title: A giant GTPase, very large inducible GTPase-1, is inducible by IFNs.
abstract: The complex, partially overlapping, cellular responses to IFN type I (IFN-alpha and -beta) and IFN type II (IFN-gamma) involve several hundred genes that can be largely classified in terms of specific cellular programs functional in innate and adaptive immunity. Among these programs are previously unconsidered mechanisms of cell-autonomous resistance against various pathogens mediated by dedicated, largely novel families of GTPases. We report here the identification and characterization of a new GTPase family that contributes to the cellular response to both type I and type II IFNs. We name this family the very large inducible GTPases (VLIGs). The prototype VLIG, VLIG-1, is a strongly IFN-inducible, soluble, cytosolic and nuclear protein of 280 kDa. The open reading frame of VLIG-1 is encoded on a single very large exon, and outside the canonical GTP-binding motifs, sequence and structural prediction suggest a unique family without significant relationship to other known protein families. Within the GTPase superfamily the VLIG family is more closely related to IFN-inducible GTPases mediating cell-autonomous resistance than to other GTPase families. In addition, we provide evidence that VLIG-1 is polymorphic in mice of different genetic backgrounds and is a member of a small gene family on mouse chromosome 7 with a conserved homologue located on human chromosome 11.
authors.affiliation: Institute for Genetics, University of Cologne, Cologne, Germany.
authors.forename: Thorsten
authors.initials: T
authors.lastname: Klamp
authors.forename: Ulrich
authors.initials: U
authors.lastname: Boehm
authors.forename: Daniela
authors.initials: D
authors.lastname: Schenk
authors.forename: Klaus
authors.initials: K
authors.lastname: Pfeffer
authors.forename: Jonathan C
authors.initials: JC
authors.lastname: Howard
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D002874:Chromosome Mapping; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics; D003001:Cloning, Molecular / Q000379:methods; D016207:Cytokines / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000502:physiology; D020558:GTP Phosphohydrolases / Q000096:biosynthesis* / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism; D005786:Gene Expression Regulation / Q000276:immunology*; D006150:Guanine Nucleotides / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000378:metabolism; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics; D050856:Interferon Regulatory Factor-1; D007371:Interferon-gamma / Q000494:pharmacology; D007372:Interferons / Q000502:physiology*; D008088:Listeriosis / Q000201:enzymology / Q000276:immunology; D008099:Liver / Q000201:enzymology / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D005810:Multigene Family; D009687:Nuclear Proteins / Q000096:biosynthesis* / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism; D009928:Organ Specificity / Q000235:genetics / Q000276:immunology; D010750:Phosphoproteins / Q000502:physiology; D011110:Polymorphism, Genetic; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000096:biosynthesis / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity; D013347:Subcellular Fractions / Q000378:metabolism; D014157:Transcription Factors / Q000502:physiology
chemical_list: D016207:Cytokines; D004268:DNA-Binding Proteins; D006150:Guanine Nucleotides; C494257:IRF1 protein, human; D050856:Interferon Regulatory Factor-1; C494258:Irf1 protein, mouse; D009687:Nuclear Proteins; D010750:Phosphoproteins; D012333:RNA, Messenger; D014157:Transcription Factors; D007371:Interferon-gamma; D006160:Guanosine Triphosphate; D007372:Interferons; D020558:GTP Phosphohydrolases; C477972:GVINP1 protein, human