P42566 (EPS15_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Epidermal growth factor receptor substrate 15
Short name=Protein Eps15

Alternative name(s):
Protein AF-1p

Gene names

Name:	EPS15
Synonyms:	AF1P

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	896 AA.
Sequence status	Complete.
Protein existence	Evidence 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). 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. Ref.15 Ref.19 Ref.26 Ref.31
Subunit structure	Interacts with SGIP1 By similarity. 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 with FCHO1. Interacts with FCHO2. Interacts (via EH domains) with DAB2. Ref.8 Ref.9 Ref.10 Ref.11 Ref.12 Ref.15 Ref.22 Ref.24 Ref.26 Ref.27
Subcellular location	Cytoplasm. Cell membrane; Peripheral membrane protein; Cytoplasmic side. Membrane › clathrin-coated pit. Note: Recruited to the plasma membrane upon EGFR activation and localizes to coated pits. Ref.15 Ref.31 Ref.32 Isoform 2: Early endosome membrane; Peripheral membrane protein; Cytoplasmic side. Note: Colocalizes with HGS on bilayered clathrin coats on endosomes. Ref.15 Ref.31 Ref.32
Tissue specificity	Ubiquitously expressed.
Domain	The EH domain interacts with Asn-Pro-Phe (NPF) motifs of target proteins. Ref.30
Post-translational modification	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.
Involvement in disease	A chromosomal aberration involving EPS15 is found in acute leukemias. Translocation t(1;11)(p32;q23) with MLL/HRX. The result is a rogue activator protein.
Sequence similarities	Contains 2 EF-hand domains. Contains 3 EH domains. Contains 2 UIM (ubiquitin-interacting motif) repeats.
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 (Ref.26).

Ontologies

Keywords
Biological process	Endocytosis Protein transport Transport
Cellular component	Cell membrane Coated pit Cytoplasm Endosome Membrane
Coding sequence diversity	Alternative splicing Chromosomal rearrangement Polymorphism
Disease	Proto-oncogene
Domain	Repeat SH3-binding
Ligand	Calcium Metal-binding
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cell proliferation Traceable author statement Ref.1. Source: ProtInc clathrin coat assembly Inferred from direct assay PubMed 12807910. Source: BHF-UCL endocytic recycling Inferred by curator PubMed 12807910. Source: BHF-UCL endocytosis Inferred from electronic annotation. Source: UniProtKB-KW epidermal growth factor receptor signaling pathway Traceable author statement. Source: Reactome negative regulation of epidermal growth factor receptor signaling pathway Traceable author statement. Source: Reactome protein transport Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	AP-2 adaptor complex Inferred from electronic annotation. Source: Compara cilium membrane Inferred from electronic annotation. Source: Compara coated pit Traceable author statement PubMed 9762922. Source: UniProtKB cytosol Traceable author statement. Source: Reactome early endosome membrane Inferred from electronic annotation. Source: UniProtKB-SubCell intracellular membrane-bounded organelle Inferred from direct assay. Source: HPA plasma membrane Inferred from direct assay PubMed 15465819. Source: HGNC
Molecular_function	calcium ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
FCHO2	Q0JRZ9	3	EBI-396684,EBI-2609756
Fcho2	Q3UQN2	3	EBI-396684,EBI-6094986	From a different organism.
NCK1	P16333	2	EBI-396684,EBI-389883

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P42566-1)

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: P42566-2)

Also known as: Eps15b;

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

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 896

896

Epidermal growth factor receptor substrate 15

PRO_0000146116

Regions

Domain

15 – 104

90

EH 1

Domain

128 – 216

89

EH 2

Domain

160 – 195

36

EF-hand 1

Domain

223 – 258

36

EF-hand 2

Domain

224 – 314

91

EH 3

Repeat

599 – 601

3

1

Repeat

623 – 625

3

2

Repeat

629 – 631

3

3

Repeat

634 – 636

3

4

Repeat

640 – 642

3

5

Repeat

645 – 647

3

6

Repeat

651 – 653

3

7

Repeat

664 – 666

3

8

Repeat

672 – 674

3

9

Repeat

692 – 694

3

10

Repeat

709 – 711

3

11

Repeat

737 – 739

3

12

Repeat

798 – 800

3

13

Repeat

804 – 806

3

14

Repeat

825 – 827

3

15

Repeat

851 – 870

20

UIM 1

Repeat

877 – 896

20

UIM 2

Calcium binding

173 – 184

12

1

Calcium binding

236 – 247

12

2

Region

2 – 330

329

Interaction with DAB2 By similarity

Region

599 – 827

229

15 X 3 AA repeats of D-P-F

Motif

768 – 774

7

SH3-binding

Compositional bias

768 – 850

83

Pro-rich

Amino acid modifications

Modified residue

108

1

Phosphoserine Ref.20

Modified residue

140

1

Phosphoserine Ref.18

Modified residue

323

1

Phosphoserine Ref.13 Ref.18 Ref.20

Modified residue

324

1

Phosphoserine Ref.20 Ref.21 Ref.25

Modified residue

467

1

Phosphoserine Ref.21

Modified residue

470

1

Phosphoserine Ref.21

Modified residue

485

1

Phosphoserine Ref.14 Ref.18 Ref.25

Modified residue

562

1

Phosphoserine By similarity

Modified residue

563

1

Phosphoserine By similarity

Modified residue

777

1

Phosphothreonine By similarity

Modified residue

779

1

Phosphothreonine By similarity

Modified residue

790

1

Phosphoserine Ref.21 Ref.25

Modified residue

796

1

Phosphoserine Ref.16 Ref.21 Ref.25

Modified residue

814

1

Phosphoserine Ref.16 Ref.18 Ref.20 Ref.21 Ref.25

Modified residue

849

1

Phosphotyrosine; by EGFR Ref.20

Natural variations

Alternative sequence

1 – 314

314

Missing in isoform 2.

VSP_036168

Alternative sequence

315 – 346

32

SLQKN…IVDLQ → MYLKSDSGLGGWITIPAVAD VLKYSCIVCWSS in isoform 2.

VSP_036169

Natural variant

822

1

I → M. Ref.1
Corresponds to variant rs17567 [ dbSNP | Ensembl ].

VAR_016142

Experimental info

Mutagenesis

154

1

V → E: Loss of interaction with STON2 NPF motifs. Ref.32

Mutagenesis

169

1

W → A: Loss of interaction with STON2 NPF motifs. Ref.32

Sequence conflict

446

1

Missing in BX647676. Ref.5

Secondary structure

1

.

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896

Helix Strand Turn

Details...

Helix

126 – 136

11

Beta strand

142 – 144

3

Beta strand

145 – 147

3

Helix

148 – 156

9

Turn

157 – 159

3

Helix

162 – 172

11

Beta strand

177 – 179

3

Helix

182 – 197

16

Turn

207 – 209

3

Helix

212 – 214

3

Helix

223 – 235

13

Beta strand

240 – 243

4

Helix

245 – 253

9

Turn

254 – 256

3

Helix

259 – 269

11

Beta strand

274 – 278

5

Turn

279 – 281

3

Helix

282 – 293

12

Turn

305 – 307

3

Helix

723 – 726

4

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified June 7, 2005. Version 2. Checksum: A1B9FE15B47ABAFF	FASTA	896	98,656
	10 20 30 40 50 60 MAAAAQLSLT QLSSGNPVYE KYYRQVDTGN TGRVLASDAA AFLKKSGLPD LILGKIWDLA 70 80 90 100 110 120 DTDGKGILNK QEFFVALRLV ACAQNGLEVS LSSLNLAVPP PRFHDTSSPL LISGTSAAEL 130 140 150 160 170 180 PWAVKPEDKA KYDAIFDSLS PVNGFLSGDK VKPVLLNSKL PVDILGRVWE LSDIDHDGML 190 200 210 220 230 240 DRDEFAVAMF LVYCALEKEP VPMSLPPALV PPSKRKTWVV SPAEKAKYDE IFLKTDKDMD 250 260 270 280 290 300 GFVSGLEVRE IFLKTGLPST LLAHIWSLCD TKDCGKLSKD QFALAFHLIS QKLIKGIDPP 310 320 330 340 350 360 HVLTPEMIPP SDRASLQKNI IGSSPVADFS AIKELDTLNN EIVDLQREKN NVEQDLKEKE 370 380 390 400 410 420 DTIKQRTSEV QDLQDEVQRE NTNLQKLQAQ KQQVQELLDE LDEQKAQLEE QLKEVRKKCA 430 440 450 460 470 480 EEAQLISSLK AELTSQESQI STYEEELAKA REELSRLQQE TAELEESVES GKAQLEPLQQ 490 500 510 520 530 540 HLQDSQQEIS SMQMKLMEMK DLENHNSQLN WCSSPHSILV NGATDYCSLS TSSSETANLN 550 560 570 580 590 600 EHVEGQSNLE SEPIHQESPA RSSPELLPSG VTDENEVTTA VTEKVCSELD NNRHSKEEDP 610 620 630 640 650 660 FNVDSSSLTG PVADTNLDFF QSDPFVGSDP FKDDPFGKID PFGGDPFKGS DPFASDCFFR 670 680 690 700 710 720 QSTDPFATSS TDPFSAANNS SITSVETLKH NDPFAPGGTV VAASDSATDP FASVFGNESF 730 740 750 760 770 780 GGGFADFSTL SKVNNEDPFR SATSSSVSNV VITKNVFEET SVKSEDEPPA LPPKIGTPTR 790 800 810 820 830 840 PCPLPPGKRS INKLDSPDPF KLNDPFQPFP GNDSPKEKDP EIFCDPFTSA TTTTNKEADP 850 860 870 880 890 SNFANFSAYP SEEDMIEWAK RESEREEEQR LARLNQQEQE DLELAIALSK SEISEA
	Isoform 2 (Eps15b) [UniParc]. Checksum: 2A7BACA24604E8CA	FASTA	582	64,376
	10 20 30 40 50 60 MYLKSDSGLG GWITIPAVAD VLKYSCIVCW SSREKNNVEQ DLKEKEDTIK QRTSEVQDLQ 70 80 90 100 110 120 DEVQRENTNL QKLQAQKQQV QELLDELDEQ KAQLEEQLKE VRKKCAEEAQ LISSLKAELT 130 140 150 160 170 180 SQESQISTYE EELAKAREEL SRLQQETAEL EESVESGKAQ LEPLQQHLQD SQQEISSMQM 190 200 210 220 230 240 KLMEMKDLEN HNSQLNWCSS PHSILVNGAT DYCSLSTSSS ETANLNEHVE GQSNLESEPI 250 260 270 280 290 300 HQESPARSSP ELLPSGVTDE NEVTTAVTEK VCSELDNNRH SKEEDPFNVD SSSLTGPVAD 310 320 330 340 350 360 TNLDFFQSDP FVGSDPFKDD PFGKIDPFGG DPFKGSDPFA SDCFFRQSTD PFATSSTDPF 370 380 390 400 410 420 SAANNSSITS VETLKHNDPF APGGTVVAAS DSATDPFASV FGNESFGGGF ADFSTLSKVN 430 440 450 460 470 480 NEDPFRSATS SSVSNVVITK NVFEETSVKS EDEPPALPPK IGTPTRPCPL PPGKRSINKL 490 500 510 520 530 540 DSPDPFKLND PFQPFPGNDS PKEKDPEIFC DPFTSATTTT NKEADPSNFA NFSAYPSEED 550 560 570 580 MIEWAKRESE REEEQRLARL NQQEQEDLEL AIALSKSEIS EA

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The human eps15 gene, encoding a tyrosine kinase substrate, is conserved in evolution and maps to 1p31-p32." Wong W.T., Kraus M.H., Carlomagno F., Zelano A., Druck T., Croce C.M., Huebner K., di Fiore P.P. Oncogene 9:1591-1597(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT MET-822. Tissue: Melanoma.
[2]	"A novel gene, AF-1p, fused to HRX in t(1;11)(p32;q23), is not related to AF-4, AF-9 nor ENL." Bernard O.A., Mauchauffe M., Mecucci C., van den Berghe H., Berger R. Oncogene 9:1039-1045(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[3]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Trachea.
[4]	"Eps15 in human umbilical vein endothelial cells." Kronstein R., Grossklaus S., Schnittler H.-J. Submitted (JAN-2006) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[5]	"The full-ORF clone resource of the German cDNA consortium." Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I. BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
[6]	"The DNA sequence and biological annotation of human chromosome 1." Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R. Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]	"Interaction between the amino-terminal SH3 domain of CRK and its natural target proteins." Matsuda M., Ota S., Tanimura R., Nakamura H., Matuoka K., Takenawa T., Nagashima K., Kurata T. J. Biol. Chem. 271:14468-14472(1996) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH CRK.
[9]	"Epsin is an EH-domain-binding protein implicated in clathrin-mediated endocytosis." Chen H., Fre S., Slepnev V.I., Capua M.R., Takei K., Butler M.H., Di Fiore P.P., De Camilli P. Nature 394:793-797(1998) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH EPN1.
[10]	"STAM and Hrs are subunits of a multivalent ubiquitin-binding complex on early endosomes." Bache K.G., Raiborg C., Mehlum A., Stenmark H. J. Biol. Chem. 278:12513-12521(2003) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH HGS AND STAM2.
[11]	"TTP specifically regulates the internalization of the transferrin receptor." Tosoni D., Puri C., Confalonieri S., Salcini A.E., De Camilli P., Tacchetti C., Di Fiore P.P. Cell 123:875-888(2005) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH SH3BP4.
[12]	"Endosomal transport of ErbB-2: mechanism for nuclear entry of the cell surface receptor." Giri D.K., Ali-Seyed M., Li L.Y., Lee D.F., Ling P., Bartholomeusz G., Wang S.C., Hung M.C. Mol. Cell. Biol. 25:11005-11018(2005) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH ERBB2.
[13]	"A probability-based approach for high-throughput protein phosphorylation analysis and site localization." Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P. Nat. Biotechnol. 24:1285-1292(2006) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-323, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[14]	"ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage." Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J. Science 316:1160-1166(2007) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-485, MASS SPECTROMETRY. Tissue: Embryonic kidney.
[15]	"An endosomally localized isoform of Eps15 interacts with Hrs to mediate degradation of epidermal growth factor receptor." Roxrud I., Raiborg C., Pedersen N.M., Stang E., Stenmark H. J. Cell Biol. 180:1205-1218(2008) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, ALTERNATIVE SPLICING (ISOFORM 2), SUBCELLULAR LOCATION (ISOFORM 2), INTERACTION WITH HSG AND AP2A2.
[16]	"Phosphoproteome of resting human platelets." Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J., Schuetz C., Walter U., Gambaryan S., Sickmann A. J. Proteome Res. 7:526-534(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-796 AND SER-814, MASS SPECTROMETRY. Tissue: Platelet.
[17]	"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle." Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M. Mol. Cell 31:438-448(2008) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Cervix carcinoma.
[18]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-140; SER-323; SER-485 AND SER-814, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[19]	"Endocytic accessory proteins are functionally distinguished by their differential effects on the maturation of clathrin-coated pits." Mettlen M., Stoeber M., Loerke D., Antonescu C.N., Danuser G., Schmid S.L. Mol. Biol. Cell 20:3251-3260(2009) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[20]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-108; SER-323; SER-324; SER-814 AND TYR-849, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[21]	"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis." Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M. Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-324; SER-467; SER-470; SER-790; SER-796 AND SER-814, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[22]	"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.
[23]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[24]	"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.
[25]	"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation." Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B. Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-324; SER-485; SER-790; SER-796 AND SER-814, MASS SPECTROMETRY.
[26]	"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: FUNCTION, INTERACTION WITH DAB2.
[27]	"Distinct and separable activities of the endocytic clathrin-coat components Fcho1/2 and AP-2 in developmental patterning." Umasankar P.K., Sanker S., Thieman J.R., Chakraborty S., Wendland B., Tsang M., Traub L.M. Nat. Cell Biol. 14:488-501(2012) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH FCHO1.
[28]	"Structure and Asn-Pro-Phe binding pocket of the Eps15 homology domain." de Beer T., Carter R.E., Lobel-Rice K.E., Sorkin A., Overduin M. Science 281:1357-1360(1998) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF 121-215 IN COMPLEX WITH CALCIUM IONS.
[29]	"Solution structure of Eps15's third EH domain reveals coincident Phe-Trp and Asn-Pro-Phe binding sites." Enmon J.L., de Beer T., Overduin M. Biochemistry 39:4309-4319(2000) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF 217-311 IN COMPLEX WITH CALCIUM IONS.
[30]	"Molecular mechanism of NPF recognition by EH domains." de Beer T., Hoofnagle A.N., Enmon J.L., Bowers R.C., Yamabhai M., Kay B.K., Overduin M. Nat. Struct. Biol. 7:1018-1022(2000) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF 121-215 IN COMPLEX WITH PEPTIDE LIGAND AND CALCIUM IONS, DOMAIN.
[31]	"Role of the AP2 beta-appendage hub in recruiting partners for clathrin-coated vesicle assembly." Schmid E.M., Ford M.G.J., Burtey A., Praefcke G.J.K., Peak-Chew S.-Y., Mills I.G., Benmerah A., McMahon H.T. PLoS Biol. 4:E262-E262(2006) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 719-730 IN COMPLEX WITH AP2B1, MASS SPECTROMETRY, SUBCELLULAR LOCATION, FUNCTION.
[32]	"Structure of the Eps15-stonin2 complex provides a molecular explanation for EH-domain ligand specificity." Rumpf J., Simon B., Jung N., Maritzen T., Haucke V., Sattler M., Groemping Y. EMBO J. 27:558-569(2008) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF 121-215 IN COMPLEX WITH STON2 AND CALCIUM IONS, MUTAGENESIS OF VAL-154 AND TRP-169, SUBCELLULAR LOCATION.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

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.
AL671986, AC104170 Genomic DNA. Translation: CAI13030.1.
CH471059 Genomic DNA. Translation: EAX06823.1.

IPI

IPI00292134.
IPI00916208.

PIR

S43074.

RefSeq

NP_001153441.1. NM_001159969.1.
NP_001972.1. NM_001981.2.

UniGene

Hs.83722.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1C07	NMR	-	A	217-311	[»]
1EH2	NMR	-	A	121-218	[»]
1F8H	NMR	-	A	121-215	[»]
1FF1	NMR	-	A	121-215	[»]
2IV9	X-ray	1.90	P	719-730	[»]
2JXC	NMR	-	A	121-215	[»]

ProteinModelPortal

P42566.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-33064N.

IntAct

P42566. 33 interactions.

MINT

MINT-107223.

STRING

9606.ENSP00000360798.

PTM databases

PhosphoSite

P42566.

Polymorphism databases

DMDM

67476728.

2D gel databases

OGP

P42566.

Proteomic databases

PaxDb

P42566.

PeptideAtlas

P42566.

PRIDE

P42566.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000371733; ENSP00000360798; ENSG00000085832.

GeneID

2060.

KEGG

hsa:2060.

UCSC

uc001csp.3. human.
uc001csq.1. human.

Organism-specific databases

CTD

2060.

GeneCards

GC01M051819.

HGNC

HGNC:3419. EPS15.

HPA

CAB010164.
HPA008451.

MIM

600051. gene.

neXtProt

NX_P42566.

PharmGKB

PA27838.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG301764.

HOGENOM

HOG000004804.

HOVERGEN

HBG005591.

InParanoid

P42566.

KO

K12472.

OMA

FCDPFTS.

OrthoDB

EOG4BRWKB.

PhylomeDB

P42566.

Enzyme and pathway databases

Reactome

REACT_111102. Signal Transduction.
REACT_116125. Disease.

Gene expression databases

ArrayExpress

P42566.

Bgee

P42566.

CleanEx

HS_EPS15.

Genevestigator

P42566.

GermOnline

ENSG00000085832. Homo sapiens.

Family and domain databases

Gene3D

1.10.238.10. 3 hits.

InterPro

IPR011992. EF-hand-like_dom.
IPR018247. EF_Hand_1_Ca_BS.
IPR002048. EF_hand_dom.
IPR000261. EPS15_homology.
IPR003903. Ubiquitin-int_motif.
[Graphical view]

SMART

SM00054. EFh. 3 hits.
SM00027. EH. 3 hits.
SM00726. UIM. 3 hits.
[Graphical view]

PROSITE

PS00018. EF_HAND_1. 2 hits.
PS50222. EF_HAND_2. 4 hits.
PS50031. EH. 3 hits.
PS50330. UIM. 2 hits.
[Graphical view]

ProtoNet

Search...

Other

ChiTaRS

EPS15. human.

EvolutionaryTrace

P42566.

GenomeRNAi

2060.

NextBio

8377.

SOURCE

Search...

Entry information

Entry name

EPS15_HUMAN

Accession

Primary (citable) accession number: P42566
Secondary accession number(s): B2R8J7, D3DPJ2, Q5SRH4

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1995
Last sequence update:	June 7, 2005
Last modified:	May 1, 2013
This is version 148 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.