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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
Related
suppressor of variegation, enhancer of zeste & Trithorax (SET) gene
General
nuclear protein
phosphoprotein
proto oncogene protein
Properties
SIZE: entity length = 290 aa
MW = 33 kD
COMPARTMENT: cytoplasm
cell nucleus
endoplasmic reticulum
MOTIF: Ser phosphorylation site {S7}
Ser phosphorylation site {S30}
acidic region {239-290}
MOTIF: acidic residue (SEVERAL)
Breakpoint {283-284}
Database Correlations
OMIM 600960
UniProt Q01105
Pfam PF00956
References
- UniProt :accession Q01105
- Atlas of Genetics & cytogenetics in oncology & Haematology
http://atlasgeneticsoncology.org/Genes/SETID42272ch9q34.html
Component-of
SET complex