Reactome | UniProt:P42566 EPS15

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UniProt:P42566 EPS15 Show undefined attributes

chain	initiator methionine:1 chain:2-896
checksum	A1B9FE15B47ABAFF
comment	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.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:10393179, PubMed:9723620).SUBUNIT (Microbial infection) Interacts with vaccinia virus protein A36.INTERACTION 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.SUBCELLULAR LOCATION Colocalizes with HGS on bilayered clathrin coats on endosomes.ALTERNATIVE PRODUCTS Ubiquitously expressed.DOMAIN The EH domain interacts with Asn-Pro-Phe (NPF) motifs of target proteins.DOMAIN The UIM (ubiquitin-interacting motif) repeats specifically bind 'Lys-33'-linked ubiquitin.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.PTM Ubiquitinated.DISEASE 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.CAUTION Studies in clathrin-mediated endocytosis of ITGB1 and TFR used a siRNA mixture of EPS15 and EPS15L1, and a Dab2 mutant with impaired binding to EH domain-containing proteins EPS15 and ITSN1 suggesting a partially overlapping role of the EH domain-containing proteins.
crossReference	[DatabaseIdentifier:11561836] ENSEMBL:ENSP00000516332 [DatabaseIdentifier:12353348] RefSeq:NP_001972.1 [DatabaseIdentifier:12353349] RefSeq:NP_001153441.1 [DatabaseIdentifier:12281298] Pharos - Targets:P42566 [DatabaseIdentifier:12259317] PRO:P42566 [DatabaseIdentifier:12151876] PDB:5AWU [DatabaseIdentifier:12151870] PDB:1EH2 [DatabaseIdentifier:12151877] PDB:1FF1 [DatabaseIdentifier:12151873] PDB:5JP2 [DatabaseIdentifier:12151871] PDB:2IV9 [DatabaseIdentifier:12151874] PDB:5AWT [DatabaseIdentifier:12151872] PDB:1C07 [DatabaseIdentifier:12143841] PDB:4S0G [DatabaseIdentifier:12143844] PDB:4RH5 [DatabaseIdentifier:12151875] PDB:1F8H [DatabaseIdentifier:12139353] PDB:2JXC [DatabaseIdentifier:12143837] PDB:4RHG [DatabaseIdentifier:12143845] PDB:4RH9 [DatabaseIdentifier:12120963] OpenTargets:ENSG00000085832 [DatabaseIdentifier:11836489] HPA:ENSG00000085832-EPS15 [DatabaseIdentifier:11798977] GlyGen:P42566 [DatabaseIdentifier:11783380] GeneCards:EPS15 [DatabaseIdentifier:11684535] ENSEMBL:ENST00000371733 [DatabaseIdentifier:11684536] ENSEMBL:ENST00000493793 [DatabaseIdentifier:11466318] ENSEMBL:ENSG00000085832 [DatabaseIdentifier:11561837] ENSEMBL:ENSP00000360798
databaseName	UniProt
dbId	54350
description	recommendedName: Epidermal growth factor receptor substrate 15 shortName: Protein Eps15 alternativeName: Protein AF-1p
displayName	UniProt:P42566 EPS15
geneName	EPS15 AF1P
identifier	P42566
isSequenceChanged	false
keyword	3D-structure Acetylation Alternative splicing Calcium Cell membrane Chromosomal rearrangement Coated pit Cytoplasm Endocytosis Endosome Host-virus interaction Membrane Metal-binding Phosphoprotein Protein transport Proteomics identification Proto-oncogene Reference proteome Repeat SH3-binding Transport Ubl conjugation
modified	[InstanceEdit:9963647] Weiser, Joel, 2025-08-15
moleculeType	Protein
name	EPS15
physicalEntity	[EntityWithAccessionedSequence:R-HSA-182920] EPS15 [cytosol] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-8867028] p-Y849 EPS15 [cytosol] - Homo sapiens
referenceDatabase	[ReferenceDatabase:2] UniProt
referenceGene	[ReferenceDNASequence:ensembl:ENSG00000085832] ENSEMBL:ENSG00000085832 EPS15 [ReferenceDNASequence:12681884] UCSC:P42566 EPS15 [ReferenceDNASequence:12106719] OMIM:600051 EPS15 [ReferenceDNASequence:12044642] NCBI Gene:2060 EPS15 [ReferenceDNASequence:11960549] Monarch:2060 EPS15 [ReferenceDNASequence:11872616] KEGG:hsa:2060 EPS15 [ReferenceDNASequence:11814996] HGNC:3419 EPS15 [ReferenceDNASequence:11330760] BioGPS Gene:2060 EPS15 [ReferenceDNASequence:11392344] COSMIC - genes:EPS15 EPS15 [ReferenceDNASequence:11407029] CTD Gene:2060 EPS15 [ReferenceDNASequence:11428115] dbSNP Gene:2060 EPS15
referenceTranscript	[ReferenceRNASequence:12535216] RefSeq:NM_001981.3 EPS15 [ReferenceRNASequence:12535215] RefSeq:NM_001159969.2 EPS15
schemaClass	ReferenceGeneProduct
secondaryIdentifier	EPS15_HUMAN B2R8J7 D3DPJ2 Q5SRH4
sequenceLength	896
species	[Species:48887] Homo sapiens
stId	uniprot:P42566
url	http://purl.uniprot.org/uniprot/P42566

Referrals

(referenceEntity)	[EntityWithAccessionedSequence:R-HSA-182920] EPS15 [cytosol] [EntityWithAccessionedSequence:R-HSA-8867028] p-Y849 EPS15 [cytosol]
(referenceSequence)	[ModifiedResidue:8867030] O4'-phospho-L-tyrosine at 849
(interactor)	[UndirectedInteraction:11160213] UniProt:O14965 <-> UniProt:P42566 (IntAct) [UndirectedInteraction:11163981] UniProt:P46108 <-> UniProt:P42566 (IntAct) [UndirectedInteraction:11182123] UniProt:Q96FJ0 <-> UniProt:P42566 (IntAct) [UndirectedInteraction:11215969] UniProt:P52594 <-> UniProt:P42566 (IntAct) [UndirectedInteraction:11249561] UniProt:Q9UBC2 <-> UniProt:P42566 (IntAct) [UndirectedInteraction:11254727] UniProt:Q9Y6I3 <-> UniProt:P42566 (IntAct) [UndirectedInteraction:11268779] UniProt:P42566 <-> UniProt:Q8WXE9 (IntAct) [UndirectedInteraction:11268781] UniProt:P42566 <-> UniProt:P53680 (IntAct) [UndirectedInteraction:11268783] UniProt:P42566 <-> UniProt:P49757 (IntAct) [UndirectedInteraction:11268785] UniProt:P42566 <-> UniProt:Q96CW1 (IntAct) [UndirectedInteraction:11268787] UniProt:P42566 <-> UniProt:Q9JJ50 (IntAct) [UndirectedInteraction:11268789] UniProt:P42566 <-> UniProt:Q0JRZ9 (IntAct) [UndirectedInteraction:11268791] UniProt:P42566 <-> UniProt:P63010 (IntAct) [UndirectedInteraction:11268793] UniProt:P42566 <-> UniProt:P42566 (IntAct) [UndirectedInteraction:11268793] UniProt:P42566 <-> UniProt:P42566 (IntAct) [UndirectedInteraction:11268795] UniProt:P42566 <-> UniProt:Q9P0V3 (IntAct) [UndirectedInteraction:11268797] UniProt:P42566 <-> UniProt:Q13492 (IntAct) [UndirectedInteraction:11268799] UniProt:P42566 <-> UniProt:Q15811 (IntAct) [UndirectedInteraction:11268801] UniProt:P42566 <-> UniProt:Q3UQN2 (IntAct) [UndirectedInteraction:11268803] UniProt:P42566 <-> UniProt:Q9UMX0 (IntAct) [UndirectedInteraction:11268805] UniProt:P42566 <-> UniProt:Q9QYW3 (IntAct) [UndirectedInteraction:11268807] UniProt:P42566 <-> UniProt:Q9QZS3-1 (IntAct) [UndirectedInteraction:11268809] UniProt:P42566 <-> UniProt:Q9QZS3-2 (IntAct) [UndirectedInteraction:11268811] UniProt:P42566 <-> UniProt:Q9NVZ3 (IntAct) [UndirectedInteraction:11268813] UniProt:P42566 <-> UniProt:P0C7W6 (IntAct) [UndirectedInteraction:11268815] UniProt:P42566 <-> UniProt:Q8N5S1 (IntAct) [UndirectedInteraction:11268817] UniProt:P42566 <-> UniProt:Q8NBZ0 (IntAct) [UndirectedInteraction:11268819] UniProt:P42566 <-> UniProt:Q9HBM1 (IntAct) [UndirectedInteraction:11268821] UniProt:P42566 <-> UniProt:P19320 (IntAct) [UndirectedInteraction:11268823] UniProt:P42566 <-> UniProt:Q10567 (IntAct) [UndirectedInteraction:11268825] UniProt:P42566 <-> UniProt:Q86X29 (IntAct) [UndirectedInteraction:11268827] UniProt:P42566 <-> UniProt:O94973 (IntAct) [UndirectedInteraction:11268829] UniProt:P42566 <-> UniProt:P55809 (IntAct) [UndirectedInteraction:11268831] UniProt:P42566 <-> UniProt:O95782 (IntAct) [UndirectedInteraction:11268833] UniProt:P42566 <-> UniProt:P09497 (IntAct) [UndirectedInteraction:11268835] UniProt:P42566 <-> UniProt:Q15287 (IntAct) [UndirectedInteraction:11268839] UniProt:P42566 <-> UniProt:P98078-1 (IntAct)

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