UniProtKB - P42567 (EPS15_MOUSE)
Epidermal growth factor receptor substrate 15
Eps15
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.
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Metal bindingi | 173 | Calcium 1PROSITE-ProRule annotation | 1 | |
Metal bindingi | 175 | Calcium 1PROSITE-ProRule annotation | 1 | |
Metal bindingi | 177 | Calcium 1PROSITE-ProRule annotation | 1 | |
Metal bindingi | 179 | Calcium 1PROSITE-ProRule annotation | 1 | |
Metal bindingi | 184 | Calcium 1PROSITE-ProRule annotation | 1 | |
Metal bindingi | 236 | Calcium 2PROSITE-ProRule annotation | 1 | |
Metal bindingi | 238 | Calcium 2PROSITE-ProRule annotation | 1 | |
Metal bindingi | 240 | Calcium 2PROSITE-ProRule annotation | 1 | |
Metal bindingi | 242 | Calcium 2PROSITE-ProRule annotation | 1 | |
Metal bindingi | 247 | Calcium 2PROSITE-ProRule annotation | 1 |
GO - Molecular functioni
- calcium ion binding Source: InterPro
- identical protein binding Source: IntAct
- polyubiquitin modification-dependent protein binding Source: UniProtKB
- SH3 domain binding Source: UniProtKB-KW
GO - Biological processi
- clathrin coat assembly Source: MGI
- endocytosis Source: GO_Central
- endosomal transport Source: GO_Central
- Golgi to endosome transport Source: UniProtKB
- protein transport Source: UniProtKB-KW
- receptor-mediated endocytosis of virus by host cell Source: MGI
- regulation of protein localization Source: MGI
- viral entry into host cell Source: MGI
Keywordsi
Biological process | Endocytosis, Protein transport, Transport |
Ligand | Calcium, Metal-binding |
Enzyme and pathway databases
Reactomei | R-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 15Short name: Protein Eps15 Alternative name(s): Protein AF-1p |
Gene namesi | Name:Eps15 |
Organismi | Mus musculus (Mouse) |
Taxonomic identifieri | 10090 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus |
Proteomesi |
|
Organism-specific databases
MGIi | MGI:104583, Eps15 |
VEuPathDBi | HostDB:ENSMUSG00000028552 |
Subcellular locationi
Plasma membrane
Cytoplasm and Cytosol
Other locations
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
Endosome
- Early endosome membrane By similarity; Peripheral membrane protein By similarity; Cytoplasmic side By similarity
Note: Colocalizes with HGS on bilayered clathrin coats on endosomes.By similarity
Cytosol
- cytosol Source: MGI
Endosome
- early endosome membrane Source: UniProtKB-SubCell
Plasma Membrane
- AP-2 adaptor complex Source: UniProtKB
- ciliary membrane Source: MGI
- clathrin coat of coated pit Source: MGI
- clathrin-coated pit Source: MGI
- plasma membrane Source: UniProtKB
Other locations
- aggresome Source: MGI
- clathrin-coated vesicle Source: UniProtKB
- intracellular membrane-bounded organelle Source: MGI
Keywords - Cellular componenti
Cell membrane, Coated pit, Cytoplasm, Endosome, MembranePathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 850 | Y → F: Inefficient EGFR internalization. 1 Publication | 1 | |
Mutagenesisi | 863 | E → A: Loss of interaction with UBQLN1; when associated with A-864 and A-865. 1 Publication | 1 | |
Mutagenesisi | 864 | S → A: Loss of interaction with UBQLN1; when associated with A-863 and A-865. 1 Publication | 1 | |
Mutagenesisi | 865 | E → A: Loss of interaction with UBQLN1; when associated with A-863 and A-864. 1 Publication | 1 | |
Mutagenesisi | 883 | L → A: Loss of ubiquitination and interaction with UBQLN1; when associated with A-885. 1 Publication | 1 | |
Mutagenesisi | 885 | L → A: Loss of ubiquitination and interaction with UBQLN1; when associated with A-883. 1 Publication | 1 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Initiator methioninei | RemovedBy similarity | |||
ChainiPRO_0000146117 | 2 – 897 | Epidermal growth factor receptor substrate 15Add BLAST | 896 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 2 | N-acetylalanineBy similarity | 1 | |
Modified residuei | 108 | PhosphoserineBy similarity | 1 | |
Modified residuei | 140 | PhosphoserineCombined sources | 1 | |
Modified residuei | 321 | PhosphothreonineCombined sources | 1 | |
Modified residuei | 323 | PhosphoserineBy similarity | 1 | |
Modified residuei | 324 | PhosphoserineCombined sources | 1 | |
Modified residuei | 467 | PhosphoserineBy similarity | 1 | |
Modified residuei | 470 | PhosphoserineBy similarity | 1 | |
Modified residuei | 485 | PhosphoserineBy similarity | 1 | |
Modified residuei | 561 | PhosphoserineCombined sources | 1 | |
Modified residuei | 562 | PhosphoserineCombined sources | 1 | |
Modified residuei | 748 | PhosphoserineBy similarity | 1 | |
Modified residuei | 779 | PhosphothreonineCombined sources | 1 | |
Modified residuei | 781 | PhosphothreonineCombined sources | 1 | |
Modified residuei | 798 | PhosphoserineBy similarity | 1 | |
Modified residuei | 816 | PhosphoserineCombined sources | 1 | |
Modified residuei | 850 | Phosphotyrosine; by EGFR1 Publication | 1 |
Post-translational modificationi
Keywords - PTMi
Acetylation, Phosphoprotein, Ubl conjugationProteomic databases
EPDi | P42567 |
jPOSTi | P42567 |
PaxDbi | P42567 |
PeptideAtlasi | P42567 |
PRIDEi | P42567 |
ProteomicsDBi | 275463 [P42567-1] 275464 [P42567-2] |
PTM databases
iPTMneti | P42567 |
PhosphoSitePlusi | P42567 |
Expressioni
Gene expression databases
Bgeei | ENSMUSG00000028552, Expressed in dentate gyrus of hippocampal formation and 319 other tissues |
ExpressionAtlasi | P42567, baseline and differential |
Genevisiblei | P42567, 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.
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).
By similarity7 PublicationsBinary interactionsi
P42567
With | #Exp. | IntAct |
---|---|---|
Dab2 [P98078] | 2 | EBI-443923,EBI-1391846 |
itself | 4 | EBI-443923,EBI-443923 |
Eps15l1 [Q60902] | 2 | EBI-443923,EBI-443931 |
REPS2 [Q8NFH8] from Homo sapiens. | 10 | EBI-443923,EBI-7067016 |
GO - Molecular functioni
- identical protein binding Source: IntAct
- polyubiquitin modification-dependent protein binding Source: UniProtKB
- SH3 domain binding Source: UniProtKB-KW
Protein-protein interaction databases
BioGRIDi | 199489, 49 interactors |
CORUMi | P42567 |
DIPi | DIP-29052N |
ELMi | P42567 |
IntActi | P42567, 9 interactors |
MINTi | P42567 |
STRINGi | 10090.ENSMUSP00000099790 |
Miscellaneous databases
RNActi | P42567, protein |
Structurei
Secondary structure
3D structure databases
SMRi | P42567 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | P42567 |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 15 – 104 | EH 1PROSITE-ProRule annotationAdd BLAST | 90 | |
Domaini | 48 – 83 | EF-hand 1PROSITE-ProRule annotationAdd BLAST | 36 | |
Domaini | 128 – 216 | EH 2PROSITE-ProRule annotationAdd BLAST | 89 | |
Domaini | 160 – 195 | EF-hand 2PROSITE-ProRule annotationAdd BLAST | 36 | |
Domaini | 223 – 258 | EF-hand 3PROSITE-ProRule annotationAdd BLAST | 36 | |
Domaini | 224 – 314 | EH 3PROSITE-ProRule annotationAdd BLAST | 91 | |
Domaini | 262 – 292 | EF-hand 4PROSITE-ProRule annotationAdd BLAST | 31 | |
Repeati | 599 – 601 | 1 | 3 | |
Repeati | 623 – 625 | 2 | 3 | |
Repeati | 629 – 631 | 3 | 3 | |
Repeati | 634 – 636 | 4 | 3 | |
Repeati | 640 – 642 | 5 | 3 | |
Repeati | 645 – 647 | 6 | 3 | |
Repeati | 651 – 653 | 7 | 3 | |
Repeati | 665 – 667 | 8 | 3 | |
Repeati | 673 – 675 | 9 | 3 | |
Repeati | 693 – 695 | 10 | 3 | |
Repeati | 711 – 713 | 11 | 3 | |
Repeati | 806 – 808 | 12 | 3 | |
Repeati | 827 – 829 | 13 | 3 | |
Domaini | 852 – 871 | UIM 1PROSITE-ProRule annotationAdd BLAST | 20 | |
Domaini | 878 – 897 | UIM 2PROSITE-ProRule annotationAdd BLAST | 20 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 2 – 330 | Interaction with DAB21 PublicationAdd BLAST | 329 | |
Regioni | 528 – 607 | DisorderedSequence analysisAdd BLAST | 80 | |
Regioni | 599 – 829 | 13 X 3 AA repeats of D-P-FAdd BLAST | 231 | |
Regioni | 667 – 692 | DisorderedSequence analysisAdd BLAST | 26 | |
Regioni | 741 – 849 | DisorderedSequence analysisAdd BLAST | 109 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 528 – 568 | Polar residuesSequence analysisAdd BLAST | 41 | |
Compositional biasi | 585 – 603 | Basic and acidic residuesSequence analysisAdd BLAST | 19 | |
Compositional biasi | 667 – 690 | Polar residuesSequence analysisAdd BLAST | 24 | |
Compositional biasi | 741 – 757 | Polar residuesSequence analysisAdd BLAST | 17 | |
Compositional biasi | 773 – 792 | Pro residuesSequence analysisAdd BLAST | 20 | |
Compositional biasi | 827 – 849 | Polar residuesSequence analysisAdd BLAST | 23 |
Domaini
Keywords - Domaini
Repeat, SH3-bindingPhylogenomic databases
eggNOGi | KOG0998, Eukaryota |
GeneTreei | ENSGT00940000155751 |
InParanoidi | P42567 |
PhylomeDBi | P42567 |
TreeFami | TF324293 |
Family and domain databases
CDDi | cd00052, EH, 3 hits |
InterProi | View protein in InterPro IPR011992, EF-hand-dom_pair IPR018247, EF_Hand_1_Ca_BS IPR002048, EF_hand_dom IPR000261, EH_dom IPR003903, UIM_dom |
Pfami | View protein in Pfam PF12763, EF-hand_4, 3 hits |
SMARTi | View protein in SMART SM00054, EFh, 4 hits SM00027, EH, 3 hits SM00726, UIM, 2 hits |
SUPFAMi | SSF47473, SSF47473, 3 hits |
PROSITEi | View protein in PROSITE PS00018, EF_HAND_1, 2 hits PS50222, EF_HAND_2, 4 hits PS50031, EH, 3 hits PS50330, UIM, 2 hits |
s (2+)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry describes 2 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 2 described isoforms and 6 potential isoforms that are computationally mapped.Show allAlign All
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
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
Computationally mapped potential isoform sequencesi
There are 6 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketH3BK65 | H3BK65_MOUSE | Epidermal growth factor receptor su... | Eps15 | 933 | Annotation score: | ||
F6W2Q5 | F6W2Q5_MOUSE | Epidermal growth factor receptor su... | Eps15 | 764 | Annotation score: | ||
Q5JC28 | Q5JC28_MOUSE | Epidermal growth factor receptor pa... | Eps15 | 793 | Annotation score: | ||
A0A0R4J0A0 | A0A0R4J0A0_MOUSE | Epidermal growth factor receptor su... | Eps15 | 583 | Annotation score: | ||
H3BLE4 | H3BLE4_MOUSE | Epidermal growth factor receptor su... | Eps15 | 150 | Annotation score: | ||
H3BJB8 | H3BJB8_MOUSE | Epidermal growth factor receptor su... | Eps15 | 103 | Annotation score: |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_036170 | 1 – 314 | Missing in isoform 2. 1 PublicationAdd BLAST | 314 | |
Alternative sequenceiVSP_036171 | 315 – 346 | SLQKN…IVDLQ → MYSDSGLGGWIAIPAVADVL RYSCIVCWSS in isoform 2. 1 PublicationAdd BLAST | 32 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | L21768 mRNA Translation: AAA02912.1 AK083176 mRNA Translation: BAC38796.1 AL669905 Genomic DNA No translation available. |
CCDSi | CCDS18462.1 [P42567-1] |
PIRi | A54696 |
RefSeqi | NP_001153436.1, NM_001159964.1 NP_031969.1, NM_007943.3 [P42567-1] |
Genome annotation databases
Ensembli | ENSMUST00000102729; ENSMUSP00000099790; ENSMUSG00000028552 [P42567-1] |
GeneIDi | 13858 |
KEGGi | mmu:13858 |
UCSCi | uc008ucf.2, mouse [P42567-1] uc008ucg.2, mouse [P42567-2] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
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 No translation available. |
CCDSi | CCDS18462.1 [P42567-1] |
PIRi | A54696 |
RefSeqi | NP_001153436.1, NM_001159964.1 NP_031969.1, NM_007943.3 [P42567-1] |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
1KYF | X-ray | 1.22 | P | 627-632 | [»] | |
1KYU | X-ray | 1.80 | P | 627-632 | [»] | |
1QJT | NMR | - | A | 7-105 | [»] | |
SMRi | P42567 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 199489, 49 interactors |
CORUMi | P42567 |
DIPi | DIP-29052N |
ELMi | P42567 |
IntActi | P42567, 9 interactors |
MINTi | P42567 |
STRINGi | 10090.ENSMUSP00000099790 |
PTM databases
iPTMneti | P42567 |
PhosphoSitePlusi | P42567 |
Proteomic databases
EPDi | P42567 |
jPOSTi | P42567 |
PaxDbi | P42567 |
PeptideAtlasi | P42567 |
PRIDEi | P42567 |
ProteomicsDBi | 275463 [P42567-1] 275464 [P42567-2] |
Protocols and materials databases
Antibodypediai | 1916, 245 antibodies from 31 providers |
DNASUi | 13858 |
Genome annotation databases
Ensembli | ENSMUST00000102729; ENSMUSP00000099790; ENSMUSG00000028552 [P42567-1] |
GeneIDi | 13858 |
KEGGi | mmu:13858 |
UCSCi | uc008ucf.2, mouse [P42567-1] uc008ucg.2, mouse [P42567-2] |
Organism-specific databases
CTDi | 2060 |
MGIi | MGI:104583, Eps15 |
VEuPathDBi | HostDB:ENSMUSG00000028552 |
Phylogenomic databases
eggNOGi | KOG0998, Eukaryota |
GeneTreei | ENSGT00940000155751 |
InParanoidi | P42567 |
PhylomeDBi | P42567 |
TreeFami | TF324293 |
Enzyme and pathway databases
Reactomei | R-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
BioGRID-ORCSi | 13858, 0 hits in 63 CRISPR screens |
ChiTaRSi | Eps15, mouse |
EvolutionaryTracei | P42567 |
PROi | PR:P42567 |
RNActi | P42567, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSMUSG00000028552, Expressed in dentate gyrus of hippocampal formation and 319 other tissues |
ExpressionAtlasi | P42567, baseline and differential |
Genevisiblei | P42567, MM |
Family and domain databases
CDDi | cd00052, EH, 3 hits |
InterProi | View protein in InterPro IPR011992, EF-hand-dom_pair IPR018247, EF_Hand_1_Ca_BS IPR002048, EF_hand_dom IPR000261, EH_dom IPR003903, UIM_dom |
Pfami | View protein in Pfam PF12763, EF-hand_4, 3 hits |
SMARTi | View protein in SMART SM00054, EFh, 4 hits SM00027, EH, 3 hits SM00726, UIM, 2 hits |
SUPFAMi | SSF47473, SSF47473, 3 hits |
PROSITEi | View protein in PROSITE PS00018, EF_HAND_1, 2 hits PS50222, EF_HAND_2, 4 hits PS50031, EH, 3 hits PS50330, UIM, 2 hits |
MobiDBi | Search... |
Entry informationi
Entry namei | EPS15_MOUSE | |
Accessioni | P42567Primary (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: | February 23, 2022 | |
This is version 203 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
3D-structure, Direct protein sequencing, Reference proteomeDocuments
- MGD cross-references
Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references