Protein: CASP4_MOUSE
Sequence: MAENKHPDKPLKVLEQLGKEVLTEYLEKLVQSNVLKLKEEDKQKFNNAERSDKRWVFVDAMKKKHSKVGEMLLQTFFSVDPGSHHGEANLEMEEPEESLNTLKLCSPEEFTRLCREKTQEIYPIKEANGRTRKALIICNTEFKHLSLRYGANFDIIGMKGLLEDLGYDVVVKEELTAEGMESEMKDFAALSEHQTSDSTFLVLMSHGTLHGICGTMHSEKTPDVLQYDTIYQIFNNCHCPGLRDKPKVIIVQACRGGNSGEMWIRESSKPQLCRGVDLPRNMEADAVKLSHVEKDFIAFYSTTPHHLSYRDKTGGSYFITRLISCFRKHACSCHLFDIFLKVQQSFEKASIHSQMPTIDRATLTRYFYLFPGN
What is the function of this protein?
Inflammatory caspase that acts as the effector of the non-canonical inflammasome by mediating lipopolysaccharide (LPS)-induced pyroptosis (PubMed:22002608, PubMed:23348507, PubMed:23887873, PubMed:24031018, PubMed:25119034, PubMed:30135078).  Also indirectly activates the NLRP3 and NLRP6 inflammasomes (PubMed:26320999, PubMed:30392956).  Acts as a thiol protease that cleaves a tetrapeptide after an Asp residue at position P1: catalyzes cleavage of CGAS, GSDMD and IL18 (PubMed:26375003, PubMed:28314590, PubMed:30392956).  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 and IL18 (PubMed:22002608, PubMed:22895188, PubMed:23348507, PubMed:23887873, PubMed:24031018, PubMed:26320999, PubMed:26375003, PubMed:30135078, PubMed:30589883).  In the non-canonical inflammasome, CASP4/CASP11 is activated by direct binding to LPS without the need of an upstream sensor (PubMed:22002608, PubMed:23348507, PubMed:25119034).  LPS-binding promotes CASP4/CASP11 activation and CASP4/CASP11-mediated cleavage of GSDMD, followed by pyroptosis of infected cells and their extrusion into the gut lumen (PubMed:22002608, PubMed:23348507, PubMed:25119034).  Also indirectly promotes secretion of mature cytokines (IL1A, IL18 and HMGB1) downstream of GSDMD-mediated pyroptosis via activation of the NLRP3 and NLRP6 inflammasomes (By similarity).  Involved in NLRP3-dependent CASP1 activation and IL1B and IL18 secretion in response to non-canonical activators, such as UVB radiation or cholera enterotoxin (PubMed:26320999).  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 and IL18 secretion (PubMed:30392956).  Involved in LPS-induced IL6 secretion; this activity may not require caspase enzymatic activity (By similarity).  The non-canonical inflammasome is required for innate immunity to cytosolic, but not vacuolar, bacteria (PubMed:23348507).  Plays a crucial role in the restriction of S. typhimurium replication in colonic epithelial cells during infection (PubMed:25121752, PubMed:26375003, PubMed:34671164).  Pyroptosis limits bacterial replication, while cytokine secretion promotes the recruitment and activation of immune cells and triggers mucosal inflammation (PubMed:25121752).  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) (PubMed:27103670).  Cleavage of GSDMD is not strictly dependent on the consensus cleavage site but depends on an exosite interface on CASP4/CASP11 that recognizes and binds the Gasdermin-D, C-terminal (GSDMD-CT) part (PubMed:32109412, PubMed:32554464).  Catalyzes cleavage and maturation of IL18 (By similarity).  In contrast, it does not directly process IL1B (PubMed:8702803, PubMed:9038361).  During non-canonical inflammasome activation, cuts CGAS and may play a role in the regulation of antiviral innate immune activation (PubMed:28314590).
What are the official names of this protein?
Caspase-4, CASP-4, Caspase-11, CASP-11, Protease ICH-3.
What is the protein family that this protein belongs to?
Belongs to the peptidase C14A family.
What are the subcellular locations of this protein?
Cytoplasm, cytosol. Cytoplasm. Endoplasmic reticulum membrane; Peripheral membrane protein; Cytoplasmic side. Mitochondrion. Inflammasome. Secreted. Note=Predominantly localizes to the endoplasmic reticulum (ER). Association with the ER membrane requires TMEM214. Released in the extracellular milieu by keratinocytes following UVB irradiation.