Human XB130 was discovered in Dr. Mingyao Lius laboratory (University of Toronto) in the process of cloning human actin filament associated protein (afap) gene. Using chicken AFAP protein sequence to search human cDNA library in GenBank, XB130 was found as an EST clone (GenBank accession number 1154093) with 34% sequence similarity to chicken AFAP protein. The clone contains partial coding sequence and 3 UTR. The upstream sequence was obtained using 5 rapid amplification of cDNA ends (RACE) from human lung alveolar epithelial cell mRNA. Western blot shows the protein molecular weight is 130 kD (Xu et al., 2007).
In 2003, the XB130 knockout mice were established through the collaboration of Drs. Mingyao Liu and Tak W. Mak at the University of Toronto.

Human xb130 genes contains 19 exons, which are covering the whole coding sequence.

The transcript size of xb130 is 3751 bp. There may be 7 splicing variants based on Ensembl data (www.ensembl.org). XB130 mRNA is highly expressed in the thyroid, parathyroid and spleen; moderately expressed in brain, pancreas, lung and kidney.

XB130 is a novel adaptor protein, member of the actin filament associated protein (AFAP) family (Snyder et al., 2011). Accordingly, it is also known as AFAP1L2. The full length protein consists of 818 amino acids with a molecular weight of approximately 130 kDa by western blotting (Xu et al., 2007). As an adaptor protein, XB130 has no enzymatic domains or activity. Sequence structure analysis has revealed 23 putative tyrosine phosphorylation sites and 27 putative phosphorylation sites for serine/threonine kinases (Xu et al., 2007). The N-terminal of XB130 contains a proline rich, SH3 domain binding motif, three tyrosine containing SH2 domain binding sites (Xu et al., 2007), of which a YXXM motif is for PI3 kinase subunit p85 binding (Lodyga et al., 2009). In the middle region, there are two pleckstrin homology domains and another tyrosine binding motif (Xu et al., 2007). The C-terminal contains a coiled-coil region, which may be important for molecular trafficking or dimerization (Xu et al., 2007).

In normal human tissue, the 4 kb mRNA transcript of XB130 is expressed highly in spleen and thyroid with lower expression in kidney, brain, lung and pancreas (Xu et al., 2007). Newer RNA sequencing by Illumina body map using RNA obtained from 16 normal human tissues shows high expression of XB130 in thyroid with lower expression in lymph nodes, brain, colon, adipocytes, kidney, lung, adrenal glands, breast, ovary, prostate and testis followed by whole blood, heart, skeletal muscles and liver (www.genecards.org).
XB130 protein is detected in normal tissues of thyroid, parathyroid, brain, kidney, skin and GI-tracks (www.proteinatlas.org).
XB130 protein expresses in human thyroid, colorectal, gastric and hepatocellular carcinomas (Shi et al., 2012; Shiozaki et al., 2013; Shiozaki et al., 2011; Zuo et al., 2012). Expression of XB130 has also been observed in a variety of cancer cell lines, including thyroid, lung, esophageal, pancreatic and colon cancers (Shi et al., 2012; Shiozaki et al., 2013; Zuo et al., 2012).

XB130 is distributed mainly in the cytoplasm and perinuclear region of lung epithelial BEAS-2B cells and several other cell types (Xu et al., 2007). Unlike AFAP, XB130 does not associate or co-localize with actin filament stress fibler (Lodyga et al., 2010). Stimulation of cells with EGF, PMA, or overexpression of constitutive Rac results in a translocation of XB130 to the cell periphery and leading edge of migrating cells (Lodyga et al., 2010).

XB130 is an adaptor protein that acts as a key mediator to drive signal transduction pathways. XB130 has been shown to bind to tyrosine kinase c-Src to enhance kinase activity and subsequently regulates Src-mediated AP-1/SRE transcription activation (Xu et al., 2007). XB130 is also highly involved in the PI3K/Akt pathway and effects cell proliferation, cell cycle progression and cell survival through binding to p85 alpha subunit of PI3K (Lodyga et al., 2009). XB130 may also play a role in the innate immune response, where knockdown of XB130 was shown to decrease IL-6 and IL-8 cytokine levels in human lung epithelial cells (Xu et al., 2007). XB130 is also involved in cell migration via association with Rac-GTPase and plays a significant role in lateral cell migration and cell invasion in both normal and cancer cell lines (Lodyga et al., 2010).
Yamanaka et al. reported phosphorylated XB130 affects cAMP-dependent DNA synthesis in rat thyroid cells (Yamanaka et al., 2012).
XB130 is aberrantly expressed in human cancers and has been shown to control tumour growth in vivo (Shiozaki et al., 2011). XB130 regulates thyroid cancer cell proliferation by controlling microRNA miR-33a, 149a and 193a expression to alter oncogenes Myc, FosL1, and SCL7A5 protein levels (Takeshita et al., 2013).

XB130 shares similar sequence and domain structure cellular as AFAP and AFAP1L1 (Snyder et al., 2011).

Somatic mutations of XB130 are reported in a variety of cancer tissues. Based on the data of Sanger Institute database (www.sanger.ac.uk), XB130 mutation sites have been identified in multiple tumor tissues, including lung, large intestine, ovary, skin, prostate, endometrium. Among these samples, 70% of identified cases are XB130 substitution missense mutation.