NLRP1

Disease related genes, Human disease related genes, Plasma proteins

Intracellular

Cell type enhanced (Early spermatids, Muller glia cells)

Low immune cell specificity

Cell line enhanced (HDLM-2, Karpas-707, U-266/70)

Interacts (via LRR repeats) with BCL2 and BCL2L1 (via the loop between motifs BH4 and BH3); these interactions reduce NLRP1 inflammasome-induced CASP1 activation and IL1B release, possibly by impairing NLRP1 interaction with PYCARD (PubMed:17418785). Interacts with NOD2; this interaction is enhanced in the presence of muramyl dipeptide (MDP) and increases IL1B release (PubMed:18511561). Interacts with EIF2AK2/PKR; this interaction requires EIF2AK2 activity, is accompanied by EIF2AK2 autophosphorylation and promotes inflammasome assembly in response to danger-associated signals (PubMed:22801494). Interacts with MEFV; this interaction targets NLRP1 to degradation by autophagy, hence preventing excessive IL1B- and IL18-mediated inflammation (PubMed:17431422, PubMed:26347139). Binds (via LRR domain) to dsDNA and dsRNA (PubMed:33243852). Interacts with DPP9; leading to inhibit activation of the inflammasome (PubMed:30291141, PubMed:31525884, PubMed:33731932). DPP9 acts via formation of a ternary complex, composed of a DPP9 homodimer, one full-length NLRP1 protein, and one cleaved C-terminus of NLRP1 (NACHT, LRR and PYD domains-containing protein 1, C-terminus) (PubMed:33731932). Interacts with DPP8; leading to inhibit activation of the inflammasome, probably via formation of a ternary complex with DPP8 (PubMed:31525884). [NACHT, LRR and PYD domains-containing protein 1, N-terminus]: Interacts with the C-terminal part of NLRP1 (NACHT, LRR and PYD domains-containing protein 1, C-terminus) in absence of pathogens and other damage-associated signals. [NACHT, LRR and PYD domains-containing protein 1, C-terminus]: Interacts with the N-terminal part of NLRP1 (NACHT, LRR and PYD domains-containing protein 1, N-terminus) in absence of pathogens and other damage-associated signals (PubMed:33093214). Homomultimer; forms the NLRP1 inflammasome polymeric complex, a filament composed of homopolymers of this form in response to pathogens and other damage-associated signals (PubMed:33420028, PubMed:33420033). The NLRP1 inflammasome polymeric complex associates with PYCARD/ASC (PubMed:22665479, PubMed:12191486, PubMed:17418785, PubMed:17349957). Interacts (via CARD domain) with PYCARD/ASC (via CARD domain); leading to pro-caspase-1 (proCASP1) recruitment (PubMed:22665479, PubMed:12191486, PubMed:17418785). Pro-caspase-1 (proCASP1) filament formation increases local enzyme concentration, resulting in trans-autocleavage and activation (PubMed:22665479, PubMed:12191486, PubMed:17349957). Active CASP1 then processes IL1B and IL18 precursors, leading to the release of mature cytokines in the extracellular milieu and inflammatory response (PubMed:22665479, PubMed:12191486, PubMed:17349957). (Microbial infection) Interacts with vaccinia virus protein F1 (PubMed:16439990).

Hydrolase, Protease