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)

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