EPS15_HUMAN
ID EPS15_HUMAN Reviewed; 896 AA.
AC P42566; B2R8J7; D3DPJ2; Q5SRH4;
DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT 07-JUN-2005, sequence version 2.
DT 03-AUG-2022, entry version 226.
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; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC 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 conserved
RT 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 to
RT 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., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., 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., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA 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., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA 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., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., 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., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., 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., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., 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., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., 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 natural
RT 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 EPN1 AND REPS2.
RX PubMed=10393179; DOI=10.1093/emboj/18.13.3629;
RA Nakashima S., Morinaka K., Koyama S., Ikeda M., Kishida M., Okawa K.,
RA Iwamatsu A., Kishida S., Kikuchi A.;
RT "Small G protein Ral and its downstream molecules regulate endocytosis of
RT EGF and insulin receptors.";
RL EMBO J. 18:3629-3642(1999).
RN [11]
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 on
RT early endosomes.";
RL J. Biol. Chem. 278:12513-12521(2003).
RN [12]
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 [13]
RP INTERACTION WITH UBQLN1, AND SUBCELLULAR LOCATION.
RX PubMed=16159959; DOI=10.1242/jcs.02571;
RA Regan-Klapisz E., Sorokina I., Voortman J., de Keizer P., Roovers R.C.,
RA Verheesen P., Urbe S., Fallon L., Fon E.A., Verkleij A., Benmerah A.,
RA van Bergen en Henegouwen P.M.;
RT "Ubiquilin recruits Eps15 into ubiquitin-rich cytoplasmic aggregates via a
RT UIM-UBL interaction.";
RL J. Cell Sci. 118:4437-4450(2005).
RN [14]
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 cell
RT surface receptor.";
RL Mol. Cell. Biol. 25:11005-11018(2005).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-323, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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 phosphorylation
RT analysis and site localization.";
RL Nat. Biotechnol. 24:1285-1292(2006).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-485, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic kidney;
RX PubMed=17525332; DOI=10.1126/science.1140321;
RA Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E.,
RA Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y.,
RA 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 [17]
RP FUNCTION, ALTERNATIVE SPLICING (ISOFORM 2), SUBCELLULAR LOCATION (ISOFORM
RP 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 mediate
RT degradation of epidermal growth factor receptor.";
RL J. Cell Biol. 180:1205-1218(2008).
RN [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-796 AND SER-814, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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 [19]
RP INTERACTION WITH UBQLN1 AND UBQLN2.
RX PubMed=18199683; DOI=10.1091/mbc.e07-08-0775;
RA N'Diaye E.N., Hanyaloglu A.C., Kajihara K.K., Puthenveedu M.A., Wu P.,
RA von Zastrow M., Brown E.J.;
RT "The ubiquitin-like protein PLIC-2 is a negative regulator of G protein-
RT coupled receptor endocytosis.";
RL Mol. Biol. Cell 19:1252-1260(2008).
RN [20]
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 the
RT kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [21]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-140; SER-323; SER-485 AND
RP SER-814, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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 [22]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [23]
RP FUNCTION.
RX PubMed=19458185; DOI=10.1091/mbc.e09-03-0256;
RA Mettlen M., Stoeber M., Loerke D., Antonescu C.N., Danuser G., 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 [24]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-108; SER-323; SER-324;
RP SER-814 AND TYR-849, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
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 [25]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-324; SER-467; SER-470;
RP SER-790; SER-796 AND SER-814, AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
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., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [26]
RP INTERACTION WITH FCHO2.
RX PubMed=20448150; DOI=10.1126/science.1188462;
RA Henne W.M., Boucrot E., Meinecke M., Evergren E., Vallis Y., Mittal R.,
RA McMahon H.T.;
RT "FCHo proteins are nucleators of clathrin-mediated endocytosis.";
RL Science 328:1281-1284(2010).
RN [27]
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., Buerckstuemmer T.,
RA 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 [28]
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 [29]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-324; SER-485; SER-790;
RP SER-796 AND SER-814, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [30]
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 regulate
RT integrin beta1 endocytosis.";
RL Mol. Biol. Cell 23:2905-2916(2012).
RN [31]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=22223895; DOI=10.1074/mcp.m111.015131;
RA Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T.,
RA Giglione C.;
RT "Comparative large-scale characterisation of plant vs. mammal proteins
RT reveals similar and idiosyncratic N-alpha acetylation features.";
RL Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012).
RN [32]
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 [33]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
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., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [34]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-324; SER-746; THR-777;
RP SER-790; SER-796 AND SER-814, AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [35]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-324; THR-777; SER-796 AND
RP SER-814, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [36]
RP INTERACTION WITH CORO7.
RX PubMed=24768539; DOI=10.1016/j.molcel.2014.03.035;
RA Yuan W.C., Lee Y.R., Lin S.Y., Chang L.Y., Tan Y.P., Hung C.C., Kuo J.C.,
RA Liu C.H., Lin M.Y., Xu M., Chen Z.J., Chen R.H.;
RT "K33-linked polyubiquitination of coronin 7 by Cul3-KLHL20 ubiquitin E3
RT ligase regulates protein trafficking.";
RL Mol. Cell 54:586-600(2014).
RN [37]
RP INTERACTION WITH VACCINIA VIRUS PROTEIN A36 (MICROBIAL INFECTION).
RX PubMed=27670116; DOI=10.1038/nmicrobiol.2016.141;
RA Snetkov X., Weisswange I., Pfanzelter J., Humphries A.C., Way M.;
RT "NPF motifs in the vaccinia virus protein A36 recruit intersectin-1 to
RT promote Cdc42:N-WASP-mediated viral release from infected cells.";
RL Nat. Microbiol. 1:16141-16141(2016).
RN [38]
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 domain.";
RL Science 281:1357-1360(1998).
RN [39]
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-Trp
RT and Asn-Pro-Phe binding sites.";
RL Biochemistry 39:4309-4319(2000).
RN [40]
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., Kay B.K.,
RA Overduin M.;
RT "Molecular mechanism of NPF recognition by EH domains.";
RL Nat. Struct. Biol. 7:1018-1022(2000).
RN [41]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 719-730 IN COMPLEX WITH AP2B1,
RP IDENTIFICATION BY 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 clathrin-
RT coated vesicle assembly.";
RL PLoS Biol. 4:E262-E262(2006).
RN [42]
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 explanation
RT for EH-domain ligand specificity.";
RL EMBO J. 27:558-569(2008).
RN [43]
RP X-RAY CRYSTALLOGRAPHY (2.70 ANGSTROMS) OF 645-654, AND INTERACTION WITH
RP SGIP1.
RX PubMed=26822536; DOI=10.1038/srep19565;
RA Shimada A., Yamaguchi A., Kohda D.;
RT "Structural basis for the recognition of two consecutive mutually
RT interacting DPF motifs by the SGIP1 mu homology domain.";
RL Sci. Rep. 6:19565-19565(2016).
CC -!- FUNCTION: Involved in cell growth regulation. May be involved in the
CC regulation of mitogenic signals and control of cell proliferation.
CC Involved in the internalization of ligand-inducible receptors of the
CC receptor tyrosine kinase (RTK) type, in particular EGFR. Plays a role
CC in the assembly of clathrin-coated pits (CCPs). Acts as a clathrin
CC adapter required for post-Golgi trafficking. Seems to be involved in
CC CCPs maturation including invagination or budding. Involved in
CC endocytosis of integrin beta-1 (ITGB1) and transferrin receptor (TFR);
CC internalization of ITGB1 as DAB2-dependent cargo but not TFR seems to
CC require association with DAB2. {ECO:0000269|PubMed:16903783,
CC ECO:0000269|PubMed:18362181, ECO:0000269|PubMed:19458185,
CC ECO:0000269|PubMed:22648170}.
CC -!- SUBUNIT: Interacts with SGIP1 (PubMed:26822536). Interacts with HGS;
CC the interaction bridges the interaction of STAM or STAM2 with EPS15.
CC Isoform 2 interacts with HGS and AP2A2. Part of a complex at least
CC composed of EPS15, HGS, and either STAM or STAM2. Binds AP2A2.
CC Interacts with AP2B1; clathrin competes with EPS15. Binds STON2.
CC Interacts (via its SH3-binding sites) with CRK. Interacts with
CC SH3BP4/TTP. Interacts with ERBB2. Interacts with FCHO1. Interacts with
CC FCHO2. Interacts (via EH domains) with DAB2. Interacts (via UIM
CC repeats) with CORO7 (when ubiquitinated at 'Lys-472'). Interacts (via
CC UIM domains) with UBQLN1 (via ubiquitin-like domain) and can interact
CC with both the ubiquitinated and the non-ubiquitinated forms of UBQLN1.
CC Interacts with UBQLN2 (By similarity) (PubMed:10757979,
CC PubMed:11062555, PubMed:12551915, PubMed:16159959, PubMed:16314522,
CC PubMed:16325581, PubMed:16903783, PubMed:18199683, PubMed:18200045,
CC PubMed:18362181, PubMed:20448150, PubMed:21762413, PubMed:22484487,
CC PubMed:22648170, PubMed:24768539, PubMed:8662907, PubMed:9721102,
CC PubMed:9723620). Interacts with REPS2; the interaction is direct
CC (PubMed:10393179). Interacts with EPN1; the interaction is direct
CC (PubMed:9723620, PubMed:10393179). {ECO:0000250|UniProtKB:P42567,
CC ECO:0000269|PubMed:10393179, ECO:0000269|PubMed:10757979,
CC ECO:0000269|PubMed:11062555, ECO:0000269|PubMed:12551915,
CC ECO:0000269|PubMed:16159959, ECO:0000269|PubMed:16314522,
CC ECO:0000269|PubMed:16325581, ECO:0000269|PubMed:16903783,
CC ECO:0000269|PubMed:18199683, ECO:0000269|PubMed:18200045,
CC ECO:0000269|PubMed:18362181, ECO:0000269|PubMed:20448150,
CC ECO:0000269|PubMed:21762413, ECO:0000269|PubMed:22484487,
CC ECO:0000269|PubMed:22648170, ECO:0000269|PubMed:24768539,
CC ECO:0000269|PubMed:26822536, ECO:0000269|PubMed:8662907,
CC ECO:0000269|PubMed:9721102, ECO:0000269|PubMed:9723620}.
CC -!- SUBUNIT: (Microbial infection) Interacts with vaccinia virus protein
CC A36. {ECO:0000269|PubMed:27670116}.
CC -!- INTERACTION:
CC P42566; P52594: AGFG1; NbExp=3; IntAct=EBI-396684, EBI-996560;
CC P42566; P63010: AP2B1; NbExp=2; IntAct=EBI-396684, EBI-432924;
CC P42566; P98082: DAB2; NbExp=2; IntAct=EBI-396684, EBI-1171238;
CC P42566; Q9Y6I3: EPN1; NbExp=2; IntAct=EBI-396684, EBI-713198;
CC P42566; P58107: EPPK1; NbExp=5; IntAct=EBI-396684, EBI-297954;
CC P42566; Q0JRZ9: FCHO2; NbExp=3; IntAct=EBI-396684, EBI-2609756;
CC P42566; Q15811: ITSN1; NbExp=3; IntAct=EBI-396684, EBI-602041;
CC P42566; P16333: NCK1; NbExp=2; IntAct=EBI-396684, EBI-389883;
CC P42566; P49757: NUMB; NbExp=4; IntAct=EBI-396684, EBI-915016;
CC P42566; Q13492: PICALM; NbExp=2; IntAct=EBI-396684, EBI-2803688;
CC P42566; Q9P0V3: SH3BP4; NbExp=2; IntAct=EBI-396684, EBI-1049513;
CC P42566; Q8WXE9: STON2; NbExp=18; IntAct=EBI-396684, EBI-539742;
CC P42566; Q9UMX0: UBQLN1; NbExp=7; IntAct=EBI-396684, EBI-741480;
CC P42566; Q9UHD9: UBQLN2; NbExp=2; IntAct=EBI-396684, EBI-947187;
CC P42566; Q3UQN2: Fcho2; Xeno; NbExp=3; IntAct=EBI-396684, EBI-6094986;
CC P42566; Q9QZS3-1: Numb; Xeno; NbExp=3; IntAct=EBI-396684, EBI-9547433;
CC P42566; Q9QZS3-2: Numb; Xeno; NbExp=3; IntAct=EBI-396684, EBI-3896014;
CC P42566-1; P26045: PTPN3; NbExp=4; IntAct=EBI-15895294, EBI-1047946;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Cell membrane; Peripheral membrane
CC protein; Cytoplasmic side. Membrane, clathrin-coated pit.
CC Note=Recruited to the plasma membrane upon EGFR activation and
CC localizes to coated pits. Colocalizes with UBQLN1 in ubiquitin-rich
CC cytoplasmic aggregates that are not endocytic compartments and in
CC cytoplasmic juxtanuclear structures called aggresomes.
CC {ECO:0000269|PubMed:16159959}.
CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Early endosome membrane
CC {ECO:0000269|PubMed:18362181}; Peripheral membrane protein
CC {ECO:0000269|PubMed:18362181}; Cytoplasmic side
CC {ECO:0000269|PubMed:18362181}. Note=Colocalizes with HGS on bilayered
CC 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 target
CC proteins. {ECO:0000269|PubMed:11062555}.
CC -!- DOMAIN: The UIM (ubiquitin-interacting motif) repeats specifically bind
CC 'Lys-33'-linked ubiquitin. {ECO:0000269|PubMed:11062555,
CC ECO:0000269|PubMed:24768539}.
CC -!- PTM: Phosphorylation on Tyr-849 is involved in the internalization of
CC EGFR. Not required for membrane translocation after EGF treatment or
CC for targeting to coated pits, but essential for a subsequent step in
CC EGFR endocytosis (By similarity). Phosphorylated on serine upon DNA
CC damage, probably by ATM or ATR. {ECO:0000250}.
CC -!- PTM: Ubiquitinated. {ECO:0000250|UniProtKB:P42567}.
CC -!- DISEASE: Note=A chromosomal aberration involving EPS15 is found in
CC acute leukemias. Translocation t(1;11)(p32;q23) with KMT2A/MLL1. The
CC result is a rogue activator protein.
CC -!- CAUTION: Studies in clathrin-mediated endocytosis of ITGB1 and TFR used
CC a siRNA mixture of EPS15 and EPS15L1, and a Dab2 mutant with impaired
CC binding to EH domain-containing proteins EPS15 and ITSN1 suggesting a
CC partially overlapping role of the EH domain-containing proteins.
CC {ECO:0000305|PubMed:22648170}.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/AF1pID11.html";
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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; AC104170; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL671986; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471059; EAX06823.1; -; Genomic_DNA.
DR CCDS; CCDS557.1; -. [P42566-1]
DR PIR; S43074; S43074.
DR RefSeq; NP_001153441.1; NM_001159969.1. [P42566-2]
DR RefSeq; NP_001972.1; NM_001981.2. [P42566-1]
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=723-730.
DR PDB; 2JXC; NMR; -; A=121-215.
DR PDB; 4RH5; X-ray; 1.60 A; B=846-854.
DR PDB; 4RH9; X-ray; 1.60 A; B=846-854.
DR PDB; 4RHG; X-ray; 1.58 A; B=846-854.
DR PDB; 4S0G; X-ray; 1.72 A; B=846-854.
DR PDB; 5AWT; X-ray; 2.70 A; B=640-649.
DR PDB; 5AWU; X-ray; 2.70 A; B=645-654.
DR PDB; 5JP2; X-ray; 2.40 A; E/F=615-637.
DR PDBsum; 1C07; -.
DR PDBsum; 1EH2; -.
DR PDBsum; 1F8H; -.
DR PDBsum; 1FF1; -.
DR PDBsum; 2IV9; -.
DR PDBsum; 2JXC; -.
DR PDBsum; 4RH5; -.
DR PDBsum; 4RH9; -.
DR PDBsum; 4RHG; -.
DR PDBsum; 4S0G; -.
DR PDBsum; 5AWT; -.
DR PDBsum; 5AWU; -.
DR PDBsum; 5JP2; -.
DR AlphaFoldDB; P42566; -.
DR SMR; P42566; -.
DR BioGRID; 108374; 200.
DR CORUM; P42566; -.
DR DIP; DIP-33064N; -.
DR ELM; P42566; -.
DR IntAct; P42566; 155.
DR MINT; P42566; -.
DR STRING; 9606.ENSP00000360798; -.
DR BindingDB; P42566; -.
DR ChEMBL; CHEMBL4295760; -.
DR MoonDB; P42566; Curated.
DR MoonProt; P42566; -.
DR GlyGen; P42566; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P42566; -.
DR PhosphoSitePlus; P42566; -.
DR BioMuta; EPS15; -.
DR DMDM; 67476728; -.
DR OGP; P42566; -.
DR CPTAC; CPTAC-966; -.
DR CPTAC; CPTAC-967; -.
DR EPD; P42566; -.
DR jPOST; P42566; -.
DR MassIVE; P42566; -.
DR MaxQB; P42566; -.
DR PaxDb; P42566; -.
DR PeptideAtlas; P42566; -.
DR PRIDE; P42566; -.
DR ProteomicsDB; 55515; -. [P42566-1]
DR ProteomicsDB; 55516; -. [P42566-2]
DR Antibodypedia; 1916; 256 antibodies from 31 providers.
DR DNASU; 2060; -.
DR Ensembl; ENST00000371733.8; ENSP00000360798.3; ENSG00000085832.17. [P42566-1]
DR GeneID; 2060; -.
DR KEGG; hsa:2060; -.
DR MANE-Select; ENST00000371733.8; ENSP00000360798.3; NM_001981.3; NP_001972.1.
DR UCSC; uc001csq.2; human. [P42566-1]
DR CTD; 2060; -.
DR DisGeNET; 2060; -.
DR GeneCards; EPS15; -.
DR HGNC; HGNC:3419; EPS15.
DR HPA; ENSG00000085832; Low tissue specificity.
DR MIM; 600051; gene.
DR neXtProt; NX_P42566; -.
DR OpenTargets; ENSG00000085832; -.
DR PharmGKB; PA27838; -.
DR VEuPathDB; HostDB:ENSG00000085832; -.
DR eggNOG; KOG0998; Eukaryota.
DR GeneTree; ENSGT00940000155751; -.
DR InParanoid; P42566; -.
DR OMA; NSQLNWC; -.
DR OrthoDB; 597979at2759; -.
DR PhylomeDB; P42566; -.
DR TreeFam; TF324293; -.
DR PathwayCommons; P42566; -.
DR Reactome; R-HSA-182971; EGFR downregulation.
DR Reactome; R-HSA-6807004; Negative regulation of MET activity.
DR Reactome; R-HSA-8856825; Cargo recognition for clathrin-mediated endocytosis.
DR Reactome; R-HSA-8856828; Clathrin-mediated endocytosis.
DR Reactome; R-HSA-8875360; InlB-mediated entry of Listeria monocytogenes into host cell.
DR SignaLink; P42566; -.
DR SIGNOR; P42566; -.
DR BioGRID-ORCS; 2060; 11 hits in 1079 CRISPR screens.
DR ChiTaRS; EPS15; human.
DR EvolutionaryTrace; P42566; -.
DR GeneWiki; EPS15; -.
DR GenomeRNAi; 2060; -.
DR Pharos; P42566; Tchem.
DR PRO; PR:P42566; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; P42566; protein.
DR Bgee; ENSG00000085832; Expressed in endothelial cell and 211 other tissues.
DR ExpressionAtlas; P42566; baseline and differential.
DR Genevisible; P42566; HS.
DR GO; GO:0016235; C:aggresome; IDA:UniProtKB.
DR GO; GO:0030132; C:clathrin coat of coated pit; IBA:GO_Central.
DR GO; GO:0005905; C:clathrin-coated pit; TAS:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
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:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:HGNC-UCL.
DR GO; GO:0045296; F:cadherin binding; HDA:BHF-UCL.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0031593; F:polyubiquitin modification-dependent protein binding; IDA:UniProtKB.
DR GO; GO:0017124; F:SH3 domain binding; IEA:UniProtKB-KW.
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; IBA:GO_Central.
DR GO; GO:0016197; P:endosomal transport; IBA:GO_Central.
DR GO; GO:0006895; P:Golgi to endosome transport; IMP:UniProtKB.
DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW.
DR GO; GO:0019065; P:receptor-mediated endocytosis of virus by host cell; IMP:CACAO.
DR GO; GO:0016050; P:vesicle organization; TAS:UniProtKB.
DR GO; GO:0046718; P:viral entry into host cell; IMP:CACAO.
DR CDD; cd00052; EH; 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; EH_dom.
DR InterPro; IPR003903; UIM_dom.
DR Pfam; PF12763; EF-hand_4; 3.
DR SMART; SM00054; EFh; 3.
DR SMART; SM00027; EH; 3.
DR SMART; SM00726; UIM; 3.
DR SUPFAM; SSF47473; SSF47473; 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; Cell membrane;
KW Chromosomal rearrangement; Coated pit; Cytoplasm; Endocytosis; Endosome;
KW Host-virus interaction; Membrane; Metal-binding; Phosphoprotein;
KW Protein transport; Proto-oncogene; Reference proteome; Repeat; SH3-binding;
KW Transport; Ubl conjugation.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:19413330,
FT ECO:0007744|PubMed:22223895, ECO:0007744|PubMed:22814378"
FT CHAIN 2..896
FT /note="Epidermal growth factor receptor substrate 15"
FT /id="PRO_0000146116"
FT DOMAIN 15..104
FT /note="EH 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00077"
FT DOMAIN 48..83
FT /note="EF-hand 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DOMAIN 128..216
FT /note="EH 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00077"
FT DOMAIN 160..195
FT /note="EF-hand 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DOMAIN 223..258
FT /note="EF-hand 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DOMAIN 224..314
FT /note="EH 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00077"
FT DOMAIN 262..292
FT /note="EF-hand 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT REPEAT 599..601
FT /note="1"
FT REPEAT 623..625
FT /note="2"
FT REPEAT 629..631
FT /note="3"
FT REPEAT 634..636
FT /note="4"
FT REPEAT 640..642
FT /note="5"
FT REPEAT 645..647
FT /note="6"
FT REPEAT 651..653
FT /note="7"
FT REPEAT 664..666
FT /note="8"
FT REPEAT 672..674
FT /note="9"
FT REPEAT 692..694
FT /note="10"
FT REPEAT 709..711
FT /note="11"
FT REPEAT 737..739
FT /note="12"
FT REPEAT 798..800
FT /note="13"
FT REPEAT 804..806
FT /note="14"
FT REPEAT 825..827
FT /note="15"
FT DOMAIN 851..870
FT /note="UIM 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00213"
FT DOMAIN 877..896
FT /note="UIM 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00213"
FT REGION 2..330
FT /note="Interaction with DAB2"
FT /evidence="ECO:0000250"
FT REGION 542..606
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 599..827
FT /note="15 X 3 AA repeats of D-P-F"
FT REGION 760..848
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 768..774
FT /note="SH3-binding"
FT COMPBIAS 542..586
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 587..601
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 771..785
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 826..848
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 173
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 175
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 177
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 179
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 184
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 236
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 238
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 240
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 247
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0007744|PubMed:19413330,
FT ECO:0007744|PubMed:22223895, ECO:0007744|PubMed:22814378"
FT MOD_RES 108
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332"
FT MOD_RES 140
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 323
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:16964243,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:19690332"
FT MOD_RES 324
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569"
FT MOD_RES 467
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231"
FT MOD_RES 470
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231"
FT MOD_RES 485
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17525332,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:21406692"
FT MOD_RES 562
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P42567"
FT MOD_RES 563
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P42567"
FT MOD_RES 746
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 777
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 779
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P42567"
FT MOD_RES 790
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163"
FT MOD_RES 796
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18088087,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569"
FT MOD_RES 814
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18088087,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569"
FT MOD_RES 849
FT /note="Phosphotyrosine; by EGFR"
FT /evidence="ECO:0007744|PubMed:19690332"
FT VAR_SEQ 1..314
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:17974005"
FT /id="VSP_036168"
FT VAR_SEQ 315..346
FT /note="SLQKNIIGSSPVADFSAIKELDTLNNEIVDLQ -> MYLKSDSGLGGWITIP
FT AVADVLKYSCIVCWSS (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:17974005"
FT /id="VSP_036169"
FT VARIANT 822
FT /note="I -> M (in dbSNP:rs17567)"
FT /evidence="ECO:0000269|PubMed:8183552"
FT /id="VAR_016142"
FT MUTAGEN 154
FT /note="V->E: Loss of interaction with STON2 NPF motifs."
FT /evidence="ECO:0000269|PubMed:18200045"
FT MUTAGEN 169
FT /note="W->A: Loss of interaction with STON2 NPF motifs."
FT /evidence="ECO:0000269|PubMed:18200045"
FT CONFLICT 446
FT /note="Missing (in Ref. 5; BX647676)"
FT /evidence="ECO:0000305"
FT HELIX 126..136
FT /evidence="ECO:0007829|PDB:1EH2"
FT STRAND 142..144
FT /evidence="ECO:0007829|PDB:1EH2"
FT STRAND 145..147
FT /evidence="ECO:0007829|PDB:2JXC"
FT HELIX 148..156
FT /evidence="ECO:0007829|PDB:1EH2"
FT TURN 157..159
FT /evidence="ECO:0007829|PDB:1EH2"
FT HELIX 162..172
FT /evidence="ECO:0007829|PDB:1EH2"
FT STRAND 177..179
FT /evidence="ECO:0007829|PDB:1EH2"
FT HELIX 182..197
FT /evidence="ECO:0007829|PDB:1EH2"
FT TURN 207..209
FT /evidence="ECO:0007829|PDB:1EH2"
FT HELIX 212..214
FT /evidence="ECO:0007829|PDB:1F8H"
FT HELIX 223..235
FT /evidence="ECO:0007829|PDB:1C07"
FT STRAND 240..243
FT /evidence="ECO:0007829|PDB:1C07"
FT HELIX 245..253
FT /evidence="ECO:0007829|PDB:1C07"
FT TURN 254..256
FT /evidence="ECO:0007829|PDB:1C07"
FT HELIX 259..269
FT /evidence="ECO:0007829|PDB:1C07"
FT STRAND 274..278
FT /evidence="ECO:0007829|PDB:1C07"
FT TURN 279..281
FT /evidence="ECO:0007829|PDB:1C07"
FT HELIX 282..293
FT /evidence="ECO:0007829|PDB:1C07"
FT TURN 305..307
FT /evidence="ECO:0007829|PDB:1C07"
FT TURN 624..627
FT /evidence="ECO:0007829|PDB:5JP2"
FT TURN 630..633
FT /evidence="ECO:0007829|PDB:5JP2"
FT HELIX 723..726
FT /evidence="ECO:0007829|PDB:2IV9"
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
