. "FUNCTION: Multitasking protein, involved in apoptosis, transcription, nucleosome assembly and histone chaperoning. Isoform 2 anti-apoptotic activity is mediated by inhibition of the GZMA-activated DNase, NME1. In the course of cytotoxic T- lymphocyte (CTL)-induced apoptosis, GZMA cleaves SET, disrupting its binding to NME1 and releasing NME1 inhibition. Isoform 1 and isoform 2 are potent inhibitors of protein phosphatase 2A. Isoform 1 and isoform 2 inhibit EP300/CREBBP and PCAF-mediated acetylation of histones (HAT) and nucleosomes, most probably by masking the accessibility of lysines of histones to the acetylases. The predominant target for inhibition is histone H4. HAT inhibition leads to silencing of HAT-dependent transcription and prevents active demethylation of DNA. Both isoforms stimulate DNA replication of the adenovirus genome complexed with viral core proteins; however, isoform 2 specific activity is higher. SUBUNIT: Headphone-shaped homodimer. Isoform 1 and isoform 2 interact directly with each other and with ANP32A within the tripartite INHAT (inhibitor of acetyltransferases) complex. Isoform 1 and isoform 2 interact also with histones. Isoform 2 is a component of the SET complex, which also contains ANP32A, APEX1, HMGB2 and NME1, but not NME2. Within this complex, directly interacts with NME1 and with HMGB2. Interacts with SETBP1. Interacts with SGOL1. Interacts with APBB1. SUBCELLULAR LOCATION: Cytoplasm, cytosol. Endoplasmic reticulum. Nucleus, nucleoplasm. Note=In the cytoplasm, found both in the cytosol and associated with the endoplasmic reticulum. Following CTL attack, moves rapidly to the nucleus, where it is found in the nucleoplasm, avoiding the nucleolus. Similar translocation to the nucleus is also observed for lymphocyte-activated killer cells after the addition of calcium. The SET complex is associated with the endoplasmic reticulum. ALTERNATIVE PRODUCTS: Event=Alternative splicing; Named isoforms=2; Name=1; Synonyms=TAF-I alpha; IsoId=Q01105-1; Sequence=Displayed; Name=2; Synonyms=TAF-I beta; IsoId=Q01105-2; Sequence=VSP_009868; Note=Acetylated on Lys-11. Phosphorylated on Ser-15 and Thr-23. Variant in position: 4:P->Q (in dbSNP:rs1141138); TISSUE SPECIFICITY: Widely expressed. Low levels in quiescent cells during serum starvation, contact inhibition or differentiation. Highly expressed in Wilms' tumor. DOMAIN: A long alpha helix in the N-terminus mediates dimerization, while the earmuff domain is responsible for core histone and dsDNA binding. The C-terminal acidic domain mediates the inhibition of histone acetyltransferases and is required for the DNA replication stimulatory activity. PTM: Isoform 2 is phosphorylated on Ser-15 and Thr-23. PTM: Isoform 2 is acetylated on Lys-11. PTM: Some glutamate residues are glycylated by TTLL8. This modification occurs exclusively on glutamate residues and results in a glycine chain on the gamma-carboxyl group (By similarity). PTM: N-terminus of isoform 1 is methylated by METTL11A/NTM1. Mainly trimethylated (By similarity). DISEASE: Note=A chromosomal aberration involving SET is found in some cases of acute undifferentiated leukemia (AUL). Translocation t(6;9)(q21;q34.1) with NUP214/CAN. SIMILARITY: Belongs to the nucleosome assembly protein (NAP) family. WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL=\"http://atlasgeneticsoncology.org/Genes/SETID42272ch9q34.html\"; GENE SYNONYMS:SET. COPYRIGHT: Protein annotation is derived from the UniProt Consortium (http://www.uniprot.org/). Distributed under the Creative Commons Attribution-NoDerivs License."^^ . "SEQUENCE 290 AA; 33489 MW; F4664118171EF230 CRC64;"^^ . . . . . . . . . . . "SET_HUMAN"^^ . "SET"^^ . "I-2PP2A"^^ . "Template-activating factor I"^^ . "TAF-I"^^ . "Phosphatase 2A inhibitor I2PP2A"^^ . "Inhibitor of granzyme A-activated DNase"^^ . "IGAAD"^^ . "PHAPII"^^ . "HLA-DR-associated protein II"^^ . . . . . . . . . . "MAPKRQSPLPPQKKKPRPPPALGPEETSASAGLPKKGEKEQQEAIEHIDEVQNEIDRLNEQASEEILKVEQKYNKLRQPFFQKRSELIAKIPNFWVTTFVNHPQVSALLGEEDEEALHYLTRVEVTEFEDIKSGYRIDFYFDENPYFENKVLSKEFHLNESGDPSSKSTEIKWKSGKDLTKRSSQTQNKASRKRQHEEPESFFTWFTDHSDAGADELGEVIKDDIWPNPLQYYLVPDMDDEEGEGEEDDDDDEEEEGLEDIDEEGDEDEGEEDEDDDEGEEGEEDEGEDD"^^ . "Protein SET"^^ .