ID   ES8L2_MOUSE             Reviewed;         729 AA.
AC   Q99K30; Q91VT7;
DT   30-MAY-2006, integrated into UniProtKB/Swiss-Prot.
DT   01-JUN-2001, sequence version 1.
DT   27-MAR-2024, entry version 161.
DE   RecName: Full=Epidermal growth factor receptor kinase substrate 8-like protein 2;
DE            Short=EPS8-like protein 2;
DE   AltName: Full=Epidermal growth factor receptor pathway substrate 8-related protein 2;
DE            Short=EPS8-related protein 2;
GN   Name=Eps8l2; Synonyms=Eps8r2;
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 [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC   STRAIN=C57BL/6J, and FVB/N; TISSUE=Mammary tumor;
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   [2]
RP   TISSUE SPECIFICITY.
RX   PubMed=14565974; DOI=10.1091/mbc.e03-06-0427;
RA   Offenhaeuser N., Borgonovo A., Disanza A., Romano P., Ponzanelli I.,
RA   Iannolo G., Di Fiore P.P., Scita G.;
RT   "The eps8 family of proteins links growth factor stimulation to actin
RT   reorganization generating functional redundancy in the Ras/Rac pathway.";
RL   Mol. Biol. Cell 15:91-98(2004).
RN   [3]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-306, 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   [4]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-306, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Brain, Kidney, Liver, Lung, and Pancreas;
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   [5]
RP   FUNCTION, DISRUPTION PHENOTYPE, TISSUE SPECIFICITY, SUBCELLULAR LOCATION,
RP   AND DEVELOPMENTAL STAGE.
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).
CC   -!- FUNCTION: Stimulates guanine exchange activity of SOS1. May play a role
CC       in membrane ruffling and remodeling of the actin cytoskeleton (By
CC       similarity). In the cochlea, is required for stereocilia maintenance in
CC       adult hair cells (PubMed:23918390). {ECO:0000250|UniProtKB:Q9H6S3,
CC       ECO:0000269|PubMed:23918390}.
CC   -!- SUBUNIT: Interacts with ABI1. Part of a complex that contains SOS1,
CC       ABI1 and EPS8L2. Associates with F-actin (By similarity).
CC       {ECO:0000250|UniProtKB:Q9H6S3}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q9H6S3}. Cell
CC       projection, stereocilium {ECO:0000269|PubMed:23918390}. Note=Localizes
CC       at the tips of the stereocilia of the inner and outer hair cells.
CC       {ECO:0000269|PubMed:23918390}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=Q99K30-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q99K30-2; Sequence=VSP_019093, VSP_019094;
CC   -!- TISSUE SPECIFICITY: Detected in fetal kidney, adrenal gland, salivary
CC       gland, stomach, gut, cartilage and skin. Detected in adult ovary,
CC       placenta, skin, adrenal gland, salivary gland, kidney, intestine and
CC       stomach. Expressed at the tips of cochlear hair cells stereocilia
CC       (PubMed:23918390). {ECO:0000269|PubMed:14565974,
CC       ECO:0000269|PubMed:23918390}.
CC   -!- DISRUPTION PHENOTYPE: Mutant animal have a progressive and severe
CC       hearing loss at young adulthood (PubMed:23918390). The generation of
CC       receptor potentials in hair cells at lower sound pressure is impaired,
CC       which leads to a reduction in auditory nerve responses
CC       (PubMed:23918390). {ECO:0000269|PubMed:23918390}.
CC   -!- SIMILARITY: Belongs to the EPS8 family. {ECO:0000305}.
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DR   EMBL; BC005492; AAH05492.1; -; mRNA.
DR   EMBL; BC009098; AAH09098.1; -; mRNA.
DR   CCDS; CCDS22009.1; -. [Q99K30-1]
DR   RefSeq; NP_573454.2; NM_133191.2. [Q99K30-1]
DR   AlphaFoldDB; Q99K30; -.
DR   SMR; Q99K30; -.
DR   BioGRID; 221147; 4.
DR   STRING; 10090.ENSMUSP00000026577; -.
DR   iPTMnet; Q99K30; -.
DR   PhosphoSitePlus; Q99K30; -.
DR   SwissPalm; Q99K30; -.
DR   jPOST; Q99K30; -.
DR   MaxQB; Q99K30; -.
DR   PaxDb; 10090-ENSMUSP00000026577; -.
DR   PeptideAtlas; Q99K30; -.
DR   ProteomicsDB; 275948; -. [Q99K30-1]
DR   ProteomicsDB; 275949; -. [Q99K30-2]
DR   Antibodypedia; 22613; 296 antibodies from 28 providers.
DR   DNASU; 98845; -.
DR   Ensembl; ENSMUST00000026577.13; ENSMUSP00000026577.7; ENSMUSG00000025504.15. [Q99K30-1]
DR   GeneID; 98845; -.
DR   KEGG; mmu:98845; -.
DR   UCSC; uc009kkt.1; mouse. [Q99K30-1]
DR   AGR; MGI:2138828; -.
DR   CTD; 64787; -.
DR   MGI; MGI:2138828; Eps8l2.
DR   VEuPathDB; HostDB:ENSMUSG00000025504; -.
DR   eggNOG; KOG3557; Eukaryota.
DR   GeneTree; ENSGT00940000160990; -.
DR   HOGENOM; CLU_014510_0_0_1; -.
DR   InParanoid; Q99K30; -.
DR   OMA; ANQRYKG; -.
DR   OrthoDB; 2997036at2759; -.
DR   PhylomeDB; Q99K30; -.
DR   TreeFam; TF313069; -.
DR   BioGRID-ORCS; 98845; 1 hit in 77 CRISPR screens.
DR   ChiTaRS; Eps8l2; mouse.
DR   PRO; PR:Q99K30; -.
DR   Proteomes; UP000000589; Chromosome 7.
DR   RNAct; Q99K30; Protein.
DR   Bgee; ENSMUSG00000025504; Expressed in oral epithelium and 184 other cell types or tissues.
DR   ExpressionAtlas; Q99K30; baseline and differential.
DR   GO; GO:0005813; C:centrosome; ISO:MGI.
DR   GO; GO:0005829; C:cytosol; ISO:MGI.
DR   GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR   GO; GO:0032991; C:protein-containing complex; ISO:MGI.
DR   GO; GO:0001726; C:ruffle; ISO:MGI.
DR   GO; GO:0032587; C:ruffle membrane; ISO:MGI.
DR   GO; GO:0032421; C:stereocilium bundle; IDA:UniProtKB.
DR   GO; GO:0032426; C:stereocilium tip; IDA:UniProtKB.
DR   GO; GO:0003779; F:actin binding; ISO:MGI.
DR   GO; GO:0051015; F:actin filament binding; ISO:MGI.
DR   GO; GO:0005085; F:guanyl-nucleotide exchange factor activity; IEA:Ensembl.
DR   GO; GO:1900029; P:positive regulation of ruffle assembly; ISO:MGI.
DR   GO; GO:0016601; P:Rac protein signal transduction; ISO:MGI.
DR   GO; GO:0035023; P:regulation of Rho protein signal transduction; ISO:MGI.
DR   GO; GO:0007266; P:Rho protein signal transduction; ISO:MGI.
DR   GO; GO:0007605; P:sensory perception of sound; IDA:UniProtKB.
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:SF20; EPIDERMAL GROWTH FACTOR RECEPTOR KINASE SUBSTRATE 8-LIKE PROTEIN 2; 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; PS01179; PID; 1.
DR   PROSITE; PS50002; SH3; 1.
DR   Genevisible; Q99K30; MM.
PE   1: Evidence at protein level;
KW   Alternative splicing; Cell projection; Cytoplasm; Phosphoprotein;
KW   Reference proteome; SH3 domain.
FT   CHAIN           1..729
FT                   /note="Epidermal growth factor receptor kinase substrate 8-
FT                   like protein 2"
FT                   /id="PRO_0000239085"
FT   DOMAIN          46..202
FT                   /note="PID"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00148"
FT   DOMAIN          495..554
FT                   /note="SH3"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00192"
FT   REGION          1..25
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          182..247
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          449..492
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          695..729
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        449..476
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOD_RES         242
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q9H6S3"
FT   MOD_RES         306
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0007744|PubMed:17242355,
FT                   ECO:0007744|PubMed:21183079"
FT   MOD_RES         573
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q9H6S3"
FT   VAR_SEQ         357..400
FT                   /note="IINTCGSPDIARSVSSPLLSTDAVSFLRGHLVPKEMTLWESLGE -> VTGA
FT                   GTGRGRGQQSDPHGFGVEETSAHLSILKLCLGSQEATVHP (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:15489334"
FT                   /id="VSP_019093"
FT   VAR_SEQ         401..729
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:15489334"
FT                   /id="VSP_019094"
FT   CONFLICT        177
FT                   /note="G -> R (in Ref. 1; AAH09098)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   729 AA;  82229 MW;  A11DE82FF2C0BD18 CRC64;
     MSQSASMSCC PGAANGSLGR SDGVPRMSAK DLFEQRKKYS NSNVIMHETS QYHVQHLATF
     IMDKSEAIAS VDDAIRKLVQ LSSKEKVWAQ EVLLQVNDKS LRLLDVESQE ELENFPLPTV
     QHSQTVLNQL RYPSVLLLVC QDSDQNKPDI HFFHCDEVEA ELVQEDIESA LADYRLGKKM
     RPQTLKGHQE KIRQRQSILP PPQSPAPIPF QRQPGDSPQA KNRVGLPLPV PFSEPGYRRR
     ESQDEEPRAV LAQRIEKETQ ILNCTLDDIE WFVARLQKAA EAFKQLNQRK KGKKKNKKGP
     AEGVLTLRAR PPSEGEFVDC FQKTKLAINL LAKLQKHIQN PSAAELVHFL FGPLDLIINT
     CGSPDIARSV SSPLLSTDAV SFLRGHLVPK EMTLWESLGE TWMRPRSEWP REPQVPLYVP
     KFRSGWEPPL DVLQEAPWEV EGLASVPSDQ LTPKNRLSVR HSPKHSLSSE SQAPEDIAPP
     GSSPHANRGY QPTPAMTKYV KILYDFTARN ANELSVLKDE VLEVLEDGRQ WWKLRNRSGQ
     AGYVPCNILA EARQEDVGAP LEQSGQKYWG PASPTHKLPP IFAGNKEELI HHMDEVNDEL
     MKKISHIKTQ PQRNFRVERS QPVHLPLTFE SGPDEVRAWL EAKAFSARIV ENLGILTGPQ
     LFSLNKEELK KVCGEEGSRV YSQLTVQKAF LEKQQSGSEL EKLMSKIRRA EDSYTSQHTS
     PESEGAPHL
//