SMCR8

Entrez Summary: N/A
UniProt Summary: Component of the C9orf72-SMCR8 complex, a complex that has guanine nucleotide exchange factor (GEF) activity and regulates autophagy (PubMed:20562859, PubMed:27193190, PubMed:27103069, PubMed:27559131, PubMed:27617292, PubMed:28195531). 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 (PubMed:20562859, PubMed:27103069, PubMed:27617292, PubMed:28195531). 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 (PubMed:27617292, PubMed:28195531). Acts as a regulator of mTORC1 signaling by promoting phosphorylation of mTORC1 substrates (PubMed:27559131, PubMed:28195531). 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 (PubMed:28195531). {ECO:0000269|PubMed:20562859, ECO:0000269|PubMed:27103069, ECO:0000269|PubMed:27193190, ECO:0000269|PubMed:27559131, ECO:0000269|PubMed:27617292, ECO:0000269|PubMed:28195531}.

Pfam Domains GO Terms

Compound Hit Most Correlated Genes in Chemogenomics Tissues where Essential in the Avana Dataset (DepMap 20Q1)

Global Fraction of Cell Lines Where Essential: 0/739

Tissue	Fraction Of Cell Lines Where Essential
1290807.0	0/1
909776.0	0/1
bile duct	0/28
blood	0/28
bone	0/26
breast	0/33
central nervous system	0/56
cervix	0/4
colorectal	0/17
esophagus	0/13
fibroblast	0/1
gastric	0/16
kidney	0/21
liver	0/20
lung	0/75
lymphocyte	0/16
ovary	0/26
pancreas	0/24
peripheral nervous system	0/16
plasma cell	0/15
prostate	0/1
skin	0/24
soft tissue	0/9
thyroid	0/2
upper aerodigestive	0/22
urinary tract	0/29
uterus	0/5

Expression Distribution

positive regulation of autophagosome maturation
Atg1/ULK1 kinase complex
regulation of autophagosome maturation
guanyl-nucleotide exchange factor complex
negative regulation of autophagosome assembly
protein kinase inhibitor activity
negative regulation of macroautophagy
regulation of autophagosome assembly
positive regulation of protein complex disassembly
Rab guanyl-nucleotide exchange factor activity
negative regulation of organelle assembly
positive regulation of TOR signaling
regulation of TORC1 signaling
regulation of vacuole organization
positive regulation of macroautophagy
negative regulation of autophagy
regulation of TOR signaling
regulation of protein complex disassembly
chromatin
positive regulation of autophagy
regulation of macroautophagy
regulation of organelle assembly
negative regulation of protein kinase activity
negative regulation of kinase activity
negative regulation of cellular catabolic process
autophagy
process utilizing autophagic mechanism
negative regulation of transferase activity
negative regulation of catabolic process
regulation of autophagy
positive regulation of cellular catabolic process
negative regulation of organelle organization
negative regulation of protein phosphorylation
positive regulation of catabolic process
negative regulation of phosphorylation
protein kinase binding
negative regulation of phosphate metabolic process
negative regulation of phosphorus metabolic process
negative regulation of protein modification process
positive regulation of organelle organization