Arf and Rab family small GTPases and their regulators, GTPase-activating proteins (GAPs) and guanine nucleotide exchange factors (GEFs), play a central role in membrane trafficking. In this study, we focused on a recently reported GAP for Arf (and potentially Rab) proteins, the CSW complex, a part of a small family of longin domain-containing proteins that form complexes with GAP activity. This family also includes folliculin and GATOR1, which are GAPs for the Rag/Gtr GTPases. All three complexes are associated with lysosomes and play a role in nutrient signaling, the latter two being directly involved in the mTOR pathway. The role of CSW is not clear, but in addition to having GAP activity on Arf proteins in vitro, its mutation causes severe neurodegenerative diseases. Here we update the reported pan-eukaryotic presence of folliculin and GATOR1, and demonstrate that CSW is also found throughout eukaryotes, though with sporadic distribution. We identify highly conserved motifs in all CSW subunits, some shared with the catalytic subunits of folliculin and GATOR1, that provide new potential avenues for experimental exploration. Remarkably, one such conserved sequence, the "GP" motif, is also found in structurally related longin proteins present in the archaeal ancestor of eukaryotes.

• Klíčová slova
• Arf GTPases, DENN domain, GTPase‐activating proteins, LECA, molecular phylogenetics, nutrient signaling, pan‐eukaryotic homology search, structural modeling,
• MeSH
• lidé MeSH
• monomerní proteiny vázající GTP * metabolismus   MeSH
• proteinové domény MeSH
• proteiny aktivující GTPasu * metabolismus   genetika   chemie   MeSH
• výměnné faktory guaninnukleotidů metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• monomerní proteiny vázající GTP * MeSH
• proteiny aktivující GTPasu * MeSH
• výměnné faktory guaninnukleotidů MeSH