NLRP12

This gene encodes a member of the CATERPILLER family of cytoplasmic proteins. The encoded protein, which contains an N-terminal pyrin domain, a NACHT domain, a NACHT-associated domain, and a C-terminus leucine-rich repeat region, functions as an attenuating factor of inflammation by suppressing inflammatory responses in activated monocytes. Mutations in this gene cause familial cold autoinflammatory syndrome type 2. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2013]

Full Name

NLR Family Pyrin Domain Containing 12

Function

Plays an essential role as an potent mitigator of inflammation (PubMed:30559449).
Primarily expressed in dendritic cells and macrophages, inhibits both canonical and non-canonical NF-kappa-B and ERK activation pathways (PubMed:15489334, PubMed:17947705).
Functions as a negative regulator of NOD2 by targeting it to degradation via the proteasome pathway (PubMed:30559449).
In turn, promotes bacterial tolerance (PubMed:30559449).
Inhibits also the DDX58-mediated immune signaling against RNA viruses by reducing the E3 ubiquitin ligase TRIM25-mediated 'Lys-63'-linked DDX58 activation but enhancing the E3 ubiquitin ligase RNF125-mediated 'Lys-48'-linked DDX58 degradation (PubMed:30902577).
Acts also as a negative regulator of inflammatory response to mitigate obesity and obesity-associated diseases in adipose tissue (By similarity).

Biological Process

Activation of cysteine-type endopeptidase activity involved in apoptotic process1 PublicationNAS:UniProtKB
Cellular response to cytokine stimulusManual Assertion Based On ExperimentIBA:GO_Central
Dendritic cell migrationIEA:Ensembl
Negative regulation of cytokine productionManual Assertion Based On ExperimentIDA:HGNC-UCL
Negative regulation of ERK1 and ERK2 cascadeIEA:Ensembl
Negative regulation of I-kappaB kinase/NF-kappaB signalingManual Assertion Based On ExperimentIDA:HGNC-UCL
Negative regulation of inflammatory responseManual Assertion Based On ExperimentIMP:BHF-UCL
Negative regulation of interleukin-1 productionManual Assertion Based On ExperimentIDA:HGNC-UCL
Negative regulation of interleukin-6 productionManual Assertion Based On ExperimentIDA:HGNC-UCL
Negative regulation of NF-kappaB transcription factor activityManual Assertion Based On ExperimentIDA:BHF-UCL
Negative regulation of NIK/NF-kappaB signalingManual Assertion Based On ExperimentIDA:UniProtKB
Negative regulation of protein autophosphorylationManual Assertion Based On ExperimentIDA:HGNC-UCL
Negative regulation of signal transductionManual Assertion Based On ExperimentIDA:HGNC-UCL
Negative regulation of Toll signaling pathwayManual Assertion Based On ExperimentIDA:HGNC-UCL
Positive regulation of inflammatory response1 PublicationNAS:UniProtKB
Positive regulation of interleukin-1 beta production1 PublicationNAS:UniProtKB
Positive regulation of MHC class I biosynthetic processManual Assertion Based On ExperimentIDA:MGI
Positive regulation of NIK/NF-kappaB signalingManual Assertion Based On ExperimentIDA:UniProtKB
Regulation of cysteine-type endopeptidase activity involved in apoptotic processManual Assertion Based On ExperimentIDA:MGI
Regulation of I-kappaB kinase/NF-kappaB signalingManual Assertion Based On ExperimentIDA:MGI
Regulation of interleukin-18 production1 PublicationNAS:UniProtKB
Signal transduction1 PublicationNAS:UniProtKB

Cellular Location

Cytoplasm

Involvement in disease

Familial cold autoinflammatory syndrome 2 (FCAS2):
A rare autosomal dominant systemic inflammatory disease characterized by recurrent episodes of maculopapular rash associated with arthralgias, myalgias, fever and chills, swelling of the extremities, and conjunctivitis after generalized exposure to cold.