cd08321

Pyrin Death Domain found in ASC

CDD entry
Member databaseCDD
CDD typedomain
Short namePyrin_ASC-like
SetDD

Description

Pyrin Death Domain found in ASC (Apoptosis-associated speck-like protein containing a CARD) and similar proteins. ASC is an adaptor molecule that functions in the assembly of the 'inflammasome', a multiprotein platform, which is responsible for caspase-1 activation and regulation of IL-1beta maturation. ASC contains two domains from the Death Domain (DD) superfamily, an N-terminal pyrin-like domain and a C-terminal Caspase activation and recruitment domain (CARD). Through these 2 domains, ASC serves as an adaptor for inflammasome integrity and oligomerizes to form supramolecular assemblies. Included in this family is human PYNOD (also known as NLRP10 or NOD8) which via its Pyrin domain suppresses oligomerization of ASC, and ASC-mediated NF-kappaB activation. Other members of this subfamily are associated with ATPase domains and their function remains unknown. In general, Pyrin is a subfamily of the DD superfamily and functions in several signaling pathways. DDs are protein-protein interaction domains found in a variety of domain architectures. Their common feature is that they form homodimers by self-association or heterodimers by associating with other members of the DD superfamily including CARD and Death Effector Domain (DED). They serve as adaptors in signaling pathways and can recruit other proteins into signaling complexes.
[12, 14, 13, 6, 8, 15, 1, 5, 4, 7, 10, 2, 3, 11, 9]

References

1.The PYRIN domain in signal transduction. Stehlik C. Curr Protein Pept Sci 8, 293-310, (2007). PMID: 17584123

2.Cutting edge: critical role for PYCARD/ASC in the development of experimental autoimmune encephalomyelitis. Shaw PJ, Lukens JR, Burns S, Chi H, McGargill MA, Kanneganti TD. J Immunol 184, 4610-4, (2010). PMID: 20368281

3.Inflammasome-independent role of apoptosis-associated speck-like protein containing a CARD (ASC) in T cell priming is critical for collagen-induced arthritis. Ippagunta SK, Brand DD, Luo J, Boyd KL, Calabrese C, Stienstra R, Van de Veerdonk FL, Netea MG, Joosten LA, Lamkanfi M, Kanneganti TD. J Biol Chem 285, 12454-62, (2010). PMID: 20177071

4.Structure and interdomain dynamics of apoptosis-associated speck-like protein containing a CARD (ASC). de Alba E. J. Biol. Chem. 284, 32932-41, (2009). View articlePMID: 19759015

5.Regulatory molecules involved in inflammasome formation with special reference to a key mediator protein, ASC. Taniguchi S, Sagara J. Semin Immunopathol 29, 231-8, (2007). PMID: 17805543

6.The inflammasome: a caspase-1-activation platform that regulates immune responses and disease pathogenesis. Franchi L, Eigenbrod T, Munoz-Planillo R, Nunez G. Nat Immunol 10, 241-7, (2009). PMID: 19221555

7.Structure and dynamics of ASC2, a pyrin domain-only protein that regulates inflammatory signaling. Natarajan A, Ghose R, Hill JM. J. Biol. Chem. 281, 31863-75, (2006). View articlePMID: 16905547

8.TIR, CARD and PYRIN: three domains for an antimicrobial triad. Werts C, Girardin SE, Philpott DJ. Cell Death Differ 13, 798-815, (2006). PMID: 16528382

9.¹H, ¹³C and ¹⁵N resonance assignments of the pyrin domain from human PYNOD. Su MY, Chang CI, Chang CF. Biomol NMR Assign 7, 141-3, (2013). PMID: 22618865

10.The death-domain fold of the ASC PYRIN domain, presenting a basis for PYRIN/PYRIN recognition. Liepinsh E, Barbals R, Dahl E, Sharipo A, Staub E, Otting G. J. Mol. Biol. 332, 1155-63, (2003). View articlePMID: 14499617

11.A splice variant of ASC regulates IL-1beta release and aggregates differently from intact ASC. Matsushita K, Takeoka M, Sagara J, Itano N, Kurose Y, Nakamura A, Taniguchi S. Mediators Inflamm 2009, 287387, (2009). PMID: 19759850

12.The death domain superfamily in intracellular signaling of apoptosis and inflammation. Park HH, Lo YC, Lin SC, Wang L, Yang JK, Wu H. Annu. Rev. Immunol. 25, 561-86, (2007). View articlePMID: 17201679

13.The inflammasomes: mechanisms of activation and function. Latz E. Curr Opin Immunol 22, 28-33, (2010). PMID: 20060699

14.The inflammasomes. Schroder K, Tschopp J. Cell 140, 821-32, (2010). PMID: 20303873

15.The PYRIN domain: a member of the death domain-fold superfamily. Fairbrother WJ, Gordon NC, Humke EW, O'Rourke KM, Starovasnik MA, Yin JP, Dixit VM. Protein Sci. 10, 1911-8, (2001). View articlePMID: 11514682

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