TSPAN12

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.

Function

Its main binding partner is the ADAM10 protein,{{cite journal | vauthors = Xu D, Sharma C, Hemler ME | title = Tetraspanin12 regulates ADAM10-dependent cleavage of amyloid precursor protein | journal = FASEB J. | volume = 23 | issue = 11 | pages = 3674–81 |date=November 2009 | pmid = 19587294 | pmc = 2775005 | doi = 10.1096/fj.09-133462 | doi-access = free }} 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.{{cite journal | vauthors = 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 | title = ADAM10 is upregulated in melanoma metastasis compared with primary melanoma | journal = J. Invest. Dermatol. | volume = 130 | issue = 3 | pages = 763–73 |date=March 2010 | pmid = 19865098 | doi = 10.1038/jid.2009.335 | doi-access = free }}{{cite journal | vauthors = 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 | title = ADAM10 is the constitutive functional sheddase of CD44 in human melanoma cells | journal = J. Invest. Dermatol. | volume = 129 | issue = 6 | pages = 1471–82 |date=June 2009 | pmid = 18971959 | doi = 10.1038/jid.2008.323 | doi-access = free }} 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.{{cite journal | vauthors = Lafleur MA, Xu D, Hemler ME | title = Tetraspanin proteins regulate membrane type-1 matrix metalloproteinase-dependent pericellular proteolysis | journal = Mol. Biol. Cell | volume = 20 | issue = 7 | pages = 2030–40 |date=April 2009 | pmid = 19211836 | pmc = 2663921 | doi = 10.1091/mbc.E08-11-1149 }} TSPAN12 also seems to regulate vascular development, as shown by a study involving TSPAN12 knockout mice.{{cite journal | vauthors = Junge HJ, Yang S, Burton JB, Paes K, Shu X, French DM, Costa M, Rice DS, Ye W | title = TSPAN12 regulates retinal vascular development by promoting Norrin- but not Wnt-induced FZD4/beta-catenin signaling | journal = Cell | volume = 139 | issue = 2 | pages = 299–311 |date=October 2009 | pmid = 19837033 | doi = 10.1016/j.cell.2009.07.048 | s2cid = 2276711 | doi-access = free }} TSPAN12 is a significant contributor to primary and metastatic cancer and is responsible for protecting β-catenin from degradation.{{cite journal | vauthors = Knoblich K, Wang HX, Sharma C, Fletcher AL, Turley SJ, Hemler ME | title = Tetraspanin TSPAN12 regulates tumor growth and metastasis and inhibits β-catenin degradation | journal = Cell Mol Life Sci | volume = 71 | issue = 7 | pages = 1305–14 |date=April 2014 | pmid = 23955570 | doi = 10.1007/s00018-013-1444-8 | s2cid = 16135992 | pmc = 11113286 }}

References

External links

[https://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=fevr GeneReviews/NCBI/NIH/UW entry on Familial Exudative Vitreoretinopathy, Autosomal Dominant]

Category:Integral membrane proteins