TBC1 domain family member 5 (TBC1D5)

Function

• GTPase activating protein for Rab family protein (putative)
• may act as a GAP for RAB7A
  • can displace RAB7A & retromer CSC subcomplex from the endosomal membrane to the cytosol
• required for retrograde transport of cargo proteins from endosomes to the trans-Golgi network
• role in regulation of autophagy
• may act as a molecular switch between endosomal & autophagosomal transport
• role in trafficking of ATG9A upon activation of autophagy
  • may regulate recruitment of ATG9A-AP2-containing vesicles to autophagic membranes
• interacts with MAP1LC3A, MAP1LC3B, MAP1LC3C, GABARAP, GABARAPL1, GABARAPL2
• interacts with VPS29 & VPS35
  • associates with retromer CSC subcomplex
• MAP1LC3A & VPS29 compete for binding to TBC1D5
• interacts with AP2M1; associates with AP2 complex
• interacts with ULK1 & ATG13 (phosphorylated)
  • associates with activated ULK1-ATG13-FIP200 complex
• interacts with AP2-clathrin-associated ATG9A

Structure

• the arginine & glutamine fingers are critical for the GTPase-activating mechanism
• the LIR motif (LC3-interacting region) mediates interaction with ATG8 family proteins.
• LIR 1 is also implicated in interaction with retromer
• LIR 2 is only implicated in interaction with ATG8 family proteins
• contains 1 Rab-GAP TBC domain

Compartment

• endosome membrane, cytoplasmic vesicle, autophagosome
• during starvation induced autophagy, TBC1D5 is relocalized from endosomal localization to LC3-positive autophagosomes

Alternative splicing

named isoforms=2

More general terms

• TBC1 domain family member

Database

• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=9779
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:9779
• OMIM: https://mirror.omim.org/entry/615740
• UniProt: http://www.uniprot.org/uniprot/Q92609.html