| Modification Notes |
PHIP (pleckstrin homology domain interacting protein), also known as ndrp or WDR11, is a 1,821 amino acid protein that contains eight N-terminal WD40 repeats and two bromodomains. It is expressed in skeletal muscle (localizing to the cytosol and nucleus) and primary ∫ cells (localizing to the nucleus) and acts as a transcriptional activator. PHIP is known to interact with various members of the insulin receptor substrate (IRS) family. The IRS family of proteins mediate insulin receptor signaling and play an important role in insulin-producing ∫ cell proliferation and survival. PHIP specifically associates with the PH domain of IRS-1 and may function to link IRS-1 to insulin receptors, indicating a vital role of PHIP in the regulation of insulin signaling. Further supporting this role of PHIP, mutations in the gene encoding PHIP disrupt IRS-mediated signaling pathways resulting in the inhibition of GLUT4 translocation in muscle cells. PHIP is also known to bind IRS-2 and may play a similar role; linking IRS-2 to insulin receptors. |