Recombinant PHIP (1302-1434) protein

The peptide corresponding to amino acids 1302 - 1434 that contains the bromodomain sequences of PHIP (accession number NP_060404.3) was expressed in E. coli and contains an N-terminal His tag and C-terminal FLAG tag with an observed molecular weight of 21.994 kDa. PH-interacting protein (PHIP), also known as WDR11 or BRWD2, is a member of the WD repeat protein family. This family is characterized by regions of approximately 40 amino acids bracketed by gly-his and trp-asp (GH-WD), that potentially facilitate the formation of heterotrimeric or multimeric protein complexes. They also contain bromodomains that recognize acetylated histone lysine residues and function as ïreaders' of these epigenetic histone marks to regulate chromatin structure and gene expression by linking associated proteins to the recognized acetylated nucleosomal targets. PHIP was isolated as a factor that binds to the pleckstrin homology (PH) domain of insulin receptor substrate-1 (IRS-1). PHIP was determined not to be a substrate of the insulin receptor but may instead regulate the insulin and insulin-like growth factor signaling pathways by linking IRS-1 to the insulin receptor. PHIP also stimulates cell proliferation through regulation of cyclin transcription and anti-apoptotic activity through AKT1 phosphorylation and activation. PHIP has also been shown to regulate cell morphology and cytoskeletal organization. In addition, PHIP has been implicated as a positive regulator of beta cell mitogenesis and survival.