Q3UMB5 · SMCR8_MOUSE

  • Protein
    Guanine nucleotide exchange protein SMCR8
  • Gene
    Smcr8
  • Status
    UniProtKB reviewed (Swiss-Prot)
  • Amino acids
  • Protein existence
    Evidence at protein level
  • Annotation score
    5/5

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).

GO annotations

all annotationsall molecular functionvirus receptor activitydna bindingrna bindingcytoskeletal motor activitycatalytic activitygtpase activitystructural molecule activitytransporter activitycytoskeletal protein bindinglipid bindingcyclase activityantioxidant activityoxidoreductase activitytransferase activityhydrolase activitylyase activityisomerase activityligase activityprotein tag activitycargo receptor activityhistone bindingprotein folding chaperonetranslation regulator activitynutrient reservoir activityreceptor ligand activitymolecular transducer activitymolecular adaptor activitytoxin activitycell adhesion mediator activitymolecular function regulator activityvirus coreceptor activitycatalytic activity, acting on a proteincatalytic activity, acting on dnacatalytic activity, acting on rnamolecular carrier activitytranscription regulator activitygeneral transcription initiation factor activitymolecular sensor activitymolecular sequestering activityatp-dependent activityother molecular functionall biological processmitotic cell cyclecytokinesiscytoplasmic translationimmune system processmuscle system processcirculatory system processrenal system processrespiratory system processcarbohydrate metabolic processgeneration of precursor metabolites and energydna replicationdna repairdna recombinationchromatin organizationdna-templated transcriptionregulation of dna-templated transcriptiontrna metabolic processprotein foldingprotein glycosylationamino acid metabolic processmodified amino acid metabolic processlipid metabolic processvitamin metabolic processsulfur compound metabolic processintracellular protein transportnucleocytoplasmic transportautophagyinflammatory responsemitochondrion organizationcytoskeleton organizationmicrotubule-based movementperoxisome organizationlysosome organizationchromosome segregationcell adhesionestablishment or maintenance of cell polarityprogrammed cell deathphotosynthesismrna metabolic processsnrna metabolic processvesicle-mediated transportreproductive processdigestive system processsignalingcell differentiationprotein catabolic processextracellular matrix organizationregulatory ncrna-mediated gene silencingtelomere organizationcell junction organizationwound healingribosome biogenesiscilium organizationanatomical structure developmentcell motilitynervous system processendocrine processprotein maturationtransmembrane transportnucleobase-containing small molecule metabolic processhepaticobiliary system processmembrane organizationprotein-containing complex assemblycell wall organization or biogenesisnitrogen cycle metabolic processprotein localization to plasma membranedefense response to other organismdetoxificationmeiotic nuclear divisionmitotic nuclear divisionmitochondrial gene expressioncarbohydrate derivative metabolic processother biological processall cellular componentnuclear chromosomeextracellular regionextracellular spacecell wallnucleusnuclear envelopenucleoplasmchromosomenucleolusmitochondrionlysosomeendosomevacuoleperoxisomeendoplasmic reticulumgolgi apparatuslipid dropletmicrotubule organizing centercytosolribosomecytoskeletonplasma membraneciliumplastidthylakoidexternal encapsulating structureextracellular matrixcytoplasmic vesicleorganelleother cellular component
Cell color indicative of number of GO terms
AspectTerm
Cellular ComponentAtg1/ULK1 kinase complex
Cellular Componentcell projection
Cellular Componentchromatin
Cellular Componentcytoplasm
Cellular Componentguanyl-nucleotide exchange factor complex
Cellular Componentnucleoplasm
Cellular Componentpostsynapse
Cellular Componentpresynapse
Molecular FunctionGTPase activator activity
Molecular Functionguanyl-nucleotide exchange factor activity
Molecular Functionprotein kinase binding
Molecular Functionprotein kinase inhibitor activity
Biological Processautophagy
Biological Processnegative regulation of autophagosome assembly
Biological Processnegative regulation of exocytosis
Biological Processnegative regulation of gene expression
Biological Processnegative regulation of immune response
Biological Processnegative regulation of macroautophagy
Biological Processpositive regulation of autophagosome maturation
Biological Processpositive regulation of GTPase activity
Biological Processpositive regulation of TOR signaling
Biological Processregulation of autophagy
Biological Processregulation of TORC1 signaling

Keywords

Names & Taxonomy

Protein names

  • Recommended name
    Guanine nucleotide exchange protein SMCR8
  • Alternative names
    • Smith-Magenis syndrome chromosomal region candidate gene 8 protein homolog

Gene names

    • Name
      Smcr8

Organism names

  • Taxonomic identifier
  • Strain
    • C57BL/6J
  • Taxonomic lineage
    Eukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus

Accessions

  • Primary accession
    Q3UMB5
  • Secondary accessions
    • Q5U4H2
    • Q8BNG6
    • Q8C704

Proteomes

Organism-specific databases

Subcellular Location

Keywords

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.

Go to variant viewer

PTM/Processing

Features

Showing features for chain, modified residue.

TypeIDPosition(s)Description
ChainPRO_00002874701-935Guanine nucleotide exchange protein SMCR8
Modified residue416Phosphoserine
Modified residue467Phosphoserine
Modified residue470Phosphoserine
Modified residue488Phosphoserine
Modified residue491Phosphoserine
Modified residue497Phosphoserine
Modified residue788Phosphoserine
Modified residue794Phosphothreonine; by TBK1

Post-translational modification

Phosphorylation by TBK1 is required to promote autophagosome maturation. Phosphorylated by ULK1.

Keywords

Proteomic databases

PTM databases

Expression

Tissue specificity

Widely expressed (PubMed:11997338).
Expressed in the forebrain and hippocampus (at protein level) (PubMed:31651360).

Gene expression 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).

Protein-protein interaction databases

Miscellaneous

Structure

Family & Domains

Features

Showing features for region, domain, compositional bias.

TypeIDPosition(s)Description
Region1-349Required for the homodimerization of the C9orf72-SMCR8 complex
Domain48-220uDENN FLCN/SMCR8-type
Region257-291Disordered
Compositional bias268-291Polar residues
Domain318-833cDENN FLCN/SMCR8-type
Region383-402Disordered
Region677-699Disordered
Domain842-908dDENN FLCN/SMCR8-type
Region860-912Interacts with WDR41 within the C9orf72-SMCR8 complex

Sequence similarities

Belongs to the SMCR8 family.

Phylogenomic databases

Family and domain databases

Sequence & Isoform

Align isoforms (2)
  • Sequence status
    Complete

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.

  • Length
    935
  • Mass (Da)
    104,957
  • Last updated
    2007-05-15 v2
  • Checksum
    6950CE4A0C50D8EE
MISAPDVVAFTKEDEYEEEPYNEPALPEEYSVPLFPYASQGANPWSKLSGAKFSRDFILISEFSEQVGPQPLLTIPNDTKVFGTFDLNYFSLRIMSVDYQASFVGHPPGSAYPKLNFVEDSKVVLGDSKEGAFAYVHHLTLYDLEARGFVRPFCMAYISADQHKIMQQFQELSAEFSKASECLKMGNRKAFAGELEKKLKDLDYTRTVLHTETEIQKKANDKGFYSSQAIEKANELANVEKSIIEHQDLLRQIRSYPRQKTKIPDLQPGDTEHTQDQADQVSTTSNPEESANADLYTCRPAYTPKLIKAKSTKCFDKKLKTLEELCDTEYFTQTLAQLSHIEHMFRGDLCYLLTSQIDRVLRKQQPITNFLFEDFVEVDDRMEKQENVPSQPSQDRLPPKPVEECPIPKVLISVGSYKSSVESVLIKMEQELGDEEYTGVEATEARSFDPQENLDYLDMDMKGSISSGESIEVLGTEKSASVLSKSDSQASLTVPLSPHVVRSKAVSHRTISEDSIEVLSTCPSEALIPDDFKASYPSAINEEEAYADNEGAIHFQASAGSPEPDETQEGNLENIPSQIDSSCCIGKESEGHLVPLPTPAYTLSDEDSVVSIPPQRYIQKDQGLHVDFGVENTDPSPRDNSCEMFPAYELDPSCLLASRDVSKMSLDNYSDTTSYMGSAASTSSDRIPSAPPAGLSSERHKKRAGQNALKFIRQYPFAHPAIYSLLSGRTLVVLGEDETIVRKLVTALSIFVPNYGCYAKPVKHWISSPLHIMDFQKWKLIGLQRVASPANVGTLHTLSRYSRYTSILDLDSKTLRCPLYRGTLVPRLADHRTQIKRGSTYYLHVQSMLTQLCSKAFLYTFCHHLHLPAHSEETQEAVASRQTSFLKLNLGLVNEDIRVVQYLAELLKLHYMQESPGTTHPLLRFDYVPSFLYKI

Q3UMB5-2

  • Name
    2
  • See also
    sequence in UniParc or sequence clusters in UniRef
  • Differences from canonical

Features

Showing features for sequence conflict, compositional bias, alternative sequence.

TypeIDPosition(s)Description
Sequence conflict7in Ref. 3; AAH85095
Compositional bias268-291Polar residues
Sequence conflict291in Ref. 1; BAE26183
Sequence conflict360in Ref. 1; BAE26183
Sequence conflict506in Ref. 1; BAE26183
Alternative sequenceVSP_025488786-935in isoform 2

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
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

Genome annotation databases

Similar Proteins

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. Our staff consists of biologists and biochemists that are not trained to give medical advice.
We'd like to inform you that we have updated our Privacy Notice to comply with Europe’s new General Data Protection Regulation (GDPR) that applies since 25 May 2018.
FeedbackHelp