The human TIE1 gene spans 22115 bp, encoding for 23 exons in forward strand.

Longest mRNA contains 3882 bp. Alternatively spliced forms have been reported, including transcript variant 5 (EU826590.1) coding for a soluble TIE1 ectodomain (Jin et al., 2008).

See figure above.

Human TIE1 contains 1138 aa. It belongs to the protein kinase superfamily, protein receptor tyrosine kinase family, TIE subfamily. It contains 3 Ig (immunoglobulin)-like domains (I set type), 3 EGF (epidermal growth factor)-like domains, 3 fibronectin type-III domains, a single transmembrane domain and 1 intracellular split tyrosine kinase domain (Partanen et al., 1992).

TIE1 is almost exclusively expressed in endothelial cells both in human and in mouse. High expression of TIE1 mRNA is found in adult lung, heart, and placenta, some expression in kidney, whereas muscle, brain, liver and pancreas contain less TIE1 mRNA. Tie1 mRNA is present widely in fetal tissues starting at embryonic day 8,5 (Korhonen et al., 1992). Tie1 mRNA is detected in differentiating angioblasts of the head mesenchyme, in the splanchnopleure and dorsal aorta as well as in migrating endothelial cells of the developing heart, in the heart endocardium and in the endothelial cells forming the lung vasculature (Korhonen et al., 1992).
TIE1 is also expressed on cultured endothelial cells, some haemopoietic progenitor cells, some myeloid leukemia cell lines having erythroid and megakaryoblastoid characteristics (Batard et al., 1996) and in adult acute myelogenous leukemia (Kivivuori et al., 2007). TIE1 expression is increased in angiogenic endothelial cells during wound-healing, in proliferating ovarial capillaries during hormone-induced superovulation and in tumor blood vessels (Korhonen et al., 1992; Kaipainen et al., 1994). Tie1 is downregulated in endothelial cells by shear stress (Chen-Konak et al., 2003), but specifically induced in the mouse vasculature by disturbed flow in vascular bifurcations and branching points along the arteries (Porat et al., 2004).
TIE1 along with ANGPT2 and TEK mRNAs were strongly expressed in cells of Kaposis sarcoma tumor cells, and cutaneous angiosarcomas, in contrast to the focal low-level expression in normal skin biopsies (Brown et al., 2000).

Cell membrane.

Studies of Tie1 gene targeted mice have revealed that Tie1 is critical for the development of blood (Puri et al., 1995) and lymphatic vasculatures (DAmico et al., 2010; Qu et al., 2010) after midgestation. Tie1 is essential for endothelial cell survival in the developing microvasculature undergoing angiogenic sprouting, and essentially in all blood vessels in adult (Partanen et al., 1996). Tie1^-/- embryos die around embryonic day 13,5, depending on the background (Puri et al., 1995; DAmico et al., 2010). The Tie1 deficient or hypomorphic embryos show also signs of edema, due to lymphatic defects involving abnormally patterned lymph sacs and peripheral lymphatic vessels (DAmico et al., 2010; Qu et al., 2010).
The molecular function of TIE1 is not completely understood, as it does not directly bind the angiopoietin growth factors, which are the ligands for TEK (TIE2). However, TIE1 tyrosine phosphorylation is induced by angiopoietin-1 (Saharinen et al., 2005; Yuan et al., 2007), most likely in a complex with TEK (Marron et al., 2000; Saharinen et al., 2005). Angiopoietins activate TEK in a unique manner, which involves the translocation of TEK to endothelial cell-cell contacts, and TIE1 is also present in these complexes (Saharinen et al., 2008). Activation of the TIE1 kinase activity using chimeric TIE1 receptors was found to result in the activation of the Akt pathway (Kontos et al., 2002). The TIE1 ectodomain is proteolytically cleaved, and the cleavage is enhanced by PMA, VEGF and TNF-α (Yabkowitz et al., 1999). The proteolytic processing of TIE1 may regulate TEK activity (Marron et al., 2007).
The deletion of both Tie1 and Tek results in a more severe phenotype than the deletions of either Tie1 or Tek alone (Sato et al., 1995; Puri et al., 1999). The deletion of both Tie1 and Angpt1 resulted in impaired development of the right-hand, but not left-hand side venous system in the mouse embryo (Loughna and Sato, 2001).
TIE1 has been implicated as a proinflammatory gene and its silencing in cultured endothelial cells reduced the expression of proinflammatory genes (Chan and Sukhatme, 2009), while TIE1 overexpression upregulated adhesion molecules including VCAM-1, E-selectin and ICAM-1 (Chan et al., 2008).

H. sapiens: TIE1; M. musculus: Tie1; R. novergicus: Tie1; D. rerio: tie1; X. tropicalis: tie1.

Somatic missense mutations and synonymous substitutions in TIE1 have been detected in human cancers, but their significance remains to be found out.