C9orf72 - C9orf72-SMCR8 complex subunit (human)
- Create:2016-09-14
- Modify:2025-01-29
The C9orf72 gene provides instructions for making a protein that is found in various tissues. The protein is abundant in nerve cells (neurons) in the outer layers of the brain (cerebral cortex) and in specialized neurons in the brain and spinal cord that control movement (motor neurons). The C9orf72 protein is thought to be located at the tip of the neuron in a region called the presynaptic terminal. This area is important for sending and receiving signals between neurons.
The C9orf72 protein likely plays a role in many processes involving the chemical cousin of DNA, known as RNA. This protein is thought to influence the production of RNA from genes, the production of proteins from RNA, and the transport of RNA within the cell.
The C9orf72 gene contains a segment of DNA made up of a series of six DNA building blocks (nucleotides), four guanines followed by two cytosines (written as GGGGCC). This segment (known as a hexanucleotide repeat) can occur once or be repeated multiple times in a row; estimates suggest repeats of up to 30 times have no negative effect on gene function.
- ALSFTD
- DENND9
- DENNL72
- FTDALS
- FTDALS1
- guanine nucleotide exchange factor C9orf72
- guanine nucleotide exchange C9orf72
- protein C9orf72
- Chromosome 9 Open Reading Frame 72 Protein
- Guanine Nucleotide Exchange Factor C9orf72
Component of the C9orf72-SMCR8 complex, a complex that has guanine nucleotide exchange factor (GEF) activity and regulates autophagy (PMID: 27103069, PMID: 27193190, PMID: 27617292, PMID: 28195531, PMID: 32303654). In the complex, C9orf72 and SMCR8 probably constitute the catalytic subunits that promote the exchange of GDP to GTP, converting inactive GDP-bound RAB8A and RAB39B into their active GTP-bound form, thereby promoting autophagosome maturation (PMID: 27103069). 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 (PMID: 27617292). As part of the C9orf72-SMCR8 complex, stimulates RAB8A and RAB11A GTPase activity in vitro (PMID: 32303654). Positively regulates initiation of autophagy by regulating the RAB1A-dependent trafficking of the ULK1/ATG1 kinase complex to the phagophore which leads to autophagosome formation (PMID: 27334615). Acts as a regulator of mTORC1 signaling by promoting phosphorylation of mTORC1 substrates (PMID: 27559131). Plays a role in endosomal trafficking (PMID: 24549040). May be involved in regulating the maturation of phagosomes to lysosomes (By similarity). Promotes the lysosomal localization and lysosome-mediated degradation of CARM1 which leads to inhibition of starvation-induced lipid metabolism (By similarity). Regulates actin dynamics in motor neurons by inhibiting the GTP-binding activity of ARF6, leading to ARF6 inactivation (PMID: 27723745). This reduces the activity of the LIMK1 and LIMK2 kinases which are responsible for phosphorylation and inactivation of cofilin, leading to CFL1/cofilin activation (PMID: 27723745). Positively regulates axon extension and axon growth cone size in spinal motor neurons (PMID: 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 (By similarity). Plays a role within the hematopoietic system in restricting inflammation and the development of autoimmunity (By similarity).
Regulates stress granule assembly in response to cellular stress.
Does not play a role in regulation of stress granule assembly in response to cellular stress.
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