InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: APBB1

Summary

InnateDB Protein

IDBP-28787.7

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

APBB1

Protein Name

amyloid beta (A4) precursor protein-binding, family B, member 1 (Fe65)

Synonyms

FE65; MGC:9072; RIR;

Species

Homo sapiens

Ensembl Protein

ENSP00000299402

InnateDB Gene

IDBG-28785 (APBB1)

Protein Structure

UniProt Annotation

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). {ECO:0000269PubMed:15031292, ECO:0000269PubMed:18468999, ECO:0000269PubMed:18922798, ECO:0000269PubMed:19234442, ECO:0000269PubMed:19343227}.

Subcellular Localization

Cell membrane. Cytoplasm. Nucleus. Cell projection, growth cone {ECO:0000250}. 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. Colocalizes with NEK6 at the nuclear speckles. Phosphorylation at Ser-610 by SGK1 promotes its localization to the nucleus (By similarity). {ECO:0000250}.

Disease Associations

Tissue Specificity

Highly expressed in brain; strongly reduced in post-mortem elderly subjects with Alzheimer disease. {ECO:0000269PubMed:19343227}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 84 experimentally validated interaction(s) in this database.
They are also associated with 6 interaction(s) predicted by orthology.

Experimentally validated
Total	84 [view]
Protein-Protein	83 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	1 [view]
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	6 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0001540	beta-amyloid binding
GO:0003682	chromatin binding
GO:0005515	protein binding
GO:0008134	transcription factor binding
GO:0042393	histone binding
GO:0070064	proline-rich region binding

Biological Process

GO:0006351	transcription, DNA-templated
GO:0006355	regulation of transcription, DNA-templated
GO:0006915	apoptotic process
GO:0006974	cellular response to DNA damage stimulus
GO:0007050	cell cycle arrest
GO:0007165	signal transduction
GO:0007409	axonogenesis
GO:0030308	negative regulation of cell growth
GO:0043065	positive regulation of apoptotic process
GO:0043967	histone H4 acetylation
GO:0045893	positive regulation of transcription, DNA-templated
GO:0050760	negative regulation of thymidylate synthase biosynthetic process