Phosphatase Subfamily Tensin
Phosphatase Classification: Superfamily CC1: Family PTEN: Subfamily Tensin
Tensins are PTEN-related phosphatases involved in integrin signaling.
Evolution
Tensins are found throughout holozoa. Drosophilids have a truncated ortholog (blistery) which lacks the phosphatase domain, though the full-length form is seen in mosquitoes. One of the four human members, TNS4, is also truncated.
Domain Structure
Tensins are long proteins, with an N-terminal phosphatase domain followed immediately by a PTEN_C2 domain, which acts as a lipid-binding domain. They have a poorly conserved middle region and and SH2 and usually PTB domains at the C-terminus. Human TENC1 and some invertebrate Tensins also have an N-terminal C1 domain. Humans also have a homologous TNS4 protein which is N-terminally truncated and has lost the phosphatase domain. The phosphatase domain is divergent and not picked by by many domain tools.
The TNS1 phosphatase domain is predicted to be catalytically inactive (The catalytic C is changed to N), and TNS2 may also be inactive (catalytic R in HCx5R changed to K), though catalytic activity has been reported (below). These may function as binding domains for phosphatidyl inositols.
Functions
Tensin are localized to integrin-mediated focal adhesions. The PTB domain binds to the cytoplasmic region of integrins, and they bind actin through an N-terminal region. SH2 domains interact with a variety of tyrosine-phosphorylated proteins, including PI3K, FAK, and p130Cas. The catalytic functions of the phosphatase domain are not well understood. TNS2 (TENC1) induced in vivo dephosporylation of phosphatidylinositol 3,4,5-trisphosphate, though the activity could not be replaced in vitro [1]. Another report[2] showed TNS2 protein tyrosine phosphatase activity on IRS-1
References
- Hafizi S, Gustafsson A, Oslakovic C, Idevall-Hagren O, Tengholm A, Sperandio O, Villoutreix BO, and Dahlbäck B. Tensin2 reduces intracellular phosphatidylinositol 3,4,5-trisphosphate levels at the plasma membrane. Biochem Biophys Res Commun. 2010 Aug 27;399(3):396-401. DOI:10.1016/j.bbrc.2010.07.085 |
- Koh A, Lee MN, Yang YR, Jeong H, Ghim J, Noh J, Kim J, Ryu D, Park S, Song P, Koo SH, Leslie NR, Berggren PO, Choi JH, Suh PG, and Ryu SH. C1-Ten is a protein tyrosine phosphatase of insulin receptor substrate 1 (IRS-1), regulating IRS-1 stability and muscle atrophy. Mol Cell Biol. 2013 Apr;33(8):1608-20. DOI:10.1128/MCB.01447-12 |
