Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Epidermal growth factor receptor substrate 15

Gene

Eps15

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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.

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Calcium bindingi173 – 1841PROSITE-ProRule annotationAdd BLAST12
Calcium bindingi236 – 2472PROSITE-ProRule annotationAdd BLAST12

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Biological processi

Endocytosis, Protein transport, Transport

Keywords - Ligandi

Calcium, Metal-binding

Enzyme and pathway databases

ReactomeiR-MMU-182971. EGFR downregulation.
R-MMU-6807004. Negative regulation of MET activity.
R-MMU-8856825. Cargo recognition for clathrin-mediated endocytosis.
R-MMU-8856828. Clathrin-mediated endocytosis.

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
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 4

Organism-specific databases

MGIiMGI:104583. Eps15.

Subcellular locationi

  • Cytoplasm
  • Cell membrane; Peripheral membrane protein; Cytoplasmic side
  • Membraneclathrin-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.By similarity
Isoform 2 :

GO - Cellular componenti

  • aggresome Source: MGI
  • AP-2 adaptor complex Source: UniProtKB
  • apical plasma membrane Source: Ensembl
  • basal plasma membrane Source: Ensembl
  • cell-cell adherens junction Source: MGI
  • ciliary membrane Source: MGI
  • clathrin-coated pit Source: MGI
  • clathrin-coated vesicle Source: UniProtKB
  • clathrin coat of coated pit Source: MGI
  • cytoplasm Source: MGI
  • cytosol Source: Ensembl
  • early endosome membrane Source: UniProtKB-SubCell
  • intracellular membrane-bounded organelle Source: MGI
  • membrane Source: MGI
  • plasma membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Coated pit, Cytoplasm, Endosome, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi850Y → F: Inefficient EGFR internalization. 1 Publication1
Mutagenesisi863E → A: Loss of interaction with UBQLN1; when associated with A-864 and A-865. 1 Publication1
Mutagenesisi864S → A: Loss of interaction with UBQLN1; when associated with A-863 and A-865. 1 Publication1
Mutagenesisi865E → A: Loss of interaction with UBQLN1; when associated with A-863 and A-864. 1 Publication1
Mutagenesisi883L → A: Loss of ubiquitination and interaction with UBQLN1; when associated with A-885. 1 Publication1
Mutagenesisi885L → A: Loss of ubiquitination and interaction with UBQLN1; when associated with A-883. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedBy similarity
ChainiPRO_00001461172 – 897Epidermal growth factor receptor substrate 15Add BLAST896

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanineBy similarity1
Modified residuei108PhosphoserineBy similarity1
Modified residuei140PhosphoserineCombined sources1
Modified residuei321PhosphothreonineCombined sources1
Modified residuei323PhosphoserineBy similarity1
Modified residuei324PhosphoserineCombined sources1
Modified residuei467PhosphoserineBy similarity1
Modified residuei470PhosphoserineBy similarity1
Modified residuei485PhosphoserineBy similarity1
Modified residuei561PhosphoserineCombined sources1
Modified residuei562PhosphoserineCombined sources1
Modified residuei748PhosphoserineBy similarity1
Modified residuei779PhosphothreonineCombined sources1
Modified residuei781PhosphothreonineCombined sources1
Modified residuei798PhosphoserineBy similarity1
Modified residuei816PhosphoserineCombined sources1
Modified residuei850Phosphotyrosine; by EGFR1 Publication1

Post-translational modificationi

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.By similarity1 Publication
Ubiquitinated.1 Publication

Keywords - PTMi

Acetylation, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiP42567.
PaxDbiP42567.
PeptideAtlasiP42567.
PRIDEiP42567.

PTM databases

iPTMnetiP42567.
PhosphoSitePlusiP42567.

Expressioni

Gene expression databases

BgeeiENSMUSG00000028552.
ExpressionAtlasiP42567. baseline and differential.
GenevisibleiP42567. MM.

Interactioni

Subunit structurei

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 (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).By similarity6 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
itself4EBI-443923,EBI-443923
Dab2P980782EBI-443923,EBI-1391846
Eps15l1Q609022EBI-443923,EBI-443931
REPS2Q8NFH810EBI-443923,EBI-7067016From a different organism.

GO - Molecular functioni

Protein-protein interaction databases

BioGridi199489. 17 interactors.
DIPiDIP-29052N.
IntActiP42567. 8 interactors.
MINTiMINT-86610.
STRINGi10090.ENSMUSP00000099790.

Structurei

Secondary structure

1897
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi9 – 12Combined sources4
Turni13 – 15Combined sources3
Helixi18 – 26Combined sources9
Helixi37 – 44Combined sources8
Beta strandi46 – 48Combined sources3
Helixi50 – 60Combined sources11
Beta strandi63 – 67Combined sources5
Helixi71 – 83Combined sources13
Turni84 – 86Combined sources3
Helixi91 – 93Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1KYFX-ray1.22P627-632[»]
1KYUX-ray1.80P627-632[»]
1QJTNMR-A7-105[»]
ProteinModelPortaliP42567.
SMRiP42567.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP42567.

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
Repeati665 – 66783
Repeati673 – 67593
Repeati693 – 695103
Repeati711 – 713113
Repeati806 – 808123
Repeati827 – 829133
Domaini852 – 871UIM 1PROSITE-ProRule annotationAdd BLAST20
Domaini878 – 897UIM 2PROSITE-ProRule annotationAdd BLAST20

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni2 – 330Interaction with DAB21 PublicationAdd BLAST329
Regioni599 – 82913 X 3 AA repeats of D-P-FAdd BLAST231

Domaini

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

Sequence similaritiesi

Contains 2 EF-hand domains.PROSITE-ProRule annotation
Contains 3 EH domains.PROSITE-ProRule annotation
Contains 2 UIM (ubiquitin-interacting motif) domains.PROSITE-ProRule annotation

Keywords - Domaini

Repeat, SH3-binding

Phylogenomic databases

eggNOGiKOG0998. Eukaryota.
ENOG410XTDR. LUCA.
GeneTreeiENSGT00760000118985.
HOGENOMiHOG000004804.
HOVERGENiHBG005591.
InParanoidiP42567.
KOiK12472.
PhylomeDBiP42567.
TreeFamiTF324293.

Family and domain databases

Gene3Di1.10.238.10. 3 hits.
InterProiIPR011992. EF-hand-dom_pair.
IPR018247. EF_Hand_1_Ca_BS.
IPR002048. EF_hand_dom.
IPR000261. EH_dom.
IPR003903. UIM_dom.
[Graphical view]
PfamiPF12763. EF-hand_4. 3 hits.
[Graphical view]
SMARTiSM00054. EFh. 4 hits.
SM00027. EH. 3 hits.
SM00726. UIM. 2 hits.
[Graphical view]
SUPFAMiSSF47473. SSF47473. 3 hits.
PROSITEiPS00018. EF_HAND_1. 2 hits.
PS50222. EF_HAND_2. 4 hits.
PS50031. EH. 3 hits.
PS50330. UIM. 2 hits.
[Graphical view]

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

Isoform 1 (identifier: P42567-1) [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 KYYRQVEAGN TGRVLALDAA AFLKKSGLPD
60 70 80 90 100
LILGKIWDLA DTDGKGVLSK QEFFVALRLV ACAQNGLEVS LSSLSLAVPP
110 120 130 140 150
PRFHDSSSPL LTSGPSVAEL PWAVKSEDKA KYDAIFDSLS PVDGFLSGDK
160 170 180 190 200
VKPVLLNSKL PVEILGRVWE LSDIDHDGKL DRDEFAVAMF LVYCALEKEP
210 220 230 240 250
VPMSLPPALV PPSKRKTWVV SPAEKAKYDE IFLKTDKDMD GYVSGLEVRE
260 270 280 290 300
TFLKTGLPSA LLAHIWSLCD TKGCGKLSKD QFALAFHLIN QKLIKGIDPP
310 320 330 340 350
HSLTPEMIPP SDRSSLQKNI TGSSPVADFS AIKELDTLNN EIVDLQREKN
360 370 380 390 400
NVEQDLKEKE DTVKQRTSEV QDLQDEVQRE SINLQKLQAQ KQQVQELLGE
410 420 430 440 450
LDEQKAQLEE QLQEVRKKCA EEAQLISSLK AEITSQESQI SSYEEELLKA
460 470 480 490 500
REELSRLQQE TAQLEESVES GKAQLEPLQQ HLQESQQEIS SMQMRLEMKD
510 520 530 540 550
LETDNNQSNW SSSPQSVLVN GATDYCSLST SSSETANFNE HAEGQNNLES
560 570 580 590 600
EPTHQESSVR SSPEIAPSDV TDESEAVTVA GNEKVTPRFD DDKHSKEEDP
610 620 630 640 650
FNVESSSLTD AVADTNLDFF QSDPFVGSDP FKDDPFGKID PFGGDPFKGS
660 670 680 690 700
DPFASDCFFK QTSTDPFTTS STDPFSASSN SSNTSVETWK HNDPFAPGGT
710 720 730 740 750
VVAAASDSAT DPFASVFGNE SFGDGFADFS TLSKVNNEDA FNPTISSSTS
760 770 780 790 800
SVTIAKPMLE ETASKSEDVP PALPPKVGTP TRPCPPPPGK RPINKLDSSD
810 820 830 840 850
PLKLNDPFQP FPGNDSPKEK DPDMFCDPFT SSTTTNKEAD PSNFANFSAY
860 870 880 890
PSEEDMIEWA KRESEREEEQ RLARLNQQEQ EDLELAIALS KSEISEA
Length:897
Mass (Da):98,471
Last modified:November 1, 1995 - v1
Checksum:i08A0C0D423F873C2
GO
Isoform 2 (identifier: P42567-2) [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: SLQKNITGSSPVADFSAIKELDTLNNEIVDLQ → MYSDSGLGGWIAIPAVADVLRYSCIVCWSS

Show »
Length:581
Mass (Da):64,071
Checksum:i9209CDDDB4446D1C
GO

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0361701 – 314Missing in isoform 2. 1 PublicationAdd BLAST314
Alternative sequenceiVSP_036171315 – 346SLQKN…IVDLQ → MYSDSGLGGWIAIPAVADVL RYSCIVCWSS in isoform 2. 1 PublicationAdd BLAST32

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L21768 mRNA. Translation: AAA02912.1.
AK083176 mRNA. Translation: BAC38796.1.
AL669905 Genomic DNA. Translation: CAM13653.1.
CCDSiCCDS18462.1. [P42567-1]
PIRiA54696.
RefSeqiNP_001153436.1. NM_001159964.1.
NP_031969.1. NM_007943.3. [P42567-1]
UniGeneiMm.318250.

Genome annotation databases

EnsembliENSMUST00000102729; ENSMUSP00000099790; ENSMUSG00000028552. [P42567-1]
GeneIDi13858.
KEGGimmu:13858.
UCSCiuc008ucf.2. mouse. [P42567-1]
uc008ucg.2. mouse. [P42567-2]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L21768 mRNA. Translation: AAA02912.1.
AK083176 mRNA. Translation: BAC38796.1.
AL669905 Genomic DNA. Translation: CAM13653.1.
CCDSiCCDS18462.1. [P42567-1]
PIRiA54696.
RefSeqiNP_001153436.1. NM_001159964.1.
NP_031969.1. NM_007943.3. [P42567-1]
UniGeneiMm.318250.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1KYFX-ray1.22P627-632[»]
1KYUX-ray1.80P627-632[»]
1QJTNMR-A7-105[»]
ProteinModelPortaliP42567.
SMRiP42567.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi199489. 17 interactors.
DIPiDIP-29052N.
IntActiP42567. 8 interactors.
MINTiMINT-86610.
STRINGi10090.ENSMUSP00000099790.

PTM databases

iPTMnetiP42567.
PhosphoSitePlusiP42567.

Proteomic databases

EPDiP42567.
PaxDbiP42567.
PeptideAtlasiP42567.
PRIDEiP42567.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000102729; ENSMUSP00000099790; ENSMUSG00000028552. [P42567-1]
GeneIDi13858.
KEGGimmu:13858.
UCSCiuc008ucf.2. mouse. [P42567-1]
uc008ucg.2. mouse. [P42567-2]

Organism-specific databases

CTDi2060.
MGIiMGI:104583. Eps15.

Phylogenomic databases

eggNOGiKOG0998. Eukaryota.
ENOG410XTDR. LUCA.
GeneTreeiENSGT00760000118985.
HOGENOMiHOG000004804.
HOVERGENiHBG005591.
InParanoidiP42567.
KOiK12472.
PhylomeDBiP42567.
TreeFamiTF324293.

Enzyme and pathway databases

ReactomeiR-MMU-182971. EGFR downregulation.
R-MMU-6807004. Negative regulation of MET activity.
R-MMU-8856825. Cargo recognition for clathrin-mediated endocytosis.
R-MMU-8856828. Clathrin-mediated endocytosis.

Miscellaneous databases

EvolutionaryTraceiP42567.
PROiP42567.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000028552.
ExpressionAtlasiP42567. baseline and differential.
GenevisibleiP42567. MM.

Family and domain databases

Gene3Di1.10.238.10. 3 hits.
InterProiIPR011992. EF-hand-dom_pair.
IPR018247. EF_Hand_1_Ca_BS.
IPR002048. EF_hand_dom.
IPR000261. EH_dom.
IPR003903. UIM_dom.
[Graphical view]
PfamiPF12763. EF-hand_4. 3 hits.
[Graphical view]
SMARTiSM00054. EFh. 4 hits.
SM00027. EH. 3 hits.
SM00726. UIM. 2 hits.
[Graphical view]
SUPFAMiSSF47473. SSF47473. 3 hits.
PROSITEiPS00018. EF_HAND_1. 2 hits.
PS50222. EF_HAND_2. 4 hits.
PS50031. EH. 3 hits.
PS50330. UIM. 2 hits.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiEPS15_MOUSE
AccessioniPrimary (citable) accession number: P42567
Secondary accession number(s): Q8C431
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: November 1, 1995
Last modified: November 30, 2016
This is version 168 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.