P51878 · CASP5_HUMAN
- ProteinCaspase-5
- GeneCASP5
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids434 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Thiol protease that acts as a mediator of programmed cell death (PubMed:28314590, PubMed:29898893).
Initiates pyroptosis, a programmed lytic cell death pathway through cleavage of Gasdermin-D (GSDMD): cleavage releases the N-terminal gasdermin moiety (Gasdermin-D, N-terminal) that binds to membranes and forms pores, triggering pyroptosis (PubMed:29898893).
Also mediates cleavage and maturation of IL18 (PubMed:37993714).
Cleavage of GSDMD and IL18 is not strictly dependent on the consensus cleavage site but depends on an exosite interface on CASP4 (PubMed:37993714).
During non-canonical inflammasome activation, cuts CGAS and may play a role in the regulation of antiviral innate immune activation (PubMed:28314590).
Initiates pyroptosis, a programmed lytic cell death pathway through cleavage of Gasdermin-D (GSDMD): cleavage releases the N-terminal gasdermin moiety (Gasdermin-D, N-terminal) that binds to membranes and forms pores, triggering pyroptosis (PubMed:29898893).
Also mediates cleavage and maturation of IL18 (PubMed:37993714).
Cleavage of GSDMD and IL18 is not strictly dependent on the consensus cleavage site but depends on an exosite interface on CASP4 (PubMed:37993714).
During non-canonical inflammasome activation, cuts CGAS and may play a role in the regulation of antiviral innate immune activation (PubMed:28314590).
Catalytic activity
Features
Showing features for active site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Active site | 267 | |||||
Sequence: H | ||||||
Active site | 315 | |||||
Sequence: C |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | cytoplasm | |
Cellular Component | cytosol | |
Cellular Component | NLRP1 inflammasome complex | |
Molecular Function | cysteine-type endopeptidase activity | |
Molecular Function | cysteine-type peptidase activity | |
Biological Process | apoptotic process | |
Biological Process | cellular response to mechanical stimulus | |
Biological Process | positive regulation of inflammatory response | |
Biological Process | positive regulation of neuron apoptotic process | |
Biological Process | protein maturation | |
Biological Process | proteolysis | |
Biological Process | substantia nigra development |
Keywords
- Molecular function
- Biological process
Enzyme and pathway databases
Protein family/group databases
Names & Taxonomy
Protein names
- Recommended nameCaspase-5
- EC number
- Short namesCASP-5
- Alternative names
- Cleaved into 2 chains
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionP51878
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Disease & Variants
Features
Showing features for natural variant, mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_047216 | 19 | in dbSNP:rs45483102 | |||
Sequence: K → N | ||||||
Natural variant | VAR_047217 | 26 | in dbSNP:rs1792778 | |||
Sequence: L → W | ||||||
Natural variant | VAR_024403 | 29 | in dbSNP:rs3181320 | |||
Sequence: F → L | ||||||
Natural variant | VAR_054480 | 75 | in dbSNP:rs45585331 | |||
Sequence: L → R | ||||||
Natural variant | VAR_047218 | 106 | in dbSNP:rs507879 | |||
Sequence: T → A | ||||||
Natural variant | VAR_024404 | 168 | in dbSNP:rs3181179 | |||
Sequence: R → H | ||||||
Natural variant | VAR_024405 | 217 | in dbSNP:rs3181326 | |||
Sequence: V → L | ||||||
Natural variant | VAR_054481 | 298 | in dbSNP:rs45464699 | |||
Sequence: R → H | ||||||
Mutagenesis | 315 | Abolishes protease activity. | ||||
Sequence: C → A | ||||||
Mutagenesis | 324 | Abolished ability to cleave IL18. | ||||
Sequence: W → L | ||||||
Natural variant | VAR_047219 | 334 | in dbSNP:rs523104 | |||
Sequence: L → V | ||||||
Mutagenesis | 348-350 | Abolished ability to cleave IL18. | ||||
Sequence: VCK → NCA | ||||||
Natural variant | VAR_047220 | 353 | in dbSNP:rs45619739 | |||
Sequence: E → K | ||||||
Natural variant | VAR_054482 | 382 | in dbSNP:rs45458695 | |||
Sequence: E → Q |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 655 variants from UniProt as well as other sources including ClinVar and dbSNP.
Organism-specific databases
Miscellaneous
Chemistry
Genetic variation databases
PTM/Processing
Features
Showing features for propeptide, chain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Propeptide | PRO_0000004604 | 1-136 | ||||
Sequence: MAEDSGKKKRRKNFEAMFKGILQSGLDNFVINHMLKNNVAGQTSIQTLVPNTDQKSTSVKKDNHKKKTVKMLEYLGKDVLHGVFNYLAKHDVLTLKEEEKKKYYDTKIEDKALILVDSLRKNRVAHQMFTQTLLNM | ||||||
Chain | PRO_0000004605 | 137-327 | Caspase-5 subunit p20 | |||
Sequence: DQKITSVKPLLQIEAGPPESAESTNILKLCPREEFLRLCKKNHDEIYPIKKREDRRRLALIICNTKFDHLPARNGAHYDIVGMKRLLQGLGYTVVDEKNLTARDMESVLRAFAARPEHKSSDSTFLVLMSHGILEGICGTAHKKKKPDVLLYDTIFQIFNNRNCLSLKDKPKVIIVQACRGEKHGELWVRD | ||||||
Propeptide | PRO_0000004606 | 328-346 | ||||
Sequence: SPASLALISSQSSENLEAD | ||||||
Chain | PRO_0000004607 | 347-434 | Caspase-5 subunit p10 | |||
Sequence: SVCKIHEEKDFIAFCSSTPHNVSWRDRTRGSIFITELITCFQKYSCCCHLMEIFRKVQKSFEVPQAKAQMPTIERATLTRDFYLFPGN |
Post-translational modification
The two subunits are derived from the precursor sequence by an autocatalytic mechanism.
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Expressed in barely detectable amounts in most tissues except brain, highest levels being found in lung, liver and skeletal muscle.
Induction
Up-regulated by bacterial lipopolysaccharides (LPS).
Gene expression databases
Organism-specific databases
Interaction
Subunit
Heterotetramer that consists of two anti-parallel arranged heterodimers, each one formed by a 20 kDa (p20) and a 10 kDa (p10) subunits (By similarity).
Interacts with MEFV (PubMed:17431422).
Interacts with SERPINB1; this interaction regulates CASP5 activity (PubMed:30692621).
Interacts with MEFV (PubMed:17431422).
Interacts with SERPINB1; this interaction regulates CASP5 activity (PubMed:30692621).
Protein-protein interaction databases
Chemistry
Miscellaneous
Structure
Family & Domains
Features
Showing features for domain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Domain | 56-148 | CARD | ||||
Sequence: STSVKKDNHKKKTVKMLEYLGKDVLHGVFNYLAKHDVLTLKEEEKKKYYDTKIEDKALILVDSLRKNRVAHQMFTQTLLNMDQKITSVKPLLQ |
Sequence similarities
Belongs to the peptidase C14A family.
Phylogenomic databases
Family and domain databases
Sequence & Isoforms
- Sequence statusComplete
- Sequence processingThe displayed sequence is further processed into a mature form.
This entry describes 6 isoforms produced by Alternative splicing & Alternative initiation.
P51878-1
This isoform has been chosen as the canonical sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
- Name1
- Synonymscaspase-5/a
- NoteMost abundant isoform.
- Length434
- Mass (Da)49,736
- Last updated2010-04-20 v3
- ChecksumC5257C2BF15EB6D5
P51878-2
- Name2
- SynonymsCaspase-5/b
- NoteMost abundant isoform.
- Differences from canonical
- 5-62: Missing
P51878-3
- Name3
- SynonymsCaspase-5/c
- Differences from canonical
- 1-145: MAEDSGKKKRRKNFEAMFKGILQSGLDNFVINHMLKNNVAGQTSIQTLVPNTDQKSTSVKKDNHKKKTVKMLEYLGKDVLHGVFNYLAKHDVLTLKEEEKKKYYDTKIEDKALILVDSLRKNRVAHQMFTQTLLNMDQKITSVKP → MAA
P51878-4
- Name4
- SynonymsCaspase-5/e
- NoteMay be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.
P51878-5
- Name5
- SynonymsCaspase-5/f
- Differences from canonical
- 1-2: MA → MAAVPRVEGVFIFLI
P51878-6
- Name6
- SynonymsCaspase-5-S
- NoteProduced by alternative initiation at Met-71 of isoform 1.
- Differences from canonical
- 1-70: Missing
Computationally mapped potential isoform sequences
There are 2 potential isoforms mapped to this entry
Sequence caution
Features
Showing features for alternative sequence.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Alternative sequence | VSP_038992 | 1-2 | in isoform 5 | |||
Sequence: MA → MAAVPRVEGVFIFLI | ||||||
Alternative sequence | VSP_038991 | 1-70 | in isoform 6 | |||
Sequence: Missing | ||||||
Alternative sequence | VSP_038990 | 1-145 | in isoform 3 | |||
Sequence: MAEDSGKKKRRKNFEAMFKGILQSGLDNFVINHMLKNNVAGQTSIQTLVPNTDQKSTSVKKDNHKKKTVKMLEYLGKDVLHGVFNYLAKHDVLTLKEEEKKKYYDTKIEDKALILVDSLRKNRVAHQMFTQTLLNMDQKITSVKP → MAA | ||||||
Alternative sequence | VSP_038993 | 5-62 | in isoform 2 and isoform 4 | |||
Sequence: Missing | ||||||
Alternative sequence | VSP_038994 | 145-166 | in isoform 4 | |||
Sequence: PLLQIEAGPPESAESTNILKLC → HLSNKKERGPQTPGSHHMQYKV | ||||||
Alternative sequence | VSP_038995 | 167-434 | in isoform 4 | |||
Sequence: Missing |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
DQ228672 EMBL· GenBank· DDBJ | ABB58698.1 EMBL· GenBank· DDBJ | mRNA | ||
DQ228673 EMBL· GenBank· DDBJ | ABB58699.1 EMBL· GenBank· DDBJ | mRNA | ||
DQ228674 EMBL· GenBank· DDBJ | ABB58700.1 EMBL· GenBank· DDBJ | mRNA | ||
DQ228676 EMBL· GenBank· DDBJ | ABB58702.1 EMBL· GenBank· DDBJ | mRNA | ||
DQ228677 EMBL· GenBank· DDBJ | ABB58703.1 EMBL· GenBank· DDBJ | mRNA | ||
AK296660 EMBL· GenBank· DDBJ | BAG59257.1 EMBL· GenBank· DDBJ | mRNA | Frameshift | |
AP001153 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
U28015 EMBL· GenBank· DDBJ | AAA75172.1 EMBL· GenBank· DDBJ | mRNA | Different initiation | |
BC074994 EMBL· GenBank· DDBJ | AAH74994.1 EMBL· GenBank· DDBJ | mRNA | Different initiation | |
BC113406 EMBL· GenBank· DDBJ | AAI13407.1 EMBL· GenBank· DDBJ | mRNA | Different initiation | |
X94993 EMBL· GenBank· DDBJ | CAA64450.1 EMBL· GenBank· DDBJ | mRNA | Different initiation | |
DQ508420 EMBL· GenBank· DDBJ | ABF47103.1 EMBL· GenBank· DDBJ | Genomic DNA | Different initiation | |
CH471065 EMBL· GenBank· DDBJ | EAW67054.1 EMBL· GenBank· DDBJ | Genomic DNA |