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Unless otherwise stated all data on this page refer to the human proteins. Gene information is provided for human (Hs), mouse (Mm) and rat (Rn).
The nucleotide-binding oligomerization domain, leucine-rich repeat (NLR) family of receptors (nomenclature recommended by the NC-IUPHAR subcommittee on pattern recognition receptors ) share a common domain organisation. This consists of an N-terminal effector domain, a central nucleotide-binding and oligomerization domain (NOD; also referred to as a NACHT domain), and C-terminal leucine-rich repeats (LRR) which have regulatory and ligand recognition functions. The type of effector domain has resulted in the division of NLR family members into two major sub-families, NLRC and NLRP, along with three smaller sub-families NLRA, NLRB and NLRX . NLRC members express an N-terminal caspase recruitment domain (CARD) and NLRP members an N-terminal Pyrin domain (PYD).
Upon activation the NLRC family members NOD1 (NLRC1) and NOD2 (NLRC2) recruit a serine/threonine kinase RIPK2 (receptor interacting serine/threonine kinase 2, O43353, also known as CARD3, CARDIAK, RICK, RIP2) leading to signalling through NFκB and MAP kinase. Activation of NLRC4 (previously known as IPAF) and members of the NLRP3 family, including NLRP1 and NLRP3, leads to formation of a large multiprotein complex known as the inflammasome. In addition to NLR proteins other key members of the inflammasome include the adaptor protein ASC (apoptosis-associated speck-like protein containing a CARD, also known as PYCARD, CARD5, TMS1, Q9ULZ3) and inflammatory caspases. The inflammasome activates the pro-inflammatory cytokines IL-1β (IL1B, P01584) and IL-18 (IL18, Q14116) [1,3].
* Key recommended reading is highlighted with an asterisk
* Bryant CE, Orr S, Ferguson B, Symmons MF, Boyle JP, Monie TP. (2015) International Union of Basic and Clinical Pharmacology. XCVI. Pattern recognition receptors in health and disease. Pharmacol. Rev., 67 (2): 462-504. [PMID:25829385]
1. Bryant CE, Orr S, Ferguson B, Symmons MF, Boyle JP, Monie TP. (2015) International Union of Basic and Clinical Pharmacology. XCVI. Pattern recognition receptors in health and disease. Pharmacol. Rev., 67 (2): 462-504. [PMID:25829385]
2. Coll RC, Robertson AA, Chae JJ, Higgins SC, Muñoz-Planillo R, Inserra MC, Vetter I, Dungan LS, Monks BG, Stutz A et al.. (2015) A small-molecule inhibitor of the NLRP3 inflammasome for the treatment of inflammatory diseases. Nat. Med., [Epub ahead of print]. [PMID:25686105]
3. Davis BK, Wen H, Ting JP. (2011) The inflammasome NLRs in immunity, inflammation, and associated diseases. Annu. Rev. Immunol., 29: 707-35. [PMID:21219188]
4. Martinon F, Pétrilli V, Mayor A, Tardivel A, Tschopp J. (2006) Gout-associated uric acid crystals activate the NALP3 inflammasome. Nature, 440 (7081): 237-41. [PMID:16407889]
5. Sabbah A, Chang TH, Harnack R, Frohlich V, Tominaga K, Dube PH, Xiang Y, Bose S. (2009) Activation of innate immune antiviral responses by Nod2. Nat. Immunol., 10 (10): 1073-80. [PMID:19701189]
6. Schroder K, Tschopp J. (2010) The inflammasomes. Cell, 140 (6): 821-32. [PMID:20303873]
7. Ting JP, Lovering RC, Alnemri ES, Bertin J, Boss JM, Davis BK, Flavell RA, Girardin SE, Godzik A, Harton JA et al.. (2008) The NLR gene family: a standard nomenclature. Immunity, 28 (3): 285-7. [PMID:18341998]
Database page citation:
Clare Bryant, Tom Monie. NOD-like receptor family. Accessed on 27/05/2016. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=317.
Concise Guide to PHARMACOLOGY citation:
Alexander SPH, Fabbro D, Kelly E, Marrion N, Peters JA, Benson HE, Faccenda E, Pawson AJ, Sharman JL, Southan C, Davies JA and CGTP Collaborators (2015) The Concise Guide to PHARMACOLOGY 2015/16: Catalytic receptors. Br J Pharmacol. 172: 5979-6023.