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RefSeq (mRNA)



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Tetraspanin-12 (Tspan-12) also known as tetraspan NET-2 (NET2) or transmembrane 4 superfamily member 12 (TM4SF12) is a tetraspanin protein that in humans is encoded by the TSPAN12 gene. 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,[1] 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.[2][3] 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.[4] TSPAN12 also seems to regulate vascular development, as shown by a study involving TSPAN12 knockout mice.[5] TSPAN12 is a significant contributor to primary and metastatic cancer and is responsible for protecting β-catenin from degradation.[6]


  1. Xu D, Sharma C, Hemler ME (November 2009). "Tetraspanin12 regulates ADAM10-dependent cleavage of amyloid precursor protein". FASEB J. 23 (11): 3674–81. doi:10.1096/fj.09-133462. PMC 2775005. PMID 19587294.
  2. 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. PMID 19865098.
  3. 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. PMID 18971959.
  4. Lafleur MA, Xu D, Hemler ME (April 2009). "Tetraspanin proteins regulate membrane type-1 matrix metalloproteinase-dependent pericellular proteolysis". Mol. Biol. Cell. 20 (7): 2030–40. doi:10.1091/mbc.E08-11-1149. PMC 2663921. PMID 19211836.
  5. 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. PMID 19837033.
  6. 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. PMID 23955570.

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