Q3UMB5 · SMCR8_MOUSE
- ProteinGuanine nucleotide exchange protein SMCR8
- GeneSmcr8
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids935 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
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 ULK1/ATG1 kinase complex and inhibiting its protein kinase activity (PubMed:27617292).
As part of the C9orf72-SMCR8 complex, stimulates RAB8A and RAB11A GTPase activity in vitro (By similarity).
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).
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 ULK1/ATG1 kinase complex and inhibiting its protein kinase activity (PubMed:27617292).
As part of the C9orf72-SMCR8 complex, stimulates RAB8A and RAB11A GTPase activity in vitro (By similarity).
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).
GO annotations
all annotations | all molecular function | virus receptor activity | dna binding | rna binding | cytoskeletal motor activity | catalytic activity | gtpase activity | structural molecule activity | transporter activity | cytoskeletal protein binding | lipid binding | cyclase activity | antioxidant activity | oxidoreductase activity | transferase activity | hydrolase activity | lyase activity | isomerase activity | ligase activity | protein tag activity | cargo receptor activity | histone binding | protein folding chaperone | translation regulator activity | nutrient reservoir activity | receptor ligand activity | molecular transducer activity | molecular adaptor activity | toxin activity | cell adhesion mediator activity | molecular function regulator activity | virus coreceptor activity | catalytic activity, acting on a protein | catalytic activity, acting on dna | catalytic activity, acting on rna | molecular carrier activity | transcription regulator activity | general transcription initiation factor activity | molecular sensor activity | molecular sequestering activity | atp-dependent activity | other molecular function | all biological process | mitotic cell cycle | cytokinesis | cytoplasmic translation | immune system process | muscle system process | circulatory system process | renal system process | respiratory system process | carbohydrate metabolic process | generation of precursor metabolites and energy | dna replication | dna repair | dna recombination | chromatin organization | dna-templated transcription | regulation of dna-templated transcription | trna metabolic process | protein folding | protein glycosylation | amino acid metabolic process | modified amino acid metabolic process | lipid metabolic process | vitamin metabolic process | sulfur compound metabolic process | intracellular protein transport | nucleocytoplasmic transport | autophagy | inflammatory response | mitochondrion organization | cytoskeleton organization | microtubule-based movement | peroxisome organization | lysosome organization | chromosome segregation | cell adhesion | establishment or maintenance of cell polarity | programmed cell death | photosynthesis | mrna metabolic process | snrna metabolic process | vesicle-mediated transport | reproductive process | digestive system process | signaling | cell differentiation | protein catabolic process | extracellular matrix organization | regulatory ncrna-mediated gene silencing | telomere organization | cell junction organization | wound healing | ribosome biogenesis | cilium organization | anatomical structure development | cell motility | nervous system process | endocrine process | protein maturation | transmembrane transport | nucleobase-containing small molecule metabolic process | hepaticobiliary system process | membrane organization | protein-containing complex assembly | cell wall organization or biogenesis | nitrogen cycle metabolic process | protein localization to plasma membrane | defense response to other organism | detoxification | meiotic nuclear division | mitotic nuclear division | mitochondrial gene expression | carbohydrate derivative metabolic process | other biological process | all cellular component | nuclear chromosome | extracellular region | extracellular space | cell wall | nucleus | nuclear envelope | nucleoplasm | chromosome | nucleolus | mitochondrion | lysosome | endosome | vacuole | peroxisome | endoplasmic reticulum | golgi apparatus | lipid droplet | microtubule organizing center | cytosol | ribosome | cytoskeleton | plasma membrane | cilium | plastid | thylakoid | external encapsulating structure | extracellular matrix | cytoplasmic vesicle | organelle | other cellular component | |||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Keywords
- Molecular function
- Biological process
Names & Taxonomy
Protein names
- Recommended nameGuanine nucleotide exchange protein SMCR8
- Alternative names
Gene names
Organism names
- Organism
- Strain
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus
Accessions
- Primary accessionQ3UMB5
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Note: Localizes mainly in the cytoplasm.
Keywords
- Cellular component
Phenotypes & Variants
Disruption phenotype
Cells lacking display impaired autophagy induction.
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 46 variants from UniProt as well as other sources including ClinVar and dbSNP.
PTM/Processing
Features
Showing features for chain, modified residue.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000287470 | 1-935 | Guanine nucleotide exchange protein SMCR8 | |||
Sequence: MISAPDVVAFTKEDEYEEEPYNEPALPEEYSVPLFPYASQGANPWSKLSGAKFSRDFILISEFSEQVGPQPLLTIPNDTKVFGTFDLNYFSLRIMSVDYQASFVGHPPGSAYPKLNFVEDSKVVLGDSKEGAFAYVHHLTLYDLEARGFVRPFCMAYISADQHKIMQQFQELSAEFSKASECLKMGNRKAFAGELEKKLKDLDYTRTVLHTETEIQKKANDKGFYSSQAIEKANELANVEKSIIEHQDLLRQIRSYPRQKTKIPDLQPGDTEHTQDQADQVSTTSNPEESANADLYTCRPAYTPKLIKAKSTKCFDKKLKTLEELCDTEYFTQTLAQLSHIEHMFRGDLCYLLTSQIDRVLRKQQPITNFLFEDFVEVDDRMEKQENVPSQPSQDRLPPKPVEECPIPKVLISVGSYKSSVESVLIKMEQELGDEEYTGVEATEARSFDPQENLDYLDMDMKGSISSGESIEVLGTEKSASVLSKSDSQASLTVPLSPHVVRSKAVSHRTISEDSIEVLSTCPSEALIPDDFKASYPSAINEEEAYADNEGAIHFQASAGSPEPDETQEGNLENIPSQIDSSCCIGKESEGHLVPLPTPAYTLSDEDSVVSIPPQRYIQKDQGLHVDFGVENTDPSPRDNSCEMFPAYELDPSCLLASRDVSKMSLDNYSDTTSYMGSAASTSSDRIPSAPPAGLSSERHKKRAGQNALKFIRQYPFAHPAIYSLLSGRTLVVLGEDETIVRKLVTALSIFVPNYGCYAKPVKHWISSPLHIMDFQKWKLIGLQRVASPANVGTLHTLSRYSRYTSILDLDSKTLRCPLYRGTLVPRLADHRTQIKRGSTYYLHVQSMLTQLCSKAFLYTFCHHLHLPAHSEETQEAVASRQTSFLKLNLGLVNEDIRVVQYLAELLKLHYMQESPGTTHPLLRFDYVPSFLYKI | ||||||
Modified residue | 416 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 467 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 470 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 488 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 491 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 497 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 788 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 794 | Phosphothreonine; by TBK1 | ||||
Sequence: T |
Post-translational modification
Phosphorylation by TBK1 is required to promote autophagosome maturation. Phosphorylated by ULK1.
Keywords
- PTM
Proteomic databases
PTM databases
Interaction
Subunit
Component of the C9orf72-SMCR8 complex, at least composed of C9orf72, SMCR8 and WDR41 (Probable). The complex is formed of two protomers, each individually consisting of one molecule each of C9orf72, SMCR8 and WDR41 (By similarity).
The protomers homodimerize via an interaction between C9orf72 (via C-terminus) and SMCR8 (via N-terminus) (By similarity).
Within each protomer SMCR8 (via DENN domain) acts as a bridging protein between WDR41 (via C-terminus and N-terminus) and C9orf72 (via C-terminus) (By similarity).
The C9orf72-SMCR8 complex associates with the ULK1/ATG1 kinase complex (By similarity).
Interacts with C9orf72; the interaction is direct (PubMed:27875531).
Interacts with DLG4/PSD-95 (PubMed:31651360).
The protomers homodimerize via an interaction between C9orf72 (via C-terminus) and SMCR8 (via N-terminus) (By similarity).
Within each protomer SMCR8 (via DENN domain) acts as a bridging protein between WDR41 (via C-terminus and N-terminus) and C9orf72 (via C-terminus) (By similarity).
The C9orf72-SMCR8 complex associates with the ULK1/ATG1 kinase complex (By similarity).
Interacts with C9orf72; the interaction is direct (PubMed:27875531).
Interacts with DLG4/PSD-95 (PubMed:31651360).
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for region, domain, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 1-349 | Required for the homodimerization of the C9orf72-SMCR8 complex | ||||
Sequence: MISAPDVVAFTKEDEYEEEPYNEPALPEEYSVPLFPYASQGANPWSKLSGAKFSRDFILISEFSEQVGPQPLLTIPNDTKVFGTFDLNYFSLRIMSVDYQASFVGHPPGSAYPKLNFVEDSKVVLGDSKEGAFAYVHHLTLYDLEARGFVRPFCMAYISADQHKIMQQFQELSAEFSKASECLKMGNRKAFAGELEKKLKDLDYTRTVLHTETEIQKKANDKGFYSSQAIEKANELANVEKSIIEHQDLLRQIRSYPRQKTKIPDLQPGDTEHTQDQADQVSTTSNPEESANADLYTCRPAYTPKLIKAKSTKCFDKKLKTLEELCDTEYFTQTLAQLSHIEHMFRGDL | ||||||
Domain | 48-220 | uDENN FLCN/SMCR8-type | ||||
Sequence: LSGAKFSRDFILISEFSEQVGPQPLLTIPNDTKVFGTFDLNYFSLRIMSVDYQASFVGHPPGSAYPKLNFVEDSKVVLGDSKEGAFAYVHHLTLYDLEARGFVRPFCMAYISADQHKIMQQFQELSAEFSKASECLKMGNRKAFAGELEKKLKDLDYTRTVLHTETEIQKKAN | ||||||
Region | 257-291 | Disordered | ||||
Sequence: PRQKTKIPDLQPGDTEHTQDQADQVSTTSNPEESA | ||||||
Compositional bias | 268-291 | Polar residues | ||||
Sequence: PGDTEHTQDQADQVSTTSNPEESA | ||||||
Domain | 318-833 | cDENN FLCN/SMCR8-type | ||||
Sequence: KLKTLEELCDTEYFTQTLAQLSHIEHMFRGDLCYLLTSQIDRVLRKQQPITNFLFEDFVEVDDRMEKQENVPSQPSQDRLPPKPVEECPIPKVLISVGSYKSSVESVLIKMEQELGDEEYTGVEATEARSFDPQENLDYLDMDMKGSISSGESIEVLGTEKSASVLSKSDSQASLTVPLSPHVVRSKAVSHRTISEDSIEVLSTCPSEALIPDDFKASYPSAINEEEAYADNEGAIHFQASAGSPEPDETQEGNLENIPSQIDSSCCIGKESEGHLVPLPTPAYTLSDEDSVVSIPPQRYIQKDQGLHVDFGVENTDPSPRDNSCEMFPAYELDPSCLLASRDVSKMSLDNYSDTTSYMGSAASTSSDRIPSAPPAGLSSERHKKRAGQNALKFIRQYPFAHPAIYSLLSGRTLVVLGEDETIVRKLVTALSIFVPNYGCYAKPVKHWISSPLHIMDFQKWKLIGLQRVASPANVGTLHTLSRYSRYTSILDLDSKTLRCPLYRGTLVPRLADHRT | ||||||
Region | 383-402 | Disordered | ||||
Sequence: EKQENVPSQPSQDRLPPKPV | ||||||
Region | 677-699 | Disordered | ||||
Sequence: GSAASTSSDRIPSAPPAGLSSER | ||||||
Domain | 842-908 | dDENN FLCN/SMCR8-type | ||||
Sequence: YLHVQSMLTQLCSKAFLYTFCHHLHLPAHSEETQEAVASRQTSFLKLNLGLVNEDIRVVQYLAELLK | ||||||
Region | 860-912 | Interacts with WDR41 within the C9orf72-SMCR8 complex | ||||
Sequence: TFCHHLHLPAHSEETQEAVASRQTSFLKLNLGLVNEDIRVVQYLAELLKLHYM |
Sequence similarities
Belongs to the SMCR8 family.
Phylogenomic databases
Family and domain databases
Sequence & Isoform
- Sequence statusComplete
This entry describes 2 isoforms produced by Alternative splicing.
Q3UMB5-1
This isoform has been chosen as the canonical sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
- Name1
- Length935
- Mass (Da)104,957
- Last updated2007-05-15 v2
- Checksum6950CE4A0C50D8EE
Q3UMB5-2
- Name2
- Differences from canonical
- 786-935: Missing
Features
Showing features for sequence conflict, compositional bias, alternative sequence.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 7 | in Ref. 3; AAH85095 | ||||
Sequence: V → A | ||||||
Compositional bias | 268-291 | Polar residues | ||||
Sequence: PGDTEHTQDQADQVSTTSNPEESA | ||||||
Sequence conflict | 291 | in Ref. 1; BAE26183 | ||||
Sequence: A → T | ||||||
Sequence conflict | 360 | in Ref. 1; BAE26183 | ||||
Sequence: V → A | ||||||
Sequence conflict | 506 | in Ref. 1; BAE26183 | ||||
Sequence: V → I | ||||||
Alternative sequence | VSP_025488 | 786-935 | in isoform 2 | |||
Sequence: Missing |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AK052754 EMBL· GenBank· DDBJ | BAC35133.1 EMBL· GenBank· DDBJ | mRNA | ||
AK083739 EMBL· GenBank· DDBJ | BAC39010.1 EMBL· GenBank· DDBJ | mRNA | ||
AK145010 EMBL· GenBank· DDBJ | BAE26183.1 EMBL· GenBank· DDBJ | mRNA | ||
AL596215 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
BC085095 EMBL· GenBank· DDBJ | AAH85095.1 EMBL· GenBank· DDBJ | mRNA |