CASP4 report

I. Expression across cell types

II. Expression across tissues

III. Associated gene sets

GO_0070059Biological processintrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress
GO_1903265Biological processpositive regulation of tumor necrosis factor-mediated signaling pathway
GO_0006954Biological processinflammatory response
GO_0045087Biological processinnate immune response
GO_0016540Biological processprotein autoprocessing
GO_0070269Biological processpyroptotic inflammatory response
GO_0050727Biological processregulation of inflammatory response
GO_0043525Biological processpositive regulation of neuron apoptotic process
GO_0097193Biological processintrinsic apoptotic signaling pathway
GO_0050830Biological processdefense response to Gram-positive bacterium
GO_0006508Biological processproteolysis
GO_0042742Biological processdefense response to bacterium
GO_0160075Biological processnon-canonical inflammasome complex assembly
GO_0006915Biological processapoptotic process
GO_0050729Biological processpositive regulation of inflammatory response
GO_1904646Biological processcellular response to amyloid-beta
GO_2000494Biological processpositive regulation of interleukin-18-mediated signaling pathway
GO_0051604Biological processprotein maturation
GO_0072558Cellular componentNLRP1 inflammasome complex
GO_0005576Cellular componentextracellular region
GO_0005886Cellular componentplasma membrane
GO_0005789Cellular componentendoplasmic reticulum membrane
GO_0005739Cellular componentmitochondrion
GO_0032991Cellular componentprotein-containing complex
GO_0005783Cellular componentendoplasmic reticulum
GO_0005829Cellular componentcytosol
GO_0005737Cellular componentcytoplasm
GO_0160074Cellular componentnon-canonical inflammasome complex
GO_0050700Molecular functionCARD domain binding
GO_0008289Molecular functionlipid binding
GO_0097153Molecular functioncysteine-type endopeptidase activity involved in apoptotic process
GO_0001530Molecular functionlipopolysaccharide binding
GO_0004197Molecular functioncysteine-type endopeptidase activity
GO_0005515Molecular functionprotein binding

IV. Literature review

[source]
Gene nameCASP4
Protein nameCaspase 4
Caspase-4 (CASP-4) (EC 3.4.22.57) (ICE and Ced-3 homolog 2) (ICH-2) (ICE(rel)-II) (Mih1) (Protease TX) [Cleaved into: Caspase-4 subunit p10; Caspase-4 subunit p20]
SynonymsICH2
DescriptionFUNCTION: Inflammatory caspase that acts as the effector of the non-canonical inflammasome by mediating lipopolysaccharide (LPS)-induced pyroptosis . Also indirectly activates the NLRP3 and NLRP6 inflammasomes . Acts as a thiol protease that cleaves a tetrapeptide after an Asp residue at position P1: catalyzes cleavage of CGAS, GSDMD and IL18 . Effector of the non-canonical inflammasome independently of NLRP3 inflammasome and CASP1: the non-canonical inflammasome promotes pyroptosis through GSDMD cleavage without involving secretion of cytokine IL1B . In the non-canonical inflammasome, CASP4 is activated by direct binding to the lipid A moiety of LPS without the need of an upstream sensor . LPS-binding promotes CASP4 activation and CASP4-mediated cleavage of GSDMD and IL18, followed by IL18 secretion through the GSDMD pore, pyroptosis of infected cells and their extrusion into the gut lumen . Also indirectly promotes secretion of mature cytokines (IL1A and HMGB1) downstream of GSDMD-mediated pyroptosis via activation of the NLRP3 and NLRP6 inflammasomes . Involved in NLRP3-dependent CASP1 activation and IL1B secretion in response to non-canonical activators, such as UVB radiation or cholera enterotoxin . Involved in NLRP6 inflammasome-dependent activation in response to lipoteichoic acid (LTA), a cell-wall component of Gram-positive bacteria, which leads to CASP1 activation and IL1B secretion . Involved in LPS-induced IL6 secretion; this activity may not require caspase enzymatic activity . The non-canonical inflammasome is required for innate immunity to cytosolic, but not vacuolar, bacteria (By similarity). Plays a crucial role in the restriction of S.typhimurium replication in colonic epithelial cells during infection . Pyroptosis limits bacterial replication, while cytokine secretion promotes the recruitment and activation of immune cells and triggers mucosal inflammation . May also act as an activator of adaptive immunity in dendritic cells, following activation by oxidized phospholipid 1-palmitoyl-2-arachidonoyl- sn-glycero-3-phosphorylcholine, an oxidized phospholipid (oxPAPC) (By similarity). Involved in cell death induced by endoplasmic reticulum stress and by treatment with cytotoxic APP peptides found in Alzheimer's patient brains . Cleavage of GSDMD is not strictly dependent on the consensus cleavage site but depends on an exosite interface on CASP4 that recognizes and binds the Gasdermin-D, C-terminal (GSDMD-CT) part . Catalyzes cleavage and maturation of IL18; IL18 processing also depends of the exosite interface on CASP4 . In contrast, it does not directly process IL1B . During non-canonical inflammasome activation, cuts CGAS and may play a role in the regulation of antiviral innate immune activation . .; FUNCTION: (Microbial infection) In response to the Td92 surface protein of the periodontal pathogen T.denticola, activated by cathepsin CTSG which leads to production and secretion of IL1A and pyroptosis of gingival fibroblasts. .

AccessionsENST00000417440.2
E9PMT1
ENST00000393150.7 [P49662-2]
P49662
H0YD34
ENST00000533252.1
ENST00000444739.7 [P49662-1]