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HGNC Approved Gene Symbol: ABI1
Cytogenetic location: 10p12.1 Genomic coordinates (GRCh38) : 10:26,746,596-26,860,958 (from NCBI)
Taki et al. (1998) identified the ABI1 gene as the fusion partner with MLL (159555) in a patient with acute myeloid leukemia (AML) and a t(10;11)(p11.2;q23) ABI1 is a human homolog of mouse Abl-interactor-1 (Abi1). The ABI1 protein exhibited sequence similarity to protein of homeotic genes, contained several polyproline stretches, and included a Src homology-3 (SH3) domain at the C terminus that is required for binding of mouse Abi1 protein to Abl proteins. Three types of the ABI1 gene were expressed in normal peripheral blood. The MLL-ABI1 fusion transcript in this patient was formed by an alternatively spliced ABI1. In-frame MLL-ABI1 fusion transcripts combined the MLL AT-hook motifs and DNA methyltransferase homology region with the homeodomain homologous region, polyproline stretches, and SH3 domain of the alternatively spliced transcript of ABI1. The results suggested that ABI1 plays a role in the leukemogenesis by translocating to MLL.
Taki et al. (1998) noted the similarity between the protein they described and the E3B1 protein described by Biesova et al. (1997), which was also isolated as a human homolog of mouse Abi1.
Taki et al. (1998) identified the ABI1 gene on chromosome 10p11.2 as the fusion partner of MLL in a patient with acute myeloid leukemia.
Scita et al. (1999) demonstrated that EPS8 (600206) and E3B1/ABI1 participate in the transduction of signals from Ras (190020) to Rac (see 602048) by regulating Rac-specific guanine nucleotide exchange factor (GEF) activities. Scita et al. (1999) also showed that EPS8, E3B1, and SOS1 (182530) form a tricomplex in vivo that exhibits Rac-specific GEF activity in vitro. Scita et al. (1999) proposed a model in which EPS8 mediates the transfer of signals between Ras and Rac by forming a complex with E3B1 and SOS1.
Epidermal growth factor receptor (EGFR; 131550) signaling involves small GTPases of the Rho family, and EGFR trafficking involves small GTPases of the Rab family. Lanzetti et al. (2000) reported that the EPS8 protein connects these signaling pathways. EPS8 is a substrate of EGFR that is held in a complex with SOS1 by the adaptor protein E3B1, thereby mediating activation of RAC. Through its SH3 domain, EPS8 interacts with RNTRE (605405). Lanzetti et al. (2000) showed that RNTRE is a RAB5 (179512) GTPase-activating protein whose activity is regulated by EGFR. By entering in a complex with EPS8, RNTRE acts on RAB5 and inhibits internalization of the EGFR. Furthermore, RNTRE diverts EPS8 from its RAC-activating function, resulting in the attenuation of RAC signaling. Thus, depending on its state of association with E3B1 or RNTRE, EPS8 participates in both EGFR signaling through RAC and EGFR trafficking through RAB5.
Using a yeast 2-hybrid assay, Tani et al. (2003) found that human ABI1 bound mouse Mena (ENAH; 609061). Binding analysis revealed that the EVH1 domain of Mena bound a polyproline structure of ABI1. Endogenous MENA and ABL1 (189980) coprecipitated with epitope-tagged ABI1 from human embryonic kidney cells. ABI1 dramatically promoted ABL1-mediated tyrosine phosphorylation of MENA, but not of other substrates. Mutation analysis demonstrated that Mena was tyrosine phosphorylated on tyr296.
Biesova, Z., Piccoli, C., Wong, W. T. Isolation and characterization of e3B1, an eps8 binding protein that regulates cell growth. Oncogene 14: 233-241, 1997. [PubMed: 9010225] [Full Text: https://doi.org/10.1038/sj.onc.1200822]
Lanzetti, L., Rybin, V., Malabarba, M. G., Christoforidis, S., Scita, G., Zerial, M., Di Fiore, P. P. The Eps8 protein coordinates EGF receptor signalling through Rac and trafficking through Rab5. Nature 408: 374-377, 2000. [PubMed: 11099046] [Full Text: https://doi.org/10.1038/35042605]
Scita, G., Nordstrom, J., Carbone, R., Tenca, P., Giardina, G., Gutkind, S., Bjarnegard, M., Betsholtz, C., Di Fiore, P. P. EPS8 and E3B1 transduce signals from Ras to Rac. Nature 401: 290-293, 1999. [PubMed: 10499589] [Full Text: https://doi.org/10.1038/45822]
Taki, T., Shibuya, N., Taniwaki, M., Hanada, R., Morishita, K., Bessho, F., Yanagisawa, M., Hayashi, Y. ABI-1, a human homolog to mouse Abl-interactor 1, fuses the MLL gene in acute myeloid leukemia with t(10;11)(p11.2;q23). Blood 92: 1125-1130, 1998. [PubMed: 9694699]
Tani, K., Sato, S., Sukezane, T., Kojima, H., Hirose, H., Hanafusa, H., Shishido, T. Abl interactor 1 promotes tyrosine 296 phosphorylation of mammalian Enabled (Mena) by c-Abl kinase. J. Biol. Chem. 278: 21685-21692, 2003. [PubMed: 12672821] [Full Text: https://doi.org/10.1074/jbc.M301447200]