Rtl8c (retrotransposon Gag-like protein 8C; Cxx1 family) is one of a cluster of three near-identical X-linked mouse paralogs (Rtl8a/8b/8c) domesticated from a Ty3/gypsy sushi-ichi-related LTR retrotransposon. The 112-residue protein corresponds to a single truncated retroviral Gag capsid (CA)-like domain (about 70% identical to the identical Rtl8a/8b proteins) and carries a unique leucine-zipper motif; it lacks any catalytic domain. Unlike mRTL8A/8B, which localize to the nucleus, mRTL8C localizes to the cytoplasm. Murine RTL8 (the ortholog with highest homology to human RTL8C) participates in the UBQLN2 proteostasis network, and by conservation with human RTL8 the protein acts as a capsid-derived adaptor linking the retroelement capsid protein PEG10 to the shuttle factor UBQLN2. The protein has no cysteine or histidine residues and so no nucleocapsid zinc knuckle. Rtl8a-c mRNAs are highest in cerebrum and cerebellum but broadly expressed, except that Rtl8c is absent from liver. An Rtl8c flox allele has been made, but no Rtl8c loss-of-function phenotype has yet been reported; in Rtl8a/8b double-knockout mice Rtl8c remains active.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0003674 molecular_function | ND GO_REF:0000015 | ACCEPT | Summary: Root molecular function ND annotation: when it was made, no molecular function had been curated for this gene product from literature. Reason: ACCEPT under the ND acceptance rule (projects/NO_DATA.md). The evidence this review cites for the molecular function is inferred (from orthologs, family membership or sequence features) or comes from other species; none of it is literature on this gene product in this species. This was judged from the review's own content during the NO_DATA re-action pass, not from a new literature search. Earlier action: MODIFY. The mouse in vivo UBQLN2-RTL8 interaction (PMID:35247097) cannot be assigned to Rtl8a, Rtl8b or Rtl8c, so it is not literature on this gene product; the adaptor activity rests on human RTL8. The term the earlier MODIFY proposed, protein-macromolecule adaptor activity, is kept as its own NEW row. The gene's OpenScientist literature report finds no Rtl8c-specific functional study, so no study of mouse Rtl8c identifies a molecular function. Supporting Evidence: file:mouse/Rtl8c/Rtl8c-deep-research-openscientist.md No Rtl8c-isoform-specific functional study. |
| GO:0008150 biological_process | ND GO_REF:0000015 | ACCEPT | Summary: Root biological process ND annotation: when it was made, no biological process had been curated for this gene product from literature. Reason: ACCEPT under the ND acceptance rule (projects/NO_DATA.md). The evidence this review cites for the biological process is inferred (from orthologs, family membership or sequence features) or comes from other species; none of it is literature on this gene product in this species. This was judged from the review's own content during the NO_DATA re-action pass, not from a new literature search. Earlier action: MODIFY. The process rests on human RTL8 (PMID:40680123); no paralog-resolved mouse data exist. The term the earlier MODIFY proposed, positive regulation of protein catabolic process, is kept as its own NEW row. The gene's OpenScientist literature report finds no Rtl8c-specific functional study and no Rtl8c knockout phenotype, so no study of mouse Rtl8c identifies a biological process. Supporting Evidence: file:mouse/Rtl8c/Rtl8c-deep-research-openscientist.md No *Rtl8c*-knockout mouse phenotype was retrieved. |
| GO:0005737 cytoplasm | IDA PMID:39875098 Targeting of retrovirus-derived Rtl8a/8b causes late-onset o... | NEW | Summary: Overexpressed mRTL8C localizes to the cytoplasm (whereas mRTL8A localizes to nuclei/nucleoli). Reason: Not in GOA. Direct mouse localization data distinguish mRTL8C (cytoplasmic) from the nuclear mRTL8A/8B, and the cytoplasmic localization is consistent with the human RTL8 stress-granule and PEG10-regulatory roles. Supporting Evidence: PMID:39875098 the former in the nuclei (nucleoli) and the latter in the cytoplasm PMID:39875098 mRTL8A/8B with the N-terminal NLS-like signal is accumulated in the nuclei of NIH3T3 cells while mRTL8C without it is located in the cytoplasm |
| GO:0030674 protein-macromolecule adaptor activity | ISO PMID:40680123 Endogenous retrovirus-like proteins recruit UBQLN2 to stress... | NEW | Summary: Inferred protein-macromolecule adaptor activity for this gene product, proposed during the NO_DATA re-action pass. Reason: Protein-macromolecule adaptor activity is inferred for this gene product (ISO), not shown for it experimentally; the ND row for the aspect therefore stays (projects/NO_DATA.md). By conservation with human RTL8, the protein is a capsid-derived protein-macromolecule adaptor that bridges PEG10 and UBQLN2; the murine RTL8 ortholog (closest to RTL8C) participates in the UBQLN2 network. Supporting Evidence: PMID:40680123 RTL8 confers on UBQLN2 the ability to complex with and regulate PEG10 PMID:39775359 RTL8 bound to the N-terminal domain of PEG10 capsid PMID:35247097 confirmed the interaction between UBQLN2 and RTL8 both in vitro using recombinant proteins and in vivo using mouse brain tissue |
| GO:0045732 positive regulation of protein catabolic process | ISO PMID:40680123 Endogenous retrovirus-like proteins recruit UBQLN2 to stress... | NEW | Summary: Inferred positive regulation of protein catabolic process for this gene product, proposed during the NO_DATA re-action pass. Reason: Positive regulation of protein catabolic process is inferred for this gene product (ISO), not shown for it experimentally; the ND row for the aspect therefore stays (projects/NO_DATA.md). By conservation with human RTL8, which is the essential adaptor for UBQLN2-mediated turnover of PEG10, the mouse protein participates in positive regulation of protein catabolic process. Supporting Evidence: PMID:40680123 RTL8 is an essential partner for the UBQLN2-mediated turnover of PEG10 |
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Download this section (compressed HTML)Q: Why does mouse Rtl8c localize to the cytoplasm while Rtl8a/8b are nuclear, and does its leucine-zipper motif confer a distinct function?
Experiment: Test PEG10/UBQLN2 handling and stress-granule localization in Rtl8c loss- and gain-of-function cells, and compare with the nuclear Rtl8a/8b.
Hypothesis: Mouse RTL8C acts via the conserved PEG10/UBQLN2 axis in the cytoplasm.
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