| 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. Acts as a GEF for RAB39A which enables HOPS-mediated autophagosome-lysosome membrane tethering and fusion in mammalian autophagy. Component of the C9orf72-SMCR8 complex where both subunits display GEF activity and that regulates autophagy. As part of the C9orf72-SMCR8-WDR41 (CSW) complex, functions as GEF for RAB8A and RAB39B, thereby promoting autophagosome maturation. As part of the C9orf72-SMCR8 complex, also functions as GTPase activating protein (GAP) for RAB8A and RAB11A in vitro. 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. Promotes initiation of autophagy by regulating the RAB1A-dependent trafficking of the ULK1/ATG1 kinase complex to the phagophore which leads to autophagosome formation. Acts as a regulator of mTORC1 signaling by promoting phosphorylation of mTORC1 substrates. Plays a role in endosomal trafficking. May be involved in regulating the maturation of phagosomes to lysosomes. Promotes the lysosomal localization and lysosome-mediated degradation of CARM1 which leads to inhibition of starvation-induced lipid metabolism. Regulates actin dynamics in motor neurons by inhibiting the GTP-binding activity of ARF6, leading to ARF6 inactivation. This reduces the activity of the LIMK1 and LIMK2 kinases which are responsible for phosphorylation and inactivation of cofilin, leading to CFL1/cofilin activation. Positively regulates axon extension and axon growth cone size in spinal motor neurons. 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. Plays a role within the hematopoietic system in restricting inflammation and the development of autoimmunity. Isoform 1: Regulates stress granule assembly in response to cellular stress. Isoform 2: Does not play a role in regulation of stress granule assembly in response to cellular stress. |
| Protein Name | Guanine Nucleotide Exchange Factor C9orf72 |
| Database Links | |
| Cellular Localisation | CytoplasmNucleusP-BodyStress GranuleEndosomeLysosomeCytoplasmic VesicleAutophagosomeAutolysosomeSecretedCell ProjectionAxonGrowth ConePerikaryonDetected In The Cytoplasm Of Neurons From Brain TissueDetected In The Nucleus In FibroblastsDuring CorticogenesisTransitions From Being Predominantly Cytoplasmic To A More Even Nucleocytoplasmic DistributionMajorly Localized In Cytosol Under Basal ConditionsMajorly Gathered On Autolysosomes Structures Under Autophagy-Induced ConditionsIsoform 1: PerikaryonDendritePresynapsePostsynapseExpressed Diffusely Throughout The Cytoplasm And Dendritic Processes Of Cerebellar Purkinje CellsAlso Expressed Diffusely Throughout The Cytoplasm Of Spinal Motor NeuronsIsoform 2: Nucleus MembranePeripheral Membrane ProteinDetected At The Nuclear Membrane Of Cerebellar Purkinje Cells And Spinal Motor NeuronsAlso Shows Diffuse Nuclear Expression In Spinal Motor Neurons |
| Alternative Antibody Names | Anti-Guanine Nucleotide Exchange Factor C9orf72 antibodyAnti-C9orf72 antibodyAnti-DENND9 antibodyAnti-DENNL72 antibody |
Information sourced from Uniprot.org
