Protein: Rab3 GTPase-activating protein non-catalytic subunit (Rab3 GTPase-activating protein regulatory subunit) (Q9VKB9)
Organism: Drosophila melanogaster (Fruit fly)
Function: Regulatory subunit of the Rab3 GTPase-activating (Rab3GAP) complex composed of Rab3-GAP and Rab3GAP1, which has both GTPase-activating protein (GAP) activity towards Rab3, and guanine nucleotide exchange factor (GEF) activity towards Rab18. As part of the Rab3GAP complex, required for the rapid induction and sustained expression of synaptic homeostasis at the neuromuscular junction (NMJ). Also participates in the regulation of autophagy in tissues such as larval fat cells and adult muscles. The Rab3GAP complex, acts as a GAP for Rab3 by converting active Rab3-GTP to the inactive form Rab3-GDP. At the neuromuscular junction (NMJ), forms a presynaptic signaling mechanism with Rab3 that regulates progression of synaptic homeostasis at a late stage of vesicle release. Within this mechanism Rab3-GTP acts, directly or indirectly, to inhibit the progression of synaptic homeostasis, and Rab3-GAP functions to inactivate this action of Rab3-GTP. The Rab3GAP complex, acts as a GEF for Rab18 by promoting the conversion of inactive Rab18-GDP to the active form Rab18-GTP (By similarity). Regulates autophagy as part of a Rab3GAP-Rab18 module. Once Rab18 is activated by the GEF Rab3GAP complex, the Rab3GAP-Rab18 module localizes to autophagosomes, and regulates autolysosome formation and maturation together with the Rab18 interacting effector, the PI3K/Vps34 Complex I.
Subcellular location: Cytoplasm {ECO:0000305}. Autolysosome membrane {ECO:0000269|PubMed:32248620}; Peripheral membrane protein {ECO:0000269|PubMed:32248620}. Cytoplasmic vesicle, autophagosome membrane {ECO:0000269|PubMed:32248620}; Peripheral membrane protein {ECO:0000269|PubMed:32248620}. Presynaptic cell membrane {ECO:0000269|PubMed:21338884}; Peripheral membrane protein {ECO:0000269|PubMed:21338884}. Cell projection, axon {ECO:0000269|PubMed:21338884}. Note=In fat tissues detected at the membranes of autophagosomes and autolysosomes (PubMed:32248620). In larvae, detected in small puncta distributed throughout the axon and presynaptic nerve terminal (PubMed:21338884). Within individual synaptic boutons, appears to concentrate at or near the presynaptic plasma membrane (PubMed:21338884). {ECO:0000269|PubMed:21338884, ECO:0000269|PubMed:32248620}.
Interaction partners:
- Rab3 GTPase-activating protein catalytic subunit
- MAP kinase-activating death domain protein
- Dysbindin protein homolog
- GH11193p
- Ras-related protein Rab-3
- LD02690p
- Rab GDP dissociation inhibitor
Sequence:
MACEVKHCGEIRDFKKVQEYFGLGHDDNWLNAINHAISPTGELIAMAQGEKLAFLSTCWSSHGNGNTYVLGWCGELEDPNQIVTSLTCLPMTQNKSTDGAIEWTCVAVGLCSGMVTFYTDSGVKLFSQCCQEDPVIGVKLQSAPRHSEADSLLYIIYPRCLCFIQGQDILPTLNNCRHNVQRGALERSSYPTADVVPFQKYKFKQEREAVINDAAISTTQRPPTYDYIVQQTIGLGYFAKVHATPPRSSQVLAAGAEPYLGFFQAEEGYKTMSLGEVAKDVIGIAYKNLLGGIFRRAPEPLPSPEESPLPVPTKEAPMRIRCRLYDGKRDGLTLSVAPGGRLAVVTDNLDRVMLVDTHQAIILRVWKGYRDAQCAFVPVKEKSVRGIKTHKRKALFLVIYAPRMGCLDIWALQNGPKVAAFNVSKSGQLMYNNHSPLGSGGSSGSGNSSSQSRKSLAINHCLFLDPSDGSLKEIHIPFHYALSETSSQTSRDIHMLRRLRNQLRTINHGQAKDEALQEIGELASELQTLEVRQQCLEMLLKSKKLQPQVFQSIINAFIKKPLSESTGSEEFVNQIENYKRLTDLYLALSQANQREDNEPPVEYLELSDADLVTINKLVLLLDDGTEKDKPAATREVSFKLQAEHKTEEFVDYLSIFNIDSPDGISLLPEKSDKFGAVSIDLFSQFFAQGLCFGQFKQWINQACLPSRDLLKLIIWFWLEKPFKYNNCDEVVEDMSRIAAMVQTICDLAGEHIHDYAYNAISPWWQEVRELLLESKQFSGLLVAIVCKTVATNLWRNRKEGSCDESSQNEDDERWERISHDEAQWGLLTGKLEDVAVLGAILSKPLICRDPVGPEMSYEPPDCSLKSIVSSGKGIVTELTAKWLISAQLHPSKVLEISPPENELDDESKVKIKDEPTKESVDEDAESEEDLEMAKEVYAASKEAHEPILERLALLRAHFPFSLESGVLLSLMSWQYMVQWSKQLSSLDHLKAALLCLNQFRTPDWALKHGICCMLWNATLKFPLQAAAKLIQKVGRLPVDKMCQQDLEMSAGKVPEFLELSLEFLQHFTASMEHDKRELHFEQSLSEGALPLQFLALQQHHAMPQLLRLQTELCSVLHFVSFFQLRIPKPLTTLFDSMSNKALLADINKELPYVLPAPDLVLQQQRTEFLCRLVTATMDLIREDLEQLYILDHVFYMGKICALADSWEVDKLPILRRQVVELYAFGYDAEAQVLLQDISDDEELGRLLLEIAGRRLNLYAQSSQSTFLKIASVGHQLLAYLDNLKEPMTENNIQIAATKPDEIDVAALDRLLSHAYKYLCRRESKQLPIIGQMYNAVRILQN