SMCR8
entrez
140775
canonical
uniprot
Q8TEV9
canonical
ensembl
ENSG00000176994
resolver
ensembl
ENSG00000283741
resolver
ensp
ENSP00000385025
resolver
genesymbol
SMCR8
resolver
hgnc
HGNC:17921
resolver
uniprot
A5PKZ5
resolver
uniprot
Q3ZCN0
resolver
uniprot
Q6PJL3
resolver
uniprot_entry
SMCR8_HUMAN
resolver
uniprot_sec
A5PKZ5
resolver
uniprot_sec
Q3ZCN0
resolver
uniprot_sec
Q6PJL3
resolver
amino_acid_sequence
MISAPDVVAFTKEEEYEEEPYNEPALPEEYSVPLFPFASQGANPWSKLSGAKFSRDFILISEFSEQVGPQPLLTIPNDTKVFGTFDLNYFSLRIMSVDYQASFVGHPPGSAYPKLNFVEDSKVVLGDSKEGAFAYVHHLTLYDLEARGFVRPFCMAYISADQHKIMQQFQELSAEFSRASECLKTGNRKAFAGELEKKLKDLDYTRTVLHTETEIQKKANDKGFYSSQAIEKANELASVEKSIIEHQDLLKQIRSYPHRKLKGHDLCPGEMEHIQDQASQASTTSNPDESADTDLYTCRPAYTPKLIKAKSTKCFDKKLKTLEELCDTEYFTQTLAQLSHIEHMFRGDLCYLLTSQIDRALLKQQHITNFLFEDFVEVDDRMVEKQESIPSKPSQDRPPSSSLEECPIPKVLISVGSYKSSVESVLIKMEQELGDEEYKEVEVTELSSFDPQENLDYLDMDMKGSISSGESIEVLGTEKSTSVLSKSDSQASLTVPLSPQVVRSKAVSHRTISEDSIEVLSTCPSEALIPDDFKASYPSAINEEESYPDGNEGAIRFQASISPPELGETEEGSIENTPSQIDSSCCIGKESDGQLVLPSTPAHTHSDEDGVVSSPPQRHRQKDQGFRVDFSVENANPSSRDNSCEGFPAYELDPSHLLASRDISKTSLDNYSDTTSYVSSVASTSSDRIPSAYPAGLSSDRHKKRAGQNALKFIRQYPFAHPAIYSLLSGRTLVVLGEDEAIVRKLVTALAIFVPSYGCYAKPVKHWASSPLHIMDFQKWKLIGLQRVASPAGAGTLHALSRYSRYTSILDLDNKTLRCPLYRGTLVPRLADHRTQIKRGSTYYLHVQSMLTQLCSKAFLYTFCHHLHLPTHDKETEELVASRQMSFLKLTLGLVNEDVRVVQYLAELLKLHYMQESPGTSHPMLRFDYVPSFLYKI
uniprot
proteins
function
FUNCTION: Component of the C9orf72-SMCR8 complex, a complex that has guanine nucleotide exchange factor (GEF) activity and regulates autophagy (PubMed:20562859, PubMed:27103069, PubMed:27193190, PubMed:27559131, PubMed:27617292, PubMed:28195531, PubMed: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 (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 ULK1/ATG1 kinase complex and inhibiting its protein kinase activity (PubMed:27617292, PubMed:28195531). As part of the C9orf72-SMCR8 complex, stimulates RAB8A and RAB11A GTPase activity in vitro (PubMed:32303654). 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, ECO:0000269|PubMed:32303654}.
uniprot
proteins
mass_dalton
105022
uniprot
proteins
mutagenesis
MUTAGEN 147; /note="R->A: Loss of C9ORF72-SMCR8 complex-mediated stimulation of RAB8A and RAB11AGTPase activity."; MUTAGEN 402; /note="S->A: Impaired autophagosome maturation; when associated with A-796."; /evidence="ECO:0000269|PubMed:27103069"; MUTAGEN 402; /note="S->D: Phosphomimetic mutant; able to promote autophagosome maturation; when associated with D-796."; /evidence="ECO:0000269|PubMed:27103069"; MUTAGEN 796; /note="T->A: Impaired autophagosome maturation; when associated with A-402."; /evidence="ECO:0000269|PubMed:27103069"; MUTAGEN 796; /note="T->D: Phosphomimetic mutant; able to promote autophagosome maturation; when associated with D-402."; /evidence="ECO:0000269|PubMed:27103069
uniprot
proteins
post_translational_modification
PTM: Phosphorylation by TBK1 is required to promote autophagosome maturation (PubMed:27103069). Phosphorylated by ULK1 (PubMed:27103069). {ECO:0000269|PubMed:27103069}.
uniprot
proteins
protein_family
SMCR8 family
uniprot
proteins
pubmed
11997338
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
17081983
uniprot
proteins
pubmed
18669648
uniprot
proteins
pubmed
19413330
uniprot
proteins
pubmed
19690332
uniprot
proteins
pubmed
20562859
uniprot
proteins
pubmed
21406692
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
23248642
uniprot
proteins
pubmed
27103069
uniprot
proteins
pubmed
27193190
uniprot
proteins
pubmed
27559131
uniprot
proteins
pubmed
27617292
uniprot
proteins
pubmed
28195531
uniprot
proteins
pubmed
32303654
uniprot
proteins
sequence_length
937
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:27193190, ECO:0000269|PubMed:28195531}. Nucleus {ECO:0000269|PubMed:28195531}. Presynapse {ECO:0000250|UniProtKB:Q3UMB5}. Postsynapse {ECO:0000250|UniProtKB:Q3UMB5}. Note=Localizes mainly in the cytoplasm. {ECO:0000269|PubMed:28195531}.
uniprot
proteins