Cutting Edge: CATERPILLER: A Large Family of Mammalian Genes Containing CARD, Pyrin, Nucleotide-Binding, and Leucine-Rich Repeat Domains

Harton, Jonathan A.; Linhoff, Michael W.; Zhang, Jinghua; Ting, Jenny P.‐Y.

doi:10.4049/jimmunol.169.8.4088

Cited by 284 publications

(207 citation statements)

References 42 publications

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“…All of the other mouse NALP genes cluster on Chr 7 except for NALP1, which is located at Chr 11B4. This clustering suggests gene duplications (Harton et al, 2002), and the additional human NALP genes on Chr 19 not found in the mouse indicate further gene duplications. Combining phylogenetic and comparative synteny information using DiagHunter and OrthoParaMap indicates local gene duplications of human NALP 2 and 7 on chromosome 19 following speciation, local duplication of mouse NALP 9a and 9c following speciation, and probable loss of several mouse orthologs (Fig.…”

Section: Analysis Of Mouse Cias1 and Other Genes In The Nalp Familymentioning

confidence: 87%

“…The common characteristics of proteins in this family are the presence of certain structural domains such as caspase recruitment domains and pyrin domains (PYD). Several of these proteins, referred to as NALP, NOD, or CATERPILLAR proteins, also contain purine nucleotide-binding NACHT domains, and leucine-rich repeat (LRR) domains (Harton et al, 2002;Tschopp et al, 2003). Four of these proteins have been associated with human diseases, including pyrin, NOD2, major histocompatibility complex (MHC) class II transactivator (CIITA), and Cryopyrin.…”

Section: Introductionmentioning

confidence: 99%

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Structural, expression, and evolutionary analysis of mouse CIAS1

Anderson

Mueller

Rosengren

et al. 2004

Gene

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Mutations in the human CIAS1 (hCIAS1) gene have been identified in a continuum of inflammatory disorders including familial cold autoinflammatory syndrome (FCAS), MuckleWells syndrome (MWS), and neonatal onset multisystem inflammatory disease (NOMID). CIAS1 codes for the protein Cryopyrin, which appears to play a role in innate immune function by regulating the production of proinflammatory cytokines. Human and mouse Cryopyrin are highly conserved and consist of three functional domains including a pyrin domain, an NACHT domain, ☆ Supplementary data associated with this article can be found, in the online version, at doi: 10.1016/j.gene.2004.05.002.☆☆ The nucleotide sequence data reported in this paper have been submitted to GenBank and have been assigned the accession numbers for the three mouse strains (strain C57BL/6) CIAS1.mRNAThe primate sequence accession numbers are GgCIAS1.Exon1 AY337307, TgCIAS1.Exon1 AY337308, MsCIAS1.Exon1 AY337309, AbCIAS1.Exon1 AY337310, CjCIAS1.Exon1 AY337311, CmCIAS1.Exon1 AY337312, GgCIAS1.NBS AY338196, TgCIAS1.NBS AY338197, MsCIAS1.NBS AY338198, CcCIAS1.NBS AY338199, CgCIAS1.NBS AY338200, AbCIAS1.NBS AY338201, AaCIAS1.NBS AY338202, SsCIAS1.NBS AY338203, CaCIAS1.NBS AY338204, S.CIAS1.NBS AY338205, CjCIAS1.NBS AY338206, Cp.CIAS1.NBS AY338207, TbCIAS1.NBS AY338208, CmCIAS1.NBS AY338209, LcCIAS1.NBS AY338210, and VvCIAS1.NBS AY338211. The mammalian sequence accession numbers are LaCIAS1.NBS AY495378, EeCIAS1.NBS AY495379, and DnCIAS1.NBS AY495380. and a leucine-rich repeat (LRR) domain that are characteristics of the NALP family of proteins. The pyrin and NACHT domains of Cryopyrin and other NALP proteins are highly conserved among primate and nonprimate mammals, suggesting purifying selection throughout mammalian evolution. Cryopyrin expression is also very similar in human and mouse with mouse CIAS1 mRNA expression found primarily in peripheral blood leukocytes consistent with the postulated inflammatory function. We also detected significant expression in mouse eye and skin tissue, which is consistent with symptoms observed in human Cryopyrin-associated diseases. HHS Public Access

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Section: Analysis Of Mouse Cias1 and Other Genes In The Nalp Familymentioning

confidence: 87%

Section: Introductionmentioning

confidence: 99%

Structural, expression, and evolutionary analysis of mouse CIAS1

Anderson

Mueller

Rosengren

et al. 2004

Gene

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“…The p.Arg554X mutation identified in the present study is located downstream of this domain, in a region for which no accurate structural information is available, and would result in a truncated protein lacking all LRRs. LRRs are 20-29-residue sequence motifs implicated in the regulation of inflammatory and cell death pathways, both in animals and in plants (30)(31)(32). Their importance in the proper functioning of PYPAF1 has been suggested by several groups (12,15,17).…”

Section: Discussionmentioning

confidence: 99%

PYPAF1 nonsense mutation in a patient with an unusual autoinflammatory syndrome: Role of PYPAF1 in inflammation

Jéru

Hayrapetyan

Duquesnoy

et al. 2006

Arthritis & Rheumatism

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Objective. To gain insight into the pathophysiology of an unusual autoinflammatory syndrome, in a patient of Armenian origin, that mimicked familial Mediterranean fever (FMF) but with episodes triggered by generalized exposure to cold, and to further elucidate the controversial function of the protein encoded by PYPAF1, whose mutations (exclusively missense to date) have been identified in 3 hereditary recurrent fever syndromes.Methods. The patient's DNA was screened for mutations in both MEFV, the gene responsible for FMF, and PYPAF1. The ability of different recombinant PYPAF1 isoforms, expressed in HEK 293 cells, to regulate NF-B signaling was subsequently assessed.Results. No disease-causing mutation was found in MEFV. However, a nonsense mutation (p.Arg554X) was identified in PYPAF1; this defect resulted in a truncated protein lacking all leucine-rich repeats. Study of the wild-type and mutant PYPAF1 recombinant proteins revealed that PYPAF1 inhibited NF-B proinflammatory pathways, and that the identified nonsense mutation impaired this property.Conclusion. These molecular and clinical findings, together with the clinical manifestations in the patient, which call into question the current nosology of the hereditary recurrent fever syndromes, are consistent with the hypothesis that PYPAF1 acts as an inhibitor of NF-B signaling. They also provide a clear elucidation of the functional consequences of this nonsense PYPAF1 mutation not previously described in the literature, which result in a partial loss of function and may thereby explain the pathophysiology of the autoinflammatory syndrome observed in this patient.

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“…The simultaneous publication of the initial drafts of the human genome by Celera and a public consortium in early 2001 allowed a rapid acceleration of our own effort to complete the search of the CLR gene family [6]. Based on bioinformatics data culled from the Celera human genome scaffold data and the National Center for Biotechnology Information (NCBI), we described in detail the CLR family, which in humans is comprised of over 20+ family members.…”

Section: The Caterpiller (Clr) Gene Familymentioning

confidence: 99%

Monarch-1/PYPAF7 and other CATERPILLER (CLR, NOD, NLR) proteins with negative regulatory functions

Lich

Ting

2007

Microbes and Infection

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CATERPILLER is a mammalian gene family with signature NBD and LRR domains. Several members of this family are positive regulators of inflammatory responses. Others, however, exert negative effects on proinflammatory responses. These data are particularly convincing when shRNA/ siRNA are used. This review focuses on the Monarch-1/PYPAF7 gene with brief discussions of CLR16.2/NOD3, PYPAF2/PAN1/NALP2, and PYPAF3.

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Cutting Edge: CATERPILLER: A Large Family of Mammalian Genes Containing CARD, Pyrin, Nucleotide-Binding, and Leucine-Rich Repeat Domains

Abstract: Material

Cited by 284 publications

References 42 publications

Structural, expression, and evolutionary analysis of mouse CIAS1

Structural, expression, and evolutionary analysis of mouse CIAS1

PYPAF1 nonsense mutation in a patient with an unusual autoinflammatory syndrome: Role of PYPAF1 in inflammation

Monarch-1/PYPAF7 and other CATERPILLER (CLR, NOD, NLR) proteins with negative regulatory functions

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