protein
Amyloid beta precursor protein binding family B member 1
Gene
APBB1
Organism
Homo sapiens(9606)
Length
710 aa
Mass
77,244 Da
APBB1 (amyloid beta precursor protein binding family B member 1) is a transcription coregulator that functions as both a coactivator and corepressor, with dual roles in transcriptional control and DNA damage response (UniProt: O00213). The protein forms transcriptionally active complexes with the APP intracellular domain derived from gamma-secretase cleavage, and plays a central role in nuclear translocation and apoptosis induction following DNA damage. APBB1 also contributes to hippocampal neurite branching and neuromuscular junction formation, supporting spatial memory function.
APBB1 is involved in chromatin remodeling through recognition of phosphorylated histone H2AX at double-strand breaks and recruitment of pro-apoptotic factors, as well as histone acetylation via interaction with chromatin-modifying enzymes (UniProt: O00213). The protein associates with transcriptional repressor complexes containing TSHZ3, SET, and HDAC factors to inhibit caspase-4 expression.
In Alzheimer's disease, APBB1 is downregulated in post-mortem AD brain tissue compared to age-matched controls (Chaparral AD proteomics), with a mean log2 fold-change of −0.42 across subcellular fractions in TMT-labeled mass spectrometry analysis. This reduction may contribute to altered APP-mediated signaling and transcriptional dysregulation in AD pathology.
Generated from the curated entity record below. May contain errors — verify against source links.
Proteomics Evidence · AD
↓ Down in ADP3
not detected
P2
not detected
S2
not detected
S3
-0.425
Mean log₂FC across detected fractions: -0.4247 (1 of 4 fractions detected)
Human post-mortem AD brain vs age-matched controls, TMT-labeled, 4 subcellular fractions (P2, P3, S2, S3), DDA proteomics.
Related Publications
Browse all →Tau molecular diversity contributes to clinical heterogeneity in Alzheimer's disease.
Dujardin Simon et al.Nature medicine2020PMID 32572268Deep Multilayer Brain Proteomics Identifies Molecular Networks in Alzheimer's Disease Progression.
Bai Bing et al.Neuron2020PMID 31926610A Multi-network Approach Identifies Protein-Specific Co-expression in Asymptomatic and Symptomatic Alzheimer's Disease.
Seyfried Nicholas T et al.Cell systems2017PMID 27989508Large-scale deep multi-layer analysis of Alzheimer's disease brain reveals strong proteomic disease-related changes not observed at the RNA level.
Johnson Erik C B et al.Nature neuroscience2022PMID 35115731Organization and regulation of gene transcription.
Cramer PatrickNature2019PMID 31462772
Function
Transcription coregulator that can have both coactivator and corepressor functions (PubMed:15031292, PubMed:18468999, PubMed:18922798, PubMed:25342469, PubMed:33938178). Adapter protein that forms a transcriptionally active complex with the gamma-secretase-derived amyloid precursor protein (APP) intracellular domain (PubMed:15031292, PubMed:18468999, PubMed:18922798, PubMed:25342469). Plays a central role in the response to DNA damage by translocating to the nucleus and inducing apoptosis (PubMed:15031292, PubMed:18468999, PubMed:18922798, PubMed:25342469). 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 (PubMed:19234442). Required for histone H4 acetylation at double-strand breaks (DSBs) (PubMed:19234442). Its ability to specifically bind modified histones and chromatin modifying enzymes such as KAT5/TIP60, probably explains its transcription activation activity (PubMed:33938178). Functions in association with TSHZ3, SET and HDAC factors as a transcriptional repressor, that inhibits the expression of CASP4 (PubMed:19343227). Associates with chromatin in a region surrounding the CASP4 transcriptional start site(s) (PubMed:19343227). Involved in hippocampal neurite branching and neuromuscular junction formation, as a result plays a role in spatial memory functioning (By similarity). Plays a role in the maintenance of lens transparency (By similarity). May play a role in muscle cell strength (By similarity). Acts as a molecular adapter that functions in neurite outgrowth by activating the RAC1-ARF6 axis upon insulin treatment (PubMed:36250347)
Sources
Last updated 5/8/2026, 6:31:56 AM