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Details on Person UniProt:Q01105 SET

Class:Id	ReferenceGeneProduct:64350
_chainChangeLog	initiator methionine:1 added on Sat February 7 2015;chain:2-290 added on Sat February 7 2015;initiator methionine:1 for 64350 removed on Fri Nov 03 2023;initiator methionine: for 64350 added on Fri Nov 03 2023;initiator methionine: for 64350 removed on Fri Aug 15 2025;initiator methionine:1 for 64350 added on Fri Aug 15 2025
_displayName	UniProt:Q01105 SET
_timestamp	2025-08-15 21:11:05
chain	initiator methionine:1 chain:2-290
checksum	F4664118171EF230
comment	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.SUBUNIT Headphone-shaped homodimer. Isoforms 1 and 2 interact directly with each other and with ANP32A within the tripartite INHAT (inhibitor of acetyltransferases) complex. Isoform 1 and isoform 2 interact also with histones. Isoform 2 is a component of the SET complex, composed of at least ANP32A, APEX1, HMGB2, NME1, SET and TREX1, but not NME2 or TREX2. Within this complex, directly interacts with ANP32A, NME1, HMGB2 and TREX1; the interaction with ANP32A is enhanced after cleavage. Interacts with APBB1, CHTOP, SETBP1, SGO1.SUBUNIT (Microbial infection) Interacts with herpes simplex virus 1 VP22.INTERACTION 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.ALTERNATIVE PRODUCTS Widely expressed. Low levels in quiescent cells during serum starvation, contact inhibition or differentiation. Highly expressed in Wilms' tumor.DOMAIN 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.PTM Isoform 2 is phosphorylated on Ser-15 and Ser-24.PTM Isoform 2 is acetylated on Lys-11.PTM 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).PTM N-terminus of isoform 1 is methylated by METTL11A/NTM1. Mainly trimethylated (By similarity).PTM Cleaved after Lys-176 by GZMA. The cleavage inhibits its nucleosome assembly activity and disrupts the inhibition on NME1.DISEASE 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.DISEASE The disease is caused by variants affecting the gene represented in this entry.SIMILARITY Belongs to the nucleosome assembly protein (NAP) family.
description	recommendedName: Protein SET alternativeName: HLA-DR-associated protein II alternativeName: Inhibitor of granzyme A-activated DNase shortName: IGAAD alternativeName: PHAPII alternativeName: Phosphatase 2A inhibitor I2PP2A shortName: I-2PP2A alternativeName: Template-activating factor I shortName: TAF-I
geneName	SET
identifier	Q01105
isSequenceChanged	FALSE
keyword	3D-structure Acetylation Alternative splicing Chaperone Chromosomal rearrangement Cytoplasm Direct protein sequencing Disease variant DNA-binding Endoplasmic reticulum Host-virus interaction Intellectual disability Isopeptide bond Methylation Nucleus Phosphoprotein Proteomics identification Proto-oncogene Reference proteome Ubl conjugation
modified	[InstanceEdit:9836292] Weiser, Joel, 2023-05-25 [InstanceEdit:9852000] Weiser, Joel, 2023-11-03 [InstanceEdit:9926675] Weiser, Joel, 2024-11-03 [InstanceEdit:9963647] Weiser, Joel, 2025-08-15
name	SET
referenceDatabase	[ReferenceDatabase:2] UniProt
referenceGene	[ReferenceDNASequence:8958271] ENSEMBL:ENSG00000119335 SET [Homo sapiens]
secondaryIdentifier	SET_HUMAN A5A5H4 A6NGV1 B4DUE2 Q15541 Q5VXV1 Q5VXV2 Q6FHZ5
sequenceLength	290
species	[Species:48887] Homo sapiens
(isoformParent)	[ReferenceIsoform:153738] UniProt:Q01105-2 SET [Homo sapiens] [ReferenceIsoform:405015] UniProt:Q01105-1 SET [Homo sapiens] [ReferenceIsoform:8965347] UniProt:Q01105-3 SET [Homo sapiens] [ReferenceIsoform:8965348] UniProt:Q01105-4 SET [Homo sapiens]
(referenceEntity)	[EntityWithAccessionedSequence:451201] SET [nucleoplasm] [Homo sapiens] [EntityWithAccessionedSequence:8957981] SET [extracellular region] [Homo sapiens]
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No pathways have been reviewed or authored by UniProt:Q01105 SET (64350)