Human Gene EPS8 (ENST00000281172.10_8) from GENCODE V45lift37
Description: 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. (from UniProt Q12929) RefSeq Summary (NM_004447): 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]. Gencode Transcript: ENST00000281172.10_8 Gencode Gene: ENSG00000151491.14_19 Transcript (Including UTRs) Position: hg19 chr12:15,773,068-15,942,322 Size: 169,255 Total Exon Count: 21 Strand: - Coding Region Position: hg19 chr12:15,774,251-15,835,885 Size: 61,635 Coding Exon Count: 20
ID:EPS8_HUMAN DESCRIPTION: RecName: Full=Epidermal growth factor receptor kinase substrate 8; 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. SUBUNIT: Homodimer. Part of a complex consisting of ABI1, EPS8 and SOS1. Interacts with MYO15A and WHRN. Interacts with LANCL1 (By similarity). Interacts with EGFR; mediates EPS8 phosphorylation (By similarity). Interacts with BAIAP2. Interacts with SHB. INTERACTION: Q12929; P49419: ALDH7A1; NbExp=2; IntAct=EBI-375576, EBI-726842; Q12929; Q9UQB8: BAIAP2; NbExp=10; IntAct=EBI-375576, EBI-525456; Q12929; Q9UQB8-4: BAIAP2; NbExp=4; IntAct=EBI-375576, EBI-6174091; Q12929; Q9UHR4: BAIAP2L1; NbExp=4; IntAct=EBI-375576, EBI-2483278; Q12929; Q96GS4: BORCS6; NbExp=3; IntAct=EBI-375576, EBI-10193358; Q12929; Q13895: BYSL; NbExp=3; IntAct=EBI-375576, EBI-358049; Q12929; Q9UFG5: C19orf25; NbExp=3; IntAct=EBI-375576, EBI-741214; Q12929; O14936: CASK; NbExp=3; IntAct=EBI-375576, EBI-1215506; Q12929; P00533: EGFR; NbExp=4; IntAct=EBI-375576, EBI-297353; Q12929; Q969U6-1: FBXW5; NbExp=3; IntAct=EBI-375576, EBI-16031873; Q12929; Q0D2H9: GOLGA8DP; NbExp=3; IntAct=EBI-375576, EBI-10181276; Q12929; P62993: GRB2; NbExp=3; IntAct=EBI-375576, EBI-401755; Q12929; P07910: HNRNPC; NbExp=3; IntAct=EBI-375576, EBI-357966; Q12929; Q15735: INPP5J; NbExp=3; IntAct=EBI-375576, EBI-10236940; Q12929; Q06455-4: RUNX1T1; NbExp=3; IntAct=EBI-375576, EBI-10224192; Q12929; Q969G3: SMARCE1; NbExp=3; IntAct=EBI-375576, EBI-455078; SUBCELLULAR LOCATION: Cytoplasm, cell cortex Cell projection, ruffle membrane Cell projection, growth cone Cell projection, stereocilium napse, 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. 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. 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). DOMAIN: The SH3 domain mediates interaction with SHB. PTM: 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). PTM: 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. DISEASE: 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. Note=The disease is caused by variants affecting the gene represented in this entry. DISEASE: 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. SIMILARITY: Belongs to the EPS8 family. WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="https://atlasgeneticsoncology.org/gene/40476/EPS8";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on Q12929
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Gene Ontology (GO) Annotations with Structured Vocabulary
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Common Gene Haplotype Alleles 
