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| Figure 2. XB130 functional domains and motifs. Human XB130 has 818 amino acids. It contains the following motif/domains: proline-rich region: residues 98-107; tyrosine phosphorylation motif: residues 54-57, 124-127; 148-151; 457-460; PH domain: residues 175-272; 353-445; coiled-coil region: residues 652-749. |
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Description | 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).
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Expression | 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). |
Localisation | 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). |
Function | 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). |
Homology | XB130 shares similar sequence and domain structure cellular as AFAP and AFAP1L1 (Snyder et al., 2011). |
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Entity | Various cancers |
Note | XB130 plays important roles in tumor progression by promoting cell proliferation, survival, motility and invasion in various cancer cells. Recently, XB130 has been identified in thyroid carcinoma (Shiozaki et al., 2011), esophageal squamous cell carcinoma (Shiozaki et al., 2013), and gastric cancer (Shi et al., 2012). |
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Entity | Colorectal cancer |
Note | Tyrosine phosphorylated XB130 in colorectal cancer. |
Prognosis | Using mass spectrometry, Emaduddin et al. reported several proteins as tyrosine phosphorylated form are maintained at high level in colorectal cancer cells isolated from patients. XB130 is identified as one of these proteins. Therefore, tyrosine phosphorylated XB130 has a potential to be a biomarker of colorectal cancer (Emaduddin et al., 2008). |
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Entity | Gastric cancer (GC) |
Note | XB130 expression level associates with the prognosis of gastric cancer. |
Prognosis | Based on the anlysis GC tissue samples from 411 patients with various stages, lower expression of XB130 mRNA as well as protein is significantly correlated with reduced patient survival time and shorter disease-free period (Shi et al., 2012). |
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Entity | Thyroid cancer |
Note | XB130 as a tumor promoting gene, enhancing thyroid cancer cell growth. |
Oncogenesis | Knockdown XB130 using siRNA in thyroid cancer cell (WRO) is accompanied with an inhibition of G1-S phase cell cycle progression and enhanced apoptosis. The volume of tumors generated in nude mice after injecting these cells are smaller than those formed from cells with a normal XB130 expression (Shiozaki et al., 2011). |
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Entity | Esophageal squamous cell carcinoma (ESCC) |
Note | XB130 protein is identified in ESCC primary cell lines and tumor samples. |
Oncogenesis | XB130 protein is highly expression in ESCC primary cells. XB130 protein is examined by immunohistochemistry staining from ESCC tissues collected from 52 patients. Positive XB130 staining is observed in 71% of ESCC samples, which indicates the association of XB130 protein and ESCC (Shiozaki et al., 2013). |
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Entity | Soft tissue tumor |
Note | Decreased XB130 expression leads to a local aggressiveness of soft tissue tumor. |
Oncogenesis | Analysis of gene expression profile of 102 tumor samples with varying stages of soft tissue tumor shows a decreased XB130 expression in malignant mesenchymal tumors (Cunha et al., 2010). |
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Identification of genes associated with local aggressiveness and metastatic behavior in soft tissue tumors. |
Cunha IW, Carvalho KC, Martins WK, Marques SM, Muto NH, Falzoni R, Rocha RM, Aguiar S, Simoes AC, Fahham L, Neves EJ, Soares FA, Reis LF. |
Transl Oncol. 2010 Feb;3(1):23-32. |
PMID 20165692 |
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Odin (ANKS1A) is a Src family kinase target in colorectal cancer cells. |
Emaduddin M, Edelmann MJ, Kessler BM, Feller SM. |
Cell Commun Signal. 2008 Oct 9;6:7. doi: 10.1186/1478-811X-6-7. |
PMID 18844995 |
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Adaptor protein XB130 is a Rac-controlled component of lamellipodia that regulates cell motility and invasion. |
Lodyga M, Bai XH, Kapus A, Liu M. |
J Cell Sci. 2010 Dec 1;123(Pt 23):4156-69. doi: 10.1242/jcs.071050. |
PMID 21084565 |
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XB130, a tissue-specific adaptor protein that couples the RET/PTC oncogenic kinase to PI 3-kinase pathway. |
Lodyga M, De Falco V, Bai XH, Kapus A, Melillo RM, Santoro M, Liu M. |
Oncogene. 2009 Feb 19;28(7):937-49. doi: 10.1038/onc.2008.447. Epub 2008 Dec 8. |
PMID 19060924 |
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Silencing of XB130 is associated with both the prognosis and chemosensitivity of gastric cancer. |
Shi M, Huang W, Lin L, Zheng D, Zuo Q, Wang L, Wang N, Wu Y, Liao Y, Liao W. |
PLoS One. 2012;7(8):e41660. doi: 10.1371/journal.pone.0041660. Epub 2012 Aug 23. |
PMID 22927913 |
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XB130 as an independent prognostic factor in human esophageal squamous cell carcinoma. |
Shiozaki A, Kosuga T, Ichikawa D, Komatsu S, Fujiwara H, Okamoto K, Iitaka D, Nakashima S, Shimizu H, Ishimoto T, Kitagawa M, Nakou Y, Kishimoto M, Liu M, Otsuji E. |
Ann Surg Oncol. 2013 Sep;20(9):3140-50. doi: 10.1245/s10434-012-2474-4. Epub 2012 Jul 18. |
PMID 22805860 |
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AFAP1L1 is a novel adaptor protein of the AFAP family that interacts with cortactin and localizes to invadosomes. |
Snyder BN, Cho Y, Qian Y, Coad JE, Flynn DC, Cunnick JM. |
Eur J Cell Biol. 2011 May;90(5):376-89. doi: 10.1016/j.ejcb.2010.11.016. Epub 2011 Feb 18. |
PMID 21333378 |
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XB130, a new adaptor protein, regulates expression of tumor suppressive microRNAs in cancer cells. |
Takeshita H, Shiozaki A, Bai XH, Iitaka D, Kim H, Yang BB, Keshavjee S, Liu M. |
PLoS One. 2013;8(3):e59057. doi: 10.1371/journal.pone.0059057. Epub 2013 Mar 19. |
PMID 23527086 |
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XB130, a novel adaptor protein for signal transduction. |
Xu J, Bai XH, Lodyga M, Han B, Xiao H, Keshavjee S, Hu J, Zhang H, Yang BB, Liu M. |
J Biol Chem. 2007 Jun 1;282(22):16401-12. Epub 2007 Apr 5. |
PMID 17412687 |
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Phosphatidylinositol 3-kinase-binding protein, PI3KAP/XB130, is required for cAMP-induced amplification of IGF mitogenic activity in FRTL-5 thyroid cells. |
Yamanaka D, Akama T, Fukushima T, Nedachi T, Kawasaki C, Chida K, Minami S, Suzuki K, Hakuno F, Takahashi S. |
Mol Endocrinol. 2012 Jun;26(6):1043-55. doi: 10.1210/me.2011-1349. Epub 2012 Apr 11. |
PMID 22496359 |
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Multivariate analysis of several molecular markers and clinicopathological features in postoperative prognosis of hepatocellular carcinoma. |
Zuo Q, Huang H, Shi M, Zhang F, Sun J, Bin J, Liao Y, Liao W. |
Anat Rec (Hoboken). 2012 Mar;295(3):423-31. doi: 10.1002/ar.21531. Epub 2011 Dec 20. |
PMID 22190283 |
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