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Aliases for EPS8 Gene

Aliases for EPS8 Gene

  • Epidermal Growth Factor Receptor Pathway Substrate 8 2 3
  • Epidermal Growth Factor Receptor Kinase Substrate 8 3
  • DFNB102 3

External Ids for EPS8 Gene

Previous GeneCards Identifiers for EPS8 Gene

  • GC12M015512
  • GC12M015917
  • GC12M015673

Summaries for EPS8 Gene

Entrez Gene Summary for EPS8 Gene

  • This gene encodes a member of the EPS8 family. This protein contains one PH domain and one SH3 domain. It functions as part of the EGFR pathway, though its exact role has not been determined. Highly similar proteins in other organisms are involved in the transduction of signals from Ras to Rac and growth factor-mediated actin remodeling. Alternate transcriptional splice variants of this gene have been observed but have not been thoroughly characterized. [provided by RefSeq, Jul 2008]

GeneCards Summary for EPS8 Gene

EPS8 (Epidermal Growth Factor Receptor Pathway Substrate 8) is a Protein Coding gene. Diseases associated with EPS8 include deafness, autosomal recessive 102 and autosomal recessive non-syndromic sensorineural deafness type dfnb. Among its related pathways are Tyrosine Kinases / Adaptors and Development FGFR signaling pathway. GO annotations related to this gene include actin binding and Rac GTPase binding. An important paralog of this gene is EPS8L2.

UniProtKB/Swiss-Prot for EPS8 Gene

  • 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.

Gene Wiki entry for EPS8 Gene

No data available for Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for EPS8 Gene

Genomics for EPS8 Gene

Regulatory Elements for EPS8 Gene

Genomic Location for EPS8 Gene

Start:
15,620,141 bp from pter
End:
15,882,329 bp from pter
Size:
262,189 bases
Orientation:
Minus strand

Genomic View for EPS8 Gene

UCSC Golden Path with GeneCards custom track
Cytogenetic band:
Genomic Location for EPS8 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for EPS8 Gene

Proteins for EPS8 Gene

  • Protein details for EPS8 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q12929-EPS8_HUMAN
    Recommended name:
    Epidermal growth factor receptor kinase substrate 8
    Protein Accession:
    Q12929
    Secondary Accessions:
    • A6NMC3
    • A8K6W2
    • A8KA66
    • B4DX66
    • Q8N6J0

    Protein attributes for EPS8 Gene

    Size:
    822 amino acids
    Molecular mass:
    91882 Da
    Quaternary structure:
    • Homodimer. Part of a complex consisting of ABI1, EPS8 and SOS1. Interacts with MYO15A and DFNB31. Interacts with LANCL1 (By similarity). Interacts with EGFR; mediates EPS8 phosphorylation (By similarity). Interacts with BAIAP2. Interacts with SHB.

    Three dimensional structures from OCA and Proteopedia for EPS8 Gene

    Alternative splice isoforms for EPS8 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for EPS8 Gene

Proteomics data for EPS8 Gene at MOPED

Post-translational modifications for EPS8 Gene

  • Phosphorylation at Ser-625 and Thr-629 by MAPK following BDNF treatment promotes removal from actin and filopodia formation (By similarity). Phosphorylated by several receptor tyrosine kinases.
  • Ubiquitinated by the SCF(FBXW5) E3 ubiquitin-protein ligase complex during G2 phase, leading to its transient degradation and subsequent cell shape changes required to allow mitotic progression. Reappears at the midzone of dividing cells (By similarity).
  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

No data available for DME Specific Peptides for EPS8 Gene

Domains for EPS8 Gene

Protein Domains for EPS8 Gene

Graphical View of Domain Structure for InterPro Entry

Q12929

UniProtKB/Swiss-Prot:

EPS8_HUMAN :
  • Q12929
Domain:
  • The effector region is required for activating the Rac-specific guanine nucleotide exchange factor (GEF) activity. It mediates both barbed-end actin capping and actin bundling activities. The capping activity is mediated by an amphipathic helix that binds within the hydrophobic pocket at the barbed ends of actin blocking further addition of actin monomers, while the bundling activity is mediated by a compact 4 helix bundle, which contacts 3 actin subunits along the filament (By similarity).
  • The SH3 domain mediates interaction with SHB
  • Contains 1 PH domain.
  • Contains 1 SH3 domain.
Family:
  • Belongs to the EPS8 family.
genes like me logo Genes that share domains with EPS8: view

No data available for Gene Families for EPS8 Gene

Function for EPS8 Gene

Molecular function for EPS8 Gene

GENATLAS Biochemistry: epidermal growth factor receptor (EGFR) substrate,complexing with SSH3BP1 and putatively mediating the transfer of signals from Ras to Racs
UniProtKB/Swiss-Prot 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.

Gene Ontology (GO) - Molecular Function for EPS8 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0003779 actin binding ISS --
GO:0005070 SH3/SH2 adaptor activity TAS 8084614
GO:0005515 protein binding IPI 15289329
GO:0048365 Rac GTPase binding ISS --
genes like me logo Genes that share ontologies with EPS8: view
genes like me logo Genes that share phenotypes with EPS8: view

Animal Models for EPS8 Gene

MGI Knock Outs for EPS8:

miRNA for EPS8 Gene

miRTarBase miRNAs that target EPS8

No data available for Enzyme Numbers (IUBMB) , Transcription Factor Targeting and HOMER Transcription for EPS8 Gene

Localization for EPS8 Gene

Subcellular locations from UniProtKB/Swiss-Prot for EPS8 Gene

Cytoplasm, cell cortex. Cell projection, ruffle membrane. Cell projection, growth cone. Cell projection, stereocilium. Cell junction, synapse, synaptosome. Note=Localizes at the tips of the stereocilia of the inner and outer hair cells (By similarity). Localizes to the midzone of dividing cells. {ECO:0000250, ECO:0000250 UniProtKB:Q08509}.

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for EPS8 Gene COMPARTMENTS Subcellular localization image for EPS8 gene
Compartment Confidence
plasma membrane 4
cytosol 3
nucleus 3
cytoskeleton 2
endosome 1
golgi apparatus 1

Gene Ontology (GO) - Cellular Components for EPS8 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005938 cell cortex ISS --
GO:0014069 postsynaptic density IEA --
GO:0017146 N-methyl-D-aspartate selective glutamate receptor complex IEA --
GO:0030054 cell junction IEA --
GO:0030426 growth cone IEA --
genes like me logo Genes that share ontologies with EPS8: view

Pathways for EPS8 Gene

genes like me logo Genes that share pathways with EPS8: view

Pathways by source for EPS8 Gene

1 Qiagen pathway for EPS8 Gene
1 Cell Signaling Technology pathway for EPS8 Gene

Gene Ontology (GO) - Biological Process for EPS8 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0007165 signal transduction TAS 8084614
GO:0007173 epidermal growth factor receptor signaling pathway TAS 8084614
GO:0008283 cell proliferation TAS 8084614
GO:0008344 adult locomotory behavior IEA --
GO:0008360 regulation of cell shape ISS --
genes like me logo Genes that share ontologies with EPS8: view

Compounds for EPS8 Gene

(2) Novoseek inferred chemical compound relationships for EPS8 Gene

Compound -log(P) Hits PubMed IDs
tyrosine 55.6 18
phosphotyrosine 48.5 2
genes like me logo Genes that share compounds with EPS8: view

Transcripts for EPS8 Gene

Unigene Clusters for EPS8 Gene

Epidermal growth factor receptor pathway substrate 8:
Representative Sequences:

Alternative Splicing Database (ASD) splice patterns (SP) for EPS8 Gene

ExUns: 1a · 1b · 1c ^ 2 ^ 3 ^ 4 ^ 5 ^ 6a · 6b ^ 7 ^ 8 ^ 9a · 9b ^ 10 ^ 11 ^ 12a · 12b ^ 13a · 13b ^ 14 ^ 15a · 15b ^ 16 ^ 17 ^ 18a · 18b ^
SP1: - - - -
SP2: - - - - -
SP3: -
SP4:
SP5:
SP6:

ExUns: 19 ^ 20a · 20b ^ 21
SP1:
SP2:
SP3:
SP4:
SP5:
SP6:

Relevant External Links for EPS8 Gene

GeneLoc Exon Structure for
EPS8
ECgene alternative splicing isoforms for
EPS8

Expression for EPS8 Gene

mRNA expression in normal human tissues for EPS8 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Integrated Proteomics: protein expression from ProteomicsDB, PaxDb, MOPED, and MaxQB for EPS8 Gene

SOURCE GeneReport for Unigene cluster for EPS8 Gene Hs.591160

mRNA Expression by UniProt/SwissProt for EPS8 Gene

Q12929-EPS8_HUMAN
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
genes like me logo Genes that share expressions with EPS8: view

No data available for mRNA differential expression in normal tissues for EPS8 Gene

Orthologs for EPS8 Gene

This gene was present in the common ancestor of animals.

Orthologs for EPS8 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia EPS8 35
  • 99.39 (n)
  • 99.88 (a)
EPS8 36
  • 100 (a)
OneToOne
cow
(Bos Taurus)
Mammalia EPS8 35
  • 89.67 (n)
  • 90.93 (a)
EPS8 36
  • 89 (a)
OneToOne
dog
(Canis familiaris)
Mammalia EPS8 35
  • 92.61 (n)
  • 94.64 (a)
EPS8 36
  • 95 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Eps8 35
  • 84.49 (n)
  • 89.16 (a)
Eps8 16
Eps8 36
  • 89 (a)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia EPS8 36
  • 86 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Eps8 35
  • 84.06 (n)
  • 90.39 (a)
chicken
(Gallus gallus)
Aves EPS8 35
  • 77.99 (n)
  • 79.9 (a)
EPS8 36
  • 80 (a)
OneToOne
lizard
(Anolis carolinensis)
Reptilia EPS8 36
  • 77 (a)
OneToOne
African clawed frog
(Xenopus laevis)
Amphibia Xl.11312 35
tropical clawed frog
(Silurana tropicalis)
Amphibia eps8 35
  • 67.73 (n)
  • 67.73 (a)
Str.19077 35
zebrafish
(Danio rerio)
Actinopterygii eps8 35
  • 63.22 (n)
  • 65.4 (a)
eps8 36
  • 58 (a)
OneToOne
zgc56041 35
fruit fly
(Drosophila melanogaster)
Insecta aru 36
  • 22 (a)
ManyToMany
CG8907 36
  • 25 (a)
ManyToMany
aru 37
  • 46 (a)
worm
(Caenorhabditis elegans)
Secernentea eps-8 36
  • 23 (a)
OneToMany
sea squirt
(Ciona savignyi)
Ascidiacea -- 36
  • 38 (a)
OneToOne
Species with no ortholog for EPS8:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • platypus (Ornithorhynchus anatinus)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for EPS8 Gene

ENSEMBL:
Gene Tree for EPS8 (if available)
TreeFam:
Gene Tree for EPS8 (if available)

Paralogs for EPS8 Gene

Paralogs for EPS8 Gene

Selected SIMAP similar genes for EPS8 Gene using alignment to 9 proteins:

genes like me logo Genes that share paralogs with EPS8: view

Variants for EPS8 Gene

Sequence variations from dbSNP and Humsavar for EPS8 Gene

SNP ID Clin Chr 12 pos Sequence Context AA Info Type MAF
rs8664 -- 15,620,487(-) AAAGG(A/G)AGTGG utr-variant-3-prime
rs1053863 -- 15,790,175(+) ACCCT(C/T)ATAAC upstream-variant-2KB
rs1126786 -- 15,623,161(-) GCATT(A/G/T)GAGGT synonymous-codon, reference, missense
rs1134056 -- 15,771,660(-) GGAGA(A/G)TTTCT intron-variant
rs1802658 - 15,621,370(-) TCAGT(G/T)CTGCC reference, missense

Structural Variations from Database of Genomic Variants (DGV) for EPS8 Gene

Variant ID Type Subtype PubMed ID
dgv1379n71 CNV Loss 21882294
esv2135886 CNV Deletion 18987734
esv2663867 CNV Deletion 23128226

Relevant External Links for EPS8 Gene

HapMap Linkage Disequilibrium report
EPS8
Human Gene Mutation Database (HGMD)
EPS8

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for EPS8 Gene

Disorders for EPS8 Gene

UniProtKB/Swiss-Prot

EPS8_HUMAN
  • Deafness, autosomal recessive, 102 (DFNB102) [MIM:615974]: A form of non-syndromic deafness characterized by profound hearing loss affecting all frequencies. Vestibular function is unaffected. {ECO:0000269 PubMed:24741995}. Note=The disease is caused by mutations affecting the gene represented in this entry.
  • 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.

(2) Novoseek inferred disease relationships for EPS8 Gene

Disease -log(P) Hits PubMed IDs
tumors 0 6
cancer 0 9

Relevant External Links for EPS8

Genetic Association Database (GAD)
EPS8
Human Genome Epidemiology (HuGE) Navigator
EPS8
genes like me logo Genes that share disorders with EPS8: view

Publications for EPS8 Gene

  1. Evolutionary conservation of the EPS8 gene and its mapping to human chromosome 12q23-q24. (PMID: 8084614) Wong W.T. … di Fiore P.P. (Oncogene 1994) 2 3 4 23
  2. Molecular interactions of the Src homology 2 domain protein Shb with phosphotyrosine residues, tyrosine kinase receptors and Src homology 3 domain proteins. (PMID: 7537362) Karlsson T. … Welsh M. (Oncogene 1995) 3 4 23
  3. IRSp53/Eps8 complex is important for positive regulation of Rac and cancer cell motility/invasiveness. (PMID: 15289329) Funato Y. … Miki H. (Cancer Res. 2004) 3 4 23
  4. Regulation of cell shape by Cdc42 is mediated by the synergic actin- bundling activity of the Eps8-IRSp53 complex. (PMID: 17115031) Disanza A. … Scita G. (Nat. Cell Biol. 2006) 3 4 23
  5. Eps8 decreases chemosensitivity and affects survival of cervical cancer patients. (PMID: 18566210) Chen Y.J. … Leu T.H. (Mol. Cancer Ther. 2008) 3 4 23

Products for EPS8 Gene

Sources for EPS8 Gene

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