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Component of the C9orf72-SMCR8 complex, a complex that has guanine nucleotide exchange factor (GEF) activity and regulates autophagy. 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. The C9orf72-SMCR8 complex also acts as a negative regulator of autophagy initiation by interacting with the ATG1/ULK1 kinase complex and inhibiting its protein kinase activity. Acts as a regulator of mTORC1 signaling by promoting phosphorylation of mTORC1 substrates. In addition to its activity in the cytoplasm within the C9orf72-SMCR8 complex, SMCR8 also localizes in the nucleus, where it associates with chromatin and negatively regulates expression of suppresses ULK1 and WIPI2 genes.
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Protein Aliases: FLJ34716; Guanine nucleotide exchange protein SMCR8; Smith-Magenis syndrome chromosomal region candidate gene 8 protein; Smith-Magenis syndrome chromosomal region candidate gene 8 protein homolog; Smith-Magenis syndrome chromosome region, candidate 8 homolog
Gene Aliases: 2310076G09Rik; AI642055; D030073L15Rik; RGD1564621; SMCR8
UniProt ID: (Human) Q8TEV9, (Mouse) Q3UMB5
Entrez Gene ID: (Human) 140775, (Mouse) 237782, (Rat) 497918
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