EPS15_MOUSE
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 03-AUG-2022, entry version 205.
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, Pancreas,
RC 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}.
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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; 49.
DR CORUM; P42567; -.
DR DIP; DIP-29052N; -.
DR ELM; P42567; -.
DR IntAct; P42567; 9.
DR MINT; P42567; -.
DR STRING; 10090.ENSMUSP00000099790; -.
DR iPTMnet; P42567; -.
DR PhosphoSitePlus; P42567; -.
DR EPD; P42567; -.
DR jPOST; P42567; -.
DR PaxDb; P42567; -.
DR PeptideAtlas; P42567; -.
DR PRIDE; P42567; -.
DR ProteomicsDB; 275463; -. [P42567-1]
DR ProteomicsDB; 275464; -. [P42567-2]
DR Antibodypedia; 1916; 256 antibodies from 31 providers.
DR DNASU; 13858; -.
DR Ensembl; ENSMUST00000102729; ENSMUSP00000099790; ENSMUSG00000028552. [P42567-1]
DR GeneID; 13858; -.
DR KEGG; mmu:13858; -.
DR UCSC; uc008ucf.2; mouse. [P42567-1]
DR UCSC; uc008ucg.2; mouse. [P42567-2]
DR CTD; 2060; -.
DR MGI; MGI:104583; Eps15.
DR VEuPathDB; HostDB:ENSMUSG00000028552; -.
DR eggNOG; KOG0998; Eukaryota.
DR GeneTree; ENSGT00940000155751; -.
DR InParanoid; P42567; -.
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 74 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 263 other tissues.
DR ExpressionAtlas; P42567; baseline and differential.
DR Genevisible; P42567; MM.
DR GO; GO:0016235; C:aggresome; ISO:MGI.
DR GO; GO:0030122; C:AP-2 adaptor complex; IDA:UniProtKB.
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:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0031901; C:early endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
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:0048268; P:clathrin coat assembly; 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:0015031; P:protein transport; IEA:UniProtKB-KW.
DR GO; GO:0019065; P:receptor-mediated endocytosis of virus by host cell; ISO:MGI.
DR GO; GO:0032880; P:regulation of protein localization; IMP:MGI.
DR GO; GO:0046718; P:viral entry into host cell; ISO:MGI.
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; 4.
DR SMART; SM00027; EH; 3.
DR SMART; SM00726; UIM; 2.
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 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
