TNS2
Description
The TNS2 (tensin 2) is a protein-coding gene located on chromosome 12.
TNS2, also known as tensin-2, is a tyrosine-protein phosphatase that regulates various cellular processes, including cell motility, proliferation, and muscle response to insulin. Its phosphatase activity is mediated by binding to phosphatidylinositol-3,4,5-triphosphate (PtdIns(3,4,5)P3) via the SH2 domain. In muscles and under catabolic conditions, TNS2 dephosphorylates IRS1, leading to its degradation and muscle atrophy. It negatively regulates the PI3K-AKT pathway activation. TNS2 dephosphorylates nephrin NPHS1 in podocytes, which regulates the activity of the mTORC1 complex. Under normal glucose conditions, NPHS1 outcompetes IRS1 for binding to phosphatidylinositol 3-kinase (PI3K), balancing mTORC1 activity. However, high glucose conditions lead to up-regulation of TNS2, increased NPHS1 dephosphorylation, and activation of mTORC1, contributing to podocyte hypertrophy and proteinuria. TNS2 is essential for correct podocyte morphology, podocyte-glomerular basement membrane interaction, and integrity of the glomerular filtration barrier. It enhances RHOA activation in the presence of DLC1, playing a role in promoting DLC1-dependent remodeling of the extracellular matrix. TNS2 interacts with AXL and SYK, leading to the phosphorylation of SYK. It also interacts with SQSTM1, resulting in the sequestration of TNS2 in cytoplasmic aggregates with SQSTM1, promoting TNS2 ubiquitination and proteasomal degradation.
TNS2 is also known as C1-TEN, C1TEN, TENC1.
Associated Diseases
- hypertension, pregnancy-induced
- toxemia of pregnancy
- gastrointestinal stromal tumor
- cancer
- familial idiopathic steroid-resistant nephrotic syndrome
- congenital nephrotic syndrome, Finnish type
- focal segmental glomerulosclerosis 1
- nephrotic syndrome, type 22
- familial juvenile hyperuricemic nephropathy type 2
