Protein: Target of Myb1 membrane trafficking protein (Target of Myb protein 1) (O60784)
Organism: Homo sapiens (Human)
Function: Adapter protein that plays a role in the intracellular membrane trafficking of ubiquitinated proteins, thereby participating in autophagy, ubiquitination-dependent signaling and receptor recycling pathways. Acts as a MYO6/Myosin VI adapter protein that targets MYO6 to endocytic structures. Together with MYO6, required for autophagosomal delivery of endocytic cargo, the maturation of autophagosomes and their fusion with lysosomes. MYO6 links TOM1 with autophagy receptors, such as TAX1BP1; CALCOCO2/NDP52 and OPTN. Binds to polyubiquitinated proteins via its GAT domain. In a complex with TOLLIP, recruits ubiquitin-conjugated proteins onto early endosomes. The Tom1-Tollip complex may regulate endosomal trafficking by linking polyubiquitinated proteins to clathrin. Mediates clathrin recruitment to early endosomes by ZFYVE16. Modulates binding of TOLLIP to phosphatidylinositol 3-phosphate (PtdIns(3)P) via binding competition; the association with TOLLIP may favor the release of TOLLIP from endosomal membranes, allowing TOLLIP to commit to cargo trafficking. Acts as a phosphatidylinositol 5-phosphate (PtdIns(5)P) effector by binding to PtdIns(5)P, thereby regulating endosomal maturation. PtdIns(5)P-dependent recruitment to signaling endosomes may block endosomal maturation. Also inhibits Toll-like receptor (TLR) signaling and participates in immune receptor recycling.
Subcellular location: Cytoplasm {ECO:0000269|PubMed:14563850, ECO:0000269|PubMed:14613930, ECO:0000269|PubMed:15047686, ECO:0000269|PubMed:26320582, ECO:0000269|PubMed:31263572}. Endosome membrane {ECO:0000269|PubMed:14613930, ECO:0000269|PubMed:15047686, ECO:0000269|PubMed:23023224, ECO:0000269|PubMed:26320582, ECO:0000269|PubMed:31263572}; Peripheral membrane protein {ECO:0000305}. Early endosome membrane {ECO:0000269|PubMed:15047686, ECO:0000269|PubMed:25588840, ECO:0000269|PubMed:26320582}; Peripheral membrane protein {ECO:0000305}. Note=Localized to endo/exosomal vesicles (PubMed:31263572). Enriched on signaling endosomes (PubMed:25588840). Recruited to early endosomes by TOLLIP and by PtdIns(5)P (PubMed:15047686, PubMed:25588840, PubMed:26320582). {ECO:0000269|PubMed:15047686, ECO:0000269|PubMed:25588840, ECO:0000269|PubMed:26320582, ECO:0000269|PubMed:31263572}.
Interaction partners:
- Toll-interacting protein
- Polyubiquitin-C
- Unconventional myosin-VI
- Zinc finger FYVE domain-containing protein 16
- Ubiquitin-ribosomal protein eS31 fusion protein
- HMG domain-containing protein 4
- Polyubiquitin-B
- Ubiquitin-ribosomal protein eL40 fusion protein
- DNA replication licensing factor MCM5
- Clathrin heavy chain 1
Sequence:
MDFLLGNPFSSPVGQRIEKATDGSLQSEDWALNMEICDIINETEEGPKDALRAVKKRIVGNKNFHEVMLALTVLETCVKNCGHRFHVLVASQDFVESVLVRTILPKNNPPTIVHDKVLNLIQSWADAFRSSPDLTGVVTIYEDLRRKGLEFPMTDLDMLSPIHTPQRTVFNSETQSGQDSVGTDSSQQEDSGQHAAPLPAPPILSGDTPIAPTPEQIGKLRSELEMVSGNVRVMSEMLTELVPTQAEPADLELLQELNRTCRAMQQRVLELIPQIANEQLTEELLIVNDNLNNVFLRHERFERFRTGQTTKAPSEAEPAADLIDMGPDPAATGNLSSQLAGMNLGSSSVRAGLQSLEASGRLEDEFDMFALTRGSSLADQRKEVKYEAPQATDGLAGALDARQQSTGAIPVTQACLMEDIEQWLSTDVGNDAEEPKGVTSEEFDKFLEERAKAADRLPNLSSPSAEGPPGPPSGPAPRKKTQEKDDDMLFAL