ID EPS15_MOUSE Reviewed; 897 AA. AC P42567; Q8C431; DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1995, sequence version 1. DT 24-JAN-2024, entry version 213. DE RecName: Full=Epidermal growth factor receptor substrate 15; DE Short=Protein Eps15; DE AltName: Full=Protein AF-1p; GN Name=Eps15; OS Mus musculus (Mouse). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Mus; Mus. OX NCBI_TaxID=10090; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC TISSUE=Fibroblast; RX PubMed=7689153; DOI=10.1128/mcb.13.9.5814-5828.1993; RA Fazioli F., Minichiello L., Matoskova B., Wong W.T., di Fiore P.P.; RT "eps15, a novel tyrosine kinase substrate, exhibits transforming RT activity."; RL Mol. Cell. Biol. 13:5814-5828(1993). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC STRAIN=C57BL/6J; TISSUE=Hippocampus; RX PubMed=16141072; DOI=10.1126/science.1112014; RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J., RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.; RT "The transcriptional landscape of the mammalian genome."; RL Science 309:1559-1563(2005). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=C57BL/6J; RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112; RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S., RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., RA Eichler E.E., Ponting C.P.; RT "Lineage-specific biology revealed by a finished genome assembly of the RT mouse."; RL PLoS Biol. 7:E1000112-E1000112(2009). RN [4] RP PROTEIN SEQUENCE OF 838-862, AND IDENTIFICATION BY MASS SPECTROMETRY. RC STRAIN=OF1; TISSUE=Hippocampus; RA Lubec G., Sunyer B., Chen W.-Q.; RL Submitted (JAN-2009) to UniProtKB. RN [5] RP INTERACTION WITH 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 [6] RP PHOSPHORYLATION AT TYR-850 BY EGFR, AND MUTAGENESIS OF TYR-850. RX PubMed=10953014; DOI=10.1083/jcb.150.4.905; RA Confalonieri S., Salcini A.E., Puri C., Tacchetti C., Di Fiore P.P.; RT "Tyrosine phosphorylation of Eps15 is required for ligand-regulated, but RT not constitutive, endocytosis."; RL J. Cell Biol. 150:905-912(2000). RN [7] RP INTERACTION WITH UBQLN1, UBIQUITINATION, AND MUTAGENESIS OF GLU-863; RP SER-864; GLU-865; LEU-883 AND LEU-885. 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 [8] RP INTERACTION WITH SGIP1. RX PubMed=17626015; DOI=10.1074/jbc.m703815200; RA Uezu A., Horiuchi A., Kanda K., Kikuchi N., Umeda K., Tsujita K., RA Suetsugu S., Araki N., Yamamoto H., Takenawa T., Nakanishi H.; RT "SGIP1alpha is an endocytic protein that directly interacts with RT phospholipids and Eps15."; RL J. Biol. Chem. 282:26481-26489(2007). RN [9] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-779, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=17242355; DOI=10.1073/pnas.0609836104; RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.; RT "Large-scale phosphorylation analysis of mouse liver."; RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007). RN [10] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-324, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19144319; DOI=10.1016/j.immuni.2008.11.006; RA Trost M., English L., Lemieux S., Courcelles M., Desjardins M., RA Thibault P.; RT "The phagosomal proteome in interferon-gamma-activated macrophages."; RL Immunity 30:143-154(2009). RN [11] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Embryonic fibroblast; RX PubMed=19131326; DOI=10.1074/mcp.m800451-mcp200; RA Sweet S.M., Bailey C.M., Cunningham D.L., Heath J.K., Cooper H.J.; RT "Large scale localization of protein phosphorylation by use of electron RT capture dissociation mass spectrometry."; RL Mol. Cell. Proteomics 8:904-912(2009). RN [12] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-140; THR-321; SER-324; RP SER-561; SER-562; THR-781 AND SER-816, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, RC Pancreas, Spleen, and Testis; RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001; RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R., RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.; RT "A tissue-specific atlas of mouse protein phosphorylation and expression."; RL Cell 143:1174-1189(2010). RN [13] 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 [14] 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 [15] RP 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 [16] RP STRUCTURE BY NMR OF 7-105. RX PubMed=10471276; DOI=10.1021/bi990922i; RA Whitehead B., Tessari M., Carotenuto A., van Bergen en Henegouwen P.M., RA Vuister G.W.; RT "The EH1 domain of Eps15 is structurally classified as a member of the S100 RT subclass of EF-hand-containing proteins."; RL Biochemistry 38:11271-11277(1999). RN [17] RP X-RAY CRYSTALLOGRAPHY (1.22 ANGSTROMS) OF 628-632 IN COMPLEX WITH AP2A2. RX PubMed=12057195; DOI=10.1016/s0969-2126(02)00784-0; RA Brett T.J., Traub L.M., Fremont D.H.; RT "Accessory protein recruitment motifs in clathrin-mediated endocytosis."; RL Structure 10:797-809(2002). 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. CC -!- SUBUNIT: Interacts with HGS; the interaction bridges the interaction of CC STAM or STAM2 with EPS15. Isoform 2 interacts with HGS and AP2A2. Part CC of a complex at least composed of EPS15, HGS, and either STAM or STAM2. CC Binds AP2A2. Interacts with AP2B1; clathrin competes with EPS15. Binds CC STON2. Interacts (via its SH3-binding sites) with CRK. Interacts with CC SH3BP4/TTP. Interacts with ERBB2. Interacts (via UIM repeats) with CC CORO7 (when ubiquitinated at 'Lys-472') (By similarity). Interacts with CC FCHO1 (By similarity). Interacts with FCHO2. Interacts with SGIP1. CC Interacts (via EH domains) with DAB2. Interacts (via UIM domains) with CC UBQLN1 (via ubiquitin-like domain) and can interact with both the CC ubiquitinated and the non-ubiquitinated forms of UBQLN1. Interacts with CC UBQLN2 (By similarity). Interacts with REPS2; the interaction is direct CC (PubMed:10393179). Interacts with EPN1; the interaction is direct (By CC similarity). {ECO:0000250|UniProtKB:P42566, CC ECO:0000269|PubMed:10393179, ECO:0000269|PubMed:12057195, CC ECO:0000269|PubMed:16159959, ECO:0000269|PubMed:17626015, CC ECO:0000269|PubMed:20448150, ECO:0000269|PubMed:21762413, CC ECO:0000269|PubMed:22648170}. CC -!- INTERACTION: CC P42567; P98078: Dab2; NbExp=2; IntAct=EBI-443923, EBI-1391846; CC P42567; P42567: Eps15; NbExp=4; IntAct=EBI-443923, EBI-443923; CC P42567; Q60902: Eps15l1; NbExp=2; IntAct=EBI-443923, EBI-443931; CC P42567; Q8NFH8: REPS2; Xeno; NbExp=10; IntAct=EBI-443923, EBI-7067016; 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:0000250|UniProtKB:P42566}. CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Early endosome membrane CC {ECO:0000250}; Peripheral membrane protein {ECO:0000250}; Cytoplasmic CC side {ECO:0000250}. Note=Colocalizes with HGS on bilayered clathrin CC coats on endosomes. {ECO:0000250}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=P42567-1; Sequence=Displayed; CC Name=2; Synonyms=Eps15b; CC IsoId=P42567-2; Sequence=VSP_036170, VSP_036171; CC -!- DOMAIN: The EH domain interacts with Asn-Pro-Phe (NPF) motifs of target CC proteins. {ECO:0000250}. CC -!- DOMAIN: The UIM (ubiquitin-interacting motif) repeats specifically bind CC 'Lys-33'-linked ubiquitin. {ECO:0000250}. CC -!- PTM: Phosphorylated on serine upon DNA damage, probably by ATM or ATR CC (By similarity). Phosphorylation on Tyr-850 is involved in the CC internalization of EGFR. Not required for membrane translocation after CC EGF treatment or for targeting to coated pits, but essential for a CC subsequent step in EGFR endocytosis. {ECO:0000250, CC ECO:0000269|PubMed:10953014}. CC -!- PTM: Ubiquitinated. {ECO:0000269|PubMed:16159959}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; L21768; AAA02912.1; -; mRNA. DR EMBL; AK083176; BAC38796.1; -; mRNA. DR EMBL; AL669905; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR CCDS; CCDS18462.1; -. [P42567-1] DR PIR; A54696; A54696. DR RefSeq; NP_001153436.1; NM_001159964.1. DR RefSeq; NP_031969.1; NM_007943.3. [P42567-1] DR PDB; 1KYF; X-ray; 1.22 A; P=627-632. DR PDB; 1KYU; X-ray; 1.80 A; P=627-632. DR PDB; 1QJT; NMR; -; A=7-105. DR PDBsum; 1KYF; -. DR PDBsum; 1KYU; -. DR PDBsum; 1QJT; -. DR AlphaFoldDB; P42567; -. DR SMR; P42567; -. DR BioGRID; 199489; 51. DR CORUM; P42567; -. DR DIP; DIP-29052N; -. DR ELM; P42567; -. DR IntAct; P42567; 9. DR MINT; P42567; -. DR STRING; 10090.ENSMUSP00000099790; -. DR GlyGen; P42567; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; P42567; -. DR PhosphoSitePlus; P42567; -. DR EPD; P42567; -. DR jPOST; P42567; -. DR PaxDb; 10090-ENSMUSP00000099790; -. DR PeptideAtlas; P42567; -. DR ProteomicsDB; 275463; -. [P42567-1] DR ProteomicsDB; 275464; -. [P42567-2] DR Antibodypedia; 1916; 285 antibodies from 31 providers. DR DNASU; 13858; -. DR Ensembl; ENSMUST00000102729.10; ENSMUSP00000099790.4; ENSMUSG00000028552.14. [P42567-1] DR GeneID; 13858; -. DR KEGG; mmu:13858; -. DR UCSC; uc008ucf.2; mouse. [P42567-1] DR UCSC; uc008ucg.2; mouse. [P42567-2] DR AGR; MGI:104583; -. DR CTD; 2060; -. DR MGI; MGI:104583; Eps15. DR VEuPathDB; HostDB:ENSMUSG00000028552; -. DR eggNOG; KOG0998; Eukaryota. DR GeneTree; ENSGT00940000155751; -. DR InParanoid; P42567; -. DR OrthoDB; 12127at2759; -. DR PhylomeDB; P42567; -. DR TreeFam; TF324293; -. DR Reactome; R-MMU-182971; EGFR downregulation. DR Reactome; R-MMU-6807004; Negative regulation of MET activity. DR Reactome; R-MMU-8856825; Cargo recognition for clathrin-mediated endocytosis. DR Reactome; R-MMU-8856828; Clathrin-mediated endocytosis. DR BioGRID-ORCS; 13858; 1 hit in 79 CRISPR screens. DR ChiTaRS; Eps15; mouse. DR EvolutionaryTrace; P42567; -. DR PRO; PR:P42567; -. DR Proteomes; UP000000589; Chromosome 4. DR RNAct; P42567; Protein. DR Bgee; ENSMUSG00000028552; Expressed in CA1 field of hippocampus and 266 other cell types or tissues. DR ExpressionAtlas; P42567; baseline and differential. DR GO; GO:0016235; C:aggresome; ISO:MGI. DR GO; GO:0030122; C:AP-2 adaptor complex; IDA:UniProtKB. DR GO; GO:0016324; C:apical plasma membrane; ISO:MGI. DR GO; GO:0009925; C:basal plasma membrane; ISO:MGI. DR GO; GO:0060170; C:ciliary membrane; IDA:MGI. DR GO; GO:0030132; C:clathrin coat of coated pit; IDA:MGI. DR GO; GO:0005905; C:clathrin-coated pit; IDA:MGI. DR GO; GO:0030136; C:clathrin-coated vesicle; IDA:UniProtKB. DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central. DR GO; GO:0005829; C:cytosol; ISO:MGI. DR GO; GO:0005769; C:early endosome; ISO:MGI. DR GO; GO:0031901; C:early endosome membrane; IEA:UniProtKB-SubCell. DR GO; GO:0098978; C:glutamatergic synapse; ISO:MGI. DR GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:MGI. DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB. DR GO; GO:0098794; C:postsynapse; IEA:GOC. DR GO; GO:0045202; C:synapse; ISO:MGI. DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0031593; F:polyubiquitin modification-dependent protein binding; ISS:UniProtKB. DR GO; GO:0017124; F:SH3 domain binding; IEA:UniProtKB-KW. DR GO; GO:0043130; F:ubiquitin binding; IDA:MGI. DR GO; GO:0048268; P:clathrin coat assembly; ISO:MGI. DR GO; GO:0032456; P:endocytic recycling; ISO:MGI. 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; ISS:UniProtKB. DR GO; GO:0001921; P:positive regulation of receptor recycling; ISO:MGI. DR GO; GO:0098884; P:postsynaptic neurotransmitter receptor internalization; ISO:MGI. DR GO; GO:0019065; P:receptor-mediated endocytosis of virus by host cell; ISO:MGI. DR GO; GO:0042127; P:regulation of cell population proliferation; ISO:MGI. DR GO; GO:0032880; P:regulation of protein localization; IMP:MGI. DR GO; GO:0070086; P:ubiquitin-dependent endocytosis; IMP:MGI. DR GO; GO:0046718; P:viral entry into host cell; ISO:MGI. DR CDD; cd00052; EH; 3. DR Gene3D; 1.10.287.1490; -; 1. DR Gene3D; 1.10.238.10; EF-hand; 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 PANTHER; PTHR11216; EH DOMAIN; 1. DR PANTHER; PTHR11216:SF54; EPIDERMAL GROWTH FACTOR RECEPTOR SUBSTRATE 15; 1. DR Pfam; PF12763; EF-hand_4; 3. DR SMART; SM00054; EFh; 4. DR SMART; SM00027; EH; 3. DR SMART; SM00726; UIM; 2. DR SUPFAM; SSF47473; EF-hand; 3. DR SUPFAM; SSF90257; Myosin rod fragments; 1. DR PROSITE; PS00018; EF_HAND_1; 2. DR PROSITE; PS50222; EF_HAND_2; 4. DR PROSITE; PS50031; EH; 3. DR PROSITE; PS50330; UIM; 2. DR Genevisible; P42567; MM. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Alternative splicing; Calcium; Cell membrane; KW Coated pit; Cytoplasm; Direct protein sequencing; Endocytosis; Endosome; KW Membrane; Metal-binding; Phosphoprotein; Protein transport; KW Reference proteome; Repeat; SH3-binding; Transport; Ubl conjugation. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0000250|UniProtKB:P42566" FT CHAIN 2..897 FT /note="Epidermal growth factor receptor substrate 15" FT /id="PRO_0000146117" 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 665..667 FT /note="8" FT REPEAT 673..675 FT /note="9" FT REPEAT 693..695 FT /note="10" FT REPEAT 711..713 FT /note="11" FT REPEAT 806..808 FT /note="12" FT REPEAT 827..829 FT /note="13" FT DOMAIN 852..871 FT /note="UIM 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00213" FT DOMAIN 878..897 FT /note="UIM 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00213" FT REGION 2..330 FT /note="Interaction with DAB2" FT /evidence="ECO:0000269|PubMed:22648170" FT REGION 528..607 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 599..829 FT /note="13 X 3 AA repeats of D-P-F" FT REGION 667..692 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 741..849 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 528..568 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 585..603 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 667..690 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 741..757 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 773..792 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 827..849 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 242 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:0000250|UniProtKB:P42566" FT MOD_RES 108 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P42566" FT MOD_RES 140 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21183079" FT MOD_RES 321 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:21183079" FT MOD_RES 323 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P42566" FT MOD_RES 324 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:19144319, FT ECO:0007744|PubMed:21183079" FT MOD_RES 467 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P42566" FT MOD_RES 470 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P42566" FT MOD_RES 485 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P42566" FT MOD_RES 561 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21183079" FT MOD_RES 562 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21183079" FT MOD_RES 748 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P42566" FT MOD_RES 779 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:17242355" FT MOD_RES 781 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:21183079" FT MOD_RES 798 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P42566" FT MOD_RES 816 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21183079" FT MOD_RES 850 FT /note="Phosphotyrosine; by EGFR" FT /evidence="ECO:0000269|PubMed:10953014" FT VAR_SEQ 1..314 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:16141072" FT /id="VSP_036170" FT VAR_SEQ 315..346 FT /note="SLQKNITGSSPVADFSAIKELDTLNNEIVDLQ -> MYSDSGLGGWIAIPAV FT ADVLRYSCIVCWSS (in isoform 2)" FT /evidence="ECO:0000303|PubMed:16141072" FT /id="VSP_036171" FT MUTAGEN 850 FT /note="Y->F: Inefficient EGFR internalization." FT /evidence="ECO:0000269|PubMed:10953014" FT MUTAGEN 863 FT /note="E->A: Loss of interaction with UBQLN1; when FT associated with A-864 and A-865." FT /evidence="ECO:0000269|PubMed:16159959" FT MUTAGEN 864 FT /note="S->A: Loss of interaction with UBQLN1; when FT associated with A-863 and A-865." FT /evidence="ECO:0000269|PubMed:16159959" FT MUTAGEN 865 FT /note="E->A: Loss of interaction with UBQLN1; when FT associated with A-863 and A-864." FT /evidence="ECO:0000269|PubMed:16159959" FT MUTAGEN 883 FT /note="L->A: Loss of ubiquitination and interaction with FT UBQLN1; when associated with A-885." FT /evidence="ECO:0000269|PubMed:16159959" FT MUTAGEN 885 FT /note="L->A: Loss of ubiquitination and interaction with FT UBQLN1; when associated with A-883." FT /evidence="ECO:0000269|PubMed:16159959" FT HELIX 9..12 FT /evidence="ECO:0007829|PDB:1QJT" FT TURN 13..15 FT /evidence="ECO:0007829|PDB:1QJT" FT HELIX 18..26 FT /evidence="ECO:0007829|PDB:1QJT" FT HELIX 37..44 FT /evidence="ECO:0007829|PDB:1QJT" FT STRAND 46..48 FT /evidence="ECO:0007829|PDB:1QJT" FT HELIX 50..60 FT /evidence="ECO:0007829|PDB:1QJT" FT STRAND 63..67 FT /evidence="ECO:0007829|PDB:1QJT" FT HELIX 71..83 FT /evidence="ECO:0007829|PDB:1QJT" FT TURN 84..86 FT /evidence="ECO:0007829|PDB:1QJT" FT HELIX 91..93 FT /evidence="ECO:0007829|PDB:1QJT" SQ SEQUENCE 897 AA; 98471 MW; 08A0C0D423F873C2 CRC64; MAAAAQLSLT QLSSGNPVYE KYYRQVEAGN TGRVLALDAA AFLKKSGLPD LILGKIWDLA DTDGKGVLSK QEFFVALRLV ACAQNGLEVS LSSLSLAVPP PRFHDSSSPL LTSGPSVAEL PWAVKSEDKA KYDAIFDSLS PVDGFLSGDK VKPVLLNSKL PVEILGRVWE LSDIDHDGKL DRDEFAVAMF LVYCALEKEP VPMSLPPALV PPSKRKTWVV SPAEKAKYDE IFLKTDKDMD GYVSGLEVRE TFLKTGLPSA LLAHIWSLCD TKGCGKLSKD QFALAFHLIN QKLIKGIDPP HSLTPEMIPP SDRSSLQKNI TGSSPVADFS AIKELDTLNN EIVDLQREKN NVEQDLKEKE DTVKQRTSEV QDLQDEVQRE SINLQKLQAQ KQQVQELLGE LDEQKAQLEE QLQEVRKKCA EEAQLISSLK AEITSQESQI SSYEEELLKA REELSRLQQE TAQLEESVES GKAQLEPLQQ HLQESQQEIS SMQMRLEMKD LETDNNQSNW SSSPQSVLVN GATDYCSLST SSSETANFNE HAEGQNNLES EPTHQESSVR SSPEIAPSDV TDESEAVTVA GNEKVTPRFD DDKHSKEEDP FNVESSSLTD AVADTNLDFF QSDPFVGSDP FKDDPFGKID PFGGDPFKGS DPFASDCFFK QTSTDPFTTS STDPFSASSN SSNTSVETWK HNDPFAPGGT VVAAASDSAT DPFASVFGNE SFGDGFADFS TLSKVNNEDA FNPTISSSTS SVTIAKPMLE ETASKSEDVP PALPPKVGTP TRPCPPPPGK RPINKLDSSD PLKLNDPFQP FPGNDSPKEK DPDMFCDPFT SSTTTNKEAD PSNFANFSAY PSEEDMIEWA KRESEREEEQ RLARLNQQEQ EDLELAIALS KSEISEA //