UniprotKB/SwissProt ID: Q6DFW0 (Q6DFW0)
Gene Name:
C9orf72
Organism: Mus musculus (Mouse)
Function: Acts as a guanine-nucleotide releasing factor (GEF) for Rab GTPases by promoting the conversion of inactive RAB-GDP to the active form RAB-GTP (PubMed:27193190, PubMed:27617292). Acts as a GEF for RAB39A which enables HOPS-mediated autophagosome-lysosome membrane tethering and fusion in mammalian autophagy (By similarity). Component of the C9orf72-SMCR8 complex where both subunits display GEF activity and that regulates autophagy (PubMed:27193190, PubMed:27617292). As part of the C9orf72-SMCR8-WDR41 (CSW) complex, functions as GEF for RAB8A, and RAB39B, thereby promoting autophagosome maturation (By similarity). As part of the C9orf72-SMCR8 complex, also functions as GTPase activating protein (GAP) for RAB8A and RAB11A in vitro (By similarity). The C9orf72-SMCR8 complex also acts as a regulator of autophagy initiation by interacting with the ULK1/ATG1 kinase complex and modulating its protein kinase activity (PubMed:27193190, PubMed:27617292). Promotes initiation of autophagy by regulating the RAB1A-dependent trafficking of the ULK1/ATG1 kinase complex to the phagophore which leads to autophagosome formation (By similarity). Acts as a regulator of mTORC1 signaling by promoting phosphorylation of mTORC1 substrates (PubMed:27875531). Plays a role in endosomal trafficking (PubMed:26989253). May be involved in regulating the maturation of phagosomes to lysosomes (PubMed:26989253). Promotes the lysosomal localization and lysosome-mediated degradation of CARM1 which leads to inhibition of starvation-induced lipid metabolism (PubMed:30366907). Regulates actin dynamics in motor neurons by inhibiting the GTP-binding activity of ARF6, leading to ARF6 inactivation (PubMed:27723745). This reduces the activity of the LIMK1 and LIMK2 kinases which are responsible for phosphorylation and inactivation of CFL1/cofilin, leading to cofilin activation (PubMed:27723745). Positively regulates axon extension and axon growth cone size in spinal motor neurons (PubMed:27723745). Required for SMCR8 protein expression and localization at pre- and post-synaptic compartments in the forebrain, also regulates protein abundance of RAB3A and GRIA1/GLUR1 in post-synaptic compartments in the forebrain and hippocampus (PubMed:31651360). Plays a role within the hematopoietic system in restricting inflammation and the development of autoimmunity (PubMed:27412785)
Other Modifications: View all modification sites in dbPTM
Protein Subcellular Localization: Nucleus. Cytoplasm. Cytoplasm, P-body. Cytoplasm, Stress granule. Endosome. Lysosome. Cytoplasmic vesicle, autophagosome. Autolysosome. Secreted. Cell projection, axon. Cell projection, growth cone. Perikaryon. Perikaryon. Cell projection, dendrite. Presynapse. Postsynapse
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