ID:APBB1_HUMAN DESCRIPTION: RecName: Full=Amyloid beta A4 precursor protein-binding family B member 1; AltName: Full=Protein Fe65; 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). SUBUNIT: Component of a complex, at least composed of APBB1, RASD1/DEXRAS1 and 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. Interacts with TSHZ1 and TSHZ2 (By similarity). Interacts (via the WW domain) with histone H2AX (when phosphorylated on 'Tyr-142') and the proline-rich region of ENAH. Interacts with MAPK8. Interacts (via PID domain 1) with TSHZ3 (via homeobox domain). Interacts with SET. Found in a trimeric complex with HDAC1 and TSHZ3; the interaction between HDAC1 and APBB1 is mediated by TSHZ3. Interacts (via WWW domain) with NEK6. Interacts (via WWW domain) with ABL1. INTERACTION: P05067:APP; NbExp=5; IntAct=EBI-81694, EBI-77613; SUBCELLULAR LOCATION: Cell membrane. Cytoplasm. Nucleus. Cell projection, growth cone (By similarity). 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. Co-localizes with NEK6 at the nuclear speckles. Phosphorylation at Ser-610 by SGK1 promotes its localization to the nucleus (By similarity). TISSUE SPECIFICITY: Highly expressed in brain; strongly reduced in post-mortem elderly subjects with Alzheimer disease. PTM: 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. SIMILARITY: Contains 2 PID domains. SIMILARITY: Contains 1 WW domain.
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on O00213
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Biological Process: GO:0000122 negative regulation of transcription from RNA polymerase II promoter GO:0006302 double-strand break repair GO:0006325 chromatin organization 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:0010039 response to iron ion GO:0010976 positive regulation of neuron projection development GO:0030308 negative regulation of cell growth GO:0043065 positive regulation of apoptotic process GO:0043967 histone H4 acetylation GO:0045739 positive regulation of DNA repair GO:0045893 positive regulation of transcription, DNA-templated GO:0045944 positive regulation of transcription from RNA polymerase II promoter GO:0050714 positive regulation of protein secretion GO:0050760 negative regulation of thymidylate synthase biosynthetic process
BX538185 - Homo sapiens mRNA; cDNA DKFZp686G05200 (from clone DKFZp686G05200). EF103274 - Homo sapiens amyloid beta A4 precursor protein-binding family B member 1 transcript variant 3 (APBB1) mRNA, complete cds, alternatively spliced. AK315965 - Homo sapiens cDNA, FLJ78864 complete cds, highly similar to Amyloid beta A4 precursor protein-bindingfamily B member 1. AK293452 - Homo sapiens cDNA FLJ53874 complete cds, highly similar to Amyloid beta A4 precursor protein-binding family B member 1. AF394214 - Homo sapiens adaptor protein FE65a2 (APBB1) mRNA, APBB1-2 allele, partial cds; alternatively spliced. L77864 - Homo sapiens stat-like protein (Fe65) mRNA, complete cds. BC010854 - Homo sapiens amyloid beta (A4) precursor protein-binding, family B, member 1 (Fe65), mRNA (cDNA clone MGC:9072 IMAGE:3905603), complete cds. AK297550 - Homo sapiens cDNA FLJ57330 complete cds, highly similar to Amyloid beta A4 precursor protein-binding family B member 1. AK295425 - Homo sapiens cDNA FLJ51859 complete cds, highly similar to Amyloid beta A4 precursor protein-binding family B member 1. AK293711 - Homo sapiens cDNA FLJ53875 complete cds, highly similar to Amyloid beta A4 precursor protein-binding family B member 1. AK293550 - Homo sapiens cDNA FLJ61679 complete cds, highly similar to Amyloid beta A4 precursor protein-binding family B member 1. AK293643 - Homo sapiens cDNA FLJ53829 complete cds, highly similar to Amyloid beta A4 precursor protein-bindingfamily B member 1. AK297544 - Homo sapiens cDNA FLJ58369 complete cds, highly similar to Amyloid beta A4 precursor protein-binding family B member 1. AK293554 - Homo sapiens cDNA FLJ54642 complete cds, highly similar to Amyloid beta A4 precursor protein-binding family B member 1. AK295241 - Homo sapiens cDNA FLJ57305 complete cds, highly similar to Amyloid beta A4 precursor protein-binding family B member 1. KJ890682 - Synthetic construct Homo sapiens clone ccsbBroadEn_00076 APBB1 gene, encodes complete protein. DQ890997 - Synthetic construct clone IMAGE:100003627; FLH168362.01X; RZPDo839F1192D amyloid beta (A4) precursor protein-binding, family B, member 1 (Fe65) (APBB1) gene, encodes complete protein. DQ894175 - Synthetic construct Homo sapiens clone IMAGE:100008635; FLH168358.01L; RZPDo839F1191D amyloid beta (A4) precursor protein-binding, family B, member 1 (Fe65) (APBB1) gene, encodes complete protein. AB590204 - Synthetic construct DNA, clone: pFN21AB8012, Homo sapiens APBB1 gene for amyloid beta (A4) precursor protein-binding, family B, member 1, without stop codon, in Flexi system. AK293613 - Homo sapiens cDNA FLJ52221 complete cds, highly similar to Amyloid beta A4 precursor protein-binding family B member 1. AK311141 - Homo sapiens cDNA, FLJ18183. AK311149 - Homo sapiens cDNA, FLJ18191. AK294495 - Homo sapiens cDNA FLJ52204 complete cds, highly similar to Amyloid beta A4 precursor protein-binding family B member 1. AK297542 - Homo sapiens cDNA FLJ57329 complete cds, moderately similar to Amyloid beta A4 precursor protein-binding family B member 1. AK295837 - Homo sapiens cDNA FLJ50968 complete cds, highly similar to Amyloid beta A4 precursor protein-bindingfamily B member 1. AK098207 - Homo sapiens cDNA FLJ40888 fis, clone UTERU2000844. AK057752 - Homo sapiens cDNA FLJ25023 fis, clone CBL01860. JD174722 - Sequence 155746 from Patent EP1572962. JD493396 - Sequence 474420 from Patent EP1572962. JD387259 - Sequence 368283 from Patent EP1572962. JD427377 - Sequence 408401 from Patent EP1572962. JD221323 - Sequence 202347 from Patent EP1572962. JD065577 - Sequence 46601 from Patent EP1572962. JD367945 - Sequence 348969 from Patent EP1572962. JD238535 - Sequence 219559 from Patent EP1572962. JD555079 - Sequence 536103 from Patent EP1572962. JD374904 - Sequence 355928 from Patent EP1572962. JD145670 - Sequence 126694 from Patent EP1572962. JD231444 - Sequence 212468 from Patent EP1572962. JD219497 - Sequence 200521 from Patent EP1572962. JD410318 - Sequence 391342 from Patent EP1572962. JD216583 - Sequence 197607 from Patent EP1572962. AK311101 - Homo sapiens cDNA, FLJ18143. AK311091 - Homo sapiens cDNA, FLJ18133. AK309434 - Homo sapiens cDNA, FLJ99475. AK308782 - Homo sapiens cDNA, FLJ98823. AK308559 - Homo sapiens cDNA, FLJ98600. AK311413 - Homo sapiens cDNA, FLJ18455. AK309000 - Homo sapiens cDNA, FLJ99041. AK311725 - Homo sapiens cDNA, FLJ18767. AK309445 - Homo sapiens cDNA, FLJ99486. CU679821 - Synthetic construct Homo sapiens gateway clone IMAGE:100017463 5' read APBB1 mRNA. DQ579687 - Homo sapiens piRNA piR-47799, complete sequence. JD406650 - Sequence 387674 from Patent EP1572962.
Biochemical and Signaling Pathways
Reactome (by CSHL, EBI, and GO)
Protein O00213 (Reactome details) participates in the following event(s):
R-HSA-5683986 APBB1 and MAPK8 bind diphosphorylated H2AFX R-HSA-5693565 Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks R-HSA-5693606 DNA Double Strand Break Response R-HSA-5693532 DNA Double-Strand Break Repair R-HSA-73894 DNA Repair
US Server
Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
