Protein: Amyloid beta precursor protein binding family B member 1 (Amyloid-beta A4 precursor protein-binding family B member 1) (Protein Fe65) (O00213)
Organism: Homo sapiens (Human)
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). 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).
Subcellular location: Cell membrane {ECO:0000269|PubMed:18468999}. Cytoplasm {ECO:0000269|PubMed:18468999}. Nucleus {ECO:0000269|PubMed:15031292, ECO:0000269|PubMed:18468999, ECO:0000269|PubMed:18922798, ECO:0000269|PubMed:19343227}. Cell projection, growth cone {ECO:0000250|UniProtKB:P46933}. Nucleus speckle {ECO:0000269|PubMed:17512906}. Note=Colocalizes with TSHZ3 in axonal growth cone (By similarity). Colocalizes with TSHZ3 in the nucleus (PubMed:19343227). In normal conditions, it mainly localizes to the cytoplasm, while a small fraction is tethered to the cell membrane via its interaction with APP (PubMed:18468999). Following exposure to DNA damaging agents, it is released from cell membrane and translocates to the nucleus (PubMed:18468999). Nuclear translocation is under the regulation of APP (PubMed:18468999). Colocalizes with NEK6 at the nuclear speckles (PubMed:17512906). Phosphorylation at Ser-610 by SGK1 promotes its localization to the nucleus (By similarity). {ECO:0000250|UniProtKB:P46933, ECO:0000269|PubMed:17512906, ECO:0000269|PubMed:18468999, ECO:0000269|PubMed:19343227}.
Interaction partners:
- Histone acetyltransferase KAT5
- Amyloid-beta precursor protein
- Amyloid beta precursor like protein 1
- Amyloid beta precursor like protein 2
- Mitogen-activated protein kinase 8
- Alpha-globin transcription factor CP2
- Prolow-density lipoprotein receptor-related protein 1
- Low-density lipoprotein receptor-related protein 8
- Amyloid beta precursor protein binding family B member 2
- Protein enabled homolog
Sequence:
MSVPSSLSQSAINANSHGGPALSLPLPLHAAHNQLLNAKLQATAVGPKDLRSAMGEGGGPEPGPANAKWLKEGQNQLRRAATAHRDQNRNVTLTLAEEASQEPEMAPLGPKGLIHLYSELELSAHNAANRGLRGPGLIISTQEQGPDEGEEKAAGEAEEEEEDDDDEEEEEDLSSPPGLPEPLESVEAPPRPQALTDGPREHSKSASLLFGMRNSAASDEDSSWATLSQGSPSYGSPEDTDSFWNPNAFETDSDLPAGWMRVQDTSGTYYWHIPTGTTQWEPPGRASPSQGSSPQEESQLTWTGFAHGEGFEDGEFWKDEPSDEAPMELGLKEPEEGTLTFPAQSLSPEPLPQEEEKLPPRNTNPGIKCFAVRSLGWVEMTEEELAPGRSSVAVNNCIRQLSYHKNNLHDPMSGGWGEGKDLLLQLEDETLKLVEPQSQALLHAQPIISIRVWGVGRDSGRERDFAYVARDKLTQMLKCHVFRCEAPAKNIATSLHEICSKIMAERRNARCLVNGLSLDHSKLVDVPFQVEFPAPKNELVQKFQVYYLGNVPVAKPVGVDVINGALESVLSSSSREQWTPSHVSVAPATLTILHQQTEAVLGECRVRFLSFLAVGRDVHTFAFIMAAGPASFCCHMFWCEPNAASLSEAVQAACMLRYQKCLDARSQASTSCLPAPPAESVARRVGWTVRRGVQSLWGSLKPKRLGAHTP