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sky

Gene
sky
Protein
GTPase-activating protein skywalker
Organism
Drosophila melanogaster
Length
587 amino acids
Function
GTPase-activating protein (GAP) for Rab35 which regulates synaptic vesicle (SV) protein recycling and turnover at the neuromuscular junction boutons and possibly ventral nerve cord via endosomal trafficking (PubMed:21458671, PubMed:25422373, PubMed:27669036). Inhibits Rab35-mediated endosomal sorting which traffics old or dysfunctional SV proteins through a degradative endolysosomal route that involves the ESCRT pathway and the HOPS complex members dor, vps39 and rab7 (PubMed:21458671, PubMed:25422373). This function is essential for preventing excessive degradation and turnover of vesicles from the readily releasable pool which leads to increased neurotransmission and eventually neurodegeneration (PubMed:21458671, PubMed:25422373, PubMed:27669036). Preferentially binds phosphoinositides phosphorylated at the D5 position of the inositol ring, such as phosphatidylinositol 4,5-bisphosphate (PIP2) and phosphatidylinositol 3,4,5-trisphosphate (PIP3) (PubMed:27669036). Binding to phosphoinositides and thus membrane-association, is required for its function in regulating the turnover of synaptic-vesicle proteins (PubMed:27669036). It is therefore likely that it is recruited to vesicle membranes with high phosphoinositide content and thereby selectively prevents endolysosomal degradation of these vesicles (PubMed:27669036).
Mass
67.328 kDa
Sequence
MPYHRGGDASSQADKLSGIVEESDLYEGFAPHVETSEIKTLDFYNLPKQTGKEPALRSYTEIQQLLQQGKKRDVKNILRENSWPINSPIRAQLWPMLCGQHQTKQQMLDGFYWEMVHQVFGTTELSEKPIMLPAFVDATHCLPYHLTSTGRAVADRIVNVLGYDCPDITYSPVLYPITSILLHFMSEEEAYICLAGLVGSKEKVFINQTKLQHEVTWKTVMQIAKKHTKSATSYFQRICPGLKLERIFMDWCWWILAGLPFQHLVRIMDCYFHEGIKVLYRVALVILNLFHKECQSNNEWSPDNIKNDIGNALIKFCKKIPVSPAKLLHAAFSIRGLSTQYISRIFIKTEMLLKSRSVLTSGSKQLIKSRSSDNLPTSQSQVNIQMMSHTLTIREHFGLPGTKNFIKTWTDRQFLFTLWSWLPVRITMYQPVLLYTTEEHGCSLTTFYVRVEQHEPTLLMIKTCNNEVFGAYCSSRWFERNVKDDKGQRQAYFGTGETFLFSLYPERAKYPWVGIEGDKDLGHSSELFMAADSKMITIGGGEGQAIWMDENIRFGKTDSCKTFNNPPLCPSGDFEIRVLEVYGFVGI