Tbio SET Protein SET

Protein Summary

Description

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. The protein encoded by this gene inhibits acetylation of nucleosomes, especially histone H4, by histone acetylases (HAT). This inhibition is most likely accomplished by masking histone lysines from being acetylated, and the consequence is to silence HAT-dependent transcription. The encoded protein is part of a complex localized to the endoplasmic reticulum but is found in the nucleus and inhibits apoptosis following attack by cytotoxic T lymphocytes. This protein can also enhance DNA replication of the adenovirus genome. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]

Uniprot Accession IDs

• Q01105
• A5A5H4
• A6NGV1
• B4DUE2
• Q15541
• Q5VXV1
• Q5VXV2
• Q6FHZ5

Gene Name

• SET

Ensembl ID

• ENST00000322030
• ENSP00000318012
• ENSG00000119335
• ENST00000372686
• ENSP00000361771
• ENST00000372692
• ENSP00000361777
• ENST00000409104
• ENSP00000387321

Symbol

• 2PP2A
• IGAAD
• MRD58
• TAF-I
• I2PP2A
• IPP2A2
• PHAPII
• TAF-IBETA

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
co-expressed gene	1
kinase perturbation	1
disease perturbation	0.99
hub protein	0.99
interacting protein	0.99

Protein Classes

PANTHER Classes

Protein / Enzyme Modulator / Phosphatase Modulator / Phosphatase Inhibitor / Protein Set

Protein / Chaperone / Protein Set

DTO Classes

Protein / Enzyme Modulator / Phosphatase Modulator / Phosphatase Inhibitor / Protein Set

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 132.88   (req: < 5)

Gene RIFs: 126   (req: <= 3)

Antibodies: 347   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 132.88   (req: >= 5)

Gene RIFs: 126   (req: > 3)

Antibodies: 347   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 12

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligand: 0

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0