RTL9

RTL9 (retrotransposon Gag-like 9; also SIRH10, RGAG1, Mart9) is a eutherian-specific, X-linked (Xq23 in human) gene domesticated from a Ty3/gypsy (sushi-ichi-related) LTR retrotransposon. It encodes a large (about 1,340-1,390 residue) protein whose only recognizable structured module is a C-terminal retroviral Gag capsid-like domain (PEG10-RTL1 C-terminal capsid family); the long N-terminal region is largely disordered and has no known catalytic motif. RTL9 is expressed at low levels in the brain by microglia, where the protein localizes to lysosomes rather than being secreted. After intracerebral injection of fungal zymosan, RTL9 colocalizes with the phagocytosed zymosan in microglial lysosomes, and mice expressing an RTL9 lacking the C-terminal Gag-like region fail to degrade zymosan although its delivery to lysosomes is normal; zymosan degradation is unaffected in Rtl5/Rtl6 double knockouts. RTL9 is therefore a lysosomal effector of microglial antifungal innate immunity, acting alongside its relatives RTL5 (dsRNA) and RTL6 (LPS); whether it is itself an enzyme or a cofactor of lysosomal glucan degradation is unknown. In humans, RTL9 (RGAG1) has been reported as a somatic fusion partner of BCOR in rare sarcomas.