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SMCR8

Gene
SMCR8
Protein
Guanine nucleotide exchange protein SMCR8
Organism
Homo sapiens
Length
937 amino acids
Function
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).
Similarity
Belongs to the SMCR8 family.
Mass
105.022 kDa
Sequence
MISAPDVVAFTKEEEYEEEPYNEPALPEEYSVPLFPFASQGANPWSKLSGAKFSRDFILISEFSEQVGPQPLLTIPNDTKVFGTFDLNYFSLRIMSVDYQASFVGHPPGSAYPKLNFVEDSKVVLGDSKEGAFAYVHHLTLYDLEARGFVRPFCMAYISADQHKIMQQFQELSAEFSRASECLKTGNRKAFAGELEKKLKDLDYTRTVLHTETEIQKKANDKGFYSSQAIEKANELASVEKSIIEHQDLLKQIRSYPHRKLKGHDLCPGEMEHIQDQASQASTTSNPDESADTDLYTCRPAYTPKLIKAKSTKCFDKKLKTLEELCDTEYFTQTLAQLSHIEHMFRGDLCYLLTSQIDRALLKQQHITNFLFEDFVEVDDRMVEKQESIPSKPSQDRPPSSSLEECPIPKVLISVGSYKSSVESVLIKMEQELGDEEYKEVEVTELSSFDPQENLDYLDMDMKGSISSGESIEVLGTEKSTSVLSKSDSQASLTVPLSPQVVRSKAVSHRTISEDSIEVLSTCPSEALIPDDFKASYPSAINEEESYPDGNEGAIRFQASISPPELGETEEGSIENTPSQIDSSCCIGKESDGQLVLPSTPAHTHSDEDGVVSSPPQRHRQKDQGFRVDFSVENANPSSRDNSCEGFPAYELDPSHLLASRDISKTSLDNYSDTTSYVSSVASTSSDRIPSAYPAGLSSDRHKKRAGQNALKFIRQYPFAHPAIYSLLSGRTLVVLGEDEAIVRKLVTALAIFVPSYGCYAKPVKHWASSPLHIMDFQKWKLIGLQRVASPAGAGTLHALSRYSRYTSILDLDNKTLRCPLYRGTLVPRLADHRTQIKRGSTYYLHVQSMLTQLCSKAFLYTFCHHLHLPTHDKETEELVASRQMSFLKLTLGLVNEDVRVVQYLAELLKLHYMQESPGTSHPMLRFDYVPSFLYKI

Gene
Smcr8
Protein
Guanine nucleotide exchange protein SMCR8
Organism
Mus musculus
Length
935 amino acids
Function
Component of the C9orf72-SMCR8 complex, a complex that has guanine nucleotide exchange factor (GEF) activity and regulates autophagy (PubMed:27617292). 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 (By similarity). 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). Acts as a regulator of mTORC1 signaling by promoting phosphorylation of mTORC1 substrates (By similarity). 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 (By similarity).
Similarity
Belongs to the SMCR8 family.
Mass
104.957 kDa
Sequence
MISAPDVVAFTKEDEYEEEPYNEPALPEEYSVPLFPYASQGANPWSKLSGAKFSRDFILISEFSEQVGPQPLLTIPNDTKVFGTFDLNYFSLRIMSVDYQASFVGHPPGSAYPKLNFVEDSKVVLGDSKEGAFAYVHHLTLYDLEARGFVRPFCMAYISADQHKIMQQFQELSAEFSKASECLKMGNRKAFAGELEKKLKDLDYTRTVLHTETEIQKKANDKGFYSSQAIEKANELANVEKSIIEHQDLLRQIRSYPRQKTKIPDLQPGDTEHTQDQADQVSTTSNPEESANADLYTCRPAYTPKLIKAKSTKCFDKKLKTLEELCDTEYFTQTLAQLSHIEHMFRGDLCYLLTSQIDRVLRKQQPITNFLFEDFVEVDDRMEKQENVPSQPSQDRLPPKPVEECPIPKVLISVGSYKSSVESVLIKMEQELGDEEYTGVEATEARSFDPQENLDYLDMDMKGSISSGESIEVLGTEKSASVLSKSDSQASLTVPLSPHVVRSKAVSHRTISEDSIEVLSTCPSEALIPDDFKASYPSAINEEEAYADNEGAIHFQASAGSPEPDETQEGNLENIPSQIDSSCCIGKESEGHLVPLPTPAYTLSDEDSVVSIPPQRYIQKDQGLHVDFGVENTDPSPRDNSCEMFPAYELDPSCLLASRDVSKMSLDNYSDTTSYMGSAASTSSDRIPSAPPAGLSSERHKKRAGQNALKFIRQYPFAHPAIYSLLSGRTLVVLGEDETIVRKLVTALSIFVPNYGCYAKPVKHWISSPLHIMDFQKWKLIGLQRVASPANVGTLHTLSRYSRYTSILDLDSKTLRCPLYRGTLVPRLADHRTQIKRGSTYYLHVQSMLTQLCSKAFLYTFCHHLHLPAHSEETQEAVASRQTSFLKLNLGLVNEDIRVVQYLAELLKLHYMQESPGTTHPLLRFDYVPSFLYKI