ID EPS8_HUMAN Reviewed; 822 AA.
AC Q12929; A6NMC3; A8K6W2; A8KA66; B4DX66; Q8N6J0;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 27-MAR-2024, entry version 202.
DE RecName: Full=Epidermal growth factor receptor kinase substrate 8;
GN Name=EPS8;
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).
RX PubMed=8084614;
RA Wong W.T., Carlomagno F., Druck T., Barletta C., Croce C.M., Huebner K.,
RA Kraus M.H., di Fiore P.P.;
RT "Evolutionary conservation of the EPS8 gene and its mapping to human
RT chromosome 12q23-q24.";
RL Oncogene 9:3057-3061(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Placenta, Testis, Tongue, and 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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16541075; DOI=10.1038/nature04569;
RA Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y.,
RA Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C.,
RA Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C.,
RA Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R.,
RA Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E.,
RA Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y.,
RA Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G.,
RA Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H.,
RA Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S.,
RA Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M.,
RA Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H.,
RA Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q.,
RA Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V.,
RA Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E.,
RA Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K.,
RA Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D.,
RA Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R.,
RA David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E.,
RA D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N.,
RA Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N.,
RA Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R.,
RA Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S.,
RA LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H.,
RA Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P.,
RA Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G.,
RA Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E.,
RA Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S.,
RA Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O.,
RA Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J.,
RA Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A.,
RA Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M.,
RA Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I.,
RA Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A.,
RA Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y.,
RA Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A.,
RA Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F.,
RA Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L.,
RA Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G.,
RA Gibbs R.A.;
RT "The finished DNA sequence of human chromosome 12.";
RL Nature 440:346-351(2006).
RN [4]
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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
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 [6]
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 [7]
RP INVOLVEMENT IN CANCER.
RX PubMed=11244499; DOI=10.1038/sj.onc.1204069;
RA Maa M.C., Hsieh C.Y., Leu T.H.;
RT "Overexpression of p97Eps8 leads to cellular transformation: implication of
RT pleckstrin homology domain in p97Eps8-mediated ERK activation.";
RL Oncogene 20:106-112(2001).
RN [8]
RP INTERACTION WITH BAIAP2.
RX PubMed=15289329; DOI=10.1158/0008-5472.can-04-0327;
RA Funato Y., Terabayashi T., Suenaga N., Seiki M., Takenawa T., Miki H.;
RT "IRSp53/Eps8 complex is important for positive regulation of Rac and cancer
RT cell motility/invasiveness.";
RL Cancer Res. 64:5237-5244(2004).
RN [9]
RP FUNCTION.
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 [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT networks.";
RL Cell 127:635-648(2006).
RN [11]
RP FUNCTION.
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 INVOLVEMENT IN CANCER.
RX PubMed=17537571; DOI=10.1016/j.canlet.2007.04.008;
RA Welsch T., Endlich K., Giese T., Buchler M.W., Schmidt J.;
RT "Eps8 is increased in pancreatic cancer and required for dynamic actin-
RT based cell protrusions and intercellular cytoskeletal organization.";
RL Cancer Lett. 255:205-218(2007).
RN [13]
RP INVOLVEMENT IN CANCER.
RX PubMed=18566210; DOI=10.1158/1535-7163.mct-07-2388;
RA Chen Y.J., Shen M.R., Chen Y.J., Maa M.C., Leu T.H.;
RT "Eps8 decreases chemosensitivity and affects survival of cervical cancer
RT patients.";
RL Mol. Cancer Ther. 7:1376-1385(2008).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-476, AND IDENTIFICATION BY
RP 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 [15]
RP INVOLVEMENT IN CANCER.
RX PubMed=19008210; DOI=10.1093/carcin/bgn252;
RA Wang H., Patel V., Miyazaki H., Gutkind J.S., Yeudall W.A.;
RT "Role for EPS8 in squamous carcinogenesis.";
RL Carcinogenesis 30:165-174(2009).
RN [16]
RP INVOLVEMENT IN CANCER.
RX PubMed=19116338; DOI=10.1210/en.2008-1265;
RA Xu M., Shorts-Cary L., Knox A.J., Kleinsmidt-DeMasters B., Lillehei K.,
RA Wierman M.E.;
RT "Epidermal growth factor receptor pathway substrate 8 is overexpressed in
RT human pituitary tumors: role in proliferation and survival.";
RL Endocrinology 150:2064-2071(2009).
RN [17]
RP INVOLVEMENT IN CANCER.
RX PubMed=19448673; DOI=10.1038/onc.2009.105;
RA Yap L.F., Jenei V., Robinson C.M., Moutasim K., Benn T.M., Threadgold S.P.,
RA Lopes V., Wei W., Thomas G.J., Paterson I.C.;
RT "Upregulation of Eps8 in oral squamous cell carcinoma promotes cell
RT migration and invasion through integrin-dependent Rac1 activation.";
RL Oncogene 28:2524-2534(2009).
RN [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-223 AND SER-625, AND
RP 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 [19]
RP INVOLVEMENT IN DFNB102.
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 [20]
RP STRUCTURE BY NMR OF 699-788.
RG RIKEN structural genomics initiative (RSGI);
RT "Solution structure of the C-terminal SAM-domain of epidermal growth
RT receptor pathway substrate 8.";
RL Submitted (JUL-2007) to the PDB data bank.
RN [21]
RP VARIANT GLU-761.
RX PubMed=26721930; DOI=10.1093/hmg/ddv617;
RA Escoffier J., Lee H.C., Yassine S., Zouari R., Martinez G., Karaouzene T.,
RA Coutton C., Kherraf Z.E., Halouani L., Triki C., Nef S., Thierry-Mieg N.,
RA Savinov S.N., Fissore R., Ray P.F., Arnoult C.;
RT "Homozygous mutation of PLCZ1 leads to defective human oocyte activation
RT and infertility that is not rescued by the WW-binding protein PAWP.";
RL Hum. Mol. Genet. 25:878-891(2016).
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:15558031,
CC ECO:0000269|PubMed:17115031}.
CC -!- SUBUNIT: Homodimer. Part of a complex consisting of ABI1, EPS8 and
CC SOS1. Interacts with MYO15A and WHRN. Interacts with LANCL1 (By
CC similarity). Interacts with EGFR; mediates EPS8 phosphorylation (By
CC similarity). Interacts with BAIAP2. Interacts with SHB. {ECO:0000250,
CC ECO:0000269|PubMed:15289329, ECO:0000269|PubMed:7537362}.
CC -!- INTERACTION:
CC Q12929; P49419: ALDH7A1; NbExp=2; IntAct=EBI-375576, EBI-726842;
CC Q12929; Q9UQB8: BAIAP2; NbExp=10; IntAct=EBI-375576, EBI-525456;
CC Q12929; Q9UQB8-4: BAIAP2; NbExp=4; IntAct=EBI-375576, EBI-6174091;
CC Q12929; Q9UHR4: BAIAP2L1; NbExp=4; IntAct=EBI-375576, EBI-2483278;
CC Q12929; Q96GS4: BORCS6; NbExp=3; IntAct=EBI-375576, EBI-10193358;
CC Q12929; Q13895: BYSL; NbExp=3; IntAct=EBI-375576, EBI-358049;
CC Q12929; Q9UFG5: C19orf25; NbExp=3; IntAct=EBI-375576, EBI-741214;
CC Q12929; O14936: CASK; NbExp=3; IntAct=EBI-375576, EBI-1215506;
CC Q12929; P00533: EGFR; NbExp=4; IntAct=EBI-375576, EBI-297353;
CC Q12929; Q969U6-1: FBXW5; NbExp=3; IntAct=EBI-375576, EBI-16031873;
CC Q12929; Q0D2H9: GOLGA8DP; NbExp=3; IntAct=EBI-375576, EBI-10181276;
CC Q12929; P62993: GRB2; NbExp=3; IntAct=EBI-375576, EBI-401755;
CC Q12929; P07910: HNRNPC; NbExp=3; IntAct=EBI-375576, EBI-357966;
CC Q12929; Q15735: INPP5J; NbExp=3; IntAct=EBI-375576, EBI-10236940;
CC Q12929; Q06455-4: RUNX1T1; NbExp=3; IntAct=EBI-375576, EBI-10224192;
CC Q12929; Q969G3: SMARCE1; NbExp=3; IntAct=EBI-375576, EBI-455078;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cell cortex {ECO:0000250}. Cell
CC projection, ruffle membrane {ECO:0000250}. Cell projection, growth cone
CC {ECO:0000250}. Cell projection, stereocilium {ECO:0000250,
CC ECO:0000250|UniProtKB:Q08509}. Synapse, synaptosome {ECO:0000250}.
CC Note=Localizes at the tips of the stereocilia of the inner and outer
CC hair cells (By similarity). Localizes to the midzone of dividing cells.
CC {ECO:0000250, ECO:0000250|UniProtKB:Q08509}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q12929-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q12929-2; Sequence=VSP_056460;
CC -!- TISSUE SPECIFICITY: Expressed in all tissues analyzed, including heart,
CC brain, placenta, lung, liver, skeletal muscle, kidney and pancreas.
CC Expressed in all epithelial and fibroblastic lines examined and in
CC some, but not all, hematopoietic cells.
CC -!- DOMAIN: The effector region is required for activating the Rac-specific
CC guanine nucleotide exchange factor (GEF) activity. It mediates both
CC barbed-end actin capping and actin bundling activities. The capping
CC activity is mediated by an amphipathic helix that binds within the
CC hydrophobic pocket at the barbed ends of actin blocking further
CC addition of actin monomers, while the bundling activity is mediated by
CC a compact 4 helix bundle, which contacts 3 actin subunits along the
CC filament (By similarity). {ECO:0000250}.
CC -!- DOMAIN: The SH3 domain mediates interaction with SHB.
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 (By similarity).
CC {ECO:0000250}.
CC -!- PTM: Phosphorylation at Ser-625 and Thr-629 by MAPK following BDNF
CC treatment promotes removal from actin and filopodia formation (By
CC similarity). Phosphorylated by several receptor tyrosine kinases.
CC {ECO:0000250}.
CC -!- DISEASE: Deafness, autosomal recessive, 102 (DFNB102) [MIM:615974]: A
CC form of non-syndromic deafness characterized by profound hearing loss
CC affecting all frequencies. Vestibular function is unaffected.
CC {ECO:0000269|PubMed:24741995}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Note=Defects in EPS8 are associated with some cancers, such as
CC pancreatic, oral squamous cell carcinomas or pituitary cancers.
CC Contributes to cell transformation in response to growth factor
CC treatment and is overexpressed in a number of tumors, indicating that
CC EPS8 levels must be tightly regulated. {ECO:0000269|PubMed:11244499,
CC ECO:0000269|PubMed:18566210, ECO:0000269|PubMed:19008210,
CC ECO:0000269|PubMed:19116338, ECO:0000269|PubMed:19448673}.
CC -!- SIMILARITY: Belongs to the EPS8 family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="https://atlasgeneticsoncology.org/gene/40476/EPS8";
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DR EMBL; U12535; AAA62280.1; -; mRNA.
DR EMBL; AK291777; BAF84466.1; -; mRNA.
DR EMBL; AK292931; BAF85620.1; -; mRNA.
DR EMBL; AK301834; BAG63278.1; -; mRNA.
DR EMBL; AK316134; BAH14505.1; -; mRNA.
DR EMBL; AK316239; BAH14610.1; -; mRNA.
DR EMBL; AC022073; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC073651; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC092753; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471094; EAW96354.1; -; Genomic_DNA.
DR EMBL; CH471094; EAW96355.1; -; Genomic_DNA.
DR EMBL; BC030010; AAH30010.1; -; mRNA.
DR CCDS; CCDS31753.1; -. [Q12929-1]
DR PIR; I38728; I38728.
DR RefSeq; NP_004438.3; NM_004447.5. [Q12929-1]
DR PDB; 2E8M; NMR; -; A=699-784.
DR PDB; 7TZK; X-ray; 1.43 A; A/B=531-591.
DR PDBsum; 2E8M; -.
DR PDBsum; 7TZK; -.
DR AlphaFoldDB; Q12929; -.
DR SMR; Q12929; -.
DR BioGRID; 108373; 105.
DR CORUM; Q12929; -.
DR DIP; DIP-32859N; -.
DR IntAct; Q12929; 67.
DR MINT; Q12929; -.
DR STRING; 9606.ENSP00000494689; -.
DR GlyGen; Q12929; 1 site, 2 O-linked glycans (1 site).
DR iPTMnet; Q12929; -.
DR MetOSite; Q12929; -.
DR PhosphoSitePlus; Q12929; -.
DR BioMuta; EPS8; -.
DR DMDM; 2833239; -.
DR EPD; Q12929; -.
DR jPOST; Q12929; -.
DR MassIVE; Q12929; -.
DR MaxQB; Q12929; -.
DR PaxDb; 9606-ENSP00000281172; -.
DR PeptideAtlas; Q12929; -.
DR ProteomicsDB; 5414; -.
DR ProteomicsDB; 59033; -. [Q12929-1]
DR Antibodypedia; 1288; 404 antibodies from 39 providers.
DR DNASU; 2059; -.
DR Ensembl; ENST00000281172.10; ENSP00000281172.5; ENSG00000151491.14. [Q12929-1]
DR Ensembl; ENST00000540613.5; ENSP00000441888.1; ENSG00000151491.14. [Q12929-2]
DR Ensembl; ENST00000542903.1; ENSP00000437806.1; ENSG00000151491.14. [Q12929-2]
DR Ensembl; ENST00000543523.5; ENSP00000441867.1; ENSG00000151491.14. [Q12929-1]
DR Ensembl; ENST00000543612.5; ENSP00000442388.1; ENSG00000151491.14. [Q12929-1]
DR Ensembl; ENST00000642278.1; ENSP00000494689.1; ENSG00000151491.14. [Q12929-1]
DR Ensembl; ENST00000644374.1; ENSP00000495956.1; ENSG00000151491.14. [Q12929-1]
DR Ensembl; ENST00000645775.1; ENSP00000495824.1; ENSG00000151491.14. [Q12929-1]
DR Ensembl; ENST00000646828.1; ENSP00000494842.1; ENSG00000151491.14. [Q12929-1]
DR Ensembl; ENST00000646918.1; ENSP00000495722.1; ENSG00000151491.14. [Q12929-1]
DR Ensembl; ENST00000647087.1; ENSP00000496406.1; ENSG00000151491.14. [Q12929-1]
DR Ensembl; ENST00000647224.1; ENSP00000496516.1; ENSG00000151491.14. [Q12929-1]
DR GeneID; 2059; -.
DR KEGG; hsa:2059; -.
DR MANE-Select; ENST00000281172.10; ENSP00000281172.5; NM_004447.6; NP_004438.3.
DR UCSC; uc001rdb.4; human. [Q12929-1]
DR AGR; HGNC:3420; -.
DR CTD; 2059; -.
DR DisGeNET; 2059; -.
DR GeneCards; EPS8; -.
DR HGNC; HGNC:3420; EPS8.
DR HPA; ENSG00000151491; Low tissue specificity.
DR MalaCards; EPS8; -.
DR MIM; 600206; gene.
DR MIM; 615974; phenotype.
DR neXtProt; NX_Q12929; -.
DR OpenTargets; ENSG00000151491; -.
DR Orphanet; 90636; Rare autosomal recessive non-syndromic sensorineural deafness type DFNB.
DR PharmGKB; PA27839; -.
DR VEuPathDB; HostDB:ENSG00000151491; -.
DR eggNOG; KOG3557; Eukaryota.
DR GeneTree; ENSGT00940000156403; -.
DR HOGENOM; CLU_014510_0_0_1; -.
DR InParanoid; Q12929; -.
DR OMA; SEKYTIH; -.
DR OrthoDB; 2997036at2759; -.
DR PhylomeDB; Q12929; -.
DR TreeFam; TF313069; -.
DR PathwayCommons; Q12929; -.
DR Reactome; R-HSA-9662360; Sensory processing of sound by inner hair cells of the cochlea.
DR Reactome; R-HSA-9662361; Sensory processing of sound by outer hair cells of the cochlea.
DR SignaLink; Q12929; -.
DR SIGNOR; Q12929; -.
DR BioGRID-ORCS; 2059; 10 hits in 1147 CRISPR screens.
DR ChiTaRS; EPS8; human.
DR EvolutionaryTrace; Q12929; -.
DR GeneWiki; EPS8; -.
DR GenomeRNAi; 2059; -.
DR Pharos; Q12929; Tbio.
DR PRO; PR:Q12929; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; Q12929; Protein.
DR Bgee; ENSG00000151491; Expressed in jejunal mucosa and 214 other cell types or tissues.
DR ExpressionAtlas; Q12929; baseline and differential.
DR Genevisible; Q12929; HS.
DR GO; GO:0005903; C:brush border; IEA:Ensembl.
DR GO; GO:0005938; C:cell cortex; ISS:UniProtKB.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0098978; C:glutamatergic synapse; IEA:Ensembl.
DR GO; GO:0030426; C:growth cone; IEA:UniProtKB-SubCell.
DR GO; GO:0017146; C:NMDA selective glutamate receptor complex; IEA:Ensembl.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0014069; C:postsynaptic density; IEA:Ensembl.
DR GO; GO:0032587; C:ruffle membrane; ISS:UniProtKB.
DR GO; GO:0032420; C:stereocilium; ISS:UniProtKB.
DR GO; GO:0032426; C:stereocilium tip; IEA:Ensembl.
DR GO; GO:0031982; C:vesicle; HDA:UniProtKB.
DR GO; GO:0003779; F:actin binding; ISS:UniProtKB.
DR GO; GO:0031267; F:small GTPase binding; ISS:UniProtKB.
DR GO; GO:0051764; P:actin crosslink formation; ISS:UniProtKB.
DR GO; GO:0051017; P:actin filament bundle assembly; ISS:UniProtKB.
DR GO; GO:0070358; P:actin polymerization-dependent cell motility; ISS:UniProtKB.
DR GO; GO:0008344; P:adult locomotory behavior; IEA:Ensembl.
DR GO; GO:0051016; P:barbed-end actin filament capping; ISS:UniProtKB.
DR GO; GO:0048149; P:behavioral response to ethanol; IEA:Ensembl.
DR GO; GO:1990830; P:cellular response to leukemia inhibitory factor; IEA:Ensembl.
DR GO; GO:0036336; P:dendritic cell migration; ISS:UniProtKB.
DR GO; GO:0010458; P:exit from mitosis; ISS:UniProtKB.
DR GO; GO:1900029; P:positive regulation of ruffle assembly; IBA:GO_Central.
DR GO; GO:0016601; P:Rac protein signal transduction; ISS:UniProtKB.
DR GO; GO:0030832; P:regulation of actin filament length; ISS:UniProtKB.
DR GO; GO:0008360; P:regulation of cell shape; ISS:UniProtKB.
DR GO; GO:0099072; P:regulation of postsynaptic membrane neurotransmitter receptor levels; IEA:Ensembl.
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; cd09540; SAM_EPS8-like; 1.
DR CDD; cd11764; SH3_Eps8; 1.
DR Gene3D; 2.30.29.30; Pleckstrin-homology domain (PH domain)/Phosphotyrosine-binding domain (PTB); 1.
DR Gene3D; 2.30.30.40; SH3 Domains; 1.
DR Gene3D; 1.10.150.50; Transcription Factor, Ets-1; 1.
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:SF21; EPIDERMAL GROWTH FACTOR RECEPTOR KINASE SUBSTRATE 8; 1.
DR PANTHER; PTHR12287; EPIDERMAL GROWTH FACTOR RECEPTOR KINASE SUBSTRATE EPS8-RELATED PROTEIN; 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; SSF50729; PH domain-like; 1.
DR SUPFAM; SSF50044; SH3-domain; 1.
DR PROSITE; PS50002; SH3; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Actin-binding; Alternative splicing; Cell membrane;
KW Cell projection; Cytoplasm; Deafness; Membrane; Non-syndromic deafness;
KW Phosphoprotein; Reference proteome; SH3 domain; Synapse; Synaptosome;
KW Ubl conjugation.
FT CHAIN 1..822
FT /note="Epidermal growth factor receptor kinase substrate 8"
FT /id="PRO_0000086994"
FT DOMAIN 64..194
FT /note="PTB"
FT /evidence="ECO:0000255"
FT DOMAIN 531..590
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 202..225
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 298..320
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 612..689
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 649..822
FT /note="Effector region"
FT /evidence="ECO:0000250"
FT REGION 680..698
FT /note="Amphipathic helix"
FT /evidence="ECO:0000250"
FT REGION 718..738
FT /note="Helix bundle 1"
FT /evidence="ECO:0000250"
FT REGION 752..757
FT /note="Helix bundle 2"
FT /evidence="ECO:0000250"
FT REGION 762..767
FT /note="Helix bundle 3"
FT /evidence="ECO:0000250"
FT REGION 766..785
FT /note="Helix bundle 4"
FT /evidence="ECO:0000250"
FT REGION 787..822
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 617..646
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 651..668
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 674..689
FT /note="Basic and acidic 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:0007744|PubMed:24275569"
FT MOD_RES 317
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q08509"
FT MOD_RES 476
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 625
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 629
FT /note="Phosphothreonine; by MAPK"
FT /evidence="ECO:0000250|UniProtKB:Q08509"
FT MOD_RES 659
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q08509"
FT MOD_RES 662
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q08509"
FT MOD_RES 685
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q08509"
FT MOD_RES 811
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q08509"
FT MOD_RES 815
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q08509"
FT VAR_SEQ 1..260
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_056460"
FT VARIANT 761
FT /note="D -> E (in dbSNP:rs7137185)"
FT /evidence="ECO:0000269|PubMed:26721930"
FT /id="VAR_050971"
FT VARIANT 806
FT /note="A -> S (in dbSNP:rs1802658)"
FT /id="VAR_050972"
FT CONFLICT 73
FT /note="F -> S (in Ref. 2; BAF84466)"
FT /evidence="ECO:0000305"
FT CONFLICT 128
FT /note="F -> S (in Ref. 2; BAF84466)"
FT /evidence="ECO:0000305"
FT CONFLICT 194
FT /note="R -> G (in Ref. 2; BAF84466)"
FT /evidence="ECO:0000305"
FT CONFLICT 205
FT /note="A -> S (in Ref. 2; BAF85620)"
FT /evidence="ECO:0000305"
FT CONFLICT 497
FT /note="I -> V (in Ref. 2; BAF85620)"
FT /evidence="ECO:0000305"
FT CONFLICT 631
FT /note="A -> V (in Ref. 5; AAH30010)"
FT /evidence="ECO:0000305"
FT CONFLICT 705
FT /note="A -> T (in Ref. 2; BAF85620)"
FT /evidence="ECO:0000305"
FT STRAND 535..540
FT /evidence="ECO:0007829|PDB:7TZK"
FT STRAND 557..562
FT /evidence="ECO:0007829|PDB:7TZK"
FT STRAND 564..571
FT /evidence="ECO:0007829|PDB:7TZK"
FT STRAND 577..581
FT /evidence="ECO:0007829|PDB:7TZK"
FT HELIX 582..584
FT /evidence="ECO:0007829|PDB:7TZK"
FT STRAND 585..587
FT /evidence="ECO:0007829|PDB:7TZK"
FT HELIX 729..737
FT /evidence="ECO:0007829|PDB:2E8M"
FT HELIX 741..746
FT /evidence="ECO:0007829|PDB:2E8M"
FT STRAND 748..750
FT /evidence="ECO:0007829|PDB:2E8M"
FT HELIX 752..757
FT /evidence="ECO:0007829|PDB:2E8M"
FT HELIX 760..766
FT /evidence="ECO:0007829|PDB:2E8M"
FT HELIX 770..784
FT /evidence="ECO:0007829|PDB:2E8M"
SQ SEQUENCE 822 AA; 91882 MW; AC5EB1D28B784B3B CRC64;
MNGHISNHPS SFGMYPSQMN GYGSSPTFSQ TDREHGSKTS AKALYEQRKN YARDSVSSVS
DISQYRVEHL TTFVLDRKDA MITVDDGIRK LKLLDAKGKV WTQDMILQVD DRAVSLIDLE
SKNELENFPL NTIQHCQAVM HSCSYDSVLA LVCKEPTQNK PDLHLFQCDE VKANLISEDI
ESAISDSKGG KQKRRPDALR MISNADPSIP PPPRAPAPAP PGTVTQVDVR SRVAAWSAWA
ADQGDFEKPR QYHEQEETPE MMAARIDRDV QILNHILDDI EFFITKLQKA AEAFSELSKR
KKNKKGKRKG PGEGVLTLRA KPPPPDEFLD CFQKFKHGFN LLAKLKSHIQ NPSAADLVHF
LFTPLNMVVQ ATGGPELASS VLSPLLNKDT IDFLNYTVNG DERQLWMSLG GTWMKARAEW
PKEQFIPPYV PRFRNGWEPP MLNFMGATME QDLYQLAESV ANVAEHQRKQ EIKRLSTEHS
SVSEYHPADG YAFSSNIYTR GSHLDQGEAA VAFKPTSNRH IDRNYEPLKT QPKKYAKSKY
DFVARNNSEL SVLKDDILEI LDDRKQWWKV RNASGDSGFV PNNILDIVRP PESGLGRADP
PYTHTIQKQR MEYGPRPADT PPAPSPPPTP APVPVPLPPS TPAPVPVSKV PANITRQNSS
SSDSGGSIVR DSQRHKQLPV DRRKSQMEEV QDELIHRLTI GRSAAQKKFH VPRQNVPVIN
ITYDSTPEDV KTWLQSKGFN PVTVNSLGVL NGAQLFSLNK DELRTVCPEG ARVYSQITVQ
KAALEDSSGS SELQEIMRRR QEKISAAASD SGVESFDEGS SH
//
