EPS8

EPS8
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2E8M
Identifiers
Aliases	EPS8, DFNB102, epidermal growth factor receptor pathway substrate 8
External IDs	OMIM: 600206; MGI: 104684; HomoloGene: 3272; GeneCards: EPS8; OMA:EPS8 - orthologs
Gene location (Human) Chr. Chromosome 12 (human) Band 12p12.3 Start 15,620,158 bp End 15,882,329 bp
Gene location (Mouse) Chr. Chromosome 6 (mouse) Band 6 G1|6 66.78 cM Start 137,454,243 bp End 137,631,874 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in jejunal mucosa mucosa of sigmoid colon Achilles tendon cartilage tissue corpus epididymis pericardium tail of epididymis popliteal artery tibial arteries synovial joint Top expressed in secondary oocyte left colon zygote seminal vesicula migratory enteric neural crest cell primary oocyte ileum conjunctival fornix right kidney parotid gland More reference expression data BioGPS More reference expression data
Gene ontology Molecular function signaling adaptor activity protein binding actin binding Cellular component cytoplasm vesicle cell projection membrane postsynaptic density growth cone plasma membrane synapse NMDA selective glutamate receptor complex stereocilium ruffle membrane cell junction cell cortex brush border neuron projection extracellular exosome stereocilium bundle stereocilium tip glutamatergic synapse Biological process actin cytoskeleton reorganization actin polymerization-dependent cell motility epidermal growth factor receptor signaling pathway regulation of actin filament length adult locomotory behavior barbed-end actin filament capping exit from mitosis actin filament bundle assembly dendritic cell migration actin crosslink formation regulation of cell shape behavioral response to ethanol cell population proliferation Rac protein signal transduction signal transduction positive regulation of signal transduction cellular response to leukemia inhibitory factor Rho protein signal transduction regulation of Rho protein signal transduction regulation of postsynaptic membrane neurotransmitter receptor levels positive regulation of ruffle assembly Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 2059 13860 Ensembl ENSG00000151491 ENSMUSG00000015766 UniProt Q12929 Q08509 RefSeq (mRNA) NM_004447 NM_001271587 NM_001271588 NM_001271589 NM_001271595 NM_007945 RefSeq (protein) NP_004438 NP_001258516 NP_001258517 NP_001258518 NP_001258524 NP_031971 Location (UCSC) Chr 12: 15.62 – 15.88 Mb Chr 6: 137.45 – 137.63 Mb PubMed search
Wikidata
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Epidermal growth factor receptor kinase substrate 8 is an enzyme that in humans is encoded by the EPS8 gene.

Function

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.

Clinical significance

Mutations in EPS8 cause congenital deafness.Behlouli A, Bonnet C, Abdi S, Bouaita A, Lelli A, Hardelin JP, Schietroma C, Rous Y, Louha M, Cheknane A, Lebdi H, Boudjelida K, Makrelouf M, Zenati A, Petit C (2014). "EPS8, encoding an actin-binding protein of cochlear hair cell stereocilia, is a new causal gene for autosomal recessive profound deafness". Orphanet Journal of Rare Diseases. 9 (1): 55. doi:10.1186/1750-1172-9-55. PMC 4022326. PMID 24741995.

Interactions

EPS8 has been shown to interact with:

• ABI1,
• BAIAP2,
• DVL1,
• SHB,
• SHC1
• SOS1, and
• Src.

Further reading

• Di Fiore PP, Scita G (2002). "Eps8 in the midst of GTPases". Int. J. Biochem. Cell Biol. 34 (10): 1178–83. doi:10.1016/S1357-2725(02)00064-X. PMID 12127568.
• Cardwell C (1977). "Student or worker? International Meeting of Student Nurses (European Group)". Nursing Mirror and Midwives Journal. 143 (19): 38. PMID 1049958.
• Castagnino P, Biesova Z, Wong WT, Fazioli F, Gill GN, Di Fiore PP (1995). "Direct binding of eps8 to the juxtamembrane domain of EGFR is phosphotyrosine- and SH2-independent". Oncogene. 10 (4): 723–9. PMID 7532293.
• Karlsson T, Songyang Z, Landgren E, Lavergne C, Di Fiore PP, Anafi M, Pawson T, Cantley LC, Claesson-Welsh L, Welsh M (1995). "Molecular interactions of the Src homology 2 domain protein Shb with phosphotyrosine residues, tyrosine kinase receptors and Src homology 3 domain proteins". Oncogene. 10 (8): 1475–83. PMID 7537362.
• Avantaggiato V, Torino A, Wong WT, Di Fiore PP, Simeone A (1995). "Expression of the receptor tyrosine kinase substrate genes eps8 and eps15 during mouse development". Oncogene. 11 (6): 1191–8. PMID 7566980.
• Matoskova B, Wong WT, Salcini AE, Pelicci PG, Di Fiore PP (1995). "Constitutive phosphorylation of eps8 in tumor cell lines: relevance to malignant transformation". Mol. Cell. Biol. 15 (7): 3805–12. doi:10.1128/MCB.15.7.3805. PMC 230619. PMID 7791787.
• Fazioli F, Minichiello L, Matoska V, Castagnino P, Miki T, Wong WT, Di Fiore PP (1993). "Eps8, a substrate for the epidermal growth factor receptor kinase, enhances EGF-dependent mitogenic signals". EMBO J. 12 (10): 3799–808. doi:10.1002/j.1460-2075.1993.tb06058.x. PMC 413663. PMID 8404850.
• Matòsková B, Wong WT, Seki N, Nagase T, Nomura N, Robbins KC, Di Fiore PP (1996). "RN-tre identifies a family of tre-related proteins displaying a novel potential protein binding domain". Oncogene. 12 (12): 2563–71. PMID 8700515.
• Matòsková B, Wong WT, Nomura N, Robbins KC, Di Fiore PP (1996). "RN-tre specifically binds to the SH3 domain of eps8 with high affinity and confers growth advantage to NIH3T3 upon carboxy-terminal truncation". Oncogene. 12 (12): 2679–88. PMID 8700527.
• Biesova Z, Piccoli C, Wong WT (1997). "Isolation and characterization of e3B1, an eps8 binding protein that regulates cell growth". Oncogene. 14 (2): 233–41. doi:10.1038/sj.onc.1200822. PMID 9010225.
• Kishan KV, Scita G, Wong WT, Di Fiore PP, Newcomer ME (1997). "The SH3 domain of Eps8 exists as a novel intertwined dimer". Nat. Struct. Biol. 4 (9): 739–43. doi:10.1038/nsb0997-739. PMID 9303002. S2CID 36865189.
• Maa MC, Lai JR, Lin RW, Leu TH (1999). "Enhancement of tyrosyl phosphorylation and protein expression of eps8 by v-Src". Biochim. Biophys. Acta. 1450 (3): 341–51. doi:10.1016/S0167-4889(99)00069-5. PMID 10395945.
• Scita G, Nordstrom J, Carbone R, Tenca P, Giardina G, Gutkind S, Bjarnegård M, Betsholtz C, Di Fiore PP (1999). "EPS8 and E3B1 transduce signals from Ras to Rac". Nature. 401 (6750): 290–3. Bibcode:1999Natur.401..290S. doi:10.1038/45822. PMID 10499589. S2CID 205045006.
• Lanzetti L, Rybin V, Malabarba MG, Christoforidis S, Scita G, Zerial M, Di Fiore PP (2000). "The Eps8 protein coordinates EGF receptor signalling through Rac and trafficking through Rab5". Nature. 408 (6810): 374–7. Bibcode:2000Natur.408..374L. doi:10.1038/35042605. PMID 11099046. S2CID 4405293.
• Ion A, Crosby AH, Kremer H, Kenmochi N, Van Reen M, Fenske C, Van Der Burgt I, Brunner HG, Montgomery K, Kucherlapati RS, Patton MA, Page C, Mariman E, Jeffery S (2000). "Detailed mapping, mutation analysis, and intragenic polymorphism identification in candidate Noonan syndrome genes MYL2, DCN, EPS8, and RPL6". J. Med. Genet. 37 (11): 884–6. doi:10.1136/jmg.37.11.884. PMC 1734479. PMID 11185075.
• Scita G, Tenca P, Areces LB, Tocchetti A, Frittoli E, Giardina G, Ponzanelli I, Sini P, Innocenti M, Di Fiore PP (2001). "An effector region in Eps8 is responsible for the activation of the Rac-specific GEF activity of Sos-1 and for the proper localization of the Rac-based actin–polymerizing machine" (PDF). J. Cell Biol. 154 (5): 1031–44. doi:10.1083/jcb.200103146. PMC 2196181. PMID 11524436.