Homo sapiens Protein: EPS8
InnateDB Protein IDBP-599111.3
Last Modified 2014-10-13 [Report errors or provide feedback]
Gene Symbol EPS8
Protein Name epidermal growth factor receptor pathway substrate 8
Synonyms DFNB102;
Species Homo sapiens
Ensembl Protein ENSP00000441867
InnateDB Gene IDBG-21563 (EPS8)
Protein Structure
UniProt Annotation
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 DFNB31 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. {ECO:0000269PubMed:15558031, ECO:0000269PubMed:17115031}.
Subcellular Localization Cytoplasm, cell cortex {ECO:0000250}. Cell projection, ruffle membrane {ECO:0000250}. Cell projection, growth cone {ECO:0000250}. Cell projection, stereocilium {ECO:0000250}. Cell junction, synapse, synaptosome {ECO:0000250}. Note=Localizes to the midzone of dividing cells. {ECO:0000250}.
Disease Associations Note=Defects in EPS8 are associated with some cancers, such as pancreatic, oral squamous cell carcinomas or pituitary cancers. Contributes to cell transformation in response to growth factor treatment and is overexpressed in a number of tumors, indicating that EPS8 levels must be tightly regulated.
Tissue Specificity Expressed in all tissues analyzed, including heart, brain, placenta, lung, liver, skeletal muscle, kidney and pancreas. Expressed in all epithelial and fibroblastic lines examined and in some, but not all, hematopoietic cells.
Number of Interactions This gene and/or its encoded proteins are associated with 73 experimentally validated interaction(s) in this database.
They are also associated with 8 interaction(s) predicted by orthology.
Experimentally validated
Total 73 [view]
Protein-Protein 73 [view]
Protein-DNA 0
Protein-RNA 0
Predicted by orthology
Total 8 [view]
Gene Ontology

Molecular Function
Accession GO Term
GO:0003779 actin binding
GO:0005070 SH3/SH2 adaptor activity
GO:0005515 protein binding
GO:0016301 kinase activity
GO:0048365 Rac GTPase binding
Biological Process
GO:0007165 signal transduction
GO:0007173 epidermal growth factor receptor signaling pathway
GO:0008283 cell proliferation
GO:0008360 regulation of cell shape
GO:0009967 positive regulation of signal transduction
GO:0010458 exit from mitosis
GO:0016310 phosphorylation
GO:0016601 Rac protein signal transduction
GO:0030832 regulation of actin filament length
GO:0036336 dendritic cell migration
GO:0045087 innate immune response (InnateDB)
GO:0051016 barbed-end actin filament capping
GO:0051017 actin filament bundle assembly
GO:0051764 actin crosslink formation
GO:0070358 actin polymerization-dependent cell motility
Cellular Component
GO:0005938 cell cortex
GO:0030054 cell junction
GO:0030426 growth cone
GO:0032420 stereocilium
GO:0032587 ruffle membrane
GO:0070062 extracellular vesicular exosome
Protein Structure and Domains
InterPro IPR001452 SH3 domain
IPR006020 PTB/PI domain
IPR011511 Variant SH3 domain
IPR013625 Tensin phosphotyrosine-binding domain
IPR013761 Sterile alpha motif/pointed domain
PFAM PF00018
Post-translational Modifications
SwissProt Q12929
PhosphoSite PhosphoSite-Q12929
UniProt Splice Variant
Entrez Gene 2059
UniGene Hs.609259
RefSeq XP_005253396
OMIM 600206
HPRD 02563
EMBL AC022073 AC073651 AC092753 AK291777 AK292931 AK301834 AK316134 AK316239 BC030010 CH471094 U12535
GenPept AAA62280 AAH30010 BAF84466 BAF85620 BAG63278 BAH14505 BAH14610 EAW96354 EAW96355