Alternative titles; symbols
HGNC Approved Gene Symbol: AFAP1L2
Cytogenetic location: 10q25.3 Genomic coordinates (GRCh38): 10:114,280,725-114,405,175 (from NCBI)
By sequencing clones obtained from a size-fractionated fetal brain cDNA library, Nagase et al. (2001) cloned AFAP1L2, which they designated KIAA1914. RT-PCR ELISA detected highest expression in spleen and spinal cord, followed by ovary, kidney, and cerebellum. Expression was low to moderate in all other tissues and specific brain regions examined.
By searching databases for sequences similar to chicken Afap (608252), followed by 5-prime RACE of human lung alveolar epithelial cell mRNA, Xu et al. (2007) cloned AFAP1L2, which they called XB130. The 3-prime UTR of the transcript contains 2 consensus AU-rich elements, indicating mRNA instability. The deduced 818-amino acid protein has an N-terminal proline-rich motif, followed by 2 pleckstrin (PLEK; 173570) homology domains and a C-terminal coiled-coil region. It also has several putative SRC (190090) homology-2 (SH2) and SH3-binding motifs and multiple putative phosphorylation sites. Northern blot analysis detected a transcript of about 4 kb that was highly expressed in spleen and thyroid, with lower expression in kidney, brain, lung, and pancreas. Epitope-tagged AFAP1L2 localized to the cytoplasm of transfected rat fibroblasts. Western blot analysis detected AFAP1L2 at an apparent molecular mass of about 130 kD.
Xu et al. (2007) found that endogenous XB130 and SRC interacted in human lung epithelial cells. Coexpression of XB130 and SRC in COS-7 cells resulted in SRC activation and elevated tyrosine phosphorylation of multiple proteins, including XB130 itself. XB130 expression in HEK293 cells enhanced SRC-mediated serum response element- and AP1 (165160)-dependent transcriptional activation. Deletion of the putative N-terminal SH3-binding motif and several putative SH2-binding sites of XB130 reduced its ability to activate SRC-mediated signal transduction. Downregulation of endogenous XB130 by small interfering RNA reduced SRC activity, IL8 (146930) production, and EGF (131530)-induced phosphorylation of AKT (see AKT1; 164730) and GSK3B (605004) and altered cell cycles in human lung epithelial cells. Xu et al. (2007) concluded that XB130 is an adaptor that regulates signal transduction.
Xu et al. (2007) determined that the AFAP1L2 gene contains 19 exons and spans over 40 kb.
By FISH and genomic sequence analysis, Xu et al. (2007) mapped the AFAP1L2 gene to chromosome 10q25.3.
Nagase, T., Kikuno, R., Ohara, O. Prediction of the coding sequences of unidentified human genes. XXI. The complete sequences of 60 new cDNA clones from brain which code for large proteins. DNA Res. 8: 179-187, 2001. [PubMed: 11572484] [Full Text: https://doi.org/10.1093/dnares/8.4.179]
Xu, J., Bai, X.-H., Lodyga, M., Han, B., Xiao, H., Keshavjee, S., Hu, J., Zhang, H., Yang, B. B., Liu, M. XB130, a novel adaptor protein for signal transduction. J. Biol. Chem. 282: 16401-16412, 2007. [PubMed: 17412687] [Full Text: https://doi.org/10.1074/jbc.M701684200]