EPS8_MOUSE
ID EPS8_MOUSE Reviewed; 821 AA.
AC Q08509; Q3TM41;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 190.
DE RecName: Full=Epidermal growth factor receptor kinase substrate 8;
GN Name=Eps8;
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], FUNCTION IN CELL GROWTH, INTERACTION WITH EGFR,
RP AND PHOSPHORYLATION.
RX PubMed=8404850; DOI=10.1002/j.1460-2075.1993.tb06058.x;
RA Fazioli F., Minichiello L., Matoska V., Castagnino P., Miki T., Wong W.T.,
RA di Fiore P.P.;
RT "Eps8, a substrate for the epidermal growth factor receptor kinase,
RT enhances EGF-dependent mitogenic signals.";
RL EMBO J. 12:3799-3808(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Bone marrow, and Lung;
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 MRNA].
RC STRAIN=FVB/N; TISSUE=Kidney;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP INTERACTION WITH SHB.
RX PubMed=7537362;
RA Karlsson T., Songyang Z., Landgren E., Lavergne C., Di Fiore P.P.,
RA Anafi M., Pawson T., Cantley L.C., Claesson-Welsh L., Welsh M.;
RT "Molecular interactions of the Src homology 2 domain protein Shb with
RT phosphotyrosine residues, tyrosine kinase receptors and Src homology 3
RT domain proteins.";
RL Oncogene 10:1475-1483(1995).
RN [5]
RP FUNCTION, IDENTIFICATION IN A COMPLEX WITH ABI1 AND SOS1, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=10499589; DOI=10.1038/45822;
RA Scita G., Nordstrom J., Carbone R., Tenca P., Giardina G., Gutkind S.,
RA Bjarnegard M., Betsholtz C., Di Fiore P.P.;
RT "EPS8 and E3B1 transduce signals from Ras to Rac.";
RL Nature 401:290-293(1999).
RN [6]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH SOS1.
RX PubMed=11524436; DOI=10.1083/jcb.200103146;
RA Scita G., Tenca P., Areces L.B., Tocchetti A., Frittoli E., Giardina G.,
RA Ponzanelli I., Sini P., Innocenti M., Di Fiore P.P.;
RT "An effector region in Eps8 is responsible for the activation of the Rac-
RT specific GEF activity of Sos-1 and for the proper localization of the Rac-
RT based actin-polymerizing machine.";
RL J. Cell Biol. 154:1031-1044(2001).
RN [7]
RP REVIEW ON FUNCTION.
RX PubMed=12127568; DOI=10.1016/s1357-2725(02)00064-x;
RA Di Fiore P.P., Scita G.;
RT "Eps8 in the midst of GTPases.";
RL Int. J. Biochem. Cell Biol. 34:1178-1183(2002).
RN [8]
RP FUNCTION, AND INTERACTION WITH ABI1.
RX PubMed=15558031; DOI=10.1038/ncb1199;
RA Disanza A., Carlier M.F., Stradal T.E., Didry D., Frittoli E.,
RA Confalonieri S., Croce A., Wehland J., Di Fiore P.P., Scita G.;
RT "Eps8 controls actin-based motility by capping the barbed ends of actin
RT filaments.";
RL Nat. Cell Biol. 6:1180-1188(2004).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=15592455; DOI=10.1038/nbt1046;
RA Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H.,
RA Zha X.-M., Polakiewicz R.D., Comb M.J.;
RT "Immunoaffinity profiling of tyrosine phosphorylation in cancer cells.";
RL Nat. Biotechnol. 23:94-101(2005).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=16452087; DOI=10.1074/mcp.t500041-mcp200;
RA Trinidad J.C., Specht C.G., Thalhammer A., Schoepfer R., Burlingame A.L.;
RT "Comprehensive identification of phosphorylation sites in postsynaptic
RT density preparations.";
RL Mol. Cell. Proteomics 5:914-922(2006).
RN [11]
RP FUNCTION, AND INTERACTION WITH BAIAP2.
RX PubMed=17115031; DOI=10.1038/ncb1502;
RA Disanza A., Mantoani S., Hertzog M., Gerboth S., Frittoli E., Steffen A.,
RA Berhoerster K., Kreienkamp H.J., Milanesi F., Di Fiore P.P., Ciliberto A.,
RA Stradal T.E., Scita G.;
RT "Regulation of cell shape by Cdc42 is mediated by the synergic actin-
RT bundling activity of the Eps8-IRSp53 complex.";
RL Nat. Cell Biol. 8:1337-1347(2006).
RN [12]
RP INTERACTION WITH LANCL1.
RX PubMed=19528316; DOI=10.1101/gad.1789209;
RA Zhang W., Wang L., Liu Y., Xu J., Zhu G., Cang H., Li X., Bartlam M.,
RA Hensley K., Li G., Rao Z., Zhang X.C.;
RT "Structure of human lanthionine synthetase C-like protein 1 and its
RT interaction with Eps8 and glutathione.";
RL Genes Dev. 23:1387-1392(2009).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-658, 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 [14]
RP FUNCTION, TISSUE SPECIFICITY, PHOSPHORYLATION AT SER-624 AND THR-628, AND
RP MUTAGENESIS OF SER-624 AND THR-628.
RX PubMed=19564905; DOI=10.1371/journal.pbio.1000138;
RA Menna E., Disanza A., Cagnoli C., Schenk U., Gelsomino G., Frittoli E.,
RA Hertzog M., Offenhauser N., Sawallisch C., Kreienkamp H.J., Gertler F.B.,
RA Di Fiore P.P., Scita G., Matteoli M.;
RT "Eps8 regulates axonal filopodia in hippocampal neurons in response to
RT brain-derived neurotrophic factor (BDNF).";
RL PLoS Biol. 7:E1000138-E1000138(2009).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-317; SER-658; SER-661;
RP SER-684; SER-810 AND SER-814, AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RC TISSUE=Brown adipose tissue, Kidney, and Lung;
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 [16]
RP FUNCTION, AND MUTAGENESIS OF VAL-689; LEU-693; ARG-706 AND PHE-708.
RX PubMed=20532239; DOI=10.1371/journal.pbio.1000387;
RA Hertzog M., Milanesi F., Hazelwood L., Disanza A., Liu H., Perlade E.,
RA Malabarba M.G., Pasqualato S., Maiolica A., Confalonieri S.,
RA Le Clainche C., Offenhauser N., Block J., Rottner K., Di Fiore P.P.,
RA Carlier M.F., Volkmann N., Hanein D., Scita G.;
RT "Molecular basis for the dual function of Eps8 on actin dynamics: bundling
RT and capping.";
RL PLoS Biol. 8:E1000387-E1000387(2010).
RN [17]
RP FUNCTION, INTERACTION WITH MYO15A AND WHRN, SUBCELLULAR LOCATION, AND
RP DISRUPTION PHENOTYPE.
RX PubMed=21236676; DOI=10.1016/j.cub.2010.12.046;
RA Manor U., Disanza A., Grati M., Andrade L., Lin H., Di Fiore P.P.,
RA Scita G., Kachar B.;
RT "Regulation of stereocilia length by myosin XVa and whirlin depends on the
RT actin-regulatory protein Eps8.";
RL Curr. Biol. 21:167-172(2011).
RN [18]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=21835647; DOI=10.1016/j.immuni.2011.07.007;
RA Frittoli E., Matteoli G., Palamidessi A., Mazzini E., Maddaluno L.,
RA Disanza A., Yang C., Svitkina T., Rescigno M., Scita G.;
RT "The signaling adaptor Eps8 is an essential actin capping protein for
RT dendritic cell migration.";
RL Immunity 35:388-399(2011).
RN [19]
RP SUBCELLULAR LOCATION, AND UBIQUITINATION.
RX PubMed=23314863; DOI=10.1038/ncb2661;
RA Werner A., Disanza A., Reifenberger N., Habeck G., Becker J., Calabrese M.,
RA Urlaub H., Lorenz H., Schulman B., Scita G., Melchior F.;
RT "SCF(Fbxw5) mediates transient degradation of actin remodeller Eps8 to
RT allow proper mitotic progression.";
RL Nat. Cell Biol. 15:179-188(2013).
RN [20]
RP TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION.
RX PubMed=23918390; DOI=10.1073/pnas.1304644110;
RA Furness D.N., Johnson S.L., Manor U., Ruettiger L., Tocchetti A.,
RA Offenhauser N., Olt J., Goodyear R.J., Vijayakumar S., Dai Y.,
RA Hackney C.M., Franz C., Di Fiore P.P., Masetto S., Jones S.M., Knipper M.,
RA Holley M.C., Richardson G.P., Kachar B., Marcotti W.;
RT "Progressive hearing loss and gradual deterioration of sensory hair bundles
RT in the ears of mice lacking the actin-binding protein Eps8L2.";
RL Proc. Natl. Acad. Sci. U.S.A. 110:13898-13903(2013).
RN [21]
RP SUBCELLULAR LOCATION.
RX PubMed=24741995; DOI=10.1186/1750-1172-9-55;
RA Behlouli A., Bonnet C., Abdi S., Bouaita A., Lelli A., Hardelin J.P.,
RA Schietroma C., Rous Y., Louha M., Cheknane A., Lebdi H., Boudjelida K.,
RA Makrelouf M., Zenati A., Petit C.;
RT "EPS8, encoding an actin-binding protein of cochlear hair cell stereocilia,
RT is a new causal gene for autosomal recessive profound deafness.";
RL Orphanet J. Rare Dis. 9:55-55(2014).
RN [22]
RP X-RAY CRYSTALLOGRAPHY (1.5 ANGSTROMS) OF 532-591, AND HOMODIMERIZATION.
RX PubMed=9303002; DOI=10.1038/nsb0997-739;
RA Kishan K.V.R., Scita G., Wong W.T., di Fiore P.P., Newcomer M.E.;
RT "The SH3 domain of Eps8 exists as a novel intertwined dimer.";
RL Nat. Struct. Biol. 4:739-743(1997).
CC -!- FUNCTION: Signaling adapter that controls various cellular protrusions
CC by regulating actin cytoskeleton dynamics and architecture. Depending
CC on its association with other signal transducers, can regulate
CC different processes. Together with SOS1 and ABI1, forms a trimeric
CC complex that participates in transduction of signals from Ras to Rac by
CC activating the Rac-specific guanine nucleotide exchange factor (GEF)
CC activity. Acts as a direct regulator of actin dynamics by binding actin
CC filaments and has both barbed-end actin filament capping and actin
CC bundling activities depending on the context. Displays barbed-end actin
CC capping activity when associated with ABI1, thereby regulating actin-
CC based motility process: capping activity is auto-inhibited and
CC inhibition is relieved upon ABI1 interaction. Also shows actin bundling
CC activity when associated with BAIAP2, enhancing BAIAP2-dependent
CC membrane extensions and promoting filopodial protrusions. Involved in
CC the regulation of processes such as axonal filopodia growth,
CC stereocilia length, dendritic cell migration and cancer cell migration
CC and invasion. Acts as a regulator of axonal filopodia formation in
CC neurons: in the absence of neurotrophic factors, negatively regulates
CC axonal filopodia formation via actin-capping activity. In contrast, it
CC is phosphorylated in the presence of BDNF leading to inhibition of its
CC actin-capping activity and stimulation of filopodia formation.
CC Component of a complex with WHRN and MYO15A that localizes at
CC stereocilia tips and is required for elongation of the stereocilia
CC actin core. Indirectly involved in cell cycle progression; its
CC degradation following ubiquitination being required during G2 phase to
CC promote cell shape changes. {ECO:0000269|PubMed:10499589,
CC ECO:0000269|PubMed:11524436, ECO:0000269|PubMed:15558031,
CC ECO:0000269|PubMed:17115031, ECO:0000269|PubMed:19564905,
CC ECO:0000269|PubMed:20532239, ECO:0000269|PubMed:21236676,
CC ECO:0000269|PubMed:21835647, ECO:0000269|PubMed:8404850}.
CC -!- SUBUNIT: Homodimer. Part of a complex consisting of ABI1, EPS8 and
CC SOS1. Interacts with BAIAP2. Interacts with SHB and LANCL1. Interacts
CC with EGFR; mediates EPS8 phosphorylation. Interacts with MYO15A and
CC WHRN. {ECO:0000269|PubMed:10499589, ECO:0000269|PubMed:11524436,
CC ECO:0000269|PubMed:15558031, ECO:0000269|PubMed:17115031,
CC ECO:0000269|PubMed:19528316, ECO:0000269|PubMed:21236676,
CC ECO:0000269|PubMed:7537362, ECO:0000269|PubMed:8404850}.
CC -!- INTERACTION:
CC Q08509; Q8CBW3: Abi1; NbExp=3; IntAct=EBI-375596, EBI-375511;
CC Q08509; Q8IZP0: ABI1; Xeno; NbExp=2; IntAct=EBI-375596, EBI-375446;
CC Q08509; Q9UQB8: BAIAP2; Xeno; NbExp=8; IntAct=EBI-375596, EBI-525456;
CC Q08509; O43813: LANCL1; Xeno; NbExp=2; IntAct=EBI-375596, EBI-3046631;
CC Q08509; P27361: MAPK3; Xeno; NbExp=2; IntAct=EBI-375596, EBI-73995;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cell cortex. Cell projection, ruffle
CC membrane. Cell projection, growth cone {ECO:0000250}. Cell projection,
CC stereocilium {ECO:0000269|PubMed:23918390,
CC ECO:0000269|PubMed:24741995}. Synapse, synaptosome {ECO:0000250}.
CC Note=Localizes at the tips of the stereocilia of the inner and outer
CC hair cells (PubMed:24741995, PubMed:23918390). Localizes to the midzone
CC of dividing cells. {ECO:0000269|PubMed:23918390,
CC ECO:0000269|PubMed:24741995}.
CC -!- TISSUE SPECIFICITY: Expressed in neuronal cell body and neurites, and
CC prominently enriched in the axonal growth cone (PubMed:19564905).
CC Expressed at the tips of cochlear hair cells stereocilia
CC (PubMed:23918390). {ECO:0000269|PubMed:19564905,
CC ECO:0000269|PubMed:23918390}.
CC -!- DOMAIN: The effector region is required for activating the Rac-specific
CC guanine nucleotide exchange factor (GEF) activity (PubMed:11524436). It
CC mediates both barbed-end actin capping and actin bundling activities
CC (PubMed:20532239). The capping activity is mediated by an amphipathic
CC helix that binds within the hydrophobic pocket at the barbed ends of
CC actin blocking further addition of actin monomers, while the bundling
CC activity is mediated by a compact 4 helix bundle, which contacts 3
CC actin subunits along the filament (PubMed:20532239).
CC {ECO:0000269|PubMed:11524436, ECO:0000269|PubMed:20532239}.
CC -!- DOMAIN: The SH3 domain mediates interaction with SHB. {ECO:0000250}.
CC -!- PTM: Ubiquitinated by the SCF(FBXW5) E3 ubiquitin-protein ligase
CC complex during G2 phase, leading to its transient degradation and
CC subsequent cell shape changes required to allow mitotic progression.
CC Reappears at the midzone of dividing cells.
CC {ECO:0000269|PubMed:23314863}.
CC -!- PTM: Phosphorylation at Ser-624 and Thr-628 by MAPK following BDNF
CC treatment promotes removal from actin and filopodia formation.
CC Phosphorylated by several receptor tyrosine kinases.
CC {ECO:0000269|PubMed:19564905, ECO:0000269|PubMed:8404850}.
CC -!- DISRUPTION PHENOTYPE: No visible phenotype. Defects in PDGF-induced
CC membrane ruffling due to defects in Ras to Rac signals. Dendritic cells
CC are impaired in directional and chemotactic migration and are delayed
CC in reaching the draining lymph node in vivo after inflammatory
CC challenge. Mice show short stereocilia. {ECO:0000269|PubMed:10499589,
CC ECO:0000269|PubMed:21236676, ECO:0000269|PubMed:21835647}.
CC -!- SIMILARITY: Belongs to the EPS8 family. {ECO:0000305}.
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DR EMBL; L21671; AAA16358.1; -; mRNA.
DR EMBL; AK149683; BAE29023.1; -; mRNA.
DR EMBL; AK166156; BAE38601.1; -; mRNA.
DR EMBL; BC016890; AAH16890.1; -; mRNA.
DR CCDS; CCDS20665.1; -.
DR PIR; S39983; S39983.
DR RefSeq; NP_001258516.1; NM_001271587.1.
DR RefSeq; NP_001258517.1; NM_001271588.1.
DR RefSeq; NP_001258518.1; NM_001271589.1.
DR RefSeq; NP_001258524.1; NM_001271595.1.
DR RefSeq; NP_031971.2; NM_007945.3.
DR RefSeq; XP_011239506.1; XM_011241204.2.
DR PDB; 1AOJ; X-ray; 2.50 A; A/B=532-591.
DR PDB; 1I07; X-ray; 1.80 A; A/B=532-591.
DR PDB; 1I0C; X-ray; 2.00 A; A/B=532-591.
DR PDBsum; 1AOJ; -.
DR PDBsum; 1I07; -.
DR PDBsum; 1I0C; -.
DR AlphaFoldDB; Q08509; -.
DR SMR; Q08509; -.
DR BioGRID; 199491; 32.
DR CORUM; Q08509; -.
DR DIP; DIP-32858N; -.
DR IntAct; Q08509; 10.
DR MINT; Q08509; -.
DR STRING; 10090.ENSMUSP00000052776; -.
DR iPTMnet; Q08509; -.
DR PhosphoSitePlus; Q08509; -.
DR EPD; Q08509; -.
DR jPOST; Q08509; -.
DR MaxQB; Q08509; -.
DR PaxDb; Q08509; -.
DR PeptideAtlas; Q08509; -.
DR PRIDE; Q08509; -.
DR ProteomicsDB; 277891; -.
DR Antibodypedia; 1288; 384 antibodies from 39 providers.
DR DNASU; 13860; -.
DR Ensembl; ENSMUST00000058210; ENSMUSP00000052776; ENSMUSG00000015766.
DR Ensembl; ENSMUST00000100841; ENSMUSP00000098402; ENSMUSG00000015766.
DR Ensembl; ENSMUST00000111878; ENSMUSP00000107509; ENSMUSG00000015766.
DR GeneID; 13860; -.
DR KEGG; mmu:13860; -.
DR UCSC; uc009emz.2; mouse.
DR CTD; 2059; -.
DR MGI; MGI:104684; Eps8.
DR VEuPathDB; HostDB:ENSMUSG00000015766; -.
DR eggNOG; KOG3557; Eukaryota.
DR GeneTree; ENSGT00940000156403; -.
DR InParanoid; Q08509; -.
DR OMA; FPQMNGY; -.
DR OrthoDB; 218804at2759; -.
DR PhylomeDB; Q08509; -.
DR TreeFam; TF313069; -.
DR BioGRID-ORCS; 13860; 2 hits in 75 CRISPR screens.
DR ChiTaRS; Eps8; mouse.
DR EvolutionaryTrace; Q08509; -.
DR PRO; PR:Q08509; -.
DR Proteomes; UP000000589; Chromosome 6.
DR RNAct; Q08509; protein.
DR Bgee; ENSMUSG00000015766; Expressed in secondary oocyte and 281 other tissues.
DR ExpressionAtlas; Q08509; baseline and differential.
DR Genevisible; Q08509; MM.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0005903; C:brush border; IDA:UniProtKB.
DR GO; GO:0005938; C:cell cortex; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0098978; C:glutamatergic synapse; IDA:SynGO.
DR GO; GO:0030426; C:growth cone; IEA:UniProtKB-SubCell.
DR GO; GO:0017146; C:NMDA selective glutamate receptor complex; IDA:MGI.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0014069; C:postsynaptic density; IDA:MGI.
DR GO; GO:0032587; C:ruffle membrane; IDA:UniProtKB.
DR GO; GO:0032420; C:stereocilium; IDA:UniProtKB.
DR GO; GO:0032421; C:stereocilium bundle; IDA:UniProtKB.
DR GO; GO:0032426; C:stereocilium tip; IDA:UniProtKB.
DR GO; GO:0045202; C:synapse; IDA:MGI.
DR GO; GO:0003779; F:actin binding; IDA:UniProtKB.
DR GO; GO:0035591; F:signaling adaptor activity; IEA:InterPro.
DR GO; GO:0031267; F:small GTPase binding; IDA:UniProtKB.
DR GO; GO:0051764; P:actin crosslink formation; IDA:UniProtKB.
DR GO; GO:0031532; P:actin cytoskeleton reorganization; IMP:MGI.
DR GO; GO:0051017; P:actin filament bundle assembly; IDA:UniProtKB.
DR GO; GO:0070358; P:actin polymerization-dependent cell motility; IDA:UniProtKB.
DR GO; GO:0008344; P:adult locomotory behavior; IMP:MGI.
DR GO; GO:0051016; P:barbed-end actin filament capping; IDA:UniProtKB.
DR GO; GO:0048149; P:behavioral response to ethanol; IMP:MGI.
DR GO; GO:1990830; P:cellular response to leukemia inhibitory factor; IEP:MGI.
DR GO; GO:0036336; P:dendritic cell migration; IMP:UniProtKB.
DR GO; GO:0010458; P:exit from mitosis; IMP:UniProtKB.
DR GO; GO:1900029; P:positive regulation of ruffle assembly; IBA:GO_Central.
DR GO; GO:0016601; P:Rac protein signal transduction; IDA:UniProtKB.
DR GO; GO:0030832; P:regulation of actin filament length; IMP:UniProtKB.
DR GO; GO:0008360; P:regulation of cell shape; IMP:UniProtKB.
DR GO; GO:0099072; P:regulation of postsynaptic membrane neurotransmitter receptor levels; IDA:SynGO.
DR GO; GO:0035023; P:regulation of Rho protein signal transduction; IBA:GO_Central.
DR GO; GO:0007266; P:Rho protein signal transduction; IBA:GO_Central.
DR CDD; cd01210; PTB_EPS8; 1.
DR CDD; cd11764; SH3_Eps8; 1.
DR Gene3D; 1.10.150.50; -; 1.
DR Gene3D; 2.30.29.30; -; 1.
DR InterPro; IPR030222; EPS8.
DR InterPro; IPR039801; EPS8-like.
DR InterPro; IPR033928; EPS8_PTB.
DR InterPro; IPR035462; Eps8_SH3.
DR InterPro; IPR011993; PH-like_dom_sf.
DR InterPro; IPR013625; PTB.
DR InterPro; IPR006020; PTB/PI_dom.
DR InterPro; IPR013761; SAM/pointed_sf.
DR InterPro; IPR041418; SAM_3.
DR InterPro; IPR036028; SH3-like_dom_sf.
DR InterPro; IPR001452; SH3_domain.
DR PANTHER; PTHR12287; PTHR12287; 1.
DR PANTHER; PTHR12287:SF21; PTHR12287:SF21; 1.
DR Pfam; PF08416; PTB; 1.
DR Pfam; PF18016; SAM_3; 1.
DR Pfam; PF00018; SH3_1; 1.
DR SMART; SM00462; PTB; 1.
DR SMART; SM00326; SH3; 1.
DR SUPFAM; SSF50044; SSF50044; 1.
DR PROSITE; PS50002; SH3; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Actin-binding; Cell membrane; Cell projection; Cytoplasm;
KW Membrane; Phosphoprotein; Reference proteome; SH3 domain; Synapse;
KW Synaptosome; Ubl conjugation.
FT CHAIN 1..821
FT /note="Epidermal growth factor receptor kinase substrate 8"
FT /id="PRO_0000086995"
FT DOMAIN 69..129
FT /note="PH; first part"
FT DOMAIN 381..414
FT /note="PH; second part"
FT DOMAIN 530..589
FT /note="SH3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192"
FT REGION 1..39
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 204..224
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 295..320
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 461..525
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 610..683
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 648..821
FT /note="Effector region"
FT REGION 679..697
FT /note="Amphipathic helix"
FT REGION 717..737
FT /note="Helix bundle 1"
FT REGION 751..756
FT /note="Helix bundle 2"
FT REGION 761..766
FT /note="Helix bundle 3"
FT REGION 765..784
FT /note="Helix bundle 4"
FT REGION 800..821
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..34
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 206..220
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 463..477
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 620..645
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 650..670
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 58
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:F1M3L7"
FT MOD_RES 223
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q12929"
FT MOD_RES 317
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 475
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q12929"
FT MOD_RES 624
FT /note="Phosphoserine; by MAPK"
FT /evidence="ECO:0000269|PubMed:19564905"
FT MOD_RES 628
FT /note="Phosphothreonine; by MAPK"
FT /evidence="ECO:0000269|PubMed:19564905"
FT MOD_RES 658
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19144319,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 661
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 684
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 810
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 814
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MUTAGEN 624
FT /note="S->A: Does not detach from actin following BDNF
FT treatment; when associated with A-628."
FT /evidence="ECO:0000269|PubMed:19564905"
FT MUTAGEN 624
FT /note="S->E: Mimicks phosphorylation state; promotes
FT detachment from actin in absence of BDNF treatment; when
FT associated with E-628."
FT /evidence="ECO:0000269|PubMed:19564905"
FT MUTAGEN 628
FT /note="T->A: Does not detach from actin following BDNF
FT treatment; when associated with A-624."
FT /evidence="ECO:0000269|PubMed:19564905"
FT MUTAGEN 628
FT /note="T->E: Mimicks phosphorylation state; promotes
FT detachment from actin in absence of BDNF treatment; when
FT associated with E-624."
FT /evidence="ECO:0000269|PubMed:19564905"
FT MUTAGEN 689
FT /note="V->D: Abolishes barbed-end actin-binding without
FT affecting actin bundling activity."
FT /evidence="ECO:0000269|PubMed:20532239"
FT MUTAGEN 693
FT /note="L->D: Abolishes barbed-end actin-binding without
FT affecting actin bundling activity."
FT /evidence="ECO:0000269|PubMed:20532239"
FT MUTAGEN 706
FT /note="R->A: Impairs both actin capping and bundling
FT activities."
FT /evidence="ECO:0000269|PubMed:20532239"
FT MUTAGEN 708
FT /note="F->A: Impairs both actin capping and bundling
FT activities."
FT /evidence="ECO:0000269|PubMed:20532239"
FT CONFLICT 652
FT /note="N -> D (in Ref. 1; AAA16358 and 3; AAH16890)"
FT /evidence="ECO:0000305"
FT STRAND 534..539
FT /evidence="ECO:0007829|PDB:1I07"
FT STRAND 556..559
FT /evidence="ECO:0007829|PDB:1I07"
FT HELIX 561..563
FT /evidence="ECO:0007829|PDB:1I07"
FT STRAND 566..570
FT /evidence="ECO:0007829|PDB:1I07"
FT STRAND 576..580
FT /evidence="ECO:0007829|PDB:1I07"
FT HELIX 581..583
FT /evidence="ECO:0007829|PDB:1I07"
FT STRAND 584..587
FT /evidence="ECO:0007829|PDB:1I07"
SQ SEQUENCE 821 AA; 91737 MW; 50F691FAC3EF1304 CRC64;
MNGHMSNRSS GYGVYPSQLN GYGSSPPYSQ MDREHSSRTS AKALYEQRKN YARDSVSSVS
DVSQYRVEHL TTFVLDRKDA MITVEDGIRK LKLLDAKGKV WTQDMILQVD DRAVSLIDLE
SKNELENFPL NTISHCQAVV HACSYDSILA LVCKEPTQSK PDLHLFQCDE VKANLISEDI
ESAISDSKGG KQKRRPEALR MIAKADPGIP PPPRAPAPVP PGTVTQVDVR SRVAAWSAWA
ADQGDFEKPR QYHEQEETPE MMAARIDRDV QILNHILDDI EFFITKLQKA AEAFSELSKR
KKSKKSKRKG PGEGVLTLRA KPPPPDEFVD CFQKFKHGFN LLAKLKSHIQ NPSASDLVHF
LFTPLNMVVQ ATGGPELASS VLSPLLTKDT VDFLNYTATA EERKLWMSLG DSWVKVRAEW
PKEQFIPPYV PRFRNGWEPP MLNFMGAPTE QDMYQLAESV ANAEHQRKQD SKRLSTEHSN
VSDYPPADGY AYSSSMYHRG PHADHGEAAM PFKSTPNHQV DRNYDAVKTQ PKKYAKSKYD
FVARNSSELS VMKDDVLEIL DDRRQWWKVR NASGDSGFVP NNILDIMRTP ESGVGRADPP
YTHTIQKQRT EYGLRSADTP SAPSPPPTPA PVPVPLPPSV PAPVSVPKVP ANVTRQNSSS
SDSGGSIVRD SQRYKQLPVD RRKSQMEEVQ DELFQRLTIG RSAAQRKFHV PRQNVPVINI
TYDSSPEEVK TWLQSKGFNP VTVNSLGVLN GAQLFSLNKD ELRSVCPEGA RVFNQITVQK
AALEDSNGSS ELQEIMRRRQ EKISAAASDS GVESFDEGSS H
