InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: EPS8

Summary

InnateDB Protein

IDBP-21565.6

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

ENSP00000281172

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.

Comments

Interactions

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
DNA-DNA	0
RNA-RNA	0
DNA-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:0008344	adult locomotory behavior
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:0031532	actin cytoskeleton reorganization
GO:0036336	dendritic cell migration
GO:0045087	innate immune response (InnateDB)
GO:0048149	behavioral response to ethanol
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:0014069	postsynaptic density
GO:0017146	N-methyl-D-aspartate selective glutamate receptor complex
GO:0030054	cell junction
GO:0030426	growth cone
GO:0032420	stereocilium
GO:0032587	ruffle membrane
GO:0045202	synapse
GO:0070062	extracellular vesicular exosome

Protein Structure and Domains

PDB ID

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
PF14604
PF00640
PF14719
PF07653
PF08416

PRINTS

PR00452

PIRSF

SMART

SM00326
SM00462

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt