |
Secernentea | csp-2 31 |
|
ManyToMany |
SNP ID | Clinical significance and condition | Chr 11 pos | Variation | AA Info | Type |
---|---|---|---|---|---|
781813 | Benign: not provided | 104,944,774(-) | G/GA | FRAMESHIFT_VARIANT | |
787097 | Benign: not provided | 104,954,870(-) | C/T | MISSENSE_VARIANT,FIVE_PRIME_UTR_VARIANT | |
787387 | Benign: not provided | 104,948,606(-) | C/A | MISSENSE_VARIANT | |
rs181090259 | - | p.Arg134Cys | |||
rs55901059 | - | p.Glu284Asp |
Variant ID | Type | Subtype | PubMed ID |
---|---|---|---|
esv2750978 | CNV | gain | 17911159 |
nsv1038877 | CNV | gain | 25217958 |
nsv1040784 | CNV | loss | 25217958 |
nsv1041081 | CNV | loss | 25217958 |
nsv1046098 | CNV | loss | 25217958 |
nsv1052674 | CNV | loss | 25217958 |
nsv468862 | CNV | gain | 19166990 |
nsv469 | CNV | insertion | 18451855 |
nsv556218 | CNV | gain | 21841781 |
nsv832255 | CNV | loss | 17160897 |
nsv975222 | CNV | duplication | 23825009 |
Disorder | Aliases | PubMed IDs |
---|---|---|
cystinosis |
|
|
cardiomyopathy, familial hypertrophic, 1 |
|
|
cowpox |
|
|
neuroblastoma |
|
|