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P42567 (EPS15_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 143. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Epidermal growth factor receptor substrate 15

Short name=Protein Eps15
Alternative name(s):
Protein AF-1p
Gene names
Name:Eps15
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length897 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

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 structure

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 STAM1 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. Ref.6 Ref.10 Ref.11 Ref.12

Subcellular location

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.

Isoform 2: Early endosome membrane; Peripheral membrane protein; Cytoplasmic side By similarity. Note: Colocalizes with HGS on bilayered clathrin coats on endosomes By similarity.

Domain

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.

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. Ref.5

Sequence similarities

Contains 2 EF-hand domains.

Contains 3 EH domains.

Contains 2 UIM (ubiquitin-interacting motif) repeats.

Binary interactions

With

Entry

#Exp.

IntAct

Notes

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

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: 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.
Isoform 2 (identifier: P42567-2)

Also known as: Eps15b;

The sequence of this isoform differs from the canonical sequence as follows:
     2-314: Missing.
     315-346: SLQKNITGSSPVADFSAIKELDTLNNEIVDLQ → MYSDSGLGGWIAIPAVADVLRYSCIVCWSS

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed By similarity
Chain2 – 897896Epidermal growth factor receptor substrate 15
PRO_0000146117

Regions

Domain15 – 10490EH 1
Domain128 – 21689EH 2
Domain160 – 19536EF-hand 1
Domain223 – 25836EF-hand 2
Domain224 – 31491EH 3
Repeat599 – 60131
Repeat623 – 62532
Repeat629 – 63133
Repeat634 – 63634
Repeat640 – 64235
Repeat645 – 64736
Repeat651 – 65337
Repeat665 – 66738
Repeat673 – 67539
Repeat693 – 695310
Repeat711 – 713311
Repeat806 – 808312
Repeat827 – 829313
Repeat852 – 87120UIM 1
Repeat878 – 89720UIM 2
Calcium binding173 – 184121 Potential
Calcium binding236 – 247122 Potential
Region2 – 330329Interaction with DAB2
Region599 – 82923113 X 3 AA repeats of D-P-F

Amino acid modifications

Modified residue21N-acetylalanine By similarity
Modified residue1081Phosphoserine By similarity
Modified residue1401Phosphoserine By similarity
Modified residue3231Phosphoserine By similarity
Modified residue3241Phosphoserine Ref.8
Modified residue4671Phosphoserine By similarity
Modified residue4701Phosphoserine By similarity
Modified residue4851Phosphoserine By similarity
Modified residue7791Phosphothreonine Ref.7
Modified residue7981Phosphoserine By similarity
Modified residue8161Phosphoserine By similarity
Modified residue8501Phosphotyrosine; by EGFR Ref.5

Natural variations

Alternative sequence2 – 314313Missing in isoform 2.
VSP_036170
Alternative sequence315 – 34632SLQKN…IVDLQ → MYSDSGLGGWIAIPAVADVL RYSCIVCWSS in isoform 2.
VSP_036171

Experimental info

Mutagenesis8501Y → F: Inefficient EGFR internalization. Ref.5

Secondary structure

................... 897
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified November 1, 1995. Version 1.
Checksum: 08A0C0D423F873C2

FASTA89798,471
        10         20         30         40         50         60 
MAAAAQLSLT QLSSGNPVYE KYYRQVEAGN TGRVLALDAA AFLKKSGLPD LILGKIWDLA 

        70         80         90        100        110        120 
DTDGKGVLSK QEFFVALRLV ACAQNGLEVS LSSLSLAVPP PRFHDSSSPL LTSGPSVAEL 

       130        140        150        160        170        180 
PWAVKSEDKA KYDAIFDSLS PVDGFLSGDK VKPVLLNSKL PVEILGRVWE LSDIDHDGKL 

       190        200        210        220        230        240 
DRDEFAVAMF LVYCALEKEP VPMSLPPALV PPSKRKTWVV SPAEKAKYDE IFLKTDKDMD 

       250        260        270        280        290        300 
GYVSGLEVRE TFLKTGLPSA LLAHIWSLCD TKGCGKLSKD QFALAFHLIN QKLIKGIDPP 

       310        320        330        340        350        360 
HSLTPEMIPP SDRSSLQKNI TGSSPVADFS AIKELDTLNN EIVDLQREKN NVEQDLKEKE 

       370        380        390        400        410        420 
DTVKQRTSEV QDLQDEVQRE SINLQKLQAQ KQQVQELLGE LDEQKAQLEE QLQEVRKKCA 

       430        440        450        460        470        480 
EEAQLISSLK AEITSQESQI SSYEEELLKA REELSRLQQE TAQLEESVES GKAQLEPLQQ 

       490        500        510        520        530        540 
HLQESQQEIS SMQMRLEMKD LETDNNQSNW SSSPQSVLVN GATDYCSLST SSSETANFNE 

       550        560        570        580        590        600 
HAEGQNNLES EPTHQESSVR SSPEIAPSDV TDESEAVTVA GNEKVTPRFD DDKHSKEEDP 

       610        620        630        640        650        660 
FNVESSSLTD AVADTNLDFF QSDPFVGSDP FKDDPFGKID PFGGDPFKGS DPFASDCFFK 

       670        680        690        700        710        720 
QTSTDPFTTS STDPFSASSN SSNTSVETWK HNDPFAPGGT VVAAASDSAT DPFASVFGNE 

       730        740        750        760        770        780 
SFGDGFADFS TLSKVNNEDA FNPTISSSTS SVTIAKPMLE ETASKSEDVP PALPPKVGTP 

       790        800        810        820        830        840 
TRPCPPPPGK RPINKLDSSD PLKLNDPFQP FPGNDSPKEK DPDMFCDPFT SSTTTNKEAD 

       850        860        870        880        890 
PSNFANFSAY PSEEDMIEWA KRESEREEEQ RLARLNQQEQ EDLELAIALS KSEISEA 

« Hide

Isoform 2 (Eps15b) [UniParc].

Checksum: D5951681ED54F90C
Show »

FASTA58264,203

References

« Hide 'large scale' references
[1]"eps15, a novel tyrosine kinase substrate, exhibits transforming activity."
Fazioli F., Minichiello L., Matoskova B., Wong W.T., di Fiore P.P.
Mol. Cell. Biol. 13:5814-5828(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Fibroblast.
[2]"The transcriptional landscape of the mammalian genome."
Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. expand/collapse author list , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
Strain: C57BL/6J.
Tissue: Hippocampus.
[3]"Lineage-specific biology revealed by a finished genome assembly of the mouse."
Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. expand/collapse author list , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P.
PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: C57BL/6J.
[4]Lubec G., Sunyer B., Chen W.-Q.
Submitted (JAN-2009) to UniProtKB
Cited for: PROTEIN SEQUENCE OF 838-862, IDENTIFICATION BY MASS SPECTROMETRY.
Strain: OF1.
Tissue: Hippocampus.
[5]"Tyrosine phosphorylation of Eps15 is required for ligand-regulated, but not constitutive, endocytosis."
Confalonieri S., Salcini A.E., Puri C., Tacchetti C., Di Fiore P.P.
J. Cell Biol. 150:905-912(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT TYR-850 BY EGFR, MUTAGENESIS OF TYR-850.
[6]"SGIP1alpha is an endocytic protein that directly interacts with phospholipids and Eps15."
Uezu A., Horiuchi A., Kanda K., Kikuchi N., Umeda K., Tsujita K., Suetsugu S., Araki N., Yamamoto H., Takenawa T., Nakanishi H.
J. Biol. Chem. 282:26481-26489(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH SGIP1.
[7]"Large-scale phosphorylation analysis of mouse liver."
Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-779, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Liver.
[8]"The phagosomal proteome in interferon-gamma-activated macrophages."
Trost M., English L., Lemieux S., Courcelles M., Desjardins M., Thibault P.
Immunity 30:143-154(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-324, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[9]"Large scale localization of protein phosphorylation by use of electron capture dissociation mass spectrometry."
Sweet S.M., Bailey C.M., Cunningham D.L., Heath J.K., Cooper H.J.
Mol. Cell. Proteomics 8:904-912(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Embryonic fibroblast.
[10]"FCHo proteins are nucleators of clathrin-mediated endocytosis."
Henne W.M., Boucrot E., Meinecke M., Evergren E., Vallis Y., Mittal R., McMahon H.T.
Science 328:1281-1284(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH FCHO2.
[11]"Characterization of the EFC/F-BAR domain protein, FCHO2."
Uezu A., Umeda K., Tsujita K., Suetsugu S., Takenawa T., Nakanishi H.
Genes Cells 16:868-878(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH FCHO2.
[12]"The clathrin adaptor Dab2 recruits EH domain scaffold proteins to regulate integrin beta1 endocytosis."
Teckchandani A., Mulkearns E.E., Randolph T.W., Toida N., Cooper J.A.
Mol. Biol. Cell 23:2905-2916(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH DAB2.
[13]"The EH1 domain of Eps15 is structurally classified as a member of the S100 subclass of EF-hand-containing proteins."
Whitehead B., Tessari M., Carotenuto A., van Bergen en Henegouwen P.M., Vuister G.W.
Biochemistry 38:11271-11277(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF 7-105.
[14]"Accessory protein recruitment motifs in clathrin-mediated endocytosis."
Brett T.J., Traub L.M., Fremont D.H.
Structure 10:797-809(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.22 ANGSTROMS) OF 628-632 IN COMPLEX WITH AP2A2.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
L21768 mRNA. Translation: AAA02912.1.
AK083176 mRNA. Translation: BAC38796.1.
AL669905 Genomic DNA. Translation: CAM13653.1.
CCDSCCDS18462.1. [P42567-1]
PIRA54696.
RefSeqNP_001153436.1. NM_001159964.1.
NP_031969.1. NM_007943.3. [P42567-1]
UniGeneMm.318250.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1KYFX-ray1.22P627-632[»]
1KYUX-ray1.80P627-632[»]
1QJTNMR-A7-105[»]
ProteinModelPortalP42567.
SMRP42567. Positions 7-105, 121-215, 217-311, 336-391, 440-478.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid199489. 16 interactions.
DIPDIP-29052N.
IntActP42567. 7 interactions.
MINTMINT-86610.

PTM databases

PhosphoSiteP42567.

Proteomic databases

MaxQBP42567.
PaxDbP42567.
PRIDEP42567.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000030281; ENSMUSP00000030281; ENSMUSG00000028552.
ENSMUST00000102729; ENSMUSP00000099790; ENSMUSG00000028552. [P42567-1]
GeneID13858.
KEGGmmu:13858.
UCSCuc008ucf.2. mouse. [P42567-1]
uc008ucg.2. mouse. [P42567-2]

Organism-specific databases

CTD2060.
MGIMGI:104583. Eps15.

Phylogenomic databases

eggNOGNOG301764.
GeneTreeENSGT00750000117388.
HOGENOMHOG000004804.
HOVERGENHBG005591.
InParanoidP42567.
KOK12472.
OrthoDBEOG7JHM68.
PhylomeDBP42567.
TreeFamTF324293.

Gene expression databases

ArrayExpressP42567.
BgeeP42567.
GenevestigatorP42567.

Family and domain databases

Gene3D1.10.238.10. 3 hits.
InterProIPR011992. EF-hand-dom_pair.
IPR018247. EF_Hand_1_Ca_BS.
IPR002048. EF_hand_dom.
IPR000261. EPS15_homology.
IPR003903. Ubiquitin-int_motif.
[Graphical view]
SMARTSM00054. EFh. 4 hits.
SM00027. EH. 3 hits.
SM00726. UIM. 2 hits.
[Graphical view]
PROSITEPS00018. EF_HAND_1. 2 hits.
PS50222. EF_HAND_2. 4 hits.
PS50031. EH. 3 hits.
PS50330. UIM. 2 hits.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP42567.
NextBio284734.
PROP42567.
SOURCESearch...

Entry information

Entry nameEPS15_MOUSE
AccessionPrimary (citable) accession number: P42567
Secondary accession number(s): Q8C431
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: November 1, 1995
Last modified: July 9, 2014
This is version 143 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot