UniProt functional annotation for O94868



	UniProt functional annotation for O94868

UniProt code: O94868.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

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). {ECO:0000269|PubMed:29887380, ECO:0000269|PubMed:30249660}.

Subunit: Homodimer (PubMed:29887380). Interacts (via SH3 domain 2) with ITSN1 (via SH3 domain 4). Recruited to clathrin-coated pits during a mid-to-late stage of assembly via interaction with ITSN1. Interacts (via SH3 domain 1) with WASL (PubMed:29887380). Interacts with WAS (By similarity). Interacts with CASK and MAGI1. CASK inhibits interaction with MAGI1 (PubMed:14627983). {ECO:0000250|UniProtKB:Q3USJ8, ECO:0000269|PubMed:14627983, ECO:0000269|PubMed:29887380}.

Subcellular location: Cytoplasm {ECO:0000250|UniProtKB:Q3USJ8}. Cell junction {ECO:0000269|PubMed:14627983}. Membrane, clathrin-coated pit {ECO:0000269|PubMed:29887380, ECO:0000269|PubMed:30249660}. Cell membrane {ECO:0000269|PubMed:14627983, ECO:0000269|PubMed:29887380, ECO:0000269|PubMed:30249660}; Peripheral membrane protein {ECO:0000269|PubMed:14627983, ECO:0000269|PubMed:30249660}; Cytoplasmic side {ECO:0000269|PubMed:14627983, ECO:0000269|PubMed:30249660}. Cell projection, stereocilium {ECO:0000250|UniProtKB:Q3USJ8}. Note=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). {ECO:0000269|PubMed:14627983, ECO:0000269|PubMed:29887380, ECO:0000269|PubMed:30249660}.

Tissue specificity: Liver, brain, heart, placenta, skeletal muscle, pancreas, lung and kidney. {ECO:0000269|PubMed:14627983}.

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. {ECO:0000269|PubMed:29887380}.

Domain: Recruited to clathrin-coated pits via SH3 domain 2. {ECO:0000269|PubMed:29887380}.

Domain: The two SH3 domains cooperate to maintain the protein in an autoinhibited conformation that prevents promiscuous membrane binding. {ECO:0000269|PubMed:29887380}.

Ptm: Phosphorylated. Phosphorylation on a Ser residue is important for recruitment to the cell membrane and for its role in promoting endocytosis. {ECO:0000269|PubMed:30249660}.

Sequence caution: Sequence=BAA34489.2; Type=Erroneous initiation; Evidence={ECO:0000305};

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



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). {ECO:0000269\|PubMed:29887380, ECO:0000269\|PubMed:30249660}.


Subunit:		Homodimer (PubMed:29887380). Interacts (via SH3 domain 2) with ITSN1 (via SH3 domain 4). Recruited to clathrin-coated pits during a mid-to-late stage of assembly via interaction with ITSN1. Interacts (via SH3 domain 1) with WASL (PubMed:29887380). Interacts with WAS (By similarity). Interacts with CASK and MAGI1. CASK inhibits interaction with MAGI1 (PubMed:14627983). {ECO:0000250\|UniProtKB:Q3USJ8, ECO:0000269\|PubMed:14627983, ECO:0000269\|PubMed:29887380}.
Subcellular location:		Cytoplasm {ECO:0000250\|UniProtKB:Q3USJ8}. Cell junction {ECO:0000269\|PubMed:14627983}. Membrane, clathrin-coated pit {ECO:0000269\|PubMed:29887380, ECO:0000269\|PubMed:30249660}. Cell membrane {ECO:0000269\|PubMed:14627983, ECO:0000269\|PubMed:29887380, ECO:0000269\|PubMed:30249660}; Peripheral membrane protein {ECO:0000269\|PubMed:14627983, ECO:0000269\|PubMed:30249660}; Cytoplasmic side {ECO:0000269\|PubMed:14627983, ECO:0000269\|PubMed:30249660}. Cell projection, stereocilium {ECO:0000250\|UniProtKB:Q3USJ8}. Note=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). {ECO:0000269\|PubMed:14627983, ECO:0000269\|PubMed:29887380, ECO:0000269\|PubMed:30249660}.
Tissue specificity:		Liver, brain, heart, placenta, skeletal muscle, pancreas, lung and kidney. {ECO:0000269\|PubMed:14627983}.
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. {ECO:0000269\|PubMed:29887380}.
Domain:		Recruited to clathrin-coated pits via SH3 domain 2. {ECO:0000269\|PubMed:29887380}.
Domain:		The two SH3 domains cooperate to maintain the protein in an autoinhibited conformation that prevents promiscuous membrane binding. {ECO:0000269\|PubMed:29887380}.
Ptm:		Phosphorylated. Phosphorylation on a Ser residue is important for recruitment to the cell membrane and for its role in promoting endocytosis. {ECO:0000269\|PubMed:30249660}.
Sequence caution:		Sequence=BAA34489.2; Type=Erroneous initiation; Evidence={ECO:0000305};