UniProt functional annotation for P42566



	UniProt functional annotation for P42566

UniProt code: P42566.

Organism: Homo sapiens (Human).

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

Function: Involved in cell growth regulation. May be involved in the regulation of mitogenic signals and control of cell proliferation. Involved in the internalization of ligand-inducible receptors of the receptor tyrosine kinase (RTK) type, in particular EGFR. Plays a role in the assembly of clathrin-coated pits (CCPs). Acts as a clathrin adapter required for post-Golgi trafficking. Seems to be involved in CCPs maturation including invagination or budding. Involved in endocytosis of integrin beta-1 (ITGB1) and transferrin receptor (TFR); internalization of ITGB1 as DAB2-dependent cargo but not TFR seems to require association with DAB2. {ECO:0000269|PubMed:16903783, ECO:0000269|PubMed:18362181, ECO:0000269|PubMed:19458185, ECO:0000269|PubMed:22648170}.

Subunit: Interacts with SGIP1 (PubMed:26822536). Interacts with HGS; the interaction bridges the interaction of STAM or STAM2 with EPS15. Isoform 2 interacts with HGS and AP2A2. Part of a complex at least composed of EPS15, HGS, and either STAM or STAM2. Binds AP2A2. Interacts with AP2B1; clathrin competes with EPS15. Binds STON2. Interacts (via its SH3-binding sites) with CRK. Interacts with SH3BP4/TTP. Interacts with ERBB2. Interacts with FCHO1. Interacts with FCHO2. Interacts (via EH domains) with DAB2. Interacts (via UIM repeats) with CORO7 (when ubiquitinated at 'Lys-472'). Interacts (via UIM domains) with UBQLN1 (via ubiquitin-like domain) and can interact with both the ubiquitinated and the non-ubiquitinated forms of UBQLN1. Interacts with UBQLN2 (By similarity) (PubMed:10757979, PubMed:11062555, PubMed:12551915, PubMed:16159959, PubMed:16314522, PubMed:16325581, PubMed:16903783, PubMed:18199683, PubMed:18200045, PubMed:18362181, PubMed:20448150, PubMed:21762413, PubMed:22484487, PubMed:22648170, PubMed:24768539, PubMed:8662907, PubMed:9721102, PubMed:9723620). Interacts with REPS2; the interaction is direct (PubMed:10393179). Interacts with EPN1; the interaction is direct (PubMed:9723620, PubMed:10393179). {ECO:0000250|UniProtKB:P42567, ECO:0000269|PubMed:10393179, ECO:0000269|PubMed:10757979, ECO:0000269|PubMed:11062555, ECO:0000269|PubMed:12551915, ECO:0000269|PubMed:16159959, ECO:0000269|PubMed:16314522, ECO:0000269|PubMed:16325581, ECO:0000269|PubMed:16903783, ECO:0000269|PubMed:18199683, ECO:0000269|PubMed:18200045, ECO:0000269|PubMed:18362181, ECO:0000269|PubMed:20448150, ECO:0000269|PubMed:21762413, ECO:0000269|PubMed:22484487, ECO:0000269|PubMed:22648170, ECO:0000269|PubMed:24768539, ECO:0000269|PubMed:26822536, ECO:0000269|PubMed:8662907, ECO:0000269|PubMed:9721102, ECO:0000269|PubMed:9723620}.

Subunit: (Microbial infection) Interacts with vaccinia virus protein A36. {ECO:0000269|PubMed:27670116}.

Subcellular location: Cytoplasm. Cell membrane; Peripheral membrane protein; Cytoplasmic side. Membrane, clathrin-coated pit. Note=Recruited to the plasma membrane upon EGFR activation and localizes to coated pits. Colocalizes with UBQLN1 in ubiquitin-rich cytoplasmic aggregates that are not endocytic compartments and in cytoplasmic juxtanuclear structures called aggresomes. {ECO:0000269|PubMed:16159959}.

Subcellular location: [Isoform 2]: Early endosome membrane {ECO:0000269|PubMed:18362181}; Peripheral membrane protein {ECO:0000269|PubMed:18362181}; Cytoplasmic side {ECO:0000269|PubMed:18362181}. Note=Colocalizes with HGS on bilayered clathrin coats on endosomes.

Tissue specificity: Ubiquitously expressed.

Domain: The EH domain interacts with Asn-Pro-Phe (NPF) motifs of target proteins. {ECO:0000269|PubMed:11062555}.

Domain: The UIM (ubiquitin-interacting motif) repeats specifically bind 'Lys-33'-linked ubiquitin. {ECO:0000269|PubMed:11062555, ECO:0000269|PubMed:24768539}.

Ptm: Phosphorylation on Tyr-849 is involved in the internalization of EGFR. Not required for membrane translocation after EGF treatment or for targeting to coated pits, but essential for a subsequent step in EGFR endocytosis (By similarity). Phosphorylated on serine upon DNA damage, probably by ATM or ATR. {ECO:0000250}.

Ptm: Ubiquitinated. {ECO:0000250|UniProtKB:P42567}.

Disease: Note=A chromosomal aberration involving EPS15 is found in acute leukemias. Translocation t(1;11)(p32;q23) with KMT2A/MLL1. The result is a rogue activator protein.

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:		Involved in cell growth regulation. May be involved in the regulation of mitogenic signals and control of cell proliferation. Involved in the internalization of ligand-inducible receptors of the receptor tyrosine kinase (RTK) type, in particular EGFR. Plays a role in the assembly of clathrin-coated pits (CCPs). Acts as a clathrin adapter required for post-Golgi trafficking. Seems to be involved in CCPs maturation including invagination or budding. Involved in endocytosis of integrin beta-1 (ITGB1) and transferrin receptor (TFR); internalization of ITGB1 as DAB2-dependent cargo but not TFR seems to require association with DAB2. {ECO:0000269\|PubMed:16903783, ECO:0000269\|PubMed:18362181, ECO:0000269\|PubMed:19458185, ECO:0000269\|PubMed:22648170}.


Subunit:		Interacts with SGIP1 (PubMed:26822536). Interacts with HGS; the interaction bridges the interaction of STAM or STAM2 with EPS15. Isoform 2 interacts with HGS and AP2A2. Part of a complex at least composed of EPS15, HGS, and either STAM or STAM2. Binds AP2A2. Interacts with AP2B1; clathrin competes with EPS15. Binds STON2. Interacts (via its SH3-binding sites) with CRK. Interacts with SH3BP4/TTP. Interacts with ERBB2. Interacts with FCHO1. Interacts with FCHO2. Interacts (via EH domains) with DAB2. Interacts (via UIM repeats) with CORO7 (when ubiquitinated at 'Lys-472'). Interacts (via UIM domains) with UBQLN1 (via ubiquitin-like domain) and can interact with both the ubiquitinated and the non-ubiquitinated forms of UBQLN1. Interacts with UBQLN2 (By similarity) (PubMed:10757979, PubMed:11062555, PubMed:12551915, PubMed:16159959, PubMed:16314522, PubMed:16325581, PubMed:16903783, PubMed:18199683, PubMed:18200045, PubMed:18362181, PubMed:20448150, PubMed:21762413, PubMed:22484487, PubMed:22648170, PubMed:24768539, PubMed:8662907, PubMed:9721102, PubMed:9723620). Interacts with REPS2; the interaction is direct (PubMed:10393179). Interacts with EPN1; the interaction is direct (PubMed:9723620, PubMed:10393179). {ECO:0000250\|UniProtKB:P42567, ECO:0000269\|PubMed:10393179, ECO:0000269\|PubMed:10757979, ECO:0000269\|PubMed:11062555, ECO:0000269\|PubMed:12551915, ECO:0000269\|PubMed:16159959, ECO:0000269\|PubMed:16314522, ECO:0000269\|PubMed:16325581, ECO:0000269\|PubMed:16903783, ECO:0000269\|PubMed:18199683, ECO:0000269\|PubMed:18200045, ECO:0000269\|PubMed:18362181, ECO:0000269\|PubMed:20448150, ECO:0000269\|PubMed:21762413, ECO:0000269\|PubMed:22484487, ECO:0000269\|PubMed:22648170, ECO:0000269\|PubMed:24768539, ECO:0000269\|PubMed:26822536, ECO:0000269\|PubMed:8662907, ECO:0000269\|PubMed:9721102, ECO:0000269\|PubMed:9723620}.
Subunit:		(Microbial infection) Interacts with vaccinia virus protein A36. {ECO:0000269\|PubMed:27670116}.
Subcellular location:		Cytoplasm. Cell membrane; Peripheral membrane protein; Cytoplasmic side. Membrane, clathrin-coated pit. Note=Recruited to the plasma membrane upon EGFR activation and localizes to coated pits. Colocalizes with UBQLN1 in ubiquitin-rich cytoplasmic aggregates that are not endocytic compartments and in cytoplasmic juxtanuclear structures called aggresomes. {ECO:0000269\|PubMed:16159959}.
Subcellular location:		[Isoform 2]: Early endosome membrane {ECO:0000269\|PubMed:18362181}; Peripheral membrane protein {ECO:0000269\|PubMed:18362181}; Cytoplasmic side {ECO:0000269\|PubMed:18362181}. Note=Colocalizes with HGS on bilayered clathrin coats on endosomes.
Tissue specificity:		Ubiquitously expressed.
Domain:		The EH domain interacts with Asn-Pro-Phe (NPF) motifs of target proteins. {ECO:0000269\|PubMed:11062555}.
Domain:		The UIM (ubiquitin-interacting motif) repeats specifically bind 'Lys-33'-linked ubiquitin. {ECO:0000269\|PubMed:11062555, ECO:0000269\|PubMed:24768539}.
Ptm:		Phosphorylation on Tyr-849 is involved in the internalization of EGFR. Not required for membrane translocation after EGF treatment or for targeting to coated pits, but essential for a subsequent step in EGFR endocytosis (By similarity). Phosphorylated on serine upon DNA damage, probably by ATM or ATR. {ECO:0000250}.
Ptm:		Ubiquitinated. {ECO:0000250\|UniProtKB:P42567}.
Disease:		Note=A chromosomal aberration involving EPS15 is found in acute leukemias. Translocation t(1;11)(p32;q23) with KMT2A/MLL1. The result is a rogue activator protein.