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Details on Person UniProt:P29466 CASP1

Class:Id	ReferenceGeneProduct:56948
_chainChangeLog	propeptide:1-119 added on Fri February 6 2015;chain:120-297 added on Fri February 6 2015;propeptide:298-316 added on Fri February 6 2015;chain:317-404 added on Fri February 6 2015
_displayName	UniProt:P29466 CASP1
_timestamp	2024-11-03 19:59:57
chain	propeptide:1-119 chain:120-297 propeptide:298-316 chain:317-404
checksum	ABF33CF33CC71584
comment	FUNCTION Thiol protease involved in a variety of inflammatory processes by proteolytically cleaving other proteins, such as the precursors of the inflammatory cytokines interleukin-1 beta (IL1B) and interleukin 18 (IL18) as well as the pyroptosis inducer Gasdermin-D (GSDMD), into active mature peptides (PubMed:15326478, PubMed:15498465, PubMed:1574116, PubMed:26375003, PubMed:32051255, PubMed:37993714, PubMed:7876192, PubMed:9334240). 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).FUNCTION Apoptosis inactive.FUNCTION Apoptosis inactive.CATALYTIC ACTIVITY Strict requirement for an Asp residue at position P1 and has a preferred cleavage sequence of Tyr-Val-Ala-Asp-\|-.ACTIVITY REGULATION (Microbial infection) Specifically inhibited by the cowpox virus Crma protein.SUBUNIT Heterotetramer that consists of two anti-parallel arranged heterodimers, each one formed by a 20 kDa (Caspase-1 subunit p20) and a 10 kDa (Caspase-1 subunit p10) subunit (PubMed:32109412, PubMed:32553275, PubMed:8044845, PubMed:9987822). 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).SUBUNIT Heterotetramer that consists of two anti-parallel arranged heterodimers, each one formed by a 20 kDa (Caspase-1 subunit p20) and a 10 kDa (Caspase-1 subunit p10) subunit (PubMed:32109412, PubMed:32553275, PubMed:8044845). Can form a heterodimer with isoform epsilon which then has an inhibitory effect (PubMed:7876192).SUBUNIT Heterotetramer that consists of two anti-parallel arranged heterodimers, each one formed by a 20 kDa (Caspase-1 subunit p20) and a 10 kDa (Caspase-1 subunit p10) subunit.SUBUNIT Can form a heterodimer with Caspase-1 subunit p20 which then has an inhibitory effect.INTERACTION Additional isoforms seem to exist.TISSUE SPECIFICITY Expressed in larger amounts in spleen and lung. Detected in liver, heart, small intestine, colon, thymus, prostate, skeletal muscle, peripheral blood leukocytes, kidney and testis. No expression in the brain.INDUCTION Transcription and translation induced by M.tuberculosis and a number of different M.tuberculosis components; EsxA is the most potent activator tested (at protein level) (PubMed:20148899).PTM The two subunits are derived from the precursor sequence by an autocatalytic mechanism.PTM Ubiquitinated via 'Lys-11'-linked polyubiquitination. Deubiquitinated by USP8.PTM Cleavage in the interdomain linker region is required to induce pyroptosis.SIMILARITY Belongs to the peptidase C14A family.SEQUENCE CAUTION Truncated N-terminus.SEQUENCE CAUTION Probable cloning artifact.
description	recommendedName: Caspase-1 shortName: CASP-1 ecNumber evidence="9 21 24"3.4.22.36 alternativeName: fullName evidence="28"Interleukin-1 beta convertase shortName evidence="28"IL-1BC alternativeName: fullName evidence="26 28"Interleukin-1 beta-converting enzyme shortName evidence="26 28 30"ICE shortName evidence="26 28"IL-1 beta-converting enzyme alternativeName: p45 component recommendedName: fullName evidence="32"Caspase-1 subunit p20 /component component recommendedName: fullName evidence="32"Caspase-1 subunit p10 /component
geneName	CASP1 IL1BC IL1BCE
identifier	P29466
isSequenceChanged	FALSE
keyword	3D-structure Alternative splicing Apoptosis Cell membrane Cytoplasm Direct protein sequencing Hydrolase Isopeptide bond Membrane Phosphoprotein Protease Proteomics identification Reference proteome Thiol protease Ubl conjugation Zymogen
modified	[InstanceEdit:9836292] Weiser, Joel, 2023-05-25 [InstanceEdit:9852000] Weiser, Joel, 2023-11-03 [InstanceEdit:9909836] Weiser, Joel, 2024-05-14 [InstanceEdit:9917590] Weiser, Joel, 2024-08-09 [InstanceEdit:9926675] Weiser, Joel, 2024-11-03
name	CASP1
referenceDatabase	[ReferenceDatabase:2] UniProt
referenceGene	[ReferenceDNASequence:6798090] ENSEMBL:ENSG00000137752 CASP1 [Homo sapiens]
secondaryIdentifier	CASP1_HUMAN B5MDZ1 Q53EY6 Q6DMQ1 Q6GSS3 Q6PI75 Q9UCN3
sequenceLength	404
species	[Species:48887] Homo sapiens
(isoformParent)	[ReferenceIsoform:148660] UniProt:P29466-2 CASP1 [Homo sapiens] [ReferenceIsoform:148661] UniProt:P29466-3 CASP1 [Homo sapiens] [ReferenceIsoform:148662] UniProt:P29466-4 CASP1 [Homo sapiens] [ReferenceIsoform:148663] UniProt:P29466-5 CASP1 [Homo sapiens] [ReferenceIsoform:403574] UniProt:P29466-1 CASP1 [Homo sapiens]
(referenceEntity)	[EntityWithAccessionedSequence:448674] CASP1(298-316) [cytosol] [Homo sapiens] [EntityWithAccessionedSequence:448680] CASP1(1-119) [cytosol] [Homo sapiens] [EntityWithAccessionedSequence:448686] CASP1(120-297) [cytosol] [Homo sapiens] [EntityWithAccessionedSequence:448692] CASP1(1-404) [cytosol] [Homo sapiens] [EntityWithAccessionedSequence:448704] CASP1(317-404) [cytosol] [Homo sapiens]
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No pathways have been reviewed or authored by UniProt:P29466 CASP1 (56948)