NLRX1
Description
The NLRX1 (NLR family member X1) is a protein-coding gene located on chromosome 11.
NLRX1, or NLR family member X1, short for nucleotide-binding oligomerization domain, leucine rich repeat containing X1, is a protein encoded by the NLRX1 gene in humans. It is also known as NOD-like receptor X1, NLR family, X1, NOD5, NOD9, and CLR11.3, and is a member of the NOD-like receptor family of pattern recognition receptors. NLRX1 is an intracellular protein that plays a role in the immune system. It has been proposed to affect innate immunity to viruses by interfering with the mitochondrial antiviral signaling protein (MAVS)/retinoic-acid-inducible gene I (RIG-I) mitochondrial antiviral pathway, although this was recently questioned. NLRX1 also plays a role in host immunity during bacterial infections, such as Chlamydia trachomatis and Helicobacter pylori, by regulating bacterial burden and inflammation in mononuclear phagocytes. Mechanisms underlying the modulation of NLRX1 are not well characterized; however, computational modeling predictions suggest that levels of NLRX1 may be controlled by negative feedback circuits induced early after infection. NLRX1 has a unique protein structure composed of 3 protein domains: an N-terminal effector domain containing a mitochondrion localization signal; a central NACHT domain; a C-terminal leucine-rich repeat (LRR) domain.
NLRX1 participates in antiviral signaling, acting as a negative regulator of MAVS-mediated antiviral responses by inhibiting the virus-induced RLH (RIG-like helicase)-MAVS interaction (PubMed:18200010). It promotes autophagy through interaction with TUFM, leading to the recruitment of autophagy-related proteins ATG5 and ATG12 (PubMed:22749352). NLRX1 also regulates MAVS-dependent NLRP3 inflammasome activation, attenuating apoptosis (PubMed:27393910). It does not inhibit the NF-kappa-B signaling pathway but enhances NF-kappa-B and JUN N-terminal kinase dependent signaling via reactive oxygen species production (PubMed:18219313). NLRX1 regulates viral mediated-inflammation and energy metabolism in a sex-dependent manner (By similarity). In females, it prevents uncontrolled inflammation and energy metabolism, potentially contributing to sex differences in infectious and inflammatory diseases (By similarity).
NLRX1 is also known as CLR11.3, DLNB26, NOD26, NOD5, NOD9.
