P42567 · EPS15_MOUSE
- ProteinEpidermal growth factor receptor substrate 15
- GeneEps15
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids897 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
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.
Features
Showing features for binding site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 173 | Ca2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 175 | Ca2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 177 | Ca2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 179 | Ca2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: K | ||||||
Binding site | 184 | Ca2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: E | ||||||
Binding site | 236 | Ca2+ 2 (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 238 | Ca2+ 2 (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 240 | Ca2+ 2 (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 242 | Ca2+ 2 (UniProtKB | ChEBI) | ||||
Sequence: Y | ||||||
Binding site | 247 | Ca2+ 2 (UniProtKB | ChEBI) | ||||
Sequence: E |
GO annotations
Keywords
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameEpidermal growth factor receptor substrate 15
- Short namesProtein Eps15
- Alternative names
Gene names
Organism names
- Organism
- Strains
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus
Accessions
- Primary accessionP42567
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Cell membrane ; Peripheral membrane protein
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.
Isoform 2
Early endosome membrane ; Peripheral membrane protein
Note: Colocalizes with HGS on bilayered clathrin coats on endosomes.
Keywords
- Cellular component
Phenotypes & Variants
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 850 | Inefficient EGFR internalization. | ||||
Sequence: Y → F | ||||||
Mutagenesis | 863 | Loss of interaction with UBQLN1; when associated with A-864 and A-865. | ||||
Sequence: E → A | ||||||
Mutagenesis | 864 | Loss of interaction with UBQLN1; when associated with A-863 and A-865. | ||||
Sequence: S → A | ||||||
Mutagenesis | 865 | Loss of interaction with UBQLN1; when associated with A-863 and A-864. | ||||
Sequence: E → A | ||||||
Mutagenesis | 883 | Loss of ubiquitination and interaction with UBQLN1; when associated with A-885. | ||||
Sequence: L → A | ||||||
Mutagenesis | 885 | Loss of ubiquitination and interaction with UBQLN1; when associated with A-883. | ||||
Sequence: L → A |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 48 variants from UniProt as well as other sources including ClinVar and dbSNP.
PTM/Processing
Features
Showing features for initiator methionine, modified residue, chain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Initiator methionine | 1 | Removed | ||||
Sequence: M | ||||||
Modified residue | 2 | N-acetylalanine | ||||
Sequence: A | ||||||
Chain | PRO_0000146117 | 2-897 | Epidermal growth factor receptor substrate 15 | |||
Sequence: AAAAQLSLTQLSSGNPVYEKYYRQVEAGNTGRVLALDAAAFLKKSGLPDLILGKIWDLADTDGKGVLSKQEFFVALRLVACAQNGLEVSLSSLSLAVPPPRFHDSSSPLLTSGPSVAELPWAVKSEDKAKYDAIFDSLSPVDGFLSGDKVKPVLLNSKLPVEILGRVWELSDIDHDGKLDRDEFAVAMFLVYCALEKEPVPMSLPPALVPPSKRKTWVVSPAEKAKYDEIFLKTDKDMDGYVSGLEVRETFLKTGLPSALLAHIWSLCDTKGCGKLSKDQFALAFHLINQKLIKGIDPPHSLTPEMIPPSDRSSLQKNITGSSPVADFSAIKELDTLNNEIVDLQREKNNVEQDLKEKEDTVKQRTSEVQDLQDEVQRESINLQKLQAQKQQVQELLGELDEQKAQLEEQLQEVRKKCAEEAQLISSLKAEITSQESQISSYEEELLKAREELSRLQQETAQLEESVESGKAQLEPLQQHLQESQQEISSMQMRLEMKDLETDNNQSNWSSSPQSVLVNGATDYCSLSTSSSETANFNEHAEGQNNLESEPTHQESSVRSSPEIAPSDVTDESEAVTVAGNEKVTPRFDDDKHSKEEDPFNVESSSLTDAVADTNLDFFQSDPFVGSDPFKDDPFGKIDPFGGDPFKGSDPFASDCFFKQTSTDPFTTSSTDPFSASSNSSNTSVETWKHNDPFAPGGTVVAAASDSATDPFASVFGNESFGDGFADFSTLSKVNNEDAFNPTISSSTSSVTIAKPMLEETASKSEDVPPALPPKVGTPTRPCPPPPGKRPINKLDSSDPLKLNDPFQPFPGNDSPKEKDPDMFCDPFTSSTTTNKEADPSNFANFSAYPSEEDMIEWAKRESEREEEQRLARLNQQEQEDLELAIALSKSEISEA | ||||||
Modified residue | 108 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 140 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 321 | Phosphothreonine | ||||
Sequence: T | ||||||
Modified residue | 323 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 324 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 467 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 470 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 485 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 561 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 562 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 748 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 779 | Phosphothreonine | ||||
Sequence: T | ||||||
Modified residue | 781 | Phosphothreonine | ||||
Sequence: T | ||||||
Modified residue | 798 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 816 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 850 | Phosphotyrosine; by EGFR | ||||
Sequence: Y |
Post-translational modification
Phosphorylated on serine upon DNA damage, probably by ATM or ATR (By similarity).
Phosphorylation on Tyr-850 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
Phosphorylation on Tyr-850 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
Ubiquitinated.
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Gene expression databases
Interaction
Subunit
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 (via UIM repeats) with CORO7 (when ubiquitinated at 'Lys-472') (By similarity).
Interacts with FCHO1 (By similarity).
Interacts with FCHO2. Interacts with SGIP1. Interacts (via EH domains) with DAB2. 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).
Interacts with REPS2; the interaction is direct (PubMed:10393179).
Interacts with EPN1; the interaction is direct (By similarity).
Interacts with FCHO1 (By similarity).
Interacts with FCHO2. Interacts with SGIP1. Interacts (via EH domains) with DAB2. 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).
Interacts with REPS2; the interaction is direct (PubMed:10393179).
Interacts with EPN1; the interaction is direct (By similarity).
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | P42567 | Dab2 P98078 | 2 | EBI-443923, EBI-1391846 | |
BINARY | P42567 | Eps15 P42567 | 4 | EBI-443923, EBI-443923 | |
BINARY | P42567 | Eps15l1 Q60902 | 2 | EBI-443923, EBI-443931 | |
XENO | P42567 | REPS2 Q8NFH8 | 10 | EBI-443923, EBI-7067016 |
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for region, domain, compositional bias, repeat.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 2-330 | Interaction with DAB2 | ||||
Sequence: AAAAQLSLTQLSSGNPVYEKYYRQVEAGNTGRVLALDAAAFLKKSGLPDLILGKIWDLADTDGKGVLSKQEFFVALRLVACAQNGLEVSLSSLSLAVPPPRFHDSSSPLLTSGPSVAELPWAVKSEDKAKYDAIFDSLSPVDGFLSGDKVKPVLLNSKLPVEILGRVWELSDIDHDGKLDRDEFAVAMFLVYCALEKEPVPMSLPPALVPPSKRKTWVVSPAEKAKYDEIFLKTDKDMDGYVSGLEVRETFLKTGLPSALLAHIWSLCDTKGCGKLSKDQFALAFHLINQKLIKGIDPPHSLTPEMIPPSDRSSLQKNITGSSPVADFS | ||||||
Domain | 15-104 | EH 1 | ||||
Sequence: GNPVYEKYYRQVEAGNTGRVLALDAAAFLKKSGLPDLILGKIWDLADTDGKGVLSKQEFFVALRLVACAQNGLEVSLSSLSLAVPPPRFH | ||||||
Domain | 48-83 | EF-hand 1 | ||||
Sequence: LPDLILGKIWDLADTDGKGVLSKQEFFVALRLVACA | ||||||
Domain | 128-216 | EH 2 | ||||
Sequence: DKAKYDAIFDSLSPVDGFLSGDKVKPVLLNSKLPVEILGRVWELSDIDHDGKLDRDEFAVAMFLVYCALEKEPVPMSLPPALVPPSKRK | ||||||
Domain | 160-195 | EF-hand 2 | ||||
Sequence: LPVEILGRVWELSDIDHDGKLDRDEFAVAMFLVYCA | ||||||
Domain | 223-258 | EF-hand 3 | ||||
Sequence: AEKAKYDEIFLKTDKDMDGYVSGLEVRETFLKTGLP | ||||||
Domain | 224-314 | EH 3 | ||||
Sequence: EKAKYDEIFLKTDKDMDGYVSGLEVRETFLKTGLPSALLAHIWSLCDTKGCGKLSKDQFALAFHLINQKLIKGIDPPHSLTPEMIPPSDRS | ||||||
Domain | 262-292 | EF-hand 4 | ||||
Sequence: LAHIWSLCDTKGCGKLSKDQFALAFHLINQK | ||||||
Compositional bias | 528-568 | Polar residues | ||||
Sequence: LSTSSSETANFNEHAEGQNNLESEPTHQESSVRSSPEIAPS | ||||||
Region | 528-607 | Disordered | ||||
Sequence: LSTSSSETANFNEHAEGQNNLESEPTHQESSVRSSPEIAPSDVTDESEAVTVAGNEKVTPRFDDDKHSKEEDPFNVESSS | ||||||
Compositional bias | 585-603 | Basic and acidic residues | ||||
Sequence: VTPRFDDDKHSKEEDPFNV | ||||||
Repeat | 599-601 | 1 | ||||
Sequence: DPF | ||||||
Region | 599-829 | 13 X 3 AA repeats of D-P-F | ||||
Sequence: DPFNVESSSLTDAVADTNLDFFQSDPFVGSDPFKDDPFGKIDPFGGDPFKGSDPFASDCFFKQTSTDPFTTSSTDPFSASSNSSNTSVETWKHNDPFAPGGTVVAAASDSATDPFASVFGNESFGDGFADFSTLSKVNNEDAFNPTISSSTSSVTIAKPMLEETASKSEDVPPALPPKVGTPTRPCPPPPGKRPINKLDSSDPLKLNDPFQPFPGNDSPKEKDPDMFCDPF | ||||||
Repeat | 623-625 | 2 | ||||
Sequence: DPF | ||||||
Repeat | 629-631 | 3 | ||||
Sequence: DPF | ||||||
Repeat | 634-636 | 4 | ||||
Sequence: DPF | ||||||
Repeat | 640-642 | 5 | ||||
Sequence: DPF | ||||||
Repeat | 645-647 | 6 | ||||
Sequence: DPF | ||||||
Repeat | 651-653 | 7 | ||||
Sequence: DPF | ||||||
Repeat | 665-667 | 8 | ||||
Sequence: DPF | ||||||
Compositional bias | 667-690 | Polar residues | ||||
Sequence: FTTSSTDPFSASSNSSNTSVETWK | ||||||
Region | 667-692 | Disordered | ||||
Sequence: FTTSSTDPFSASSNSSNTSVETWKHN | ||||||
Repeat | 673-675 | 9 | ||||
Sequence: DPF | ||||||
Repeat | 693-695 | 10 | ||||
Sequence: DPF | ||||||
Repeat | 711-713 | 11 | ||||
Sequence: DPF | ||||||
Compositional bias | 741-757 | Polar residues | ||||
Sequence: FNPTISSSTSSVTIAKP | ||||||
Region | 741-849 | Disordered | ||||
Sequence: FNPTISSSTSSVTIAKPMLEETASKSEDVPPALPPKVGTPTRPCPPPPGKRPINKLDSSDPLKLNDPFQPFPGNDSPKEKDPDMFCDPFTSSTTTNKEADPSNFANFSA | ||||||
Compositional bias | 773-792 | Pro residues | ||||
Sequence: LPPKVGTPTRPCPPPPGKRP | ||||||
Repeat | 806-808 | 12 | ||||
Sequence: DPF | ||||||
Repeat | 827-829 | 13 | ||||
Sequence: DPF | ||||||
Compositional bias | 827-849 | Polar residues | ||||
Sequence: DPFTSSTTTNKEADPSNFANFSA | ||||||
Domain | 852-871 | UIM 1 | ||||
Sequence: SEEDMIEWAKRESEREEEQR | ||||||
Domain | 878-897 | UIM 2 | ||||
Sequence: QEQEDLELAIALSKSEISEA |
Domain
The EH domain interacts with Asn-Pro-Phe (NPF) motifs of target proteins.
The UIM (ubiquitin-interacting motif) repeats specifically bind 'Lys-33'-linked ubiquitin.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence & Isoform
- Sequence statusComplete
This entry describes 2 isoforms produced by Alternative splicing.
P42567-1
This isoform has been chosen as the canonical sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
- Name1
- Length897
- Mass (Da)98,471
- Last updated1995-11-01 v1
- Checksum08A0C0D423F873C2
P42567-2
- Name2
- SynonymsEps15b
Computationally mapped potential isoform sequences
There are 6 potential isoforms mapped to this entry
Features
Showing features for alternative sequence, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Alternative sequence | VSP_036170 | 1-314 | in isoform 2 | |||
Sequence: Missing | ||||||
Alternative sequence | VSP_036171 | 315-346 | in isoform 2 | |||
Sequence: SLQKNITGSSPVADFSAIKELDTLNNEIVDLQ → MYSDSGLGGWIAIPAVADVLRYSCIVCWSS | ||||||
Compositional bias | 528-568 | Polar residues | ||||
Sequence: LSTSSSETANFNEHAEGQNNLESEPTHQESSVRSSPEIAPS | ||||||
Compositional bias | 585-603 | Basic and acidic residues | ||||
Sequence: VTPRFDDDKHSKEEDPFNV | ||||||
Compositional bias | 667-690 | Polar residues | ||||
Sequence: FTTSSTDPFSASSNSSNTSVETWK | ||||||
Compositional bias | 741-757 | Polar residues | ||||
Sequence: FNPTISSSTSSVTIAKP | ||||||
Compositional bias | 773-792 | Pro residues | ||||
Sequence: LPPKVGTPTRPCPPPPGKRP | ||||||
Compositional bias | 827-849 | Polar residues | ||||
Sequence: DPFTSSTTTNKEADPSNFANFSA |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
L21768 EMBL· GenBank· DDBJ | AAA02912.1 EMBL· GenBank· DDBJ | mRNA | ||
AK083176 EMBL· GenBank· DDBJ | BAC38796.1 EMBL· GenBank· DDBJ | mRNA | ||
AL669905 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. |