Difference between revisions of "Phosphatase Subfamily Tensin"
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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, SH2 and usually PTB domains at the C-terminus. Human TNS2 (TENC1) and many 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 quite divergent and often can not be picked by Pfam or SMART. | 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, SH2 and usually PTB domains at the C-terminus. Human TNS2 (TENC1) and many 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 quite divergent and often can not be picked by Pfam or SMART. | ||
| − | + | TNS1 and TNS2 are predicted to be catalytically inactive, given the arginine residue is replaced by asparagine and lysine at CX<sub>5</sub>R motif, respectively. But, the catalytic activity of TNS2 has been reported (below). These may function as binding domains for phosphatidyl inositols. | |
===Functions=== | ===Functions=== | ||
Revision as of 16:06, 2 October 2015
Phosphatase Classification: Superfamily CC1: Family PTEN: Subfamily Tensin
Tensins are PTEN-related phosphatases involved in integrin signaling.
Evolution
Tensins are found throughout holozoa. The domain combination is under dramatic changes during evolution. 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. See domain section below.
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, SH2 and usually PTB domains at the C-terminus. Human TNS2 (TENC1) and many 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 quite divergent and often can not be picked by Pfam or SMART.
TNS1 and TNS2 are predicted to be catalytically inactive, given the arginine residue is replaced by asparagine and lysine at CX5R motif, respectively. But, the catalytic activity of TNS2 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 N-terminal regions bind actin. The SH2 domain interacts with a variety of tyrosine-phosphorylated proteins, including PI3K, FAK, and p130Cas. Several tensins are linked to cell migration and metastasis suppression and to signaling downstream of receptor tyrosine kinases.
The catalytic functions of the phosphatase domain are not well understood. TNS2 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 |
