FCHSD2
Domain
The F-BAR domain has an atypical, flat shape and binds preferentially to flat membranes. Upon heterologous expression, the isolated F-BAR domain is localized at the cell membrane, and causes the formation of cellular protrusions.
Recruited to clathrin-coated pits via SH3 domain 2.
The two SH3 domains cooperate to maintain the protein in an autoinhibited conformation that prevents promiscuous membrane binding.
Function
Adapter protein that plays a role in endocytosis via clathrin-coated pits. Contributes to the internalization of cell surface receptors, such as integrin ITGB1 and transferrin receptor (PubMed:29887380). Promotes endocytosis of EGFR in cancer cells, and thereby contributes to the down-regulation of EGFR signaling (PubMed:30249660). Recruited to clathrin-coated pits during a mid-to-late stage of assembly, where it is required for normal progress from U-shaped intermediate stage pits to terminal, omega-shaped pits (PubMed:29887380). Binds to membranes enriched in phosphatidylinositol 3,4-bisphosphate or phosphatidylinositol 3,4,5-trisphosphate (PubMed:29887380). When bound to membranes, promotes actin polymerization via its interaction with WAS and/or WASL which leads to the activation of the Arp2/3 complex. Does not promote actin polymerisation in the absence of membranes (PubMed:29887380).
Post-translational modifications
Phosphorylated. Phosphorylation on a Ser residue is important for recruitment to the cell membrane and for its role in promoting endocytosis.
Tissue Specificity
Liver, brain, heart, placenta, skeletal muscle, pancreas, lung and kidney.
Cellular localization
- Cytoplasm
- Cell junction
- Membrane
- Clathrin-coated pit
- Cell membrane
- Peripheral membrane protein
- Cytoplasmic side
- Cell projection
- Stereocilium
- Partially localized at clathrin-coated pits at the cell membrane (PubMed:30249660). Detected at the cell membrane at sites around clathrin-coated pits, very close to the clathrin-coated pits but not an intrinsic part of the clathrin-coated pits (PubMed:29887380). Colocalizes at cell-cell contacts with CDH1, but is not detected at tight junctions (PubMed:14627983).
Alternative names
KIAA0769, SH3MD3, FCHSD2, F-BAR and double SH3 domains protein 2, Carom, Protein nervous wreck 1, SH3 multiple domains protein 3, NWK1