Tetraspanin-12 (Tspan-12) also known as tetraspan NET-2 (NET2) or transmembrane 4 superfamily member 12 (TM4SF12) is a tetraspaninprotein that in humans is encoded by the TSPAN12gene. Tetraspanin-12 is found in the membrane of a variety of cells. It has an unusually long C-terminal intracellular tail of approximately 60 amino acids.
Its main binding partner is the ADAM10 protein, a sheddase that interacts with a variety of adhesion molecules that are found on the cell membrane including L1-CAM, E-Cadherin, N-Cadherin and CD44. It also binds to the MT1-MMP metalloprotease protein that is closely related to ADAM10 but has a minimal effect on promotion of expression and function. TSPAN12 also seems to regulate vascular development, as shown by a study involving TSPAN12 knockout mice. TSPAN12 is a significant contributor to primary and metastatic cancer and is responsible for protecting β-catenin from degradation.
↑Lee SB, Schramme A, Doberstein K, Dummer R, Abdel-Bakky MS, Keller S, Altevogt P, Oh ST, Reichrath J, Oxmann D, Pfeilschifter J, Mihic-Probst D, Gutwein P (March 2010). "ADAM10 is upregulated in melanoma metastasis compared with primary melanoma". J. Invest. Dermatol. 130 (3): 763–73. doi:10.1038/jid.2009.335. PMID19865098.
↑Anderegg U, Eichenberg T, Parthaune T, Haiduk C, Saalbach A, Milkova L, Ludwig A, Grosche J, Averbeck M, Gebhardt C, Voelcker V, Sleeman JP, Simon JC (June 2009). "ADAM10 is the constitutive functional sheddase of CD44 in human melanoma cells". J. Invest. Dermatol. 129 (6): 1471–82. doi:10.1038/jid.2008.323. PMID18971959.
↑Junge HJ, Yang S, Burton JB, Paes K, Shu X, French DM, Costa M, Rice DS, Ye W (October 2009). "TSPAN12 regulates retinal vascular development by promoting Norrin- but not Wnt-induced FZD4/beta-catenin signaling". Cell. 139 (2): 299–311. doi:10.1016/j.cell.2009.07.048. PMID19837033.
↑Knoblich K, Wang HX, Sharma C, Fletcher AL, Turley SJ, Hemler ME (April 2014). "Tetraspanin TSPAN12 regulates tumor growth and metastasis and inhibits β-catenin degradation". Cell Mol Life Sci. 71 (7): 1305–14. doi:10.1007/s00018-013-1444-8. PMID23955570.