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
Gene location (Human) Chr. Chromosome 12 (human) [1] Band 12p12.3 Start 15,620,158 bp [1] End 15,882,329 bp [1]
Gene location (Mouse) Chr. Chromosome 6 (mouse) [2] Band 6 G1|6 66.78 cM Start 137,454,243 bp [2] End 137,631,874 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in jejunal mucosa Achilles tendon corpus epididymis pericardium popliteal artery synovial joint bronchial epithelial cell subcutaneous adipose tissue seminal vesicula right coronary artery Top expressed in secondary oocyte left colon seminal vesicula ileum conjunctival fornix parotid gland jejunum proximal tubule kidney hair follicle 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 [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Epidermal growth factor receptor kinase substrate 8 is an enzyme that in humans is encoded by the EPS8 gene. ^{[5] [6]}

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. ^[6]

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, ^{[7] [8] [9]}
• BAIAP2, ^{[10] [11]}
• DVL1, ^[12]
• SHB, ^[13]
• SHC1 ^[14]
• SOS1, ^{[7] [15]} and
• Src. ^[16]

References

1. GRCh38: Ensembl release 89: ENSG00000151491 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000015766 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Wong WT, Carlomagno F, Druck T, Barletta C, Croce CM, Huebner K, Kraus MH, Di Fiore PP (October 1994). "Evolutionary conservation of the EPS8 gene and its mapping to human chromosome 12q23-q24". Oncogene. 9 (10): 3057–61. PMID   8084614.
6. "Entrez Gene: EPS8 epidermal growth factor receptor pathway substrate 8".
7. Offenhäuser N, Borgonovo A, Disanza A, Romano P, Ponzanelli I, Iannolo G, Di Fiore PP, Scita G (January 2004). "The eps8 family of proteins links growth factor stimulation to actin reorganization generating functional redundancy in the Ras/Rac pathway". Mol. Biol. Cell. 15 (1): 91–8. doi:10.1091/mbc.E03-06-0427. PMC   307530 . PMID   14565974.
8. Biesova Z, Piccoli C, Wong WT (January 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.
9. Lanzetti L, Rybin V, Malabarba MG, Christoforidis S, Scita G, Zerial M, Di Fiore PP (November 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.
10. Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE, Roth FP, Vidal M (October 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173–8. Bibcode:2005Natur.437.1173R. doi:10.1038/nature04209. PMID   16189514. S2CID   4427026.
11. Funato Y, Terabayashi T, Suenaga N, Seiki M, Takenawa T, Miki H (August 2004). "IRSp53/Eps8 complex is important for positive regulation of Rac and cancer cell motility/invasiveness". Cancer Res. 64 (15): 5237–44. doi:10.1158/0008-5472.CAN-04-0327. PMID   15289329. S2CID   9844872.
12. Inobe M, Katsube Ki, Miyagoe Y, Nabeshima Yi, Takeda S (December 1999). "Identification of EPS8 as a Dvl1-associated molecule". Biochem. Biophys. Res. Commun. 266 (1): 216–21. doi:10.1006/bbrc.1999.1782. PMID   10581192.
13. Karlsson T, Songyang Z, Landgren E, Lavergne C, Di Fiore PP, Anafi M, Pawson T, Cantley LC, Claesson-Welsh L, Welsh M (April 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.
14. Matoskova B, Wong WT, Salcini AE, Pelicci PG, Di Fiore PP (July 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.
15. Scita G, Nordstrom J, Carbone R, Tenca P, Giardina G, Gutkind S, Bjarnegård M, Betsholtz C, Di Fiore PP (September 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.
16. Maa MC, Lai JR, Lin RW, Leu TH (July 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.

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.