set proto-oncogene protein (suppressor of variegation, enhancer of zeste & trithorax, HLA-DR associated protein II, PHAPII, phosphatase 2A inhibitor I2PP2A, I-2PP2A, template-activating factor I, TAF-I, inhibitor of granzyme A-activated DNase, IGAAD, SET)

Function

• multitasking protein, involved in apoptosis, transcription, nucleosome assembly & 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 & releasing NME1 inhibition
• isoform 1 & isoform 2 are potent inhibitors of protein phosphatase 2A
• isoform 1 & isoform 2 inhibit EP300/CREBBP & PCAF-mediated acetylation of histones (HAT) & nucleosomes, most probably by masking the accessibility of lysines of histones to the acetylases; predominant target for inhibition is histone H4
• inhibiting acetylation of histones leads to silencing of acetylated histone-dependent transcription & prevents active demethylation of DNA
• both isoforms 1 & 2 stimulate DNA replication of adenovirus genome complexed with viral core proteins; isoform 2 specific activity is higher thanisoform 1
• isoform 1 & isoform 2 interact with histones
• isoform 2 is a component of the SET complex
• within the SET complex, directly interacts with NME1 & with HMGB2
• interacts with SETBP1
• isoform 2 is phosphorylated on Ser-15 & Thr-23
• isoform 2 is acetylated on Lys-11
• acetylated on Lys-11
• phosphorylated on Ser-15 & Thr-23

Structure

• long C-terminal acidic domain mediates inhibition of histone acetyltransferases & is required for the DNA replication stimulatory activity
• belongs to the nucleosome assembly protein (NAP) family

Compartment

• cytoplasm, endoplasmic reticulum, nucleus, nucleoplasm
• in cytoplasm, found both in cytosol & associated with the endoplasmic reticulum
• following cytotoxic T-lympohocyte 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 Ca+2

Alternative splicing

named isoforms=2

Expression

• widely expressed
• low levels in quiescent cells during serum starvation, contact inhibition or differentiation
• highly expressed in Wilms' tumor

Pathology

• chromosomal translocation t(6;9)(p23q34) of SET or DEK with CAN observed in acute myeloid leukemia
• expressed at higher levels in transformed renal epithelial cells & endothelial cells than normal cells

More general terms

• proto oncogene protein
• nuclear protein
• phosphoprotein

Component of

• SET complex

Database

• UniProt: http://www.uniprot.org/uniprot/Q01105.html
• OMIM: https://mirror.omim.org/entry/600960