NLRX1

NLR family member X1
C-terminal RNA binding domain of NLXR1 hexamer. PDB 3un9[1]
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 3UN9​
Identifiers
Symbols	NLRX1 ; CLR11.3; DLNB26; NOD26; NOD5; NOD9
External IDs	OMIM: 611947 MGI: 2429611 HomoloGene: 11623 IUPHAR: 1766 GeneCards: NLRX1 Gene
Gene ontology Molecular function • protein binding • ATP binding Cellular component • mitochondrial outer membrane Biological process • viral process • negative regulation of type I interferon production • negative regulation of interferon-beta production • negative regulation of interleukin-6 production • negative regulation of RIG-I signaling pathway • negative regulation of I-kappaB kinase/NF-kappaB signaling • innate immune response • negative regulation of innate immune response • negative regulation of inflammatory response Sources: Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	79671	270151
Ensembl	ENSG00000160703	ENSMUSG00000032109
UniProt	Q86UT6	Q3TL44
RefSeq (mRNA)	NM_001282143	NM_001163742
RefSeq (protein)	NP_001269072	NP_001157214
Location (UCSC)	Chr 11: 119.17 – 119.18 Mb	Chr 9: 44.25 – 44.27 Mb
PubMed search

NLRX1 or NLR family member X1, short for nucleotide-binding oligomerization domain, leucine rich repeat containing X1 is a protein that in humans is encoded by the NLRX1 gene.^[2][3] 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.

Function

NLRX1 is an intracellular protein that plays a role in the immune system. NLRX1 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.,^[4] although this was recently questioned.^[5][6]

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.^[7][8][9]

Structure

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.^[10]

References

1. Hong, M.; Yoon, S. I.; Wilson, I. A. (2012). "Structure and Functional Characterization of the RNA-Binding Element of the NLRX1 Innate Immune Modulator". Immunity 36 (3): 337–347. doi:10.1016/j.immuni.2011.12.018. PMID 22386589.
2. "Entrez Gene: NLR family member X1".
3. Inohara N, Nuñez G (May 2003). "NODs: intracellular proteins involved in inflammation and apoptosis". Nature Reviews. Immunology 3 (5): 371–82. doi:10.1038/nri1086. PMID 12766759.
4. O'Neill LA (Apr 2008). "Innate immunity: squelching anti-viral signalling with NLRX1". Current Biology 18 (7): R302–4. doi:10.1016/j.cub.2008.02.021. PMID 18397740.
5. Rebsamen M, Vazquez J, Tardivel A, Guarda G, Curran J, Tschopp J (Aug 2011). "NLRX1/NOD5 deficiency does not affect MAVS signalling". Cell Death and Differentiation 18 (8): 1387. doi:10.1038/cdd.2011.64. PMC 3172102. PMID 21617692.
6. Soares F, Tattoli I, Wortzman ME, Arnoult D, Philpott DJ, Girardin SE (2013). "NLRX1 does not inhibit MAVS-dependent antiviral signalling". Innate Immunity 19 (4): 438–48. doi:10.1177/1753425912467383. PMID 23212541.
7. Castaño-Rodríguez N, Kaakoush NO, Goh KL, Fock KM, Mitchell HM (2014-01-01). "The NOD-like receptor signalling pathway in Helicobacter pylori infection and related gastric cancer: a case-control study and gene expression analyses". PLOS ONE 9 (6): e98899. doi:10.1371/journal.pone.0098899. PMC 4047072. PMID 24901306.
8. Philipson CW, Bassaganya-Riera J, Viladomiu M, Kronsteiner B, Abedi V, Hoops S, Michalak P, Kang L, Girardin SE, Hontecillas R (2015-01-01). "Modeling the Regulatory Mechanisms by Which NLRX1 Modulates Innate Immune Responses to Helicobacter pylori Infection". PLOS ONE 10 (9): e0137839. doi:10.1371/journal.pone.0137839. PMC 4569576. PMID 26367386.
9. Abdul-Sater AA, Saïd-Sadier N, Lam VM, Singh B, Pettengill MA, Soares F, Tattoli I, Lipinski S, Girardin SE, Rosenstiel P, Ojcius DM (Dec 2010). "Enhancement of reactive oxygen species production and chlamydial infection by the mitochondrial Nod-like family member NLRX1". The Journal of Biological Chemistry 285 (53): 41637–45. doi:10.1074/jbc.M110.137885. PMC 3009891. PMID 20959452.
10. Meylan E, Tschopp J (Mar 2008). "NLRX1: friend or foe?". EMBO Reports 9 (3): 243–5. doi:10.1038/embor.2008.23. PMC 2267384. PMID 18311173.

Further reading

• Moore CB, Bergstralh DT, Duncan JA, Lei Y, Morrison TE, Zimmermann AG, Accavitti-Loper MA, Madden VJ, Sun L, Ye Z, Lich JD, Heise MT, Chen Z, Ting JP (Jan 2008). "NLRX1 is a regulator of mitochondrial antiviral immunity". Nature 451 (7178): 573–7. doi:10.1038/nature06501. PMID 18200010.
• Tattoli I, Carneiro LA, Jéhanno M, Magalhaes JG, Shu Y, Philpott DJ, Arnoult D, Girardin SE (Mar 2008). "NLRX1 is a mitochondrial NOD-like receptor that amplifies NF-kappaB and JNK pathways by inducing reactive oxygen species production". EMBO Reports 9 (3): 293–300. doi:10.1038/sj.embor.7401161. PMC 2267388. PMID 18219313.
• Maruyama K, Sugano S (Jan 1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene 138 (1-2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.
• Arnoult D, Soares F, Tattoli I, Castanier C, Philpott DJ, Girardin SE (Sep 2009). "An N-terminal addressing sequence targets NLRX1 to the mitochondrial matrix". Journal of Cell Science 122 (Pt 17): 3161–8. doi:10.1242/jcs.051193. PMC 2871076. PMID 19692591.
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S (Oct 1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene 200 (1-2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149.