SMCR8
Description
The SMCR8 (SMCR8-C9orf72 complex subunit) is a protein-coding gene located on chromosome 17.
SMCR8 is a component of the C9orf72-SMCR8 complex, which has guanine nucleotide exchange factor (GEF) activity and regulates autophagy. The complex promotes 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 ULK1/ATG1 kinase complex and inhibiting its protein kinase activity. As part of the C9orf72-SMCR8 complex, SMCR8 stimulates RAB8A and RAB11A GTPase activity in vitro. SMCR8 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 ULK1 and WIPI2 genes.
SMCR8 is also known as DENND8A.
Associated Diseases
- multiple sclerosis
- inflammatory bowel disease 30
- immunodeficiency due to MASP-2 deficiency
- Hirschsprung disease
- inflammatory bowel disease 1
