InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: SET

Summary

InnateDB Protein

IDBP-88486.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

SET

Protein Name

SET nuclear oncogene

Synonyms

2PP2A; I2PP2A; IGAAD; IPP2A2; PHAPII; TAF-I; TAF-IBETA;

Species

Homo sapiens

Ensembl Protein

ENSP00000361777

InnateDB Gene

IDBG-88484 (SET)

Protein Structure

UniProt Annotation

Function

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. {ECO:0000269PubMed:11555662, ECO:0000269PubMed:12628186}.

Subcellular Localization

Cytoplasm, cytosol. Endoplasmic reticulum. Nucleus, nucleoplasm. Note=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.

Disease Associations

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.

Tissue Specificity

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

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 149 experimentally validated interaction(s) in this database.
They are also associated with 36 interaction(s) predicted by orthology.

Experimentally validated
Total	149 [view]
Protein-Protein	147 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	2 [view]
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	36 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0003677	DNA binding
GO:0004864	protein phosphatase inhibitor activity
GO:0005515	protein binding
GO:0008601	protein phosphatase type 2A regulator activity
GO:0042393	histone binding

Biological Process

GO:0000278	mitotic cell cycle
GO:0006260	DNA replication
GO:0006334	nucleosome assembly
GO:0006337	nucleosome disassembly
GO:0006913	nucleocytoplasmic transport
GO:0010467	gene expression
GO:0016070	RNA metabolic process
GO:0016071	mRNA metabolic process
GO:0035067	negative regulation of histone acetylation
GO:0043086	negative regulation of catalytic activity
GO:0043524	negative regulation of neuron apoptotic process
GO:0045892	negative regulation of transcription, DNA-templated
GO:0050790	regulation of catalytic activity

Cellular Component

GO:0005634	nucleus
GO:0005654	nucleoplasm
GO:0005737	cytoplasm
GO:0005783	endoplasmic reticulum
GO:0005829	cytosol
GO:0043234	protein complex
GO:0048471	perinuclear region of cytoplasm