UniProt functional annotation for Q9VIH7



	UniProt functional annotation for Q9VIH7

UniProt code: Q9VIH7.

Organism: Drosophila melanogaster (Fruit fly).

Taxonomy: Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota; Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea; Drosophilidae; Drosophila; Sophophora.

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). {ECO:0000269|PubMed:21458671, ECO:0000269|PubMed:25422373, ECO:0000269|PubMed:27669036}.

Subcellular location: Cytoplasmic vesicle, secretory vesicle, synaptic vesicle membrane {ECO:0000269|PubMed:21458671, ECO:0000269|PubMed:27669036}; Peripheral membrane protein {ECO:0000269|PubMed:21458671, ECO:0000269|PubMed:27669036}. Endosome membrane {ECO:0000269|PubMed:21458671}; Peripheral membrane protein {ECO:0000269|PubMed:21458671}. Note=Detected at the synapses of neuromuscular junction boutons, where it displays co-localization with Rab35 (PubMed:21458671). Associates with certain types of membrane phosphoinositides such as phosphatidylinositol 4,5-bisphosphate (PIP2) and phosphatidylinositol 3,4,5-trisphosphate (PIP3) (PubMed:27669036). {ECO:0000269|PubMed:21458671, ECO:0000269|PubMed:27669036}.

Tissue specificity: Detected in the larval ventral nerve cord and neuromuscular junction boutons (at protein level). {ECO:0000269|PubMed:21458671}.

Domain: The Rab-GAP TBC domain is essential for phosphoinositide binding. {ECO:0000269|PubMed:27669036}.

Sequence caution: Sequence=AAM49859.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};

Annotations taken from UniProtKB at the EBI.


Organism:		Drosophila melanogaster (Fruit fly).
Taxonomy:		Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota; Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea; Drosophilidae; Drosophila; Sophophora.



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). {ECO:0000269\|PubMed:21458671, ECO:0000269\|PubMed:25422373, ECO:0000269\|PubMed:27669036}.


Subcellular location:		Cytoplasmic vesicle, secretory vesicle, synaptic vesicle membrane {ECO:0000269\|PubMed:21458671, ECO:0000269\|PubMed:27669036}; Peripheral membrane protein {ECO:0000269\|PubMed:21458671, ECO:0000269\|PubMed:27669036}. Endosome membrane {ECO:0000269\|PubMed:21458671}; Peripheral membrane protein {ECO:0000269\|PubMed:21458671}. Note=Detected at the synapses of neuromuscular junction boutons, where it displays co-localization with Rab35 (PubMed:21458671). Associates with certain types of membrane phosphoinositides such as phosphatidylinositol 4,5-bisphosphate (PIP2) and phosphatidylinositol 3,4,5-trisphosphate (PIP3) (PubMed:27669036). {ECO:0000269\|PubMed:21458671, ECO:0000269\|PubMed:27669036}.
Tissue specificity:		Detected in the larval ventral nerve cord and neuromuscular junction boutons (at protein level). {ECO:0000269\|PubMed:21458671}.
Domain:		The Rab-GAP TBC domain is essential for phosphoinositide binding. {ECO:0000269\|PubMed:27669036}.
Sequence caution:		Sequence=AAM49859.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};