EPS8_RAT
ID EPS8_RAT Reviewed; 822 AA.
AC F1M3L7;
DT 03-APR-2013, integrated into UniProtKB/Swiss-Prot.
DT 03-APR-2013, sequence version 2.
DT 03-AUG-2022, entry version 79.
DE RecName: Full=Epidermal growth factor receptor kinase substrate 8;
GN Name=Eps8;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway;
RX PubMed=15057822; DOI=10.1038/nature02426;
RA Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA Mockrin S., Collins F.S.;
RT "Genome sequence of the Brown Norway rat yields insights into mammalian
RT evolution.";
RL Nature 428:493-521(2004).
RN [2]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-317, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=16641100; DOI=10.1073/pnas.0600895103;
RA Hoffert J.D., Pisitkun T., Wang G., Shen R.-F., Knepper M.A.;
RT "Quantitative phosphoproteomics of vasopressin-sensitive renal cells:
RT regulation of aquaporin-2 phosphorylation at two sites.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:7159-7164(2006).
RN [3]
RP INTERACTION WITH ABI1, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=17304222; DOI=10.1038/sj.emboj.7601569;
RA Proepper C., Johannsen S., Liebau S., Dahl J., Vaida B., Bockmann J.,
RA Kreutz M.R., Gundelfinger E.D., Boeckers T.M.;
RT "Abelson interacting protein 1 (Abi-1) is essential for dendrite
RT morphogenesis and synapse formation.";
RL EMBO J. 26:1397-1409(2007).
RN [4]
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
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 [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-58; THR-317; SER-659 AND
RP SER-685, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
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 (By similarity). {ECO:0000250}.
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:17304222}.
CC -!- SUBCELLULAR LOCATION: Synapse, synaptosome. Cytoplasm, cell cortex
CC {ECO:0000250}. Cell projection, ruffle membrane {ECO:0000250}. Cell
CC projection, stereocilium {ECO:0000250, ECO:0000250|UniProtKB:Q08509}.
CC Cell projection, growth cone. Note=Localizes at the tips of the
CC stereocilia of the inner and outer hair cells (By similarity).Localizes
CC to the midzone of dividing cells. {ECO:0000250,
CC ECO:0000250|UniProtKB:Q08509}.
CC -!- TISSUE SPECIFICITY: Expressed in neuronal cell body and neurites, and
CC prominently enriched in the axonal growth cone.
CC {ECO:0000269|PubMed:17304222, ECO:0000269|PubMed:19564905}.
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. {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 (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.
CC Phosphorylated by several receptor tyrosine kinases (By similarity).
CC {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the EPS8 family. {ECO:0000305}.
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 RefSeq; XP_001072957.3; XM_001072957.6.
DR RefSeq; XP_006225179.1; XM_006225117.3.
DR RefSeq; XP_006237645.1; XM_006237583.3.
DR RefSeq; XP_008761674.1; XM_008763452.2.
DR RefSeq; XP_017458375.1; XM_017602886.1.
DR RefSeq; XP_017458376.1; XM_017602887.1.
DR RefSeq; XP_232499.6; XM_232499.9.
DR AlphaFoldDB; F1M3L7; -.
DR SMR; F1M3L7; -.
DR IntAct; F1M3L7; 1.
DR STRING; 10116.ENSRNOP00000009328; -.
DR iPTMnet; F1M3L7; -.
DR PhosphoSitePlus; F1M3L7; -.
DR PaxDb; F1M3L7; -.
DR PRIDE; F1M3L7; -.
DR GeneID; 312812; -.
DR UCSC; RGD:1310590; rat.
DR CTD; 2059; -.
DR RGD; 1310590; Eps8.
DR VEuPathDB; HostDB:ENSRNOG00000007047; -.
DR eggNOG; KOG3557; Eukaryota.
DR HOGENOM; CLU_014510_0_0_1; -.
DR InParanoid; F1M3L7; -.
DR OMA; FPQMNGY; -.
DR OrthoDB; 218804at2759; -.
DR TreeFam; TF313069; -.
DR PRO; PR:F1M3L7; -.
DR Proteomes; UP000002494; Chromosome 4.
DR Bgee; ENSRNOG00000007047; Expressed in adult mammalian kidney and 18 other tissues.
DR Genevisible; F1M3L7; RN.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0005903; C:brush border; ISO:RGD.
DR GO; GO:0005938; C:cell cortex; ISS:UniProtKB.
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; ISO:RGD.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0014069; C:postsynaptic density; IDA:SynGO.
DR GO; GO:0032587; C:ruffle membrane; ISS:UniProtKB.
DR GO; GO:0032420; C:stereocilium; ISS:UniProtKB.
DR GO; GO:0032421; C:stereocilium bundle; ISO:RGD.
DR GO; GO:0032426; C:stereocilium tip; ISO:RGD.
DR GO; GO:0045202; C:synapse; ISO:RGD.
DR GO; GO:0003779; F:actin binding; ISS:UniProtKB.
DR GO; GO:0035591; F:signaling adaptor activity; IEA:InterPro.
DR GO; GO:0031267; F:small GTPase binding; ISS:UniProtKB.
DR GO; GO:0051764; P:actin crosslink formation; ISS:UniProtKB.
DR GO; GO:0031532; P:actin cytoskeleton reorganization; ISO:RGD.
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; ISO:RGD.
DR GO; GO:0051016; P:barbed-end actin filament capping; ISS:UniProtKB.
DR GO; GO:0048149; P:behavioral response to ethanol; ISO:RGD.
DR GO; GO:1990830; P:cellular response to leukemia inhibitory factor; ISO:RGD.
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; ISO:RGD.
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 Actin-binding; Cell membrane; Cell projection; Cytoplasm; Membrane;
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_0000421990"
FT DOMAIN 69..129
FT /note="PH; first part"
FT DOMAIN 381..414
FT /note="PH; second part"
FT DOMAIN 531..590
FT /note="SH3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192"
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 460..487
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 608..685
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 206..220
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 620..649
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 652..671
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 58
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
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:16641100,
FT ECO:0007744|PubMed:22673903"
FT MOD_RES 476
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q12929"
FT MOD_RES 625
FT /note="Phosphoserine; by MAPK"
FT /evidence="ECO:0000250|UniProtKB:Q08509"
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:0007744|PubMed:22673903"
FT MOD_RES 662
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q08509"
FT MOD_RES 685
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
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"
SQ SEQUENCE 822 AA; 91929 MW; 48936318B28BF162 CRC64;
MNGHMSNHSS GYGIYPSQMN GYGSSPPYSQ MDREHCSRTS AKALYEQRKN YARDSVSSVS
DVSQYRVEHL TTFVLDRKDA MITVDDGIRK LKLLDAKGKV WTQDMILQVD DRAVSLIDLE
SKNELENFPL NTIQHCQAVA HTCSYDSILA LVCKEPTQNK PDLHLFQCDE VKANLISEDI
ESAISDSKGG KQKRRPEALR MIAKADPGIP PPPRAPAPVP PGTVTQVDVR SRVAAWSAWA
ADQGDFEKPR QYHEQEETPE MMAARIDRDV QILNHILDDI EFFITKLQKA AEAFSELSKR
KKSKKSKRKG PGEGVLTLRA KPPPPDEFVD CFQKFKHGFN LLAKLKSHIQ NPSASDLVHF
LFTPLNMVVQ ATGGPELASS VLSPLLTKDT VDFLNYTVKA EERQLWMSLG ETWMKVRAEW
PKEQFIPPYV PRFRNGWEPP MLNFMGAPTE QDMYQLAESV ANAAEQQRKQ DSKRQSTEHS
SMSDYPPADG YTFSNSMYHR GPHVDQGEAA LALKSTPNRH VDRNYDPVKT QPKKYAKSKY
DFVARNSSEL SVMKDDVLEI LDDRKQWWKV RNASGDSGFV PNNILDIMRT PESGVGRTDP
PYTHTIQKQR TEYGPRSADT PSAPSPPPTP APVPVPLPPS APAPVPVPKV PANVTRQNSS
SSESGGSIAR DSQRYKQLPV DRRKSQMEEV QDELFQRLTI GRSAAQRKFH VPRQNVPVIN
ITYDSSPEEV KTWLQSKGFN PVTVSSLGVL NGAQLFSLNK DELRSVCPEG ARVFSQITVQ
KAALEDSSGS SELQEIMRRR QEKISAAASD SGVESFDEGS SH
