CASP4
Caspase-4
Also known as: CASP4_HUMAN, ICE(rel)II, ICH-2, TX
Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene
Protein identityUniProt · HPA
- UniProt accession
- P49662
- Gene
- CASP4
- Ensembl
- ENSG00000196954
- Chromosome
- 11
- Canonical length
- 377 aa
- Protein class
- Cancer-related genes, Enzymes, Predicted intracellular proteins
- Subcellular location
- Plasma membrane,Cytosol
- Secretome location
- Intracellular and membrane
- Quaternary structure
- Homooligomer
OverviewNCBI Gene
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]
Canonical amino-acid sequenceUniProt
377 residues, UniProt reviewed canonical sequence.
>P49662|CASP4
1 MAEGNHRKKP LKVLESLGKD FLTGVLDNLV EQNVLNWKEE EKKKYYDAKT EDKVRVMADS
61 MQEKQRMAGQ MLLQTFFNID QISPNKKAHP NMEAGPPESG ESTDALKLCP HEEFLRLCKE
121 RAEEIYPIKE RNNRTRLALI ICNTEFDHLP PRNGADFDIT GMKELLEGLD YSVDVEENLT
181 ARDMESALRA FATRPEHKSS DSTFLVLMSH GILEGICGTV HDEKKPDVLL YDTIFQIFNN
241 RNCLSLKDKP KVIIVQACRG ANRGELWVRD SPASLEVASS QSSENLEEDA VYKTHVEKDF
301 IAFCSSTPHN VSWRDSTMGS IFITQLITCF QKYSWCCHLE EVFRKVQQSF ETPRAKAQMP
361 TIERLSMTRY FYLFPGNLocalizationUniProt · AlphaFold · HPA
Whether an antibody against CASP4 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
- Secreted
- Secreted
- Yes
- Transmembrane segments
- 0
- Mean surface accessibility (rSASA)
- 0.35
- Highest tissue expression
- 77 nTPM
Expression across tissuesHPA
Tissue
- tonsil: 77 nTPM
- lymph node: 75 nTPM
- urinary bladder: 71 nTPM
- spleen: 70 nTPM
- pancreas: 66 nTPM
- placenta: 66 nTPM
Single-cell type
- neutrophils: 662 nCPM
- esophageal apical cells: 510 nCPM
- platelets: 230 nCPM
- pancreatic acinar cells: 206 nCPM
- monocytes: 166 nCPM
- cytotrophoblasts: 160 nCPM
Immune cell
- neutrophil: 670 nTPM
- total PBMC: 411 nTPM
- intermediate monocyte: 313 nTPM
- classical monocyte: 292 nTPM
- T-reg: 259 nTPM
- non-classical monocyte: 257 nTPM
Brain region
- medulla oblongata: 11 nTPM
- thalamus: 10 nTPM
- cerebral cortex: 9.4 nTPM
- pons: 9.3 nTPM
- white matter: 9.3 nTPM
- choroid plexus: 8.9 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)
- 1.17
- gnomAD pLI
- 0
- gnomAD missense Z
- 0.18
- DepMap mean gene effect
- 0.17
- DepMap dependency class
- none
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 amyloid-beta
- defense response to bacterium
- defense response to Gram-positive bacterium
- innate immune response
- intrinsic apoptotic signaling pathway
- intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress
- non-canonical inflammasome complex assembly
- positive regulation of inflammatory response
- positive regulation of interleukin-18-mediated signaling pathway
- positive regulation of neuron apoptotic process
- positive regulation of tumor necrosis factor-mediated signaling pathway
- protein autoprocessing
- protein maturation
- proteolysis
- pyroptotic inflammatory response
- regulation of inflammatory response
Molecular functions
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
KeywordsUniProt
InteractionsUniProt · HPA
Protein binding partners of CASP4 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 CASP4 as an antibody target. Whether an autoantibody or antibody against CASP4 could matter depends on whether native CASP4 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.
CASP4 is annotated as secreted, so native CASP4 circulates and is directly accessible to antibodies. Secreted and cell-surface proteins are the autoantibody targets most likely to act like drugs, blocking or depleting the native protein.
Annotation status
The present source text does not explicitly label CASP4 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.
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