Tbio SMCR8 Guanine nucleotide exchange protein SMCR8

Protein Summary

Description

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).

Uniprot Accession IDs

• Q8TEV9
• A5PKZ5
• Q3ZCN0
• Q6PJL3

Gene Name

• SMCR8

Ensembl ID

• ENST00000406438
• ENSP00000385025
• ENSG00000176994
• ENST00000639332
• ENSP00000492062
• ENSG00000283741

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
transcription factor binding site profile	0.89
histone modification site profile	0.72
cell line	0.65
microRNA	0.61
PubMedID	0.54

Protein Classes

No PANTHER Classes or DTO Classes found

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 11.92   (req: < 5)

Gene RIFs: 6   (req: <= 3)

Antibodies: 30   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 11.92   (req: >= 5)

Gene RIFs: 6   (req: > 3)

Antibodies: 30   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 12

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligand: 0

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0