Full text data of EPS15
EPS15
(AF1P)
[Confidence: medium (present in either hRBCD or BSc_CH or PM22954596)]
Epidermal growth factor receptor substrate 15; Protein Eps15 (Protein AF-1p)
Epidermal growth factor receptor substrate 15; Protein Eps15 (Protein AF-1p)
UniProt
P42566
ID EPS15_HUMAN Reviewed; 896 AA.
AC P42566; B2R8J7; D3DPJ2; Q5SRH4;
DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
read moreDT 07-JUN-2005, sequence version 2.
DT 22-JAN-2014, entry version 154.
DE RecName: Full=Epidermal growth factor receptor substrate 15;
DE Short=Protein Eps15;
DE AltName: Full=Protein AF-1p;
GN Name=EPS15; Synonyms=AF1P;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT MET-822.
RC TISSUE=Melanoma;
RX PubMed=8183552;
RA Wong W.T., Kraus M.H., Carlomagno F., Zelano A., Druck T., Croce C.M.,
RA Huebner K., di Fiore P.P.;
RT "The human eps15 gene, encoding a tyrosine kinase substrate, is
RT conserved in evolution and maps to 1p31-p32.";
RL Oncogene 9:1591-1597(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=8134107;
RA Bernard O.A., Mauchauffe M., Mecucci C., van den Berghe H., Berger R.;
RT "A novel gene, AF-1p, fused to HRX in t(1;11)(p32;q23), is not related
RT to AF-4, AF-9 nor ENL.";
RL Oncogene 9:1039-1045(1994).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Trachea;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA Kronstein R., Grossklaus S., Schnittler H.-J.;
RT "Eps15 in human umbilical vein endothelial cells.";
RL Submitted (JAN-2006) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H.,
RA Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K.,
RA Ottenwaelder B., Poustka A., Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D.,
RA Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A.,
RA Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F.,
RA McDonald L., Evans R., Phillips K., Atkinson A., Cooper R., Jones C.,
RA Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P.,
RA Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K.,
RA Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G.,
RA Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D.,
RA Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G.,
RA Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J.,
RA Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R.,
RA Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D.,
RA Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G.,
RA Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M.,
RA Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J.,
RA Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M.,
RA Loveland J., Lovell J., Lush M.J., Lyne R., Martin S.,
RA Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S.,
RA Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C.,
RA Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z.,
RA Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E.,
RA Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A.,
RA Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R.,
RA Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V.,
RA Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP INTERACTION WITH CRK.
RX PubMed=8662907; DOI=10.1074/jbc.271.24.14468;
RA Matsuda M., Ota S., Tanimura R., Nakamura H., Matuoka K., Takenawa T.,
RA Nagashima K., Kurata T.;
RT "Interaction between the amino-terminal SH3 domain of CRK and its
RT natural target proteins.";
RL J. Biol. Chem. 271:14468-14472(1996).
RN [9]
RP INTERACTION WITH EPN1.
RX PubMed=9723620; DOI=10.1038/29555;
RA Chen H., Fre S., Slepnev V.I., Capua M.R., Takei K., Butler M.H.,
RA Di Fiore P.P., De Camilli P.;
RT "Epsin is an EH-domain-binding protein implicated in clathrin-mediated
RT endocytosis.";
RL Nature 394:793-797(1998).
RN [10]
RP INTERACTION WITH HGS AND STAM2.
RX PubMed=12551915; DOI=10.1074/jbc.M210843200;
RA Bache K.G., Raiborg C., Mehlum A., Stenmark H.;
RT "STAM and Hrs are subunits of a multivalent ubiquitin-binding complex
RT on early endosomes.";
RL J. Biol. Chem. 278:12513-12521(2003).
RN [11]
RP INTERACTION WITH SH3BP4.
RX PubMed=16325581; DOI=10.1016/j.cell.2005.10.021;
RA Tosoni D., Puri C., Confalonieri S., Salcini A.E., De Camilli P.,
RA Tacchetti C., Di Fiore P.P.;
RT "TTP specifically regulates the internalization of the transferrin
RT receptor.";
RL Cell 123:875-888(2005).
RN [12]
RP INTERACTION WITH ERBB2.
RX PubMed=16314522; DOI=10.1128/MCB.25.24.11005-11018.2005;
RA Giri D.K., Ali-Seyed M., Li L.Y., Lee D.F., Ling P., Bartholomeusz G.,
RA Wang S.C., Hung M.C.;
RT "Endosomal transport of ErbB-2: mechanism for nuclear entry of the
RT cell surface receptor.";
RL Mol. Cell. Biol. 25:11005-11018(2005).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-323, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=16964243; DOI=10.1038/nbt1240;
RA Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.;
RT "A probability-based approach for high-throughput protein
RT phosphorylation analysis and site localization.";
RL Nat. Biotechnol. 24:1285-1292(2006).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-485, AND MASS
RP SPECTROMETRY.
RC TISSUE=Embryonic kidney;
RX PubMed=17525332; DOI=10.1126/science.1140321;
RA Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III,
RA Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N.,
RA Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J.;
RT "ATM and ATR substrate analysis reveals extensive protein networks
RT responsive to DNA damage.";
RL Science 316:1160-1166(2007).
RN [15]
RP FUNCTION, ALTERNATIVE SPLICING (ISOFORM 2), SUBCELLULAR LOCATION
RP (ISOFORM 2), AND INTERACTION WITH HSG AND AP2A2.
RX PubMed=18362181; DOI=10.1083/jcb.200708115;
RA Roxrud I., Raiborg C., Pedersen N.M., Stang E., Stenmark H.;
RT "An endosomally localized isoform of Eps15 interacts with Hrs to
RT mediate degradation of epidermal growth factor receptor.";
RL J. Cell Biol. 180:1205-1218(2008).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-796 AND SER-814, AND
RP MASS SPECTROMETRY.
RC TISSUE=Platelet;
RX PubMed=18088087; DOI=10.1021/pr0704130;
RA Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J.,
RA Schuetz C., Walter U., Gambaryan S., Sickmann A.;
RT "Phosphoproteome of resting human platelets.";
RL J. Proteome Res. 7:526-534(2008).
RN [17]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of
RT the kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-140; SER-323; SER-485
RP AND SER-814, AND MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [19]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, MASS SPECTROMETRY, AND
RP CLEAVAGE OF INITIATOR METHIONINE.
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [20]
RP FUNCTION.
RX PubMed=19458185; DOI=10.1091/mbc.E09-03-0256;
RA Mettlen M., Stoeber M., Loerke D., Antonescu C.N., Danuser G.,
RA Schmid S.L.;
RT "Endocytic accessory proteins are functionally distinguished by their
RT differential effects on the maturation of clathrin-coated pits.";
RL Mol. Biol. Cell 20:3251-3260(2009).
RN [21]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-108; SER-323; SER-324;
RP SER-814 AND TYR-849, AND MASS SPECTROMETRY.
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [22]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-324; SER-467; SER-470;
RP SER-790; SER-796 AND SER-814, AND MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [23]
RP INTERACTION WITH FCHO2.
RX PubMed=20448150; DOI=10.1126/science.1188462;
RA Henne W.M., Boucrot E., Meinecke M., Evergren E., Vallis Y.,
RA Mittal R., McMahon H.T.;
RT "FCHo proteins are nucleators of clathrin-mediated endocytosis.";
RL Science 328:1281-1284(2010).
RN [24]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [25]
RP INTERACTION WITH FCHO2.
RX PubMed=21762413; DOI=10.1111/j.1365-2443.2011.01536.x;
RA Uezu A., Umeda K., Tsujita K., Suetsugu S., Takenawa T., Nakanishi H.;
RT "Characterization of the EFC/F-BAR domain protein, FCHO2.";
RL Genes Cells 16:868-878(2011).
RN [26]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-324; SER-485; SER-790;
RP SER-796 AND SER-814, AND MASS SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [27]
RP FUNCTION, AND INTERACTION WITH DAB2.
RX PubMed=22648170; DOI=10.1091/mbc.E11-12-1007;
RA Teckchandani A., Mulkearns E.E., Randolph T.W., Toida N., Cooper J.A.;
RT "The clathrin adaptor Dab2 recruits EH domain scaffold proteins to
RT regulate integrin beta1 endocytosis.";
RL Mol. Biol. Cell 23:2905-2916(2012).
RN [28]
RP INTERACTION WITH FCHO1.
RX PubMed=22484487; DOI=10.1038/ncb2473;
RA Umasankar P.K., Sanker S., Thieman J.R., Chakraborty S., Wendland B.,
RA Tsang M., Traub L.M.;
RT "Distinct and separable activities of the endocytic clathrin-coat
RT components Fcho1/2 and AP-2 in developmental patterning.";
RL Nat. Cell Biol. 14:488-501(2012).
RN [29]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, AND MASS SPECTROMETRY.
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [30]
RP STRUCTURE BY NMR OF 121-215 IN COMPLEX WITH CALCIUM IONS.
RX PubMed=9721102; DOI=10.1126/science.281.5381.1357;
RA de Beer T., Carter R.E., Lobel-Rice K.E., Sorkin A., Overduin M.;
RT "Structure and Asn-Pro-Phe binding pocket of the Eps15 homology
RT domain.";
RL Science 281:1357-1360(1998).
RN [31]
RP STRUCTURE BY NMR OF 217-311 IN COMPLEX WITH CALCIUM IONS.
RX PubMed=10757979; DOI=10.1021/bi9927383;
RA Enmon J.L., de Beer T., Overduin M.;
RT "Solution structure of Eps15's third EH domain reveals coincident Phe-
RT Trp and Asn-Pro-Phe binding sites.";
RL Biochemistry 39:4309-4319(2000).
RN [32]
RP STRUCTURE BY NMR OF 121-215 IN COMPLEX WITH PEPTIDE LIGAND AND CALCIUM
RP IONS, AND DOMAIN.
RX PubMed=11062555; DOI=10.1038/80924;
RA de Beer T., Hoofnagle A.N., Enmon J.L., Bowers R.C., Yamabhai M.,
RA Kay B.K., Overduin M.;
RT "Molecular mechanism of NPF recognition by EH domains.";
RL Nat. Struct. Biol. 7:1018-1022(2000).
RN [33]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 719-730 IN COMPLEX WITH
RP AP2B1, MASS SPECTROMETRY, SUBCELLULAR LOCATION, AND FUNCTION.
RX PubMed=16903783; DOI=10.1371/journal.pbio.0040262;
RA Schmid E.M., Ford M.G.J., Burtey A., Praefcke G.J.K., Peak-Chew S.-Y.,
RA Mills I.G., Benmerah A., McMahon H.T.;
RT "Role of the AP2 beta-appendage hub in recruiting partners for
RT clathrin-coated vesicle assembly.";
RL PLoS Biol. 4:E262-E262(2006).
RN [34]
RP STRUCTURE BY NMR OF 121-215 IN COMPLEX WITH STON2 AND CALCIUM IONS,
RP MUTAGENESIS OF VAL-154 AND TRP-169, AND SUBCELLULAR LOCATION.
RX PubMed=18200045; DOI=10.1038/sj.emboj.7601980;
RA Rumpf J., Simon B., Jung N., Maritzen T., Haucke V., Sattler M.,
RA Groemping Y.;
RT "Structure of the Eps15-stonin2 complex provides a molecular
RT explanation for EH-domain ligand specificity.";
RL EMBO J. 27:558-569(2008).
CC -!- FUNCTION: Involved in cell growth regulation. May be involved in
CC the regulation of mitogenic signals and control of cell
CC proliferation. Involved in the internalization of ligand-inducible
CC receptors of the receptor tyrosine kinase (RTK) type, in
CC particular EGFR. Plays a role in the assembly of clathrin-coated
CC pits (CCPs). Seems to be involved in CCPs maturation including
CC invagination or budding. Involved in endocytosis of integrin beta-
CC 1 (ITGB1) and transferrin receptor (TFR); internalization of ITGB1
CC as DAB2-dependent cargo but not TFR seems to require association
CC with DAB2.
CC -!- SUBUNIT: Interacts with SGIP1 (By similarity). Interacts with HGS;
CC the interaction bridges the interaction of STAM or STAM2 with
CC EPS15. Isoform 2 interacts with HGS and AP2A2. Part of a complex
CC at least composed of EPS15, HGS, and either STAM1 or STAM2. Binds
CC AP2A2. Interacts with AP2B1; clathrin competes with EPS15. Binds
CC STON2 and EPN1. Interacts (via its SH3-binding sites) with CRK.
CC Interacts with SH3BP4/TTP. Interacts with ERBB2. Interacts with
CC FCHO1. Interacts with FCHO2. Interacts (via EH domains) with DAB2.
CC -!- INTERACTION:
CC Q0JRZ9:FCHO2; NbExp=3; IntAct=EBI-396684, EBI-2609756;
CC Q3UQN2:Fcho2 (xeno); NbExp=3; IntAct=EBI-396684, EBI-6094986;
CC P16333:NCK1; NbExp=2; IntAct=EBI-396684, EBI-389883;
CC Q8WXE9:STON2; NbExp=17; IntAct=EBI-396684, EBI-539742;
CC Q9UMX0:UBQLN1; NbExp=5; IntAct=EBI-396684, EBI-741480;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Cell membrane; Peripheral
CC membrane protein; Cytoplasmic side. Membrane, clathrin-coated pit.
CC Note=Recruited to the plasma membrane upon EGFR activation and
CC localizes to coated pits.
CC -!- SUBCELLULAR LOCATION: Isoform 2: Early endosome membrane;
CC Peripheral membrane protein; Cytoplasmic side. Note=Colocalizes
CC with HGS on bilayered clathrin coats on endosomes.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P42566-1; Sequence=Displayed;
CC Name=2; Synonyms=Eps15b;
CC IsoId=P42566-2; Sequence=VSP_036168, VSP_036169;
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed.
CC -!- DOMAIN: The EH domain interacts with Asn-Pro-Phe (NPF) motifs of
CC target proteins.
CC -!- PTM: Phosphorylation on Tyr-849 is involved in the internalization
CC of EGFR. Not required for membrane translocation after EGF
CC treatment or for targeting to coated pits, but essential for a
CC subsequent step in EGFR endocytosis (By similarity).
CC Phosphorylated on serine upon DNA damage, probably by ATM or ATR.
CC -!- DISEASE: Note=A chromosomal aberration involving EPS15 is found in
CC acute leukemias. Translocation t(1;11)(p32;q23) with KMT2A/MLL1.
CC The result is a rogue activator protein.
CC -!- SIMILARITY: Contains 2 EF-hand domains.
CC -!- SIMILARITY: Contains 3 EH domains.
CC -!- SIMILARITY: Contains 2 UIM (ubiquitin-interacting motif) repeats.
CC -!- CAUTION: Studies in clathrin-mediated endocytosis of ITGB1 and TFR
CC used a siRNA mixture of EPS15 and EPS15L1, and a Dab2 mutant with
CC impaired binding to EH domain-containing proteins EPS15 and ITSN1
CC suggesting a partially overlapping role of the EH domain-
CC containing proteins (PubMed:22648170).
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology
CC and Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/AF1pID11.html";
CC -----------------------------------------------------------------------
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DR EMBL; U07707; AAA52101.1; -; mRNA.
DR EMBL; Z29064; CAA82305.1; -; mRNA.
DR EMBL; AK313396; BAG36194.1; -; mRNA.
DR EMBL; DQ367924; ABD34786.1; -; mRNA.
DR EMBL; BX647676; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AL671986; CAI13030.1; -; Genomic_DNA.
DR EMBL; AC104170; CAI13030.1; JOINED; Genomic_DNA.
DR EMBL; CH471059; EAX06823.1; -; Genomic_DNA.
DR PIR; S43074; S43074.
DR RefSeq; NP_001153441.1; NM_001159969.1.
DR RefSeq; NP_001972.1; NM_001981.2.
DR UniGene; Hs.83722; -.
DR PDB; 1C07; NMR; -; A=217-311.
DR PDB; 1EH2; NMR; -; A=121-218.
DR PDB; 1F8H; NMR; -; A=121-215.
DR PDB; 1FF1; NMR; -; A=121-215.
DR PDB; 2IV9; X-ray; 1.90 A; P=719-730.
DR PDB; 2JXC; NMR; -; A=121-215.
DR PDBsum; 1C07; -.
DR PDBsum; 1EH2; -.
DR PDBsum; 1F8H; -.
DR PDBsum; 1FF1; -.
DR PDBsum; 2IV9; -.
DR PDBsum; 2JXC; -.
DR ProteinModelPortal; P42566; -.
DR SMR; P42566; 7-105, 121-215, 217-311.
DR DIP; DIP-33064N; -.
DR IntAct; P42566; 40.
DR MINT; MINT-107223; -.
DR STRING; 9606.ENSP00000360798; -.
DR PhosphoSite; P42566; -.
DR DMDM; 67476728; -.
DR OGP; P42566; -.
DR PaxDb; P42566; -.
DR PeptideAtlas; P42566; -.
DR PRIDE; P42566; -.
DR Ensembl; ENST00000371733; ENSP00000360798; ENSG00000085832.
DR GeneID; 2060; -.
DR KEGG; hsa:2060; -.
DR UCSC; uc001csq.1; human.
DR CTD; 2060; -.
DR GeneCards; GC01M051819; -.
DR HGNC; HGNC:3419; EPS15.
DR HPA; CAB010164; -.
DR HPA; HPA008451; -.
DR MIM; 600051; gene.
DR neXtProt; NX_P42566; -.
DR PharmGKB; PA27838; -.
DR eggNOG; NOG301764; -.
DR HOGENOM; HOG000004804; -.
DR HOVERGEN; HBG005591; -.
DR InParanoid; P42566; -.
DR KO; K12472; -.
DR OMA; WCSSPHS; -.
DR PhylomeDB; P42566; -.
DR Reactome; REACT_111102; Signal Transduction.
DR Reactome; REACT_116125; Disease.
DR SignaLink; P42566; -.
DR ChiTaRS; EPS15; human.
DR EvolutionaryTrace; P42566; -.
DR GeneWiki; EPS15; -.
DR GenomeRNAi; 2060; -.
DR NextBio; 8377; -.
DR PRO; PR:P42566; -.
DR ArrayExpress; P42566; -.
DR Bgee; P42566; -.
DR CleanEx; HS_EPS15; -.
DR Genevestigator; P42566; -.
DR GO; GO:0030122; C:AP-2 adaptor complex; IEA:Ensembl.
DR GO; GO:0060170; C:cilium membrane; IEA:Ensembl.
DR GO; GO:0005905; C:coated pit; TAS:UniProtKB.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0031901; C:early endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR GO; GO:0005886; C:plasma membrane; IDA:HGNC.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0008283; P:cell proliferation; TAS:ProtInc.
DR GO; GO:0048268; P:clathrin coat assembly; IDA:BHF-UCL.
DR GO; GO:0032456; P:endocytic recycling; IC:BHF-UCL.
DR GO; GO:0006897; P:endocytosis; IEA:UniProtKB-KW.
DR GO; GO:0007173; P:epidermal growth factor receptor signaling pathway; TAS:Reactome.
DR GO; GO:0042059; P:negative regulation of epidermal growth factor receptor signaling pathway; TAS:Reactome.
DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW.
DR Gene3D; 1.10.238.10; -; 3.
DR InterPro; IPR011992; EF-hand-dom_pair.
DR InterPro; IPR018247; EF_Hand_1_Ca_BS.
DR InterPro; IPR002048; EF_hand_dom.
DR InterPro; IPR000261; EPS15_homology.
DR InterPro; IPR003903; Ubiquitin-int_motif.
DR SMART; SM00054; EFh; 3.
DR SMART; SM00027; EH; 3.
DR SMART; SM00726; UIM; 3.
DR PROSITE; PS00018; EF_HAND_1; 2.
DR PROSITE; PS50222; EF_HAND_2; 4.
DR PROSITE; PS50031; EH; 3.
DR PROSITE; PS50330; UIM; 2.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Calcium;
KW Cell membrane; Chromosomal rearrangement; Coated pit;
KW Complete proteome; Cytoplasm; Endocytosis; Endosome; Membrane;
KW Metal-binding; Phosphoprotein; Polymorphism; Protein transport;
KW Proto-oncogene; Reference proteome; Repeat; SH3-binding; Transport.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 896 Epidermal growth factor receptor
FT substrate 15.
FT /FTId=PRO_0000146116.
FT DOMAIN 15 104 EH 1.
FT DOMAIN 128 216 EH 2.
FT DOMAIN 160 195 EF-hand 1.
FT DOMAIN 223 258 EF-hand 2.
FT DOMAIN 224 314 EH 3.
FT REPEAT 599 601 1.
FT REPEAT 623 625 2.
FT REPEAT 629 631 3.
FT REPEAT 634 636 4.
FT REPEAT 640 642 5.
FT REPEAT 645 647 6.
FT REPEAT 651 653 7.
FT REPEAT 664 666 8.
FT REPEAT 672 674 9.
FT REPEAT 692 694 10.
FT REPEAT 709 711 11.
FT REPEAT 737 739 12.
FT REPEAT 798 800 13.
FT REPEAT 804 806 14.
FT REPEAT 825 827 15.
FT REPEAT 851 870 UIM 1.
FT REPEAT 877 896 UIM 2.
FT CA_BIND 173 184 1.
FT CA_BIND 236 247 2.
FT REGION 2 330 Interaction with DAB2 (By similarity).
FT REGION 599 827 15 X 3 AA repeats of D-P-F.
FT MOTIF 768 774 SH3-binding.
FT COMPBIAS 768 850 Pro-rich.
FT MOD_RES 2 2 N-acetylalanine.
FT MOD_RES 108 108 Phosphoserine.
FT MOD_RES 140 140 Phosphoserine.
FT MOD_RES 323 323 Phosphoserine.
FT MOD_RES 324 324 Phosphoserine.
FT MOD_RES 467 467 Phosphoserine.
FT MOD_RES 470 470 Phosphoserine.
FT MOD_RES 485 485 Phosphoserine.
FT MOD_RES 777 777 Phosphothreonine (By similarity).
FT MOD_RES 790 790 Phosphoserine.
FT MOD_RES 796 796 Phosphoserine.
FT MOD_RES 814 814 Phosphoserine.
FT MOD_RES 849 849 Phosphotyrosine; by EGFR.
FT VAR_SEQ 1 314 Missing (in isoform 2).
FT /FTId=VSP_036168.
FT VAR_SEQ 315 346 SLQKNIIGSSPVADFSAIKELDTLNNEIVDLQ -> MYLKS
FT DSGLGGWITIPAVADVLKYSCIVCWSS (in isoform
FT 2).
FT /FTId=VSP_036169.
FT VARIANT 822 822 I -> M (in dbSNP:rs17567).
FT /FTId=VAR_016142.
FT MUTAGEN 154 154 V->E: Loss of interaction with STON2 NPF
FT motifs.
FT MUTAGEN 169 169 W->A: Loss of interaction with STON2 NPF
FT motifs.
FT CONFLICT 446 446 Missing (in Ref. 5; BX647676).
FT HELIX 126 136
FT STRAND 142 144
FT STRAND 145 147
FT HELIX 148 156
FT TURN 157 159
FT HELIX 162 172
FT STRAND 177 179
FT HELIX 182 197
FT TURN 207 209
FT HELIX 212 214
FT HELIX 223 235
FT STRAND 240 243
FT HELIX 245 253
FT TURN 254 256
FT HELIX 259 269
FT STRAND 274 278
FT TURN 279 281
FT HELIX 282 293
FT TURN 305 307
FT HELIX 723 726
SQ SEQUENCE 896 AA; 98656 MW; A1B9FE15B47ABAFF CRC64;
MAAAAQLSLT QLSSGNPVYE KYYRQVDTGN TGRVLASDAA AFLKKSGLPD LILGKIWDLA
DTDGKGILNK QEFFVALRLV ACAQNGLEVS LSSLNLAVPP PRFHDTSSPL LISGTSAAEL
PWAVKPEDKA KYDAIFDSLS PVNGFLSGDK VKPVLLNSKL PVDILGRVWE LSDIDHDGML
DRDEFAVAMF LVYCALEKEP VPMSLPPALV PPSKRKTWVV SPAEKAKYDE IFLKTDKDMD
GFVSGLEVRE IFLKTGLPST LLAHIWSLCD TKDCGKLSKD QFALAFHLIS QKLIKGIDPP
HVLTPEMIPP SDRASLQKNI IGSSPVADFS AIKELDTLNN EIVDLQREKN NVEQDLKEKE
DTIKQRTSEV QDLQDEVQRE NTNLQKLQAQ KQQVQELLDE LDEQKAQLEE QLKEVRKKCA
EEAQLISSLK AELTSQESQI STYEEELAKA REELSRLQQE TAELEESVES GKAQLEPLQQ
HLQDSQQEIS SMQMKLMEMK DLENHNSQLN WCSSPHSILV NGATDYCSLS TSSSETANLN
EHVEGQSNLE SEPIHQESPA RSSPELLPSG VTDENEVTTA VTEKVCSELD NNRHSKEEDP
FNVDSSSLTG PVADTNLDFF QSDPFVGSDP FKDDPFGKID PFGGDPFKGS DPFASDCFFR
QSTDPFATSS TDPFSAANNS SITSVETLKH NDPFAPGGTV VAASDSATDP FASVFGNESF
GGGFADFSTL SKVNNEDPFR SATSSSVSNV VITKNVFEET SVKSEDEPPA LPPKIGTPTR
PCPLPPGKRS INKLDSPDPF KLNDPFQPFP GNDSPKEKDP EIFCDPFTSA TTTTNKEADP
SNFANFSAYP SEEDMIEWAK RESEREEEQR LARLNQQEQE DLELAIALSK SEISEA
//
ID EPS15_HUMAN Reviewed; 896 AA.
AC P42566; B2R8J7; D3DPJ2; Q5SRH4;
DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
read moreDT 07-JUN-2005, sequence version 2.
DT 22-JAN-2014, entry version 154.
DE RecName: Full=Epidermal growth factor receptor substrate 15;
DE Short=Protein Eps15;
DE AltName: Full=Protein AF-1p;
GN Name=EPS15; Synonyms=AF1P;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT MET-822.
RC TISSUE=Melanoma;
RX PubMed=8183552;
RA Wong W.T., Kraus M.H., Carlomagno F., Zelano A., Druck T., Croce C.M.,
RA Huebner K., di Fiore P.P.;
RT "The human eps15 gene, encoding a tyrosine kinase substrate, is
RT conserved in evolution and maps to 1p31-p32.";
RL Oncogene 9:1591-1597(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=8134107;
RA Bernard O.A., Mauchauffe M., Mecucci C., van den Berghe H., Berger R.;
RT "A novel gene, AF-1p, fused to HRX in t(1;11)(p32;q23), is not related
RT to AF-4, AF-9 nor ENL.";
RL Oncogene 9:1039-1045(1994).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Trachea;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA Kronstein R., Grossklaus S., Schnittler H.-J.;
RT "Eps15 in human umbilical vein endothelial cells.";
RL Submitted (JAN-2006) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H.,
RA Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K.,
RA Ottenwaelder B., Poustka A., Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D.,
RA Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A.,
RA Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F.,
RA McDonald L., Evans R., Phillips K., Atkinson A., Cooper R., Jones C.,
RA Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P.,
RA Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K.,
RA Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G.,
RA Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D.,
RA Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G.,
RA Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J.,
RA Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R.,
RA Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D.,
RA Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G.,
RA Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M.,
RA Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J.,
RA Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M.,
RA Loveland J., Lovell J., Lush M.J., Lyne R., Martin S.,
RA Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S.,
RA Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C.,
RA Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z.,
RA Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E.,
RA Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A.,
RA Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R.,
RA Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V.,
RA Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP INTERACTION WITH CRK.
RX PubMed=8662907; DOI=10.1074/jbc.271.24.14468;
RA Matsuda M., Ota S., Tanimura R., Nakamura H., Matuoka K., Takenawa T.,
RA Nagashima K., Kurata T.;
RT "Interaction between the amino-terminal SH3 domain of CRK and its
RT natural target proteins.";
RL J. Biol. Chem. 271:14468-14472(1996).
RN [9]
RP INTERACTION WITH EPN1.
RX PubMed=9723620; DOI=10.1038/29555;
RA Chen H., Fre S., Slepnev V.I., Capua M.R., Takei K., Butler M.H.,
RA Di Fiore P.P., De Camilli P.;
RT "Epsin is an EH-domain-binding protein implicated in clathrin-mediated
RT endocytosis.";
RL Nature 394:793-797(1998).
RN [10]
RP INTERACTION WITH HGS AND STAM2.
RX PubMed=12551915; DOI=10.1074/jbc.M210843200;
RA Bache K.G., Raiborg C., Mehlum A., Stenmark H.;
RT "STAM and Hrs are subunits of a multivalent ubiquitin-binding complex
RT on early endosomes.";
RL J. Biol. Chem. 278:12513-12521(2003).
RN [11]
RP INTERACTION WITH SH3BP4.
RX PubMed=16325581; DOI=10.1016/j.cell.2005.10.021;
RA Tosoni D., Puri C., Confalonieri S., Salcini A.E., De Camilli P.,
RA Tacchetti C., Di Fiore P.P.;
RT "TTP specifically regulates the internalization of the transferrin
RT receptor.";
RL Cell 123:875-888(2005).
RN [12]
RP INTERACTION WITH ERBB2.
RX PubMed=16314522; DOI=10.1128/MCB.25.24.11005-11018.2005;
RA Giri D.K., Ali-Seyed M., Li L.Y., Lee D.F., Ling P., Bartholomeusz G.,
RA Wang S.C., Hung M.C.;
RT "Endosomal transport of ErbB-2: mechanism for nuclear entry of the
RT cell surface receptor.";
RL Mol. Cell. Biol. 25:11005-11018(2005).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-323, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=16964243; DOI=10.1038/nbt1240;
RA Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.;
RT "A probability-based approach for high-throughput protein
RT phosphorylation analysis and site localization.";
RL Nat. Biotechnol. 24:1285-1292(2006).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-485, AND MASS
RP SPECTROMETRY.
RC TISSUE=Embryonic kidney;
RX PubMed=17525332; DOI=10.1126/science.1140321;
RA Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III,
RA Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N.,
RA Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J.;
RT "ATM and ATR substrate analysis reveals extensive protein networks
RT responsive to DNA damage.";
RL Science 316:1160-1166(2007).
RN [15]
RP FUNCTION, ALTERNATIVE SPLICING (ISOFORM 2), SUBCELLULAR LOCATION
RP (ISOFORM 2), AND INTERACTION WITH HSG AND AP2A2.
RX PubMed=18362181; DOI=10.1083/jcb.200708115;
RA Roxrud I., Raiborg C., Pedersen N.M., Stang E., Stenmark H.;
RT "An endosomally localized isoform of Eps15 interacts with Hrs to
RT mediate degradation of epidermal growth factor receptor.";
RL J. Cell Biol. 180:1205-1218(2008).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-796 AND SER-814, AND
RP MASS SPECTROMETRY.
RC TISSUE=Platelet;
RX PubMed=18088087; DOI=10.1021/pr0704130;
RA Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J.,
RA Schuetz C., Walter U., Gambaryan S., Sickmann A.;
RT "Phosphoproteome of resting human platelets.";
RL J. Proteome Res. 7:526-534(2008).
RN [17]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of
RT the kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-140; SER-323; SER-485
RP AND SER-814, AND MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [19]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, MASS SPECTROMETRY, AND
RP CLEAVAGE OF INITIATOR METHIONINE.
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [20]
RP FUNCTION.
RX PubMed=19458185; DOI=10.1091/mbc.E09-03-0256;
RA Mettlen M., Stoeber M., Loerke D., Antonescu C.N., Danuser G.,
RA Schmid S.L.;
RT "Endocytic accessory proteins are functionally distinguished by their
RT differential effects on the maturation of clathrin-coated pits.";
RL Mol. Biol. Cell 20:3251-3260(2009).
RN [21]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-108; SER-323; SER-324;
RP SER-814 AND TYR-849, AND MASS SPECTROMETRY.
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [22]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-324; SER-467; SER-470;
RP SER-790; SER-796 AND SER-814, AND MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [23]
RP INTERACTION WITH FCHO2.
RX PubMed=20448150; DOI=10.1126/science.1188462;
RA Henne W.M., Boucrot E., Meinecke M., Evergren E., Vallis Y.,
RA Mittal R., McMahon H.T.;
RT "FCHo proteins are nucleators of clathrin-mediated endocytosis.";
RL Science 328:1281-1284(2010).
RN [24]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [25]
RP INTERACTION WITH FCHO2.
RX PubMed=21762413; DOI=10.1111/j.1365-2443.2011.01536.x;
RA Uezu A., Umeda K., Tsujita K., Suetsugu S., Takenawa T., Nakanishi H.;
RT "Characterization of the EFC/F-BAR domain protein, FCHO2.";
RL Genes Cells 16:868-878(2011).
RN [26]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-324; SER-485; SER-790;
RP SER-796 AND SER-814, AND MASS SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [27]
RP FUNCTION, AND INTERACTION WITH DAB2.
RX PubMed=22648170; DOI=10.1091/mbc.E11-12-1007;
RA Teckchandani A., Mulkearns E.E., Randolph T.W., Toida N., Cooper J.A.;
RT "The clathrin adaptor Dab2 recruits EH domain scaffold proteins to
RT regulate integrin beta1 endocytosis.";
RL Mol. Biol. Cell 23:2905-2916(2012).
RN [28]
RP INTERACTION WITH FCHO1.
RX PubMed=22484487; DOI=10.1038/ncb2473;
RA Umasankar P.K., Sanker S., Thieman J.R., Chakraborty S., Wendland B.,
RA Tsang M., Traub L.M.;
RT "Distinct and separable activities of the endocytic clathrin-coat
RT components Fcho1/2 and AP-2 in developmental patterning.";
RL Nat. Cell Biol. 14:488-501(2012).
RN [29]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, AND MASS SPECTROMETRY.
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [30]
RP STRUCTURE BY NMR OF 121-215 IN COMPLEX WITH CALCIUM IONS.
RX PubMed=9721102; DOI=10.1126/science.281.5381.1357;
RA de Beer T., Carter R.E., Lobel-Rice K.E., Sorkin A., Overduin M.;
RT "Structure and Asn-Pro-Phe binding pocket of the Eps15 homology
RT domain.";
RL Science 281:1357-1360(1998).
RN [31]
RP STRUCTURE BY NMR OF 217-311 IN COMPLEX WITH CALCIUM IONS.
RX PubMed=10757979; DOI=10.1021/bi9927383;
RA Enmon J.L., de Beer T., Overduin M.;
RT "Solution structure of Eps15's third EH domain reveals coincident Phe-
RT Trp and Asn-Pro-Phe binding sites.";
RL Biochemistry 39:4309-4319(2000).
RN [32]
RP STRUCTURE BY NMR OF 121-215 IN COMPLEX WITH PEPTIDE LIGAND AND CALCIUM
RP IONS, AND DOMAIN.
RX PubMed=11062555; DOI=10.1038/80924;
RA de Beer T., Hoofnagle A.N., Enmon J.L., Bowers R.C., Yamabhai M.,
RA Kay B.K., Overduin M.;
RT "Molecular mechanism of NPF recognition by EH domains.";
RL Nat. Struct. Biol. 7:1018-1022(2000).
RN [33]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 719-730 IN COMPLEX WITH
RP AP2B1, MASS SPECTROMETRY, SUBCELLULAR LOCATION, AND FUNCTION.
RX PubMed=16903783; DOI=10.1371/journal.pbio.0040262;
RA Schmid E.M., Ford M.G.J., Burtey A., Praefcke G.J.K., Peak-Chew S.-Y.,
RA Mills I.G., Benmerah A., McMahon H.T.;
RT "Role of the AP2 beta-appendage hub in recruiting partners for
RT clathrin-coated vesicle assembly.";
RL PLoS Biol. 4:E262-E262(2006).
RN [34]
RP STRUCTURE BY NMR OF 121-215 IN COMPLEX WITH STON2 AND CALCIUM IONS,
RP MUTAGENESIS OF VAL-154 AND TRP-169, AND SUBCELLULAR LOCATION.
RX PubMed=18200045; DOI=10.1038/sj.emboj.7601980;
RA Rumpf J., Simon B., Jung N., Maritzen T., Haucke V., Sattler M.,
RA Groemping Y.;
RT "Structure of the Eps15-stonin2 complex provides a molecular
RT explanation for EH-domain ligand specificity.";
RL EMBO J. 27:558-569(2008).
CC -!- FUNCTION: Involved in cell growth regulation. May be involved in
CC the regulation of mitogenic signals and control of cell
CC proliferation. Involved in the internalization of ligand-inducible
CC receptors of the receptor tyrosine kinase (RTK) type, in
CC particular EGFR. Plays a role in the assembly of clathrin-coated
CC pits (CCPs). Seems to be involved in CCPs maturation including
CC invagination or budding. Involved in endocytosis of integrin beta-
CC 1 (ITGB1) and transferrin receptor (TFR); internalization of ITGB1
CC as DAB2-dependent cargo but not TFR seems to require association
CC with DAB2.
CC -!- SUBUNIT: Interacts with SGIP1 (By similarity). Interacts with HGS;
CC the interaction bridges the interaction of STAM or STAM2 with
CC EPS15. Isoform 2 interacts with HGS and AP2A2. Part of a complex
CC at least composed of EPS15, HGS, and either STAM1 or STAM2. Binds
CC AP2A2. Interacts with AP2B1; clathrin competes with EPS15. Binds
CC STON2 and EPN1. Interacts (via its SH3-binding sites) with CRK.
CC Interacts with SH3BP4/TTP. Interacts with ERBB2. Interacts with
CC FCHO1. Interacts with FCHO2. Interacts (via EH domains) with DAB2.
CC -!- INTERACTION:
CC Q0JRZ9:FCHO2; NbExp=3; IntAct=EBI-396684, EBI-2609756;
CC Q3UQN2:Fcho2 (xeno); NbExp=3; IntAct=EBI-396684, EBI-6094986;
CC P16333:NCK1; NbExp=2; IntAct=EBI-396684, EBI-389883;
CC Q8WXE9:STON2; NbExp=17; IntAct=EBI-396684, EBI-539742;
CC Q9UMX0:UBQLN1; NbExp=5; IntAct=EBI-396684, EBI-741480;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Cell membrane; Peripheral
CC membrane protein; Cytoplasmic side. Membrane, clathrin-coated pit.
CC Note=Recruited to the plasma membrane upon EGFR activation and
CC localizes to coated pits.
CC -!- SUBCELLULAR LOCATION: Isoform 2: Early endosome membrane;
CC Peripheral membrane protein; Cytoplasmic side. Note=Colocalizes
CC with HGS on bilayered clathrin coats on endosomes.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P42566-1; Sequence=Displayed;
CC Name=2; Synonyms=Eps15b;
CC IsoId=P42566-2; Sequence=VSP_036168, VSP_036169;
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed.
CC -!- DOMAIN: The EH domain interacts with Asn-Pro-Phe (NPF) motifs of
CC target proteins.
CC -!- PTM: Phosphorylation on Tyr-849 is involved in the internalization
CC of EGFR. Not required for membrane translocation after EGF
CC treatment or for targeting to coated pits, but essential for a
CC subsequent step in EGFR endocytosis (By similarity).
CC Phosphorylated on serine upon DNA damage, probably by ATM or ATR.
CC -!- DISEASE: Note=A chromosomal aberration involving EPS15 is found in
CC acute leukemias. Translocation t(1;11)(p32;q23) with KMT2A/MLL1.
CC The result is a rogue activator protein.
CC -!- SIMILARITY: Contains 2 EF-hand domains.
CC -!- SIMILARITY: Contains 3 EH domains.
CC -!- SIMILARITY: Contains 2 UIM (ubiquitin-interacting motif) repeats.
CC -!- CAUTION: Studies in clathrin-mediated endocytosis of ITGB1 and TFR
CC used a siRNA mixture of EPS15 and EPS15L1, and a Dab2 mutant with
CC impaired binding to EH domain-containing proteins EPS15 and ITSN1
CC suggesting a partially overlapping role of the EH domain-
CC containing proteins (PubMed:22648170).
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology
CC and Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/AF1pID11.html";
CC -----------------------------------------------------------------------
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DR EMBL; U07707; AAA52101.1; -; mRNA.
DR EMBL; Z29064; CAA82305.1; -; mRNA.
DR EMBL; AK313396; BAG36194.1; -; mRNA.
DR EMBL; DQ367924; ABD34786.1; -; mRNA.
DR EMBL; BX647676; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AL671986; CAI13030.1; -; Genomic_DNA.
DR EMBL; AC104170; CAI13030.1; JOINED; Genomic_DNA.
DR EMBL; CH471059; EAX06823.1; -; Genomic_DNA.
DR PIR; S43074; S43074.
DR RefSeq; NP_001153441.1; NM_001159969.1.
DR RefSeq; NP_001972.1; NM_001981.2.
DR UniGene; Hs.83722; -.
DR PDB; 1C07; NMR; -; A=217-311.
DR PDB; 1EH2; NMR; -; A=121-218.
DR PDB; 1F8H; NMR; -; A=121-215.
DR PDB; 1FF1; NMR; -; A=121-215.
DR PDB; 2IV9; X-ray; 1.90 A; P=719-730.
DR PDB; 2JXC; NMR; -; A=121-215.
DR PDBsum; 1C07; -.
DR PDBsum; 1EH2; -.
DR PDBsum; 1F8H; -.
DR PDBsum; 1FF1; -.
DR PDBsum; 2IV9; -.
DR PDBsum; 2JXC; -.
DR ProteinModelPortal; P42566; -.
DR SMR; P42566; 7-105, 121-215, 217-311.
DR DIP; DIP-33064N; -.
DR IntAct; P42566; 40.
DR MINT; MINT-107223; -.
DR STRING; 9606.ENSP00000360798; -.
DR PhosphoSite; P42566; -.
DR DMDM; 67476728; -.
DR OGP; P42566; -.
DR PaxDb; P42566; -.
DR PeptideAtlas; P42566; -.
DR PRIDE; P42566; -.
DR Ensembl; ENST00000371733; ENSP00000360798; ENSG00000085832.
DR GeneID; 2060; -.
DR KEGG; hsa:2060; -.
DR UCSC; uc001csq.1; human.
DR CTD; 2060; -.
DR GeneCards; GC01M051819; -.
DR HGNC; HGNC:3419; EPS15.
DR HPA; CAB010164; -.
DR HPA; HPA008451; -.
DR MIM; 600051; gene.
DR neXtProt; NX_P42566; -.
DR PharmGKB; PA27838; -.
DR eggNOG; NOG301764; -.
DR HOGENOM; HOG000004804; -.
DR HOVERGEN; HBG005591; -.
DR InParanoid; P42566; -.
DR KO; K12472; -.
DR OMA; WCSSPHS; -.
DR PhylomeDB; P42566; -.
DR Reactome; REACT_111102; Signal Transduction.
DR Reactome; REACT_116125; Disease.
DR SignaLink; P42566; -.
DR ChiTaRS; EPS15; human.
DR EvolutionaryTrace; P42566; -.
DR GeneWiki; EPS15; -.
DR GenomeRNAi; 2060; -.
DR NextBio; 8377; -.
DR PRO; PR:P42566; -.
DR ArrayExpress; P42566; -.
DR Bgee; P42566; -.
DR CleanEx; HS_EPS15; -.
DR Genevestigator; P42566; -.
DR GO; GO:0030122; C:AP-2 adaptor complex; IEA:Ensembl.
DR GO; GO:0060170; C:cilium membrane; IEA:Ensembl.
DR GO; GO:0005905; C:coated pit; TAS:UniProtKB.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0031901; C:early endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR GO; GO:0005886; C:plasma membrane; IDA:HGNC.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0008283; P:cell proliferation; TAS:ProtInc.
DR GO; GO:0048268; P:clathrin coat assembly; IDA:BHF-UCL.
DR GO; GO:0032456; P:endocytic recycling; IC:BHF-UCL.
DR GO; GO:0006897; P:endocytosis; IEA:UniProtKB-KW.
DR GO; GO:0007173; P:epidermal growth factor receptor signaling pathway; TAS:Reactome.
DR GO; GO:0042059; P:negative regulation of epidermal growth factor receptor signaling pathway; TAS:Reactome.
DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW.
DR Gene3D; 1.10.238.10; -; 3.
DR InterPro; IPR011992; EF-hand-dom_pair.
DR InterPro; IPR018247; EF_Hand_1_Ca_BS.
DR InterPro; IPR002048; EF_hand_dom.
DR InterPro; IPR000261; EPS15_homology.
DR InterPro; IPR003903; Ubiquitin-int_motif.
DR SMART; SM00054; EFh; 3.
DR SMART; SM00027; EH; 3.
DR SMART; SM00726; UIM; 3.
DR PROSITE; PS00018; EF_HAND_1; 2.
DR PROSITE; PS50222; EF_HAND_2; 4.
DR PROSITE; PS50031; EH; 3.
DR PROSITE; PS50330; UIM; 2.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Calcium;
KW Cell membrane; Chromosomal rearrangement; Coated pit;
KW Complete proteome; Cytoplasm; Endocytosis; Endosome; Membrane;
KW Metal-binding; Phosphoprotein; Polymorphism; Protein transport;
KW Proto-oncogene; Reference proteome; Repeat; SH3-binding; Transport.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 896 Epidermal growth factor receptor
FT substrate 15.
FT /FTId=PRO_0000146116.
FT DOMAIN 15 104 EH 1.
FT DOMAIN 128 216 EH 2.
FT DOMAIN 160 195 EF-hand 1.
FT DOMAIN 223 258 EF-hand 2.
FT DOMAIN 224 314 EH 3.
FT REPEAT 599 601 1.
FT REPEAT 623 625 2.
FT REPEAT 629 631 3.
FT REPEAT 634 636 4.
FT REPEAT 640 642 5.
FT REPEAT 645 647 6.
FT REPEAT 651 653 7.
FT REPEAT 664 666 8.
FT REPEAT 672 674 9.
FT REPEAT 692 694 10.
FT REPEAT 709 711 11.
FT REPEAT 737 739 12.
FT REPEAT 798 800 13.
FT REPEAT 804 806 14.
FT REPEAT 825 827 15.
FT REPEAT 851 870 UIM 1.
FT REPEAT 877 896 UIM 2.
FT CA_BIND 173 184 1.
FT CA_BIND 236 247 2.
FT REGION 2 330 Interaction with DAB2 (By similarity).
FT REGION 599 827 15 X 3 AA repeats of D-P-F.
FT MOTIF 768 774 SH3-binding.
FT COMPBIAS 768 850 Pro-rich.
FT MOD_RES 2 2 N-acetylalanine.
FT MOD_RES 108 108 Phosphoserine.
FT MOD_RES 140 140 Phosphoserine.
FT MOD_RES 323 323 Phosphoserine.
FT MOD_RES 324 324 Phosphoserine.
FT MOD_RES 467 467 Phosphoserine.
FT MOD_RES 470 470 Phosphoserine.
FT MOD_RES 485 485 Phosphoserine.
FT MOD_RES 777 777 Phosphothreonine (By similarity).
FT MOD_RES 790 790 Phosphoserine.
FT MOD_RES 796 796 Phosphoserine.
FT MOD_RES 814 814 Phosphoserine.
FT MOD_RES 849 849 Phosphotyrosine; by EGFR.
FT VAR_SEQ 1 314 Missing (in isoform 2).
FT /FTId=VSP_036168.
FT VAR_SEQ 315 346 SLQKNIIGSSPVADFSAIKELDTLNNEIVDLQ -> MYLKS
FT DSGLGGWITIPAVADVLKYSCIVCWSS (in isoform
FT 2).
FT /FTId=VSP_036169.
FT VARIANT 822 822 I -> M (in dbSNP:rs17567).
FT /FTId=VAR_016142.
FT MUTAGEN 154 154 V->E: Loss of interaction with STON2 NPF
FT motifs.
FT MUTAGEN 169 169 W->A: Loss of interaction with STON2 NPF
FT motifs.
FT CONFLICT 446 446 Missing (in Ref. 5; BX647676).
FT HELIX 126 136
FT STRAND 142 144
FT STRAND 145 147
FT HELIX 148 156
FT TURN 157 159
FT HELIX 162 172
FT STRAND 177 179
FT HELIX 182 197
FT TURN 207 209
FT HELIX 212 214
FT HELIX 223 235
FT STRAND 240 243
FT HELIX 245 253
FT TURN 254 256
FT HELIX 259 269
FT STRAND 274 278
FT TURN 279 281
FT HELIX 282 293
FT TURN 305 307
FT HELIX 723 726
SQ SEQUENCE 896 AA; 98656 MW; A1B9FE15B47ABAFF CRC64;
MAAAAQLSLT QLSSGNPVYE KYYRQVDTGN TGRVLASDAA AFLKKSGLPD LILGKIWDLA
DTDGKGILNK QEFFVALRLV ACAQNGLEVS LSSLNLAVPP PRFHDTSSPL LISGTSAAEL
PWAVKPEDKA KYDAIFDSLS PVNGFLSGDK VKPVLLNSKL PVDILGRVWE LSDIDHDGML
DRDEFAVAMF LVYCALEKEP VPMSLPPALV PPSKRKTWVV SPAEKAKYDE IFLKTDKDMD
GFVSGLEVRE IFLKTGLPST LLAHIWSLCD TKDCGKLSKD QFALAFHLIS QKLIKGIDPP
HVLTPEMIPP SDRASLQKNI IGSSPVADFS AIKELDTLNN EIVDLQREKN NVEQDLKEKE
DTIKQRTSEV QDLQDEVQRE NTNLQKLQAQ KQQVQELLDE LDEQKAQLEE QLKEVRKKCA
EEAQLISSLK AELTSQESQI STYEEELAKA REELSRLQQE TAELEESVES GKAQLEPLQQ
HLQDSQQEIS SMQMKLMEMK DLENHNSQLN WCSSPHSILV NGATDYCSLS TSSSETANLN
EHVEGQSNLE SEPIHQESPA RSSPELLPSG VTDENEVTTA VTEKVCSELD NNRHSKEEDP
FNVDSSSLTG PVADTNLDFF QSDPFVGSDP FKDDPFGKID PFGGDPFKGS DPFASDCFFR
QSTDPFATSS TDPFSAANNS SITSVETLKH NDPFAPGGTV VAASDSATDP FASVFGNESF
GGGFADFSTL SKVNNEDPFR SATSSSVSNV VITKNVFEET SVKSEDEPPA LPPKIGTPTR
PCPLPPGKRS INKLDSPDPF KLNDPFQPFP GNDSPKEKDP EIFCDPFTSA TTTTNKEADP
SNFANFSAYP SEEDMIEWAK RESEREEEQR LARLNQQEQE DLELAIALSK SEISEA
//
MIM
600051
*RECORD*
*FIELD* NO
600051
*FIELD* TI
*600051 EPIDERMAL GROWTH FACTOR RECEPTOR PATHWAY SUBSTRATE 15; EPS15
;;ALL1-FUSED GENE FROM CHROMOSOME 1; AF1P
read more*FIELD* TX
CLONING
Fazioli et al. (1993) developed an expression cloning approach which,
applied to the study of epidermal growth factor receptor
(EGFR)-activated signaling, yielded a number of murine cDNA clones,
referred to as eps (for egfr-pathway-substrate) clones. One of these
clones, eps15, encoded a protein of 140 to 150 kD. Wong et al. (1994)
cloned the human EPS15 gene.
Bakowska et al. (2005) noted that the full-length 896-amino acid EPS15
protein has 3 N-terminal EPS15 homology (EH) domains, a central
coiled-coil region, an adaptor protein-2 (see AP2A1; 601026)-binding
domain, and a proline-rich domain. Fallon et al. (2006) noted that the
C-terminal region of EPS15 contains 2 ubiquitin-interacting motifs
(UIMs).
GENE FUNCTION
Fazioli et al. (1993) found that Eps15 was phosphorylated on tyrosine
following activation of the EGFR (131550) and platelet-derived growth
factor receptor (PDGFR; 173410). Phosphorylation of eps15 appeared
relatively receptor-specific, since the erbB-2 receptor (164870), which
is highly related to EGFR, was not able to phosphorylate it efficiently.
By yeast 2-hybrid analysis, Bakowska et al. (2005) found that an
N-terminal fragment of spartin (SPG20; 607111) interacted with EPS15,
which was confirmed by protein pull-down and cellular redistribution
assays. Mutation analysis showed that a 99-residue domain near the N
terminus of spartin interacted with the C-terminal 65 amino acids of
EPS15.
Fallon et al. (2006) found that treatment of mammalian cells with human
EGF (131530) stimulated parkin (602544) binding to both Eps15 and Egfr
(131550) and promoted parkin-mediated ubiquitination of Eps15. Binding
of the parkin ubiquitin-like domain to the Eps15 ubiquitin-interacting
motifs was required for parkin-mediated Eps15 ubiquitination. Egfr
endocytosis and degradation were accelerated in parkin-deficient cells,
and Egfr signaling via the PI3K (see 171834)-Akt (164730) pathway was
reduced in parkin-knockout mouse brain. Fallon et al. (2006) proposed
that by ubiquitinating EPS15, parkin interferes with the ability of the
EPS15 UIMs to bind ubiquitinated EGFR, thereby delaying EGFR
internalization and degradation, and promoting PI3K-AKT signaling.
CYTOGENETICS
Most of the translocations affecting the chromosome band 11q23 in human
acute leukemias involve a restricted area of the MLL gene (159555),
which is also known as ALL1. Other partners in the fused gene created by
the translocation include AF4 (159557) on chromosome 4, AF9 (159558) on
chromosome 9, and ENL (159556) on chromosome 19. Indeed, at least 15
different chromosomal partners have been involved with MLL in
leukemia-producing translocations. In 2 myeloid leukemias, the
derivative chromosome 11 expressed the 1,368 N-terminal amino acids of
MLL fused to almost all the AF1P product. The predicted wildtype AF1P
product was a 98-kD acidic protein that exhibited no similarity to AF4,
AF9, and ENL gene products. It was highly similar to the murine EPS15
gene product. Bernard et al. (1994) characterized 2 t(1;11)(p32;q11)
translocations that fused the MML gene to the AF1P (EPS15) gene on 1p32.
MAPPING
Wong et al. (1994) mapped the EPS15 gene to chromosome 1p32-p31 by
analysis of human/rodent hybrids retaining various segments of human
chromosome 1. The region of assignment is one involved in deletion in
neuroblastoma, translocations in acute lymphoblastic leukemia, and a
fragile site.
*FIELD* SA
Fazioli et al. (1993)
*FIELD* RF
1. Bakowska, J. C.; Jenkins, R.; Pendleton, J.; Blackstone, C.: The
Troyer syndrome (SPG20) protein spartin interacts with Eps15. Biochem.
Biophys. Res. Commun. 334: 1042-1048, 2005.
2. Bernard, O. A.; Mauchauffe, M.; Mecucci, C.; Van Den Berghe, H.;
Berger, R.: A novel gene, AF-1p, fused to HRX in t(1;11)(p32;q23),
is not related to AF-4, AF-9 nor ENL. Oncogene 9: 1039-1045, 1994.
3. Fallon, L.; Belanger, C. M. L.; Corera, A. T.; Kontogiannea, M.;
Regan-Klapisz, E.; Moreau, F.; Voortman, J.; Haber, M.; Rouleau, G.;
Thorarinsdottir, T.; Brice, A.; van Bergen en Henegouwen, P. M. P.;
Fon, E. A.: A regulated interaction with the UIM protein Eps15 implicates
parkin in EGF receptor traffickng and PI(3)K-Akt signalling. Nature
Cell Biol. 8: 834-842, 2006.
4. Fazioli, F.; Minichiello, L.; Matoskova, B.; Wong, W. T.; Di Fiore,
P. P.: eps 15, a novel tyrosine kinase substrate, exhibits transforming
activity. Molec. Cell. Biol. 13: 5814-5828, 1993.
5. Fazioli, F.; Wong, W. T.; Ullrich, S. J.; Sakaguchi, K.; Appella,
E.; Di Fiore, P. P.: The ezrin-like family of tyrosine kinase substrates:
receptor-specific pattern of tyrosine phosphorylation and relationship
to malignant transformation. Oncogene 8: 1335-1345, 1993.
6. Wong, W. T.; Kraus, M. H.; Carlomagno, F.; Zelano, A.; Druck, T.;
Croce, C. M.; Huebner, K.; Di Fiore, P. P.: The human eps15 gene,
encoding a tyrosine kinase substrate, is conserved in evolution and
maps to 1p31-p32. Oncogene 9: 1591-1597, 1994.
*FIELD* CN
Patricia A. Hartz - updated: 11/10/2006
*FIELD* CD
Victor A. McKusick: 7/26/1994
*FIELD* ED
carol: 06/25/2009
wwang: 11/16/2006
terry: 11/10/2006
carol: 1/20/1995
carol: 1/13/1995
mimadm: 7/30/1994
jason: 7/26/1994
*RECORD*
*FIELD* NO
600051
*FIELD* TI
*600051 EPIDERMAL GROWTH FACTOR RECEPTOR PATHWAY SUBSTRATE 15; EPS15
;;ALL1-FUSED GENE FROM CHROMOSOME 1; AF1P
read more*FIELD* TX
CLONING
Fazioli et al. (1993) developed an expression cloning approach which,
applied to the study of epidermal growth factor receptor
(EGFR)-activated signaling, yielded a number of murine cDNA clones,
referred to as eps (for egfr-pathway-substrate) clones. One of these
clones, eps15, encoded a protein of 140 to 150 kD. Wong et al. (1994)
cloned the human EPS15 gene.
Bakowska et al. (2005) noted that the full-length 896-amino acid EPS15
protein has 3 N-terminal EPS15 homology (EH) domains, a central
coiled-coil region, an adaptor protein-2 (see AP2A1; 601026)-binding
domain, and a proline-rich domain. Fallon et al. (2006) noted that the
C-terminal region of EPS15 contains 2 ubiquitin-interacting motifs
(UIMs).
GENE FUNCTION
Fazioli et al. (1993) found that Eps15 was phosphorylated on tyrosine
following activation of the EGFR (131550) and platelet-derived growth
factor receptor (PDGFR; 173410). Phosphorylation of eps15 appeared
relatively receptor-specific, since the erbB-2 receptor (164870), which
is highly related to EGFR, was not able to phosphorylate it efficiently.
By yeast 2-hybrid analysis, Bakowska et al. (2005) found that an
N-terminal fragment of spartin (SPG20; 607111) interacted with EPS15,
which was confirmed by protein pull-down and cellular redistribution
assays. Mutation analysis showed that a 99-residue domain near the N
terminus of spartin interacted with the C-terminal 65 amino acids of
EPS15.
Fallon et al. (2006) found that treatment of mammalian cells with human
EGF (131530) stimulated parkin (602544) binding to both Eps15 and Egfr
(131550) and promoted parkin-mediated ubiquitination of Eps15. Binding
of the parkin ubiquitin-like domain to the Eps15 ubiquitin-interacting
motifs was required for parkin-mediated Eps15 ubiquitination. Egfr
endocytosis and degradation were accelerated in parkin-deficient cells,
and Egfr signaling via the PI3K (see 171834)-Akt (164730) pathway was
reduced in parkin-knockout mouse brain. Fallon et al. (2006) proposed
that by ubiquitinating EPS15, parkin interferes with the ability of the
EPS15 UIMs to bind ubiquitinated EGFR, thereby delaying EGFR
internalization and degradation, and promoting PI3K-AKT signaling.
CYTOGENETICS
Most of the translocations affecting the chromosome band 11q23 in human
acute leukemias involve a restricted area of the MLL gene (159555),
which is also known as ALL1. Other partners in the fused gene created by
the translocation include AF4 (159557) on chromosome 4, AF9 (159558) on
chromosome 9, and ENL (159556) on chromosome 19. Indeed, at least 15
different chromosomal partners have been involved with MLL in
leukemia-producing translocations. In 2 myeloid leukemias, the
derivative chromosome 11 expressed the 1,368 N-terminal amino acids of
MLL fused to almost all the AF1P product. The predicted wildtype AF1P
product was a 98-kD acidic protein that exhibited no similarity to AF4,
AF9, and ENL gene products. It was highly similar to the murine EPS15
gene product. Bernard et al. (1994) characterized 2 t(1;11)(p32;q11)
translocations that fused the MML gene to the AF1P (EPS15) gene on 1p32.
MAPPING
Wong et al. (1994) mapped the EPS15 gene to chromosome 1p32-p31 by
analysis of human/rodent hybrids retaining various segments of human
chromosome 1. The region of assignment is one involved in deletion in
neuroblastoma, translocations in acute lymphoblastic leukemia, and a
fragile site.
*FIELD* SA
Fazioli et al. (1993)
*FIELD* RF
1. Bakowska, J. C.; Jenkins, R.; Pendleton, J.; Blackstone, C.: The
Troyer syndrome (SPG20) protein spartin interacts with Eps15. Biochem.
Biophys. Res. Commun. 334: 1042-1048, 2005.
2. Bernard, O. A.; Mauchauffe, M.; Mecucci, C.; Van Den Berghe, H.;
Berger, R.: A novel gene, AF-1p, fused to HRX in t(1;11)(p32;q23),
is not related to AF-4, AF-9 nor ENL. Oncogene 9: 1039-1045, 1994.
3. Fallon, L.; Belanger, C. M. L.; Corera, A. T.; Kontogiannea, M.;
Regan-Klapisz, E.; Moreau, F.; Voortman, J.; Haber, M.; Rouleau, G.;
Thorarinsdottir, T.; Brice, A.; van Bergen en Henegouwen, P. M. P.;
Fon, E. A.: A regulated interaction with the UIM protein Eps15 implicates
parkin in EGF receptor traffickng and PI(3)K-Akt signalling. Nature
Cell Biol. 8: 834-842, 2006.
4. Fazioli, F.; Minichiello, L.; Matoskova, B.; Wong, W. T.; Di Fiore,
P. P.: eps 15, a novel tyrosine kinase substrate, exhibits transforming
activity. Molec. Cell. Biol. 13: 5814-5828, 1993.
5. Fazioli, F.; Wong, W. T.; Ullrich, S. J.; Sakaguchi, K.; Appella,
E.; Di Fiore, P. P.: The ezrin-like family of tyrosine kinase substrates:
receptor-specific pattern of tyrosine phosphorylation and relationship
to malignant transformation. Oncogene 8: 1335-1345, 1993.
6. Wong, W. T.; Kraus, M. H.; Carlomagno, F.; Zelano, A.; Druck, T.;
Croce, C. M.; Huebner, K.; Di Fiore, P. P.: The human eps15 gene,
encoding a tyrosine kinase substrate, is conserved in evolution and
maps to 1p31-p32. Oncogene 9: 1591-1597, 1994.
*FIELD* CN
Patricia A. Hartz - updated: 11/10/2006
*FIELD* CD
Victor A. McKusick: 7/26/1994
*FIELD* ED
carol: 06/25/2009
wwang: 11/16/2006
terry: 11/10/2006
carol: 1/20/1995
carol: 1/13/1995
mimadm: 7/30/1994
jason: 7/26/1994