LGP2

{{Short description|Protein-coding gene in the species Homo sapiens}} {{Infobox_gene}} '''Probable ATP-dependent RNA helicase DHX58''' also known as '''RIG-I-like receptor 3''' (RLR-3) or '''RIG-I-like receptor LGP2''' (RLR) is a RIG-I-like receptor dsRNA helicase enzyme that in humans is encoded by the ''DHX58'' gene.<ref name="pmid11735219">{{cite journal |vauthors=Cui Y, Li M, Walton KD, Sun K, Hanover JA, Furth PA, Hennighausen L | title = The Stat3/5 locus encodes novel endoplasmic reticulum and helicase-like proteins that are preferentially expressed in normal and neoplastic mammary tissue | journal = Genomics | volume = 78 | issue = 3 | pages = 129–34 |date=Dec 2001 | pmid = 11735219 | doi = 10.1006/geno.2001.6661 | hdl = 2027.42/175385 | hdl-access = free }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: LGP2 likely ortholog of mouse D11lgp2| url = https://www.ncbi.nlm.nih.gov/gene?Db=gene&Cmd=ShowDetailView&TermToSearch=79132}}</ref> The protein encoded by the gene '''DHX58''' is known as '''LGP2''' (Laboratory of Genetics and Physiology 2).<ref name="pmid11735219"/><ref name="Childs_2012"/><ref name="Matsumiya_2010">{{cite journal |vauthors=Matsumiya T, Stafforini DM | title = Function and regulation of retinoic acid-inducible gene-I | journal = Crit. Rev. Immunol. | volume = 30 | issue = 6 | pages = 489–513 | year = 2010 | pmid = 21175414 | pmc = 3099591 | doi=10.1615/critrevimmunol.v30.i6.10}}</ref>

== Structure and function ==

LGP2 was first identified and characterized in the context of mammary tissue in 2001,<ref name="pmid11735219"/> but its function has been found to be more relevant to the field of innate antiviral immunity. LGP2 has been found to be essential for producing effective antiviral responses against many viruses that are recognized by RIG-I and MDA5.<ref name="Satoh_2010">{{cite journal |vauthors=Satoh T, Kato H, Kumagai Y, Yoneyama M, Sato S, Matsushita K, Tsujimura T, Fujita T, Akira S, Takeuchi O | title = LGP2 is a positive regulator of RIG-I- and MDA5-mediated antiviral responses | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 107 | issue = 4 | pages = 1512–7 |date=January 2010 | pmid = 20080593 | pmc = 2824407 | doi = 10.1073/pnas.0912986107 | bibcode = 2010PNAS..107.1512S | doi-access = free }}</ref>

Since LGP2 lacks CARD domains, its effect on downstream antiviral signaling is likely due to interaction with dsRNA viral ligand or the other RLRs (RIG-I and MDA5).<ref name="Saito_2007">{{cite journal |vauthors=Saito T, Hirai R, Loo YM, Owen D, Johnson CL, Sinha SC, Akira S, Fujita T, Gale M | title = Regulation of innate antiviral defenses through a shared repressor domain in RIG-I and LGP2 | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 104 | issue = 2 | pages = 582–7 |date=January 2007 | pmid = 17190814 | pmc = 1766428 | doi = 10.1073/pnas.0606699104 | bibcode = 2007PNAS..104..582S | doi-access = free }}</ref>

LGP2 has been shown to directly interact<ref name="Saito_2007"/> with RIG-I through its C-terminal repressor domain (RD). The primary contact sites in this interaction is likely between the RD of LGP2 and the CARD or helicase domain of RIG-I as it is seen with RIG-I self-association,<ref name="Saito_2007"/> but this has not been confirmed. The helicase activity of LGP2 has been found to be essential for its positive regulation of RIG-I signaling.<ref name="Satoh_2010"/> Overexpression of LGP2 is able to inhibit RIG-I-mediated antiviral signaling both in the presence and absence of viral ligands.<ref name="Saito_2007"/><ref name="pmid16210631">{{cite journal |vauthors=Rothenfusser S, Goutagny N, DiPerna G, Gong M, Monks BG, Schoenemeyer A, Yamamoto M, Akira S, Fitzgerald KA | title = The RNA helicase Lgp2 inhibits TLR-independent sensing of viral replication by retinoic acid-inducible gene-I | journal = J. Immunol. | volume = 175 | issue = 8 | pages = 5260–8 |date=October 2005 | pmid = 16210631 | doi = 10.4049/jimmunol.175.8.5260| doi-access = free }}</ref><ref name="Yoneyama_2005">{{cite journal |vauthors=Yoneyama M, Kikuchi M, Matsumoto K, Imaizumi T, Miyagishi M, Taira K, Foy E, Loo YM, Gale M, Akira S, Yonehara S, Kato A, Fujita T | title = Shared and unique functions of the DExD/H-box helicases RIG-I, MDA5, and LGP2 in antiviral innate immunity | journal = J. Immunol. | volume = 175 | issue = 5 | pages = 2851–8 |date=September 2005 | pmid = 16116171 | doi = 10.4049/jimmunol.175.5.2851| doi-access = free }}</ref> This inhibition of RIG-I signaling is not dependent upon the ability of LGP2 to bind viral ligands and is therefore not due to ligand competition.<ref name="Childs_2012">{{cite journal |vauthors=Childs K, Randall R, Goodbourn S | title = Paramyxovirus V proteins interact with the RNA Helicase LGP2 to inhibit RIG-I-dependent interferon induction | journal = J. Virol. | volume = 86 | issue = 7 | pages = 3411–21 |date=April 2012 | pmid = 22301134 | pmc = 3302505 | doi = 10.1128/JVI.06405-11 }}</ref><ref name="Wang_2010">{{cite journal |vauthors=Wang Y, Ludwig J, Schuberth C, Goldeck M, Schlee M, Li H, Juranek S, Sheng G, Micura R, Tuschl T, Hartmann G, Patel DJ | title = Structural and functional insights into 5'-ppp RNA pattern recognition by the innate immune receptor RIG-I | journal = Nat. Struct. Mol. Biol. | volume = 17 | issue = 7 | pages = 781–7 |date=July 2010 | pmid = 20581823 | doi = 10.1038/nsmb.1863 | pmc = 3744876 }}</ref> Although LGP2 binds to dsRNA with higher affinity,<ref name="Yoneyama_2005"/> it is dispensable for RIG-I-mediated recognition of synthetic dsRNA ligands.<ref name="Satoh_2010"/> RIG-I, when overexpressed<ref name="Childs_2012"/> and in LGP2 knock-down studies,<ref name="pmid22505629">{{cite journal |vauthors=Burel SA, Machemer T, Ragone FL, Kato H, Cauntay P, Greenlee S, Salim A, Gaarde WA, Hung G, Peralta R, Freier SM, Henry SP | title = Unique O-Methoxyethyl Ribose-DNA Chimeric Oligonucleotide Induces an Atypical Melanoma Differentiation-Associated Gene 5-Dependent Induction of Type I Interferon Response | journal = J. Pharmacol. Exp. Ther. | volume = 342 | issue = 1 | pages = 150–62 |date=July 2012 | pmid = 22505629 | doi = 10.1124/jpet.112.193789 | s2cid = 1899247 }}</ref> has been shown to induce antiviral response in the absence of viral ligand.

==References== {{reflist}}

==Further reading== {{refbegin | 2}} *{{cite journal |vauthors=Maruyama K, Sugano S |title=Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides. |journal=Gene |volume=138 |issue= 1–2 |pages= 171–4 |year= 1994 |pmid= 8125298 |doi=10.1016/0378-1119(94)90802-8 }} *{{cite journal |vauthors=Bonaldo MF, Lennon G, Soares MB |title=Normalization and subtraction: two approaches to facilitate gene discovery. |journal=Genome Res. |volume=6 |issue= 9 |pages= 791–806 |year= 1997 |pmid= 8889548 |doi=10.1101/gr.6.9.791 |doi-access=free }} *{{cite journal |vauthors=Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, etal |title=Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library. |journal=Gene |volume=200 |issue= 1–2 |pages= 149–56 |year= 1997 |pmid= 9373149 |doi=10.1016/S0378-1119(97)00411-3 }} *{{cite journal |vauthors=Strausberg RL, Feingold EA, Grouse LH, etal |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899–903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899 | pmc=139241 |bibcode=2002PNAS...9916899M |doi-access=free }} *{{cite journal |vauthors=Ota T, Suzuki Y, Nishikawa T, etal |title=Complete sequencing and characterization of 21,243 full-length human cDNAs. |journal=Nat. Genet. |volume=36 |issue= 1 |pages= 40–5 |year= 2004 |pmid= 14702039 |doi= 10.1038/ng1285 |doi-access= free }} *{{cite journal |vauthors=Rual JF, Venkatesan K, Hao T, etal |title=Towards a proteome-scale map of the human protein-protein interaction network. |journal=Nature |volume=437 |issue= 7062 |pages= 1173–8 |year= 2005 |pmid= 16189514 |doi= 10.1038/nature04209 |bibcode=2005Natur.437.1173R |s2cid=4427026 }} *{{cite journal |vauthors=Komuro A, Horvath CM |title=RNA- and virus-independent inhibition of antiviral signaling by RNA helicase LGP2. |journal=J. Virol. |volume=80 |issue= 24 |pages= 12332–42 |year= 2007 |pmid= 17020950 |doi= 10.1128/JVI.01325-06 | pmc=1676302 }} {{refend}}

{{Pattern recognition receptors}}

Category:RIG-I-like receptors Category:Intracellular receptors

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