lmmol · Proteins

NACHT, LRR and PYD domains-containing protein 1

UniProt Q9C000 Organism Homo sapiens Gene CARD7, DEFCAP, KIAA0926, NAC, NALP1, NLRP1 EC 3.4.-.-, 3.6.4.-

Also known as: CARD7, DEFCAP, KIAA0926, NAC, NALP1, NLRP1

Function

Acts as the sensor component of the NLRP1 inflammasome, which mediates inflammasome activation in response to various pathogen-associated signals, leading to subsequent pyroptosis. Inflammasomes are supramolecular complexes that assemble in the cytosol in response to pathogens and other damage-associated signals and play critical roles in innate immunity and inflammation. Acts as a recognition receptor (PRR): recognizes specific pathogens and other damage-associated signals, such as cleavage by some human enteroviruses and rhinoviruses, double-stranded RNA, UV-B irradiation, or Val-boroPro inhibitor, and mediates the formation of the inflammasome polymeric complex composed of NLRP1, CASP1 and PYCARD/ASC. In response to pathogen-associated signals, the N-terminal part of NLRP1 is degraded by the proteasome, releasing the cleaved C-terminal part of the protein (NACHT, LRR and PYD domains-containing protein 1, C-terminus), which polymerizes and associates with PYCARD/ASC to initiate the formation of the inflammasome complex: the NLRP1 inflammasome recruits pro-caspase-1 (proCASP1) and promotes caspase-1 (CASP1) activation, which subsequently cleaves and activates inflammatory cytokines IL1B and IL18 and gasdermin-D (GSDMD), leading to pyroptosis. In the absence of GSDMD expression, the NLRP1 inflammasome is able to recruit and activate CASP8, leading to activation of gasdermin-E (GSDME). Activation of NLRP1 inflammasome is also required for HMGB1 secretion; the active cytokines and HMGB1 stimulate inflammatory responses. Binds ATP and shows ATPase activity. Plays an important role in antiviral immunity and inflammation in the human airway epithelium. Specifically recognizes a number of pathogen-associated signals: upon infection by human rhinoviruses 14 and 16 (HRV-14 and HRV-16), NLRP1 is cleaved and activated which triggers NLRP1-dependent inflammasome activation and IL18 secretion. Positive-strand RNA viruses, such as Semliki forest virus and long dsRNA activate the NLRP1 inflammasome, triggering IL1B release in a NLRP1-dependent fashion. Acts as a direct sensor for long dsRNA and thus RNA virus infection. May also be activated by muramyl dipeptide (MDP), a fragment of bacterial peptidoglycan, in a NOD2-dependent manner. The NLRP1 inflammasome is also activated in response to UV-B irradiation causing ribosome collisions: ribosome collisions cause phosphorylation and activation of NLRP1 in a MAP3K20-dependent manner, leading to pyroptosis.

Classification

Family (Pfam)
PF00619 CARD, PF13553 FIIND, PF00560 LRR_1, PF13516 LRR_6, PF05729 NACHT, PF17776 NLRC4_HD2, PF02758 PYRIN, PF23679 UPA-FIIND, PF17779 WHD_NOD2
InterPro
CARD, CARD8/ASC/NALP1_CARD, DAPIN, DEATH-like_dom_sf, FIIND_dom, Leu-rich_rpt, LRR_dom_sf, NACHT_NTPase, NLRP_HD2, NLRP_Inflammasome, NOD1/2_WH, P-loop_NTPase
Functional cluster
Immunoglobulin & Immune-Response Proteins

Experimental structures · PDB · 11

A predicted model is available from AlphaFold.

Gene Ontology · 39

Disease associations

Neighborhood · nearest proteins

CARD7Nlrp1Nlrp1Nlrp1CARD8NALP2DPP9
Nearest neighbours of NACHT, LRR and PYD domains-containing protein 1: 3 by sequence/function similarity (left); 3 co-cited in the literature (right).

Related proteins · sequence + function similarity

Co-cited proteins · studied together in the literature

Literature · 48 cited papers

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