HGNC Approved Gene Symbol: GAB3
Cytogenetic location: Xq28 Genomic coordinates (GRCh38): X:154,675,249-154,751,566 (from NCBI)
By searching an EST database for sequences similar to GAB1 (604439), followed by screening dendritic cell and eosinophil cDNA libraries, Wolf et al. (2002) cloned GAB3. The deduced 586-amino acid protein contains an N-terminal pleckstrin homology (PH) domain and potential SH2- and SH3-binding motifs. The PH domains of GAB1, GAB2 (606203), and GAB3 share about 50% amino acid identity, while the remainder of the proteins share about 14% identity. Wolf et al. (2002) also cloned mouse Gab3, which encodes a deduced 595-amino acid protein. RT-PCR detected mouse Gab3 expressed at high levels in spleen and thymus and at lower levels in brain, heart, lung, kidney, uterus, and embryonic stem cells, but not in other tissues examined. Gab3 was expressed in all myeloid and macrophage cell lines examined.
Wolf et al. (2002) examined the role of Gab3 in macrophage differentiation and signal transduction using a mouse myeloid progenitor cell line exogenously expressing Fms (164770), the receptor for macrophage colony-stimulating factor (MCSF; 120420). Gab3 was tyrosine phosphorylated following receptor stimulation, and it associated transiently with the SH2 domain-containing proteins Shp2 (176876) and p85 of the PI3K complex (see 171833). Overexpression of exogenous Gab3 dramatically accelerated macrophage differentiation upon MCSF stimulation. Examination of phosphorylation mutants suggested that Gab3 is important for macrophage differentiation and that differentiation requires the early phosphorylation of Gab2, followed by induction and subsequent phosphorylation of Gab3.
The International Radiation Hybrid Mapping Consortium mapped the GAB3 gene to chromosome X (RH80611).
Seiffert et al. (2003) found normal hematopoiesis in mice lacking Gab3, and macrophages developed in normal numbers and exhibited normal function. Gab3-deficient mice had no major immune deficiency in T- and B-lymphocyte responses to protein antigens or during viral infection. Allergic responses also appeared normal.
Seiffert, M., Custodio, J. M., Wolf, I., Harkey, M., Liu, Y., Blattman, J. N., Greenberg, P. D., Rohrschneider, L. R. Gab3-deficient mice exhibit normal development and hematopoiesis and are immunocompetent. Molec. Cell. Biol. 23: 2415-2424, 2003. [PubMed: 12640125] [Full Text: https://doi.org/10.1128/MCB.23.7.2415-2424.2003]
Wolf, I., Jenkins, B. J., Liu, Y., Seiffert, M., Custodio, J. M., Young, P., Rohrschneider, L. R. Gab3, a new DOS/Gab family member, facilitates macrophage differentiation. Molec. Cell. Biol. 22: 231-244, 2002. [PubMed: 11739737] [Full Text: https://doi.org/10.1128/MCB.22.1.231-244.2002]