APBB1 FE65 RIR Amyloid beta A4 precursor protein-binding family B member 1 Protein Fe65
Molecular Weight(MW)
77244 Da
Function
Transcription coregulator that can have both coactivator and corepressor functions. Adapter protein that forms a transcriptionally active complex with the gamma-secretase-derived amyloid precursor protein (APP) intracellular domain. Plays a central role in the response to DNA damage by translocating to the nucleus and inducing apoptosis. May act by specifically recognizing and binding histone H2AX phosphorylated on 'Tyr-142' (H2AXY142ph) at double-strand breaks (DSBs), recruiting other pro- apoptosis factors such as MAPK8/JNK1. Required for histone H4 acetylation at double-strand breaks (DSBs). Its ability to specifically bind modified histones and chromatin modifying enzymes such as KAT5/TIP60, probably explains its trancription activation activity. Function in association with TSHZ3, SET and HDAC factors as a transcriptional repressor, that inhibits the expression of CASP4. Associates with chromatin in a region surrounding the CASP4 transcriptional start site(s)
Tissue Specificity
Highly expressed in brain; strongly reduced in post-mortem elderly subjects with Alzheimer disease
Cellular Localization
Cell membrane. Cytoplasm. Nucleus. Cell projection, growth cone (By similarity). Nucleus speckle Note=Colocalizes with TSHZ3 in axonal growth cone (By similarity) In normal conditions, it mainly localizes to the cytoplasm, while a small fraction is tethered to the cell membrane via its interaction with APP. Following exposure to DNA damaging agents, it is released from cell membrane and translocates to the nucleus Nuclear translocation is under the regulation of APP. Colocalizes with TSHZ3 in the nucleus. Co-localizes with NEK6 at the nuclear speckles. Phosphorylation at Ser-610 by SGK1 promotes its localization to the nucleus (By similarity)