功能Multitasking protein, involved in apoptosis, transcription, nucleosome assembly and histone binding. 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.
组织特异性Widely expressed. Low levels in quiescent cells during serum starvation, contact inhibition or differentiation. Highly expressed in Wilms' tumor.
疾病相关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.
序列相似性Belongs to the nucleosome assembly protein (NAP) family.
结构域The C-terminal acidic domain mediates the inhibition of histone acetyltransferases and is required for the DNA replication stimulatory activity.
翻译后修饰Isoform 2 is phosphorylated on Ser-15 and Thr-23. Isoform 2 is acetylated on Lys-11. 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. N-terminus of isoform 1 is methylated by METTL11A/NTM1. Mainly trimethylated.
细胞定位Cytoplasm > cytosol. Endoplasmic reticulum. Nucleus > nucleoplasm. 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.