P29466 · CASP1_HUMAN
- ProteinCaspase-1
- GeneCASP1
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids404 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Plays a key role in cell immunity as an inflammatory response initiator: once activated through formation of an inflammasome complex, it initiates a pro-inflammatory response through the cleavage of the two inflammatory cytokines IL1B and IL18, releasing the mature cytokines which are involved in a variety of inflammatory processes (PubMed:15326478, PubMed:15498465, PubMed:1574116, PubMed:32051255, PubMed:7876192).
Cleaves a tetrapeptide after an Asp residue at position P1 (PubMed:15498465, PubMed:1574116, PubMed:7876192).
Also initiates pyroptosis, a programmed lytic cell death pathway, through cleavage of GSDMD (PubMed:26375003).
In contrast to cleavage of interleukin IL1B, recognition and cleavage of GSDMD is not strictly dependent on the consensus cleavage site but depends on an exosite interface on CASP1 that recognizes and binds the Gasdermin-D, C-terminal (GSDMD-CT) part (PubMed:32051255, PubMed:32109412, PubMed:32553275).
Cleaves and activates CASP7 in response to bacterial infection, promoting plasma membrane repair (PubMed:22464733).
Upon inflammasome activation, during DNA virus infection but not RNA virus challenge, controls antiviral immunity through the cleavage of CGAS, rendering it inactive (PubMed:28314590).
In apoptotic cells, cleaves SPHK2 which is released from cells and remains enzymatically active extracellularly (PubMed:20197547).
Isoform Delta
Isoform Epsilon
Catalytic activity
Activity regulation
Features
Showing features for active site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Active site | 237 | |||||
Sequence: H | ||||||
Active site | 285 | |||||
Sequence: C |
GO annotations
Keywords
- Molecular function
- Biological process
Enzyme and pathway databases
Protein family/group databases
Names & Taxonomy
Protein names
- Recommended nameCaspase-1
- EC number
- Short namesCASP-1
- 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 accessionP29466
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
Disease & Variants
Features
Showing features for natural variant, mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_048615 | 15 | in dbSNP:rs1042743 | |||
Sequence: R → H | ||||||
Mutagenesis | 285 | Loss of protease activity. Loss of SPHK2 cleavage and release in apoptotic cells. | ||||
Sequence: C → A or S | ||||||
Mutagenesis | 294 | Mediates autoprocessing but is unable to interact with Gasdermin-D (GSDMD) and mediate its cleavage. | ||||
Sequence: W → A | ||||||
Mutagenesis | 297 | In IDL(uncl); abolished cleavage in the interdomain region; when associated with 315-N-N-316. | ||||
Sequence: D → N | ||||||
Mutagenesis | 315-316 | In IDL(uncl); abolished cleavage in the interdomain region; when associated with N-297. | ||||
Sequence: DD → NN | ||||||
Mutagenesis | 318 | Mediates autoprocessing but is unable to interact with Gasdermin-D (GSDMD) and mediate its cleavage. | ||||
Sequence: I → N | ||||||
Mutagenesis | 318-320 | Abolished ability to cleave IL18. | ||||
Sequence: IKK → AKA | ||||||
Mutagenesis | 320 | Abolishes cleavage of Gasdermin-D (GSDMD). | ||||
Sequence: K → A |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 583 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, cross-link, modified residue, modified residue (large scale data).
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Propeptide | PRO_0000004521 | 1-119 | UniProt | ||||
Sequence: MADKVLKEKRKLFIRSMGEGTINGLLDELLQTRVLNKEEMEKVKRENATVMDKTRALIDSVIPKGAQACQICITYICEEDSYLAGTLGLSADQTSGNYLNMQDSQGVLSSFPAPQAVQD | |||||||
Chain | PRO_0000004522 | 120-297 | UniProt | Caspase-1 subunit p20 | |||
Sequence: NPAMPTSSGSEGNVKLCSLEEAQRIWKQKSAEIYPIMDKSSRTRLALIICNEEFDSIPRRTGAEVDITGMTMLLQNLGYSVDVKKNLTASDMTTELEAFAHRPEHKTSDSTFLVFMSHGIREGICGKKHSEQVPDILQLNAIFNMLNTKNCPSLKDKPKVIIIQACRGDSPGVVWFKD | |||||||
Cross-link | 134 | UniProt | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) | ||||
Sequence: K | |||||||
Propeptide | PRO_0000004523 | 298-316 | UniProt | Interdomain linker | |||
Sequence: SVGVSGNLSLPTTEEFEDD | |||||||
Modified residue | 302 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 306 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Chain | PRO_0000004524 | 317-404 | UniProt | Caspase-1 subunit p10 | |||
Sequence: AIKKAHIEKDFIAFCSSTPDNVSWRHPTMGSVFIGRLIEHMQEYACSCDVEEIFRKVRFSFEQPDGRAQMPTTERVTLTRCFYLFPGH |
Post-translational modification
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Induction
Gene expression databases
Organism-specific databases
Interaction
Subunit
May be a component of the inflammasome, a protein complex which also includes PYCARD, CARD8 and NLRP2 and whose function would be the activation of pro-inflammatory caspases (PubMed:15030775, PubMed:33420033).
Component of the AIM2 PANoptosome complex, a multiprotein complex that drives inflammatory cell death (PANoptosis) (By similarity).
Interacts with CARD8; interacts with the released C-terminus of CARD8 which forms an inflammasome and directly activates CASP1 to promote pyroptosis (PubMed:32051255).
Both the p10 and p20 subunits interact with MEFV (PubMed:16785446).
Interacts with CARD17P/INCA and CARD18 (PubMed:11051551, PubMed:15383541).
Interacts with SERPINB1; this interaction regulates CASP1 activity (PubMed:30692621).
Caspase-1 subunit p20
Can form a heterodimer with isoform epsilon which then has an inhibitory effect (PubMed:7876192).
Caspase-1 subunit p10
Isoform Epsilon
Binary interactions
Protein-protein interaction databases
Chemistry
Miscellaneous
Structure
Family & Domains
Features
Showing features for domain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Domain | 1-91 | CARD | ||||
Sequence: MADKVLKEKRKLFIRSMGEGTINGLLDELLQTRVLNKEEMEKVKRENATVMDKTRALIDSVIPKGAQACQICITYICEEDSYLAGTLGLSA |
Sequence similarities
Phylogenomic databases
Family and domain databases
Sequence & Isoforms
- Sequence statusComplete
- Sequence processingThe displayed sequence is further processed into a mature form.
This entry describes 5 isoforms produced by Alternative splicing. Additional isoforms seem to exist.
P29466-1
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.
- NameAlpha
- Length404
- Mass (Da)45,159
- Last updated1993-04-01 v1
- ChecksumABF33CF33CC71584
P29466-2
- NameBeta
- Differences from canonical
- 92-112: Missing
P29466-3
- NameGamma
- Differences from canonical
- 20-112: Missing
P29466-4
- NameDelta
P29466-5
- NameEpsilon
- Differences from canonical
- 20-335: Missing
Computationally mapped potential isoform sequences
There are 8 potential isoforms mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
B4DVD8 | B4DVD8_HUMAN | CASP1 | 301 | ||
H0YEC7 | H0YEC7_HUMAN | CASP1 | 240 | ||
Q5FBZ0 | Q5FBZ0_HUMAN | CASP1 | 110 | ||
B4DKN4 | B4DKN4_HUMAN | CASP1 | 162 | ||
G3V169 | G3V169_HUMAN | CASP1 | 367 | ||
A0A8Q3SI67 | A0A8Q3SI67_HUMAN | CASP1 | 375 | ||
A0A8Q3SIY2 | A0A8Q3SIY2_HUMAN | CASP1 | 365 | ||
A0A8Q3SI00 | A0A8Q3SI00_HUMAN | CASP1 | 336 |
Sequence caution
Features
Showing features for alternative sequence, sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Alternative sequence | VSP_000799 | 20-112 | in isoform Gamma and isoform Delta | |||
Sequence: Missing | ||||||
Alternative sequence | VSP_000797 | 20-335 | in isoform Epsilon | |||
Sequence: Missing | ||||||
Alternative sequence | VSP_000798 | 92-112 | in isoform Beta | |||
Sequence: Missing | ||||||
Alternative sequence | VSP_000800 | 288-335 | in isoform Delta | |||
Sequence: Missing | ||||||
Sequence conflict | 319 | in Ref. 4; BAD97223 | ||||
Sequence: K → R | ||||||
Sequence conflict | 402 | in Ref. 4; BAD97223 | ||||
Sequence: P → L |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
X65019 EMBL· GenBank· DDBJ | CAA46153.1 EMBL· GenBank· DDBJ | mRNA | ||
M87507 EMBL· GenBank· DDBJ | AAA66942.1 EMBL· GenBank· DDBJ | mRNA | ||
U13697 EMBL· GenBank· DDBJ | AAC50107.1 EMBL· GenBank· DDBJ | mRNA | ||
U13698 EMBL· GenBank· DDBJ | AAC50108.1 EMBL· GenBank· DDBJ | mRNA | ||
U13699 EMBL· GenBank· DDBJ | AAC50109.1 EMBL· GenBank· DDBJ | mRNA | ||
U13700 EMBL· GenBank· DDBJ | AAC50110.1 EMBL· GenBank· DDBJ | mRNA | ||
AK223503 EMBL· GenBank· DDBJ | BAD97223.1 EMBL· GenBank· DDBJ | mRNA | ||
AP001153 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
BC041689 EMBL· GenBank· DDBJ | AAH41689.1 EMBL· GenBank· DDBJ | mRNA | ||
BC062327 EMBL· GenBank· DDBJ | AAH62327.1 EMBL· GenBank· DDBJ | mRNA | ||
AY660536 EMBL· GenBank· DDBJ | AAT72297.1 EMBL· GenBank· DDBJ | mRNA | Sequence problems. |