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Protein

Epidermal growth factor receptor substrate 15

Gene

EPS15

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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 DAB2.4 Publications

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.1 Publication

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Calcium bindingi173 – 1841Add BLAST12
Calcium bindingi236 – 2472Add BLAST12

GO - Molecular functioni

GO - Biological processi

Keywordsi

Biological processEndocytosis, Host-virus interaction, Protein transport, Transport
LigandCalcium, Metal-binding

Enzyme and pathway databases

ReactomeiR-HSA-182971 EGFR downregulation
R-HSA-6807004 Negative regulation of MET activity
R-HSA-8856825 Cargo recognition for clathrin-mediated endocytosis
R-HSA-8856828 Clathrin-mediated endocytosis
R-HSA-8875360 InlB-mediated entry of Listeria monocytogenes into host cell
SignaLinkiP42566
SIGNORiP42566

Protein family/group databases

MoonDBiP42566 Curated
MoonProtiP42566

Names & Taxonomyi

Protein namesi
Recommended name:
Epidermal growth factor receptor substrate 15
Short name:
Protein Eps15
Alternative name(s):
Protein AF-1p
Gene namesi
Name:EPS15
Synonyms:AF1P
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

EuPathDBiHostDB:ENSG00000085832.16
HGNCiHGNC:3419 EPS15
MIMi600051 gene
neXtProtiNX_P42566

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell membrane, Coated pit, Cytoplasm, Endosome, Membrane

Pathology & Biotechi

Involvement in diseasei

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.

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi154V → E: Loss of interaction with STON2 NPF motifs. 1 Publication1
Mutagenesisi169W → A: Loss of interaction with STON2 NPF motifs. 1 Publication1

Keywords - Diseasei

Proto-oncogene

Organism-specific databases

DisGeNETi2060
OpenTargetsiENSG00000085832
PharmGKBiPA27838

Polymorphism and mutation databases

BioMutaiEPS15
DMDMi67476728

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources
ChainiPRO_00001461162 – 896Epidermal growth factor receptor substrate 15Add BLAST895

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanineCombined sources1
Modified residuei108PhosphoserineCombined sources1
Modified residuei140PhosphoserineCombined sources1
Modified residuei323PhosphoserineCombined sources1
Modified residuei324PhosphoserineCombined sources1
Modified residuei467PhosphoserineCombined sources1
Modified residuei470PhosphoserineCombined sources1
Modified residuei485PhosphoserineCombined sources1
Modified residuei562PhosphoserineBy similarity1
Modified residuei563PhosphoserineBy similarity1
Modified residuei746PhosphoserineCombined sources1
Modified residuei777PhosphothreonineCombined sources1
Modified residuei779PhosphothreonineBy similarity1
Modified residuei790PhosphoserineCombined sources1
Modified residuei796PhosphoserineCombined sources1
Modified residuei814PhosphoserineCombined sources1
Modified residuei849Phosphotyrosine; by EGFRCombined sources1

Post-translational modificationi

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.By similarity
Ubiquitinated.By similarity

Keywords - PTMi

Acetylation, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiP42566
MaxQBiP42566
PaxDbiP42566
PeptideAtlasiP42566
PRIDEiP42566
ProteomicsDBi55515
55516 [P42566-2]

2D gel databases

OGPiP42566

PTM databases

iPTMnetiP42566
PhosphoSitePlusiP42566

Expressioni

Tissue specificityi

Ubiquitously expressed.

Gene expression databases

BgeeiENSG00000085832 Expressed in 241 organ(s), highest expression level in endothelial cell
CleanExiHS_EPS15
ExpressionAtlasiP42566 baseline and differential
GenevisibleiP42566 HS

Organism-specific databases

HPAiCAB010164
HPA008451
HPA061431

Interactioni

Subunit structurei

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 and EPN1. 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).By similarity19 Publications
(Microbial infection) Interacts with vaccinia virus protein A36.1 Publication

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi108374, 163 interactors
CORUMiP42566
DIPiDIP-33064N
ELMiP42566
IntActiP42566, 79 interactors
MINTiP42566
STRINGi9606.ENSP00000360798

Structurei

Secondary structure

1896
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliP42566
SMRiP42566
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP42566

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini15 – 104EH 1PROSITE-ProRule annotationAdd BLAST90
Domaini128 – 216EH 2PROSITE-ProRule annotationAdd BLAST89
Domaini160 – 195EF-hand 1PROSITE-ProRule annotationAdd BLAST36
Domaini223 – 258EF-hand 2PROSITE-ProRule annotationAdd BLAST36
Domaini224 – 314EH 3PROSITE-ProRule annotationAdd BLAST91
Repeati599 – 60113
Repeati623 – 62523
Repeati629 – 63133
Repeati634 – 63643
Repeati640 – 64253
Repeati645 – 64763
Repeati651 – 65373
Repeati664 – 66683
Repeati672 – 67493
Repeati692 – 694103
Repeati709 – 711113
Repeati737 – 739123
Repeati798 – 800133
Repeati804 – 806143
Repeati825 – 827153
Domaini851 – 870UIM 1PROSITE-ProRule annotationAdd BLAST20
Domaini877 – 896UIM 2PROSITE-ProRule annotationAdd BLAST20

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni2 – 330Interaction with DAB2By similarityAdd BLAST329
Regioni599 – 82715 X 3 AA repeats of D-P-FAdd BLAST229

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi768 – 774SH3-binding7

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi768 – 850Pro-richAdd BLAST83

Domaini

The EH domain interacts with Asn-Pro-Phe (NPF) motifs of target proteins.1 Publication
The UIM (ubiquitin-interacting motif) repeats specifically bind 'Lys-33'-linked ubiquitin.2 Publications

Keywords - Domaini

Repeat, SH3-binding

Phylogenomic databases

eggNOGiKOG0998 Eukaryota
ENOG410XTDR LUCA
GeneTreeiENSGT00760000118985
HOGENOMiHOG000004804
HOVERGENiHBG005591
InParanoidiP42566
KOiK12472
OMAiIKGIDPP
OrthoDBiEOG091G01RG
PhylomeDBiP42566
TreeFamiTF324293

Family and domain databases

CDDicd00052 EH, 3 hits
InterProiView protein in InterPro
IPR011992 EF-hand-dom_pair
IPR018247 EF_Hand_1_Ca_BS
IPR002048 EF_hand_dom
IPR000261 EH_dom
IPR003903 UIM_dom
PfamiView protein in Pfam
PF12763 EF-hand_4, 3 hits
SMARTiView protein in SMART
SM00054 EFh, 3 hits
SM00027 EH, 3 hits
SM00726 UIM, 3 hits
SUPFAMiSSF47473 SSF47473, 3 hits
PROSITEiView protein in PROSITE
PS00018 EF_HAND_1, 2 hits
PS50222 EF_HAND_2, 4 hits
PS50031 EH, 3 hits
PS50330 UIM, 2 hits

Sequences (2+)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 2 described isoforms and 2 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: P42566-1) [UniParc]FASTAAdd to basket

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.

« Hide
        10         20         30         40         50
MAAAAQLSLT QLSSGNPVYE KYYRQVDTGN TGRVLASDAA AFLKKSGLPD
60 70 80 90 100
LILGKIWDLA DTDGKGILNK QEFFVALRLV ACAQNGLEVS LSSLNLAVPP
110 120 130 140 150
PRFHDTSSPL LISGTSAAEL PWAVKPEDKA KYDAIFDSLS PVNGFLSGDK
160 170 180 190 200
VKPVLLNSKL PVDILGRVWE LSDIDHDGML DRDEFAVAMF LVYCALEKEP
210 220 230 240 250
VPMSLPPALV PPSKRKTWVV SPAEKAKYDE IFLKTDKDMD GFVSGLEVRE
260 270 280 290 300
IFLKTGLPST LLAHIWSLCD TKDCGKLSKD QFALAFHLIS QKLIKGIDPP
310 320 330 340 350
HVLTPEMIPP SDRASLQKNI IGSSPVADFS AIKELDTLNN EIVDLQREKN
360 370 380 390 400
NVEQDLKEKE DTIKQRTSEV QDLQDEVQRE NTNLQKLQAQ KQQVQELLDE
410 420 430 440 450
LDEQKAQLEE QLKEVRKKCA EEAQLISSLK AELTSQESQI STYEEELAKA
460 470 480 490 500
REELSRLQQE TAELEESVES GKAQLEPLQQ HLQDSQQEIS SMQMKLMEMK
510 520 530 540 550
DLENHNSQLN WCSSPHSILV NGATDYCSLS TSSSETANLN EHVEGQSNLE
560 570 580 590 600
SEPIHQESPA RSSPELLPSG VTDENEVTTA VTEKVCSELD NNRHSKEEDP
610 620 630 640 650
FNVDSSSLTG PVADTNLDFF QSDPFVGSDP FKDDPFGKID PFGGDPFKGS
660 670 680 690 700
DPFASDCFFR QSTDPFATSS TDPFSAANNS SITSVETLKH NDPFAPGGTV
710 720 730 740 750
VAASDSATDP FASVFGNESF GGGFADFSTL SKVNNEDPFR SATSSSVSNV
760 770 780 790 800
VITKNVFEET SVKSEDEPPA LPPKIGTPTR PCPLPPGKRS INKLDSPDPF
810 820 830 840 850
KLNDPFQPFP GNDSPKEKDP EIFCDPFTSA TTTTNKEADP SNFANFSAYP
860 870 880 890
SEEDMIEWAK RESEREEEQR LARLNQQEQE DLELAIALSK SEISEA
Length:896
Mass (Da):98,656
Last modified:June 7, 2005 - v2
Checksum:iA1B9FE15B47ABAFF
GO
Isoform 2 (identifier: P42566-2) [UniParc]FASTAAdd to basket
Also known as: Eps15b

The sequence of this isoform differs from the canonical sequence as follows:
     1-314: Missing.
     315-346: SLQKNIIGSSPVADFSAIKELDTLNNEIVDLQ → MYLKSDSGLGGWITIPAVADVLKYSCIVCWSS

Show »
Length:582
Mass (Da):64,376
Checksum:i2A7BACA24604E8CA
GO

Computationally mapped potential isoform sequencesi

There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
B1AUU8B1AUU8_HUMAN
Epidermal growth factor receptor su...
EPS15
762Annotation score:
S4R3U1S4R3U1_HUMAN
Epidermal growth factor receptor su...
EPS15
90Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti446Missing in BX647676 (PubMed:17974005).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_016142822I → M1 PublicationCorresponds to variant dbSNP:rs17567Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0361681 – 314Missing in isoform 2. 1 PublicationAdd BLAST314
Alternative sequenceiVSP_036169315 – 346SLQKN…IVDLQ → MYLKSDSGLGGWITIPAVAD VLKYSCIVCWSS in isoform 2. 1 PublicationAdd BLAST32

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U07707 mRNA Translation: AAA52101.1
Z29064 mRNA Translation: CAA82305.1
AK313396 mRNA Translation: BAG36194.1
DQ367924 mRNA Translation: ABD34786.1
BX647676 mRNA No translation available.
AC104170 Genomic DNA No translation available.
AL671986 Genomic DNA No translation available.
CH471059 Genomic DNA Translation: EAX06823.1
CCDSiCCDS557.1 [P42566-1]
PIRiS43074
RefSeqiNP_001153441.1, NM_001159969.1 [P42566-2]
NP_001972.1, NM_001981.2 [P42566-1]
UniGeneiHs.83722

Genome annotation databases

EnsembliENST00000371733; ENSP00000360798; ENSG00000085832 [P42566-1]
GeneIDi2060
KEGGihsa:2060
UCSCiuc001csq.2 human [P42566-1]

Keywords - Coding sequence diversityi

Alternative splicing, Chromosomal rearrangement, Polymorphism

Similar proteinsi

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U07707 mRNA Translation: AAA52101.1
Z29064 mRNA Translation: CAA82305.1
AK313396 mRNA Translation: BAG36194.1
DQ367924 mRNA Translation: ABD34786.1
BX647676 mRNA No translation available.
AC104170 Genomic DNA No translation available.
AL671986 Genomic DNA No translation available.
CH471059 Genomic DNA Translation: EAX06823.1
CCDSiCCDS557.1 [P42566-1]
PIRiS43074
RefSeqiNP_001153441.1, NM_001159969.1 [P42566-2]
NP_001972.1, NM_001981.2 [P42566-1]
UniGeneiHs.83722

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1C07NMR-A217-311[»]
1EH2NMR-A121-218[»]
1F8HNMR-A121-215[»]
1FF1NMR-A121-215[»]
2IV9X-ray1.90P723-730[»]
2JXCNMR-A121-215[»]
4RH5X-ray1.60B846-854[»]
4RH9X-ray1.60B846-854[»]
4RHGX-ray1.58B846-854[»]
4S0GX-ray1.72B846-854[»]
5AWTX-ray2.70B640-649[»]
5AWUX-ray2.70B645-654[»]
5JP2X-ray2.40E/F615-637[»]
ProteinModelPortaliP42566
SMRiP42566
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi108374, 163 interactors
CORUMiP42566
DIPiDIP-33064N
ELMiP42566
IntActiP42566, 79 interactors
MINTiP42566
STRINGi9606.ENSP00000360798

Protein family/group databases

MoonDBiP42566 Curated
MoonProtiP42566

PTM databases

iPTMnetiP42566
PhosphoSitePlusiP42566

Polymorphism and mutation databases

BioMutaiEPS15
DMDMi67476728

2D gel databases

OGPiP42566

Proteomic databases

EPDiP42566
MaxQBiP42566
PaxDbiP42566
PeptideAtlasiP42566
PRIDEiP42566
ProteomicsDBi55515
55516 [P42566-2]

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000371733; ENSP00000360798; ENSG00000085832 [P42566-1]
GeneIDi2060
KEGGihsa:2060
UCSCiuc001csq.2 human [P42566-1]

Organism-specific databases

CTDi2060
DisGeNETi2060
EuPathDBiHostDB:ENSG00000085832.16
GeneCardsiEPS15
HGNCiHGNC:3419 EPS15
HPAiCAB010164
HPA008451
HPA061431
MIMi600051 gene
neXtProtiNX_P42566
OpenTargetsiENSG00000085832
PharmGKBiPA27838
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0998 Eukaryota
ENOG410XTDR LUCA
GeneTreeiENSGT00760000118985
HOGENOMiHOG000004804
HOVERGENiHBG005591
InParanoidiP42566
KOiK12472
OMAiIKGIDPP
OrthoDBiEOG091G01RG
PhylomeDBiP42566
TreeFamiTF324293

Enzyme and pathway databases

ReactomeiR-HSA-182971 EGFR downregulation
R-HSA-6807004 Negative regulation of MET activity
R-HSA-8856825 Cargo recognition for clathrin-mediated endocytosis
R-HSA-8856828 Clathrin-mediated endocytosis
R-HSA-8875360 InlB-mediated entry of Listeria monocytogenes into host cell
SignaLinkiP42566
SIGNORiP42566

Miscellaneous databases

ChiTaRSiEPS15 human
EvolutionaryTraceiP42566
GeneWikiiEPS15
GenomeRNAii2060
PROiPR:P42566
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000085832 Expressed in 241 organ(s), highest expression level in endothelial cell
CleanExiHS_EPS15
ExpressionAtlasiP42566 baseline and differential
GenevisibleiP42566 HS

Family and domain databases

CDDicd00052 EH, 3 hits
InterProiView protein in InterPro
IPR011992 EF-hand-dom_pair
IPR018247 EF_Hand_1_Ca_BS
IPR002048 EF_hand_dom
IPR000261 EH_dom
IPR003903 UIM_dom
PfamiView protein in Pfam
PF12763 EF-hand_4, 3 hits
SMARTiView protein in SMART
SM00054 EFh, 3 hits
SM00027 EH, 3 hits
SM00726 UIM, 3 hits
SUPFAMiSSF47473 SSF47473, 3 hits
PROSITEiView protein in PROSITE
PS00018 EF_HAND_1, 2 hits
PS50222 EF_HAND_2, 4 hits
PS50031 EH, 3 hits
PS50330 UIM, 2 hits
ProtoNetiSearch...

Entry informationi

Entry nameiEPS15_HUMAN
AccessioniPrimary (citable) accession number: P42566
Secondary accession number(s): B2R8J7, D3DPJ2, Q5SRH4
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: June 7, 2005
Last modified: October 10, 2018
This is version 201 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  4. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  5. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
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