Sorting nexin-6

Domain

The PX domain mediates interaction with membranes enriched in phosphatidylinositol 3,4-bisphosphate and/or phosphatidylinositol 4,5-bisphosphate.

The BAR domain is able to sense membrane curvature upon dimerization. Membrane remodeling seems to implicate insertion of an amphipathic helix (AH) in the membrane (Probable).

Function

Involved in several stages of intracellular trafficking. Interacts with membranes phosphatidylinositol 3,4-bisphosphate and/or phosphatidylinositol 4,5-bisphosphate (Probable). Acts in part as component of the retromer membrane-deforming SNX-BAR subcomplex (PubMed:19935774). The SNX-BAR retromer mediates retrograde transport of cargo proteins from endosomes to the trans-Golgi network (TGN) and is involved in endosome-to-plasma membrane transport for cargo protein recycling. The SNX-BAR subcomplex functions to deform the donor membrane into a tubular profile called endosome-to-TGN transport carrier (ETC) (Probable). Does not have in vitro vesicle-to-membrane remodeling activity (PubMed:23085988). Involved in retrograde endosome-to-TGN transport of lysosomal enzyme receptor IGF2R (PubMed:17148574). May function as link between transport vesicles and dynactin (Probable). Negatively regulates retrograde transport of BACE1 from the cell surface to the trans-Golgi network (PubMed:20354142). Involved in E-cadherin sorting and degradation; inhibits PIP5K1C isoform 3-mediated E-cadherin degradation (PubMed:24610942). In association with GIT1 involved in EGFR degradation. Promotes lysosomal degradation of CDKN1B (By similarity). May contribute to transcription regulation (Probable).

Post-translational modifications

In vitro phosphorylated by PIM1; not affecting PIM1-dependent nuclear translocation (PubMed:11591366).

Sequence Similarities

Belongs to the sorting nexin family.

Cellular localization

• Early endosome
• Early endosome membrane
• Peripheral membrane protein
• Cytoplasmic side
• Cytoplasmic vesicle
• Cytoplasm
• Nucleus
• Interaction with SNX1 or SNX2 promotes location at endosome membranes (PubMed:19935774). Only a minor proportion is seen in the nucleus.

Alternative names

Sorting nexin-6, TRAF4-associated factor 2, SNX6

Database links

swissprot:Q9UNH7 swissprot:Q9BUY3 entrezGene:58533 omim:606098