APBB1

APBB1 is a member of the Fe65 protein family. It is an adaptor protein localized in the nucleus. It interacts with the Alzheimer's disease amyloid precursor protein (APP), transcription factor CP2/LSF/LBP1 and the low-density lipoprotein receptor-related protein. APP functions as a cytosolic anchoring site that can prevent the gene product's nuclear translocation. This encoded protein could play an important role in the pathogenesis of Alzheimer's disease. It is thought to regulate transcription. Also it is observed to block cell cycle progression by downregulating thymidylate synthase expression.

Full Name

Amyloid Beta Precursor Protein Binding Family B Member 1

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 transcription activation activity. Functions 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).

Biological Process

Apoptotic process Source: UniProtKB-KW
Axonogenesis Source: UniProtKB
Cell cycle arrest Source: UniProtKB
Cellular response to DNA damage stimulus Source: UniProtKB
Double-strand break repair Source: Reactome
Histone H4 acetylation Source: UniProtKB
Negative regulation of cell growth Source: UniProtKB
Negative regulation of transcription by RNA polymerase II Source: ARUK-UCL
Positive regulation of apoptotic process Source: UniProtKB
Positive regulation of protein secretion Source: ARUK-UCL
Positive regulation of transcription, DNA-templated Source: UniProtKB
Positive regulation of transcription by RNA polymerase II Source: ARUK-UCL
Regulation of transcription, DNA-templated Source: GO_Central
Signal transduction Source: UniProtKB

Cellular Location

Cytoplasm; Cell membrane; Nucleus; Nucleus speckle; Growth cone. 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. Colocalizes with NEK6 at the nuclear speckles. Phosphorylation at Ser-610 by SGK1 promotes its localization to the nucleus (By similarity).

PTM

Polyubiquitination by RNF157 leads to degradation by the proteasome (PubMed:25342469).
Phosphorylation at Ser-610 by SGK1 promotes its localization to the nucleus (By similarity). Phosphorylated following nuclear translocation. Phosphorylation at Tyr-547 by ABL1 enhances transcriptional activation activity and reduces the affinity for RASD1/DEXRAS1.