SET/TAF-I

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.

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.

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.

Intellectual developmental disorder, autosomal dominant 58

MRD58

A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRD58 patients show delayed development, intellectual disability, language delay and speech impairment. Some patients have motor delay or incoordination, and minor dysmorphic features.

None

The disease is caused by variants affecting the gene represented in this entry.

Isoform 2 is phosphorylated on Ser-15 and Ser-24.

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 (By similarity).

N-terminus of isoform 1 is methylated by METTL11A/NTM1. Mainly trimethylated (By similarity).

Isoform 2

Cleaved after Lys-176 by GZMA. The cleavage inhibits its nucleosome assembly activity and disrupts the inhibition on NME1.

Belongs to the nucleosome assembly protein (NAP) family.

Widely expressed. Low levels in quiescent cells during serum starvation, contact inhibition or differentiation. Highly expressed in Wilms' tumor.

• Cytoplasm
• Cytosol
• Endoplasmic reticulum
• Nucleus
• Nucleoplasm
• In the cytoplasm, found both in the cytosol and associated with the endoplasmic reticulum. The SET complex is associated with the endoplasmic reticulum. Following CTL attack and cleavage by GZMA, 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.

Protein SET, HLA-DR-associated protein II, Inhibitor of granzyme A-activated DNase, PHAPII, Phosphatase 2A inhibitor I2PP2A, Template-activating factor I, IGAAD, I-2PP2A, TAF-I, SET

• entrezGene:6418
• omim:600960
• swissprot:Q01105

Proteins

Oncology

33489Da