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Description

"KH domain-containing, RNA-binding, signal transduction-associated protein 1 (UniProt Q60749, also known as GAP-associated tyrosine phosphoprotein p62, Khdrbs1,p68, p21 Ras GTPase-activating protein-associated p62, Sam68, Src-associated in mitosis 68 kDa protein) is encoded by the Khdrbs1 gene (Gene ID 20218) in murine species. Sam68 is a member of the ""signal transduction and activation of RNA"" (STAR) family of KH domain-containing RNA-binding proteins that mediates pre-mRNA splicing, mRNA export, and protein translation. It binds to UAAA, UUUA, and UUUUUU motifs with high affinity. RNA immunoprecipitation (RIP) techniques using lysates from UV cross-linked NIH 3T3 cells have identified 23 Sam68 complex-associated mRNA species, including Thrap1, bri3bp, Myl6, Copeb/KLF6/Zf9, Hmgn1, Smc6, and biglycan. In addition, Sam68 is found to be a key regulator of Nrxn1 alternative splicing in the central nervous system in a neuronal activity-dependent manner. Sam68 is phosphorylated on three tyrosine residues (pTyr435, pTyr440, and pTyr443) within the C-terminal nuclear localization signal (NLS) region by the breast tumor kinase (BRK) following EGF stimulation of breast tumor cells with pTyr440 being a principal modulator of Sam68 nuclear localization. Studies comparing wild-type and Sam68-/- knockout mice revealed a positive regulatory role of Sam68 toward adipocyte differentiation, as well as a negative impact of Sam68 against osteoblast differentiation among aged mice."