CASP1 (caspase 1, apoptosis-related cysteine peptidase (interleukin 1, beta, convertase))

2007-11-01   Yatender Kumar , Vegesna Radha , Ghanshyam Swarup 

Centre for Cellular, Molecular Biology, Uppal Road, Hyderabad - 500 007, INDIA


Atlas Image


Atlas Image


The human caspase-1 gene is comprised of 10 exons, spanning 10.6kb on chromosome 11q22.2-q22.3.


Six alternatively spliced forms of caspase-1 have been identified in Homo sapiens.
The longest termed CASP1alpha is 1364bp with an ORF encoding 404 amino acids (aa) and is the most predominant isoform. CASP1beta is 1185bp, lacks entire exon3 (275-338bp; 92-112aa), ORF encoding 383aa. CASP1gamma is 969bp, lacks most of exon2 and entire exon3 (59-338bp; 20-112aa), ORF encoding 291aa. CASP1delta is 825bp, lacks entire exon7 (863-1006bp; 288-335aa), ORF encoding 356aa. CASP1epsilon is 300bp, lacks most of exon2 and exon3 exon7 (59-1006bp; 20-335aa), ORF encoding 98aa. CASP1zeta is 1131bp, missing 79bp in prodomain of caspase-1, ORF encoding 365aa. Among these alpha, beta, gamma and zeta forms are proteolytically active and can induce apoptosis. As delta and epsilon lack part of the catalytic domain, they do not induce apoptosis and serve as inhibitors of caspase-1 when overexpressed.


COP (Card Only Protein)


Atlas Image


Caspase-1 is the prototypical member of a subclass of caspases involved in cytokine maturation termed inflammatory caspases that also include caspases-4, caspases-5, and caspases-12. It is also involved in some forms of apoptosis. Caspase-1 protein consists of an N-terminal CARD (caspase activation and recruitment domain), a large P20 subunit and a small P10 subunit. Due to its long N-terminal prodomain, caspase-1 belongs to the initiator group of caspases and is therefore suspected to act proximally in a caspase activation cascade leading to apoptosis.
Caspase-1 is synthesized as a proenzyme of 45kDa, which undergoes proteolytic cleavage at Asp residues to produce the active enzyme. The active caspase-1 enzyme is a hetrotetramer comprised of two P20 and two P10 subunits. The catalytic site is formed by amino acids from both P20 and P10 subunits, with the active cysteine located within the P20 subunit. Caspase-1 is activated through interactions with other CARD containing proteins such as ASC, RIP2 and NLRC4 via homotypic CARD-CARD interactions. Bacterial and viral proteins like SipB, IpaB, CrmA, and Serp2 which do not contain the CARD domain, also regulate caspase-1. Caspase-1 is activated by phosphorylation at serine 376 residue by PAK1 upon Helicobacter pylori infection.


Caspase-1 is highly expressed in leukocytes, monocytes and epithelial cells.
Caspase-1 gene expression is induced in response to various stimuli such as microbial infections (Mycobacterium avium, Salmonella typhimurium, Legionella pneumophila, Bacillus anthracis, Francisella tularenis and bacterial LPS), cytokines (IFN-gamma and TNF-alpha), growth factors (TGF-beta), and DNA damaging agents (Doxorubicin, UV radiation and Paclitaxel). Levels of caspase-1 mRNA are high in ischemic tissues.
Tumor suppressor p53, p73, SP1, ETS-1, IFT57/HIPPI and IRF-1 activate transcription of full length caspase-1 mRNA by binding to respective sites in the promoter, within a region 550bp upstream of the transcription start site.


Predominantly cytoplasmic. See Table-1 and Table-2.


The adaptor molecules ASC, NLRC4 and Cryopyrin/Nalp3 regulate caspase-1 within a multiprotein complex known as the "Inflammasome". Caspase-1 activation results in cleavage and activation of proinflammatory cytokines such as IL-1beta and IL-18. Caspase-1 deficient mice have a defect in the maturation of proIL-1beta and are resistant to the lethal effect of endotoxins. Various pathogens such as S.typhimurium (TypeIII secretion), L.pneumophila (Type IV secretion), B.anthracis (Lethal Toxin), F.tularenis activate caspase-1 through "inflammasomes". Caspase-1 activation also occurs upon exposure to bacterial RNA, imidazoquilone compounds, LPS, extracellular ATP, muramyl dipeptide (MDP), monosodium urate, calcium pyrophosphate dehydrate and other TLR ligands via "inflammasomes". In addition to bacterial pathogens, viral infection also induces caspase-1 activation. Caspase-1 acts apically in neuronal cell death pathways induced by hypoxia and ischaemia. Caspase-1 is also involved in p53-mediated apoptosis in a cell type specific manner. Caspase-1 sensitizes cells to death induced by agents like Fas ligand, radiation and cisplatin. Caspase-1 stimulates membrane biogenesis to repair damage caused by pore-forming toxins, thereby promoting host cell survival.


CARD of caspase-1 bears significant homology with the CARDs of Caspase-4, Caspase-5, SFRS2IP/Caspase-11, Caspase-12, ICEBERG, Nod1, NLRC4, NEDD2, cIAP2, cIAP3 and ced3.



Not Known


Not Known

Implicated in

Entity name
Various Diseases
In diseases such as ischemic and hypoxia induced brain injury, acute bacterial meningitis, ischemia of the heart and kidney. A role for caspase-1 has been implicated in Amyotrophic Lateral Sclerosis, Huntingtons disease, Parkinsons disease, Crohns disease, Age-related cognitive dysfunctions, spinalcord inflammation and gout. Caspase1- activation is enhanced in patients with CINCA syndrome.
Entity name
In ovarian Cancer and stomach Cancer: there is a decreased expression of caspase-1.


Pubmed IDLast YearTitleAuthors
150307752004NALP3 forms an IL-1beta-processing inflammasome with increased activity in Muckle-Wells autoinflammatory disorder.Agostini L et al
78761921995Cloning and expression of four novel isoforms of human interleukin-1 beta converting enzyme with different apoptotic activities.Alnemri ES et al
155617132005NF-kappaB- and C/EBPbeta-driven interleukin-1beta gene expression and PAK1-mediated caspase-1 activation play essential roles in interleukin-1beta release from Helicobacter pylori lipopolysaccharide-stimulated macrophages.Basak C et al
27844321989A pre-aspartate-specific protease from human leukocytes that cleaves pro-interleukin-1 beta.Black RA et al
167781302006Haplotypes of the caspase-1 gene, plasma caspase-1 levels, and cardiovascular risk.Blankenberg S et al
110296882000Salmonella induces macrophage death by caspase-1-dependent necrosis.Brennan MA et al
154567912004PAN1/NALP2/PYPAF2, an inducible inflammatory mediator that regulates NF-kappaB and caspase-1 activation in macrophages.Bruey JM et al
80343201994Molecular characterization of the gene for human interleukin-1 beta converting enzyme (IL1BC).Cerretti DP et al
167854462006The B30.2 domain of pyrin, the familial Mediterranean fever protein, interacts directly with caspase-1 to modulate IL-1beta production.Chae JJ et al
150104632004Anthrax lethal toxin rapidly activates caspase-1/ICE and induces extracellular release of interleukin (IL)-1beta and IL-18.Cordoba-Rodriguez R et al
102338831999Interferon gamma induces upregulation and activation of caspases 1, 3, and 8 to produce apoptosis in human erythroid progenitor cells.Dai C et al
115360162001Regulation of IL-1beta generation by Pseudo-ICE and ICEBERG, two dominant negative caspase recruitment domain proteins.Druilhe A et al
75369001995Involvement of an ICE-like protease in Fas-mediated apoptosis.Enari M et al
162040222005Caspase-1alpha is down-regulated in human ovarian cancer cells and the overexpression of caspase-1alpha induces apoptosis.Feng Q et al
166488522006Cytosolic flagellin requires Ipaf for activation of caspase-1 and interleukin 1beta in salmonella-infected macrophages.Franchi L et al
102036931998ICE, neuronal apoptosis and neurodegeneration.Friedlander RM et al
145989732003Impaired interleukin-1beta converting enzyme (ICE) activity in patients with pulmonary tuberculosis.Fujiuchi S et al
177634112007Pattern of interleukin-1beta secretion in response to lipopolysaccharide and ATP before and after interleukin-1 blockade in patients with CIAS1 mutations.Gattorno M et al
175938762007Interleukin-1beta and caspase-1: players in the regulation of age-related cognitive dysfunction.Gemma C et al
161237792006Caspase-1 activation of caspase-6 in human apoptotic neurons.Guo H et al
124594632002A nuclear protein tyrosine phosphatase activates p53 and induces caspase-1-dependent apoptosis.Gupta S et al
169901372006Caspase-1 activation of lipid metabolic pathways in response to bacterial pore-forming toxins promotes cell survival.Gurcel L et al
100516531999The Salmonella invasin SipB induces macrophage apoptosis by binding to caspase-1.Hersh D et al
93938111997The interleukin 1beta-converting enzyme, caspase 1, is activated during Shigella flexneri-induced apoptosis in human monocyte-derived macrophages.Hilbi H et al
98300391998Shigella-induced apoptosis is dependent on caspase-1 which binds to IpaB.Hilbi H et al
110515512000ICEBERG: a novel inhibitor of interleukin-1beta generation.Humke EW et al
161355202005Role of p73 in regulating human caspase-1 gene transcription induced by interferon-{gamma} and cisplatin.Jain N et al
177257142007Tumor necrosis factor-alpha-induced caspase-1 gene expression. Role of p73.Jain N et al
158097172005Loss of caspase-1 gene expression in human gastric carcinomas and cell lines.Jee CD et al
126921302003Caspase-1 and caspase-8 cleave and inactivate cellular parkin.Kahns S et al
164078882006Bacterial RNA and small antiviral compounds activate caspase-1 through cryopyrin/Nalp3.Kanneganti TD et al
87009131996Cleavage of actin by interleukin 1 beta-converting enzyme to reverse DNase I inhibition.Kayalar C et al
27875081989Identification of a monocyte specific pre-interleukin 1 beta convertase activity.Kostura MJ et al
75354751995Altered cytokine export and apoptosis in mice deficient in interleukin-1 beta converting enzyme.Kuida K et al
98752251998Cleavage of human cytosolic phospholipase A2 by caspase-1 (ICE) and caspase-8 (FLICE).Lüschen S et al
106012481999ATP treatment of human monocytes promotes caspase-1 maturation and externalization.Laliberte RE et al
153835412004INCA, a novel human caspase recruitment domain protein that inhibits interleukin-1beta generation.Lamkanfi M et al
167171172006Role of the caspase-1 inflammasome in Salmonella typhimurium pathogenesis.Lara-Tejero M et al
114328592001Cop, a caspase recruitment domain-containing protein and inhibitor of caspase-1 activation processing.Lee SH et al
168959742006Innate immune response to Francisella tularensis is mediated by TLR2 and caspase-1 activation.Li H et al
107646472000Functional role of caspase-1 and caspase-3 in an ALS transgenic mouse model.Li M et al
78592821995Mice deficient in IL-1 beta-converting enzyme are defective in production of mature IL-1 beta and resistant to endotoxic shock.Li P et al
105326341999Mice deficient in interleukin-1 converting enzyme are resistant to neonatal hypoxic-ischemic brain damage.Liu XH et al
171738592007Interaction of HIPPI with putative promoter sequence of caspase-1 in vitro and in vivo.Majumder P et al
162304742005Innate immunity against Francisella tularensis is dependent on the ASC/caspase-1 axis.Mariathasan S et al
165962692006Caspase-1 as a radio- and chemo-sensitiser in vitro and in vivo.Martín-Duque P et al
164078892006Gout-associated uric acid crystals activate the NALP3 inflammasome.Martinon F et al
103370151999Investigation of the expression of IL-1beta converting enzyme and apoptosis in normal and inflammatory bowel disease (IBD) mucosal macrophages.McAlindon ME et al
97338191998Serp2, an inhibitor of the interleukin-1beta-converting enzyme, is critical in the pathobiology of myxoma virus.Messud-Petit F et al
166488532006Cytoplasmic flagellin activates caspase-1 and secretion of interleukin 1beta via Ipaf.Miao EA et al
173606532007NF-kappaB activation by the Toll-IL-1 receptor domain protein MyD88 adapter-like is regulated by caspase-1.Miggin SM et al
82427411993Induction of apoptosis in fibroblasts by IL-1 beta-converting enzyme, a mammalian homolog of the C. elegans cell death gene ced-3.Miura M et al
117554082001Salmonella-induced macrophage death: the role of caspase-1 in death and inflammation.Monack DM et al
92508711997Interleukin-1beta-converting enzyme (ICE) and related cell death genes ICErel-II and ICErel-III map to the same PAC clone at band 11q22.2-22.3.Nasir J et al
103532491999Inhibition of caspase-1 slows disease progression in a mouse model of Huntington's disease.Ona VO et al
98610441998Caspase-1 is activated in neural cells and tissue with amyotrophic lateral sclerosis-associated mutations in copper-zinc superoxide dismutase.Pasinelli P et al
161030712005Caspase-1 is a direct target gene of ETS1 and plays a role in ETS1-induced apoptosis.Pei H et al
112263332001Inhibition of caspase 1 reduces human myocardial ischemic dysfunction via inhibition of IL-18 and IL-1beta.Pomerantz BJ et al
111720342001p53 associates with and targets Delta Np63 into a protein degradation pathway.Ratovitski EA et al
168616832006Caspase-1-mediated activation of interleukin-1beta (IL-1beta) and IL-18 contributes to innate immune defenses against Salmonella enterica serovar Typhimurium infection.Raupach B et al
13393091992Viral inhibition of inflammation: cowpox virus encodes an inhibitor of the interleukin-1 beta converting enzyme.Ray CA et al
165524442006Flagellin-deficient Legionella mutants evade caspase-1- and Naip5-mediated macrophage immunity.Ren T et al
169901282006Caspase-1 builds a new barrier to infection.Saleh M et al
162860162005IL-33, an interleukin-1-like cytokine that signals via the IL-1 receptor-related protein ST2 and induces T helper type 2-associated cytokines.Schmitz J et al
94277121998Lipopolysaccharide activates caspase-1 (interleukin-1-converting enzyme) in cultured monocytic and endothelial cells.Schumann RR et al
171885002007Activation of caspase-1 dependent interleukins in developmental brain trauma.Sifringer M et al
94214821998The role of interleukin-converting enzyme in Fas-mediated apoptosis in HIV-1 infection.Sloand EM et al
119672582002The PYRIN-CARD protein ASC is an activating adaptor for caspase-1.Srinivasula SM et al
165461002006Critical role for NALP3/CIAS1/Cryopyrin in innate and adaptive immunity through its regulation of caspase-1.Sutterwala FS et al
158458872005Proapoptotic effects of caspase-1/interleukin-converting enzyme dominate in myocardial ischemia.Syed FM et al
168179032006Involvement of caspase 1 and its activator Ipaf upstream of mitochondrial events in apoptosis.Thalappilly S et al
97059381998Identification of CARDIAK, a RIP-like kinase that associates with caspase-1.Thome M et al
15741161992A novel heterodimeric cysteine protease is required for interleukin-1 beta processing in monocytes.Thornberry NA et al
150964762004PYNOD, a novel Apaf-1/CED4-like protein is an inhibitor of ASC and caspase-1.Wang Y et al
178503382008Anthrax lethal toxin-induced inflammasome formation and caspase-1 activation are late events dependent on ion fluxes and the proteasome.Wickliffe KE et al
80358751994Structure and mechanism of interleukin-1 beta converting enzyme.Wilson KP et al
112218552001Loss of caspase-1 and caspase-3 protein expression in human prostate cancer.Winter RN et al
86628431996Activation of the native 45-kDa precursor form of interleukin-1-converting enzyme.Yamin TT et al
124591892002Nod1, a CARD protein, enhances pro-interleukin-1beta processing through the interaction with pro-caspase-1.Yoo NJ et al
160378252006Cryopyrin and pyrin activate caspase-1, but not NF-kappaB, via ASC oligomerization.Yu JW et al
164442592006The Birc1e cytosolic pattern-recognition receptor contributes to the detection and control of Legionella pneumophila infection.Zamboni DS et al
146631412003Fundamental role of the Rip2/caspase-1 pathway in hypoxia and ischemia-induced neuronal cell death.Zhang WH et al
109037232000Nitric oxide induces thymocyte apoptosis via a caspase-1-dependent mechanism.Zhou X et al

Other Information

Locus ID:

NCBI: 834
MIM: 147678
HGNC: 1499
Ensembl: ENSG00000137752


dbSNP: 834
ClinVar: 834
TCGA: ENSG00000137752


Gene IDTranscript IDUniprot

Expression (GTEx)



PathwaySourceExternal ID
Amyotrophic lateral sclerosis (ALS)KEGGko05014
Amyotrophic lateral sclerosis (ALS)KEGGhsa05014
NOD-like receptor signaling pathwayKEGGko04621
NOD-like receptor signaling pathwayKEGGhsa04621
Cytosolic DNA-sensing pathwayKEGGko04623
Cytosolic DNA-sensing pathwayKEGGhsa04623
Influenza AKEGGko05164
Influenza AKEGGhsa05164
Salmonella infectionKEGGko05132
Salmonella infectionKEGGhsa05132
Immune SystemREACTOMER-HSA-168256
Innate Immune SystemREACTOMER-HSA-168249
Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signaling pathwaysREACTOMER-HSA-168643
NOD1/2 Signaling PathwayREACTOMER-HSA-168638
The NLRP3 inflammasomeREACTOMER-HSA-844456
The IPAF inflammasomeREACTOMER-HSA-844623
The AIM2 inflammasomeREACTOMER-HSA-844615
Cytokine Signaling in Immune systemREACTOMER-HSA-1280215
Signaling by InterleukinsREACTOMER-HSA-449147
Interleukin-1 processingREACTOMER-HSA-448706
Gene ExpressionREACTOMER-HSA-74160
Generic Transcription PathwayREACTOMER-HSA-212436
Transcriptional Regulation by TP53REACTOMER-HSA-3700989
TP53 Regulates Transcription of Cell Death GenesREACTOMER-HSA-5633008
TP53 Regulates Transcription of Caspase Activators and CaspasesREACTOMER-HSA-6803207

Protein levels (Protein atlas)

Not detected


Pubmed IDYearTitleCitations
121914862002The inflammasome: a molecular platform triggering activation of inflammatory caspases and processing of proIL-beta.1466
170360482006Pannexin-1 mediates large pore formation and interleukin-1beta release by the ATP-gated P2X7 receptor.495
243563062014Cell death by pyroptosis drives CD4 T-cell depletion in HIV-1 infection.346
276696502016Mechanism and Regulation of NLRP3 Inflammasome Activation.330
183293682008Active caspase-1 is a regulator of unconventional protein secretion.307
194396632009The IL-1-like cytokine IL-33 is inactivated after maturation by caspase-1.211
119672582002The PYRIN-CARD protein ASC is an activating adaptor for caspase-1.150
120192692002PYPAF7, a novel PYRIN-containing Apaf1-like protein that regulates activation of NF-kappa B and caspase-1-dependent cytokine processing.119
179595952007The caspase-1 digestome identifies the glycolysis pathway as a target during infection and septic shock.119
167854462006The B30.2 domain of pyrin, the familial Mediterranean fever protein, interacts directly with caspase-1 to modulate IL-1beta production.114


Yatender Kumar ; Vegesna Radha ; Ghanshyam Swarup

CASP1 (caspase 1, apoptosis-related cysteine peptidase (interleukin 1, beta, convertase))

Atlas Genet Cytogenet Oncol Haematol. 2007-11-01

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