Guanine nucleotide exchange C9orf72 - Q96LT7 (CI072_HUMAN)


Protein Feature View of PDB entries mapped to a UniProtKB sequence  

Component of the C9orf72-SMCR8 complex, a complex that has guanine nucleotide exchange factor (GEF) activity and regulates autophagy (PubMed:27193190, PubMed:27103069, 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:27103069). The C9orf72-SMCR8 complex also acts as a regulator of autophagy initiation by interacting with the ATG1/ULK1 kinase complex and modulating its protein kinase activity (PubMed:27617292). Positively regulates initiation of autophagy by regulating the RAB1A-dependent trafficking of the ATG1/ULK1 kinase complex to the phagophore which leads to autophagosome formation (PubMed:27334615). Acts as a regulator of mTORC1 signaling by promoting phosphorylation of mTORC1 substrates (PubMed:27559131). Plays a role in endosomal trafficking (PubMed:24549040). May be involved in regulating the maturation of phagosomes to lysosomes (By similarity). Regulates actin dynamics in motor neurons by inhibiting the GTP-binding activity of ARF6, leading to ARF6 inactivation (PubMed:27723745). This reduces the activity of the LIMK1 and LIMK2 kinases which are responsible for phosphorylation and inactivation of cofilin, leading to cofilin activation (PubMed:27723745). Positively regulates axon extension and axon growth cone size in spinal motor neurons (PubMed:27723745). Plays a role within the hematopoietic system in restricting inflammation and the development of autoimmunity (By similarity). UniProt
Pathway Maps
      ESCHER  BiGG
Subunit Structure
Interacts with SMCR8; the interaction is direct (PubMed:27559131, PubMed:27617292). Component of the C9orf72-SMCR8 complex, at least composed of C9orf72, SMCR8 and WDR41 (PubMed:27193190, PubMed:27103069, PubMed:27559131, PubMed:27617292, PubMed:28195531). The C9orf72-SMCR8 complex associates with the ATG1/ULK1 kinase complex (PubMed:27617292, PubMed:28195531). Interacts with ATG1/ULK1 kinase complex members ULK1, ATG13 and RB1CC1 (PubMed:27334615). Interacts with HNRNPA1, HNRNPA2B1 and UBQLN2 (PubMed:24549040). Interacts with small Rab GTPase RAB1A; the interaction mediates recruitment of RAB1A to the ATG1/ULK1 kinase complex (PubMed:27334615). Also interacts with small Rab GTPase RAB7A (By similarity). Interacts with cofilin (PubMed:27723745). Interacts with GTP-binding proteins ARF1 and ARF6 (By similarity). UniProt
The Protein Feature View requires a browser that supports SVG (Scalable Vector Graphics). Mouse over tracks and labels for more information.
Data origin/color codes
The vertical color bar on the left side indicates data provenance.
Data in green originates from UniProtKB  
Variation data (sourced from UniProt) shows non-genetic variation from the ExPASy   and dbSNP   websites.
Data in yellow originates from Pfam  , by interacting with the HMMER3 web site  
Data in purple originates from Phosphosite  .
Data in orange originates from the SCOP   (version 1.75) and SCOPe   (version 2.04) classifications.
Data in grey has been calculated using BioJava  . Protein disorder predictions are based on JRONN (Troshin, P. and Barton, G. J. unpublished), a Java implementation of RONN  
  • Red: potentially disorderd region
  • Blue: probably ordered region.
Hydropathy has been calculated using a sliding window of 15 residues and summing up scores from standard hydrophobicity tables.
  • Red: hydrophobic
  • Blue: hydrophilic.
Data in lilac represent the genomic exon structure projected onto the UniProt sequence.
Data in blue originates from PDB
  • Secstruc: Secondary structure projected from representative PDB entries onto the UniProt sequence.
Sequence Mismatches It is now possible to see information about expression tags, cloning artifacts, and many other details related to sequence mismatches.
Icons represent a number of different sequence modifications that can be observed in PDB files. For example the 'T' icon T represents expression tags that have been added to the sequence. The 'E' icon E represents an engineered mutation. However, besides these two, there are many other icons. For more information about the meaning and exact position of a sequence modification, move the cursor over the icon.
Validation Track

For more details on the Validation Track (Structure Summary Page only) see the dedicated help page.

Data in red indicates combined ranges of Homology Models from the SWISS-MODEL Repository  
The PDB to UniProt mapping is based on the data provided by the EBI SIFTS project. See also Velankar et al., Nucleic Acids Research 33, D262-265 (2005).
Organism icons generated by under CC BY. The authors are: Freepik, Icons8, OCHA, Scott de Jonge.

For more details on the Protein Feature view see the dedicated help page.