XB130

XB130 (also known as AFAP1L2) is a cytosolic is_associated_with::adaptor protein and is_associated_with::signal transduction mediator. XB130 regulates cell proliferation, cell survival, cell motility and is_associated_with::gene expression. XB130 is highly similar to AFAP and is thus known as actin filament associated protein 1-like 2 (AFAP1L2). XB130 is a substrate and regulator of multiple tyrosine kinase-mediated signaling. XB130 is highly expressed in the is_associated_with::thyroid and is_associated_with::spleen.

Molecular structure
The XB130 gene is located on human chromosome 10q25.3 and encodes an 818 amino acid protein. It has a molecular weight of approximately 130 kDa and is structurally similar to actin-filament-associated protein (AFAP) and is thus known as AFAP1L2. Several tyrosine phosphorylation sites and a proline rich sequence are included in the N-terminal region of XB130, which allows it to interact and activate c-Src-containing proteins, as well as bind to p85α of PI3K. Two is_associated_with::pleckstrin-homology domains are located in the middle portion, giving XB130 its lipid-binding ability. The C-terminal region contains a coiled-coil domain, which shares partial similarity with AFAP's is_associated_with::leucine zipper domain. Both the C-terminal and N-terminal regions of XB130 are required for XB130's role in its translocation to the is_associated_with::lamellipodia. Despite XB130's structural similarity to AFAP, XB130 does not behave like an actin filament-associated protein. The actin-binding site present in AFAP is only partially present in XB130.

Role in cell cycle and survival
XB130 has been demonstrated to play a role in cell proliferation and survival through the regulation of the is_associated_with::PI3K/is_associated_with::Akt signaling pathway. When tyrosine phosphorylated, XB130 has the ability to interact with the p85ɑ subunit of PI3K through its is_associated_with::SH2 domains. This interaction leads to the subsequent activation of Akt, cell proliferation, and cell survival. Activated Akt promotes cell survival and cell cycle progression by phosphorylating and inactivating is_associated_with::p21Cip1/WAF1, p27Kip1, and is_associated_with::GSK3β, as well as inhibits is_associated_with::apoptosis by preventing the cleavage of is_associated_with::caspase-8 and is_associated_with::caspase-9, which are involved in the extrinsic and intrinsic pathways of is_associated_with::cell death, respectively. Alternatively, when the expression of XB130 is suppressed in vitro, Akt phosphorylation and therefore activation becomes significantly reduced. This, in turn, leads to cell cycle arrest at G1/S phase and accelerated apoptosis.

Role in cell motility and invasion
During is_associated_with::cytoskeletal rearrangement, a process required for cell is_associated_with::motility, XB130 translocates to the cell periphery. XB130 exhibits a high affinity for peripheral is_associated_with::F-actin structures, such as the is_associated_with::lamellipodium. The translocation of XB130 to the cell periphery is particularly important in its potential to influence cell migration and is_associated_with::metastasis.

Role in gene expression
The level of XB130 expression influences the expression of multiple genes related to cell proliferation and survival, and is_associated_with::microRNAs is_associated_with::miR-33a, 149a, and 193a-3p, all of which exhibit tumor suppressive function in thyroid cancer cells.

Role in inflammation
XB130 mediated c-Src binding and activation increases is_associated_with::Interleukin-8 (IL-8), a chemokine produce by lung epithelial cells, which contains AP-1 and SRE transcription factor binding sites. These binding sites can be activated by the downregulation of XB130 expression and lead to a decrease in IL-8 production in lung cells.

Interactions
XB130 (gene) has been known to interact with
 * is_associated_with::SH2 domain of Src
 * is_associated_with::SH3 domain of Src
 * c-Src
 * p85a subunit of PI3K
 * is_associated_with::RET/PTC
 * is_associated_with::GTPase-activating proteins (GAP)
 * is_associated_with::Phospholipase C-gamma (PLC-γ)

Clinical significance
Adaptor proteins play an important role as molecular scaffolds to mediate the transport and interaction of various proteins and is therefore highly involved in signal transduction. Deregulation of adaptor proteins is highly related to the abnormality of cellular functions and many adaptor proteins are frequently overexpressed in cancers. Clinical studies on the expression level and pattern of XB130 in various human tumors demonstrate that XB130 expression is regulated in thyroid and is_associated_with::gastrointestinal cancers  and is_associated_with::soft tissue tumors. Expression level of XB130 was significantly higher in normal and benign lesion than that of papillary and is_associated_with::anaplastic/insular carcinoma. Through the studies on many gastrointestinal cancers, the oncogenic roles of XB130 was showed. XB130 expression is significantly correlated with the survival time and disease-free period in is_associated_with::gastric cancer patients. XB130 was identified as a potential is_associated_with::colorectal cancer markers. XB130 protein level was elevated in human esophageal squamous carcinoma. In addition, XB130 was selected as one of six highly expressed genes related to local aggressiveness of soft tissue tumors in a set of 102 representative tumor samples. These findings suggest that XB130 may be involved in is_associated_with::tumorigenesis and that XB130 is a potential diagnostic is_associated_with::biomarker and therapeutic target for cancer.

Discovery
This adaptor protein was discovered during molecular cloning of human actin filament associated protein (AFAP1) in the Latner Thoracic Surgery Research Laboratories is_associated_with::Toronto, Canada. The molecule is named named XB130 after lead technician Xiaohui Bai and the molecular mass of the protein. This protein was found to have a high sequence identity to AFAP1, thus its name AFAP1L2.