RRAGD
Function
Guanine nucleotide-binding protein that plays a crucial role in the cellular response to amino acid availability through regulation of the mTORC1 signaling cascade (PubMed:20381137, PubMed:24095279, PubMed:34607910). Forms heterodimeric Rag complexes with RagA/RRAGA or RagB/RRAGB and cycles between an inactive GTP-bound and an active GDP-bound form: RagD/RRAGD is in its active form when GDP-bound RagD/RRAGD forms a complex with GTP-bound RagA/RRAGA (or RagB/RRAGB) and in an inactive form when GTP-bound RagD/RRAGD heterodimerizes with GDP-bound RagA/RRAGA (or RagB/RRAGB) (PubMed:24095279). In its active form, promotes the recruitment of mTORC1 to the lysosomes and its subsequent activation by the GTPase RHEB (PubMed:20381137, PubMed:24095279). This is a crucial step in the activation of the MTOR signaling cascade by amino acids (PubMed:20381137, PubMed:24095279). Also plays a central role in the non-canonical mTORC1 complex, which acts independently of RHEB and specifically mediates phosphorylation of MiT/TFE factors TFEB and TFE3: GDP-bound RagD/RRAGD mediates recruitment of MiT/TFE factors TFEB and TFE3 (PubMed:32612235).
Involvement in disease
Hypomagnesemia 7, renal, with or without dilated cardiomyopathy
HOMG7
An autosomal dominant renal disease characterized by hypomagnesemia, hypokalemia, salt wasting, and nephrocalcinosis. A subset of patients develop severe dilated cardiomyopathy.
None
The disease is caused by variants affecting the gene represented in this entry.
Sequence Similarities
Belongs to the GTR/RAG GTP-binding protein family.
Cellular localization
- Cytoplasm
- Nucleus
- Lysosome membrane
- Predominantly cytoplasmic (PubMed:11073942). Recruited to the lysosome surface by the Ragulator complex (PubMed:20381137). May shuttle between the cytoplasm and nucleus, depending on the bound nucleotide state of associated RRAGA (PubMed:11073942).
Alternative names
Ras-related GTP-binding protein D, Rag D, RagD, RRAGD