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Overview

Uniprot IDF1M3L7
Protein NameEpidermal growth factor receptor kinase substrate 8
Gene NameEps8
OrganismRattus norvegicus

Kla Sites from experimental identification

Position Flanking peptide
42 HCSRTSAKALYEQRK

Function

Signaling adapter that controls various cellular protrusions by regulating actin cytoskeleton dynamics and architecture. Depending on its association with other signal transducers, can regulate different processes. Together with SOS1 and ABI1, forms a trimeric complex that participates in transduction of signals from Ras to Rac by activating the Rac-specific guanine nucleotide exchange factor (GEF) activity. Acts as a direct regulator of actin dynamics by binding actin filaments and has both barbed-end actin filament capping and actin bundling activities depending on the context. Displays barbed-end actin capping activity when associated with ABI1, thereby regulating actin-based motility process: capping activity is auto-inhibited and inhibition is relieved upon ABI1 interaction. Also shows actin bundling activity when associated with BAIAP2, enhancing BAIAP2-dependent membrane extensions and promoting filopodial protrusions. Involved in the regulation of processes such as axonal filopodia growth, stereocilia length, dendritic cell migration and cancer cell migration and invasion. Acts as a regulator of axonal filopodia formation in neurons: in the absence of neurotrophic factors, negatively regulates axonal filopodia formation via actin-capping activity. In contrast, it is phosphorylated in the presence of BDNF leading to inhibition of its actin-capping activity and stimulation of filopodia formation. Component of a complex with WHRN and MYO15A that localizes at stereocilia tips and is required for elongation of the stereocilia actin core. Indirectly involved in cell cycle progression; its degradation following ubiquitination being required during G2 phase to promote cell shape changes (By similarity)

Protein Sequence

10 MNGHMSNHSS 20 GYGIYPSQMN 30 GYGSSPPYSQ 40 MDREHCSRTS 50 AKALYEQRKN 60 YARDSVSSVS 70 DVSQYRVEHL 80 TTFVLDRKDA 90 MITVDDGIRK 100 LKLLDAKGKV 110 WTQDMILQVD 120 DRAVSLIDLE 130 SKNELENFPL 140 NTIQHCQAVA 150 HTCSYDSILA 160 LVCKEPTQNK 170 PDLHLFQCDE 180 VKANLISEDI 190 ESAISDSKGG 200 KQKRRPEALR 210 MIAKADPGIP 220 PPPRAPAPVP 230 PGTVTQVDVR 240 SRVAAWSAWA 250 ADQGDFEKPR 260 QYHEQEETPE 270 MMAARIDRDV 280 QILNHILDDI 290 EFFITKLQKA 300 AEAFSELSKR 310 KKSKKSKRKG 320 PGEGVLTLRA 330 KPPPPDEFVD 340 CFQKFKHGFN 350 LLAKLKSHIQ 360 NPSASDLVHF 370 LFTPLNMVVQ 380 ATGGPELASS 390 VLSPLLTKDT 400 VDFLNYTVKA 410 EERQLWMSLG 420 ETWMKVRAEW 430 PKEQFIPPYV 440 PRFRNGWEPP 450 MLNFMGAPTE 460 QDMYQLAESV 470 ANAAEQQRKQ 480 DSKRQSTEHS 490 SMSDYPPADG 500 YTFSNSMYHR 510 GPHVDQGEAA 520 LALKSTPNRH 530 VDRNYDPVKT 540 QPKKYAKSKY 550 DFVARNSSEL 560 SVMKDDVLEI 570 LDDRKQWWKV 580 RNASGDSGFV 590 PNNILDIMRT 600 PESGVGRTDP 610 PYTHTIQKQR 620 TEYGPRSADT 630 PSAPSPPPTP 640 APVPVPLPPS 650 APAPVPVPKV 660 PANVTRQNSS 670 SSESGGSIAR 680 DSQRYKQLPV 690 DRRKSQMEEV 700 QDELFQRLTI 710 GRSAAQRKFH 720 VPRQNVPVIN 730 ITYDSSPEEV 740 KTWLQSKGFN 750 PVTVSSLGVL 760 NGAQLFSLNK 770 DELRSVCPEG 780 ARVFSQITVQ 790 KAALEDSSGS 800 SELQEIMRRR 810 QEKISAAASD 820 SGVESFDEGS SH

Gene Ontology

Classification GO ID Description
Cellular Component GO:0005903 brush border
Cellular Component GO:0005938 cell cortex
Cellular Component GO:0098978 glutamatergic synapse
Cellular Component GO:0030426 growth cone
Cellular Component GO:0017146 NMDA selective glutamate receptor complex
Cellular Component GO:0005886 plasma membrane
Cellular Component GO:0014069 postsynaptic density
Cellular Component GO:0032587 ruffle membrane
Cellular Component GO:0032420 stereocilium
Cellular Component GO:0032421 stereocilium bundle
Cellular Component GO:0032426 stereocilium tip
Cellular Component GO:0045202 synapse
Molecular Function GO:0003779 actin binding
Molecular Function GO:0031267 small GTPase binding
Biological Process GO:0051764 actin crosslink formation
Biological Process GO:0030036 actin cytoskeleton organization
Biological Process GO:0051017 actin filament bundle assembly
Biological Process GO:0070358 actin polymerization-dependent cell motility
Biological Process GO:0008344 adult locomotory behavior
Biological Process GO:0051016 barbed-end actin filament capping
Biological Process GO:0048149 behavioral response to ethanol
Biological Process GO:1990830 cellular response to leukemia inhibitory factor
Biological Process GO:0036336 dendritic cell migration
Biological Process GO:0010458 exit from mitosis
Biological Process GO:1900029 positive regulation of ruffle assembly
Biological Process GO:0016601 Rac protein signal transduction
Biological Process GO:0030832 regulation of actin filament length
Biological Process GO:0008360 regulation of cell shape
Biological Process GO:0099072 regulation of postsynaptic membrane neurotransmitter receptor levels
Biological Process GO:0035023 regulation of Rho protein signal transduction
Biological Process GO:0007266 Rho protein signal transduction

Reference

[1] Sheng L, Xu H, Wang Y, Ni J, Xiang T et al.. Systematic analysis of lysine lactylation in nucleus pulposus cells.. iScience 27(11):111157. 2024 Nov 15. PMID: 39524337.