amyloid beta A4 protein-binding family B member 1; protein Fe65 (APBB1 FE65 RIR)

Function

• binds to intracellular domain of APP
• Fe65 binds C-terminal region of APP
• after cleavage of APP by APP gamma secretase, carries APP C-terminus to nucleus
• Fe65 also binds to the cytolasmic domain of LRP1
• plays a central role in the response to DNA damage by translocating to the nucleus & inducing apoptosis
• may act by specifically recognizing & binding histone H2AX phosphorylated on Tyr-142 (H2AXY142ph) at DNA double-strand breaks), recruiting other pro-apoptosis factors such as MAPK8/JNK1
• required for histone H4 acetylation at DNA double-strand breaks
• ability to specifically bind modified histones & chromatin modifying enzymes such as KAT5/TIP60, probably explains its trancription activation activity
• phosphorylated following nuclear translocation
• phosphorylation at Tyr-546 enhances the transcription activation activity & reduces the affinity with RASD1/DEXRAS1
• component of a complex, at least composed of APBB1, RASD1/DEXRAS1 & APP
• interacts (via PID domain 2) with APP (with the intracellular domain of the beta-amyloid precursor protein)
• interacts (via PID domain 2) with RASD1/DEXRAS1; impairs the trancription activation activity
• interacts (via PID domain 1) with KAT5/TIP60
• interacts (via the WW domain) with the proline-rich region of APBB1IP (putative)
• interacts (via the WW domain) with histone H2AX (when phosphorylated on Tyr-142) & the proline-rich region of ENAH
• interacts with MAPK8

Structure

• contains 2 PID domains
• contains 1 WW domain

Compartment

• cell membrane, cytoplasm, nucleus
• in normal conditions, it mainly localizes to the cytoplasm,
• 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 & translocates to the nucleus
• nuclear translocation is under the regulation of APP

Alternative splicing

named isoforms=2

Expression

highly expressed in brain

Pathology

• mutations in Fe65 affect the ability of animals to forget

Polymorphism

• polymorphisms carry susceptibility to late onset Alzheimer's disease

More general terms

• amyloid beta A4 precursor protein binding family
• phosphoprotein

Database

• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=322
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:322
• OMIM: https://mirror.omim.org/entry/602709
• UniProt: http://www.uniprot.org/uniprot/O00213.html