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MGP002809

UniProt Annotations

Entry Information
Gene NameSET nuclear proto-oncogene
Protein EntrySET_HUMAN
UniProt IDQ01105
SpeciesHuman
Comments
Comment typeDescription
Alternative ProductsEvent=Alternative splicing; Named isoforms=4; Name=1; Synonyms=TAF-I alpha; IsoId=Q01105-1; Sequence=Displayed; Name=2; Synonyms=TAF-I beta; IsoId=Q01105-2; Sequence=VSP_009868; Note=Variant in position: 4:P->Q (in dbSNP:rs1141138). Contains a N6-acetyllysine at position 11. Contains a phosphoserine at position 15. Contains a phosphoserine at position 24.; Name=3; IsoId=Q01105-3; Sequence=VSP_045175; Name=4; IsoId=Q01105-4; Sequence=VSP_046741; Note=Gene prediction based on EST data.;
DiseaseNote=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.
DomainA 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. {ECO:0000269|PubMed:17360516}.
FunctionMultitasking 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:0000269|PubMed:11555662, ECO:0000269|PubMed:12628186}.
InteractionQ12778:FOXO1; NbExp=5; IntAct=EBI-1053182, EBI-1108782; Q00987:MDM2; NbExp=2; IntAct=EBI-1053182, EBI-389668; P10644:PRKAR1A; NbExp=2; IntAct=EBI-1053182, EBI-476431; P63000:RAC1; NbExp=8; IntAct=EBI-1053182, EBI-413628; Q15573:TAF1A; NbExp=2; IntAct=EBI-1053182, EBI-2510647; Q53T94:TAF1B; NbExp=3; IntAct=EBI-1053182, EBI-1560239; Q15572:TAF1C; NbExp=4; IntAct=EBI-1053182, EBI-2510659; P20226:TBP; NbExp=4; IntAct=EBI-1053182, EBI-355371; P17480:UBTF; NbExp=4; IntAct=EBI-1053182, EBI-396235;
PtmIsoform 2 is acetylated on Lys-11. {ECO:0000269|PubMed:19608861}.
PtmIsoform 2 is cleaved after Lys-176 by GZMA. The cleavage inhibits its nucelosome assembly activity and disrupts the inhibition on NME1. {ECO:0000269|PubMed:11555662, ECO:0000269|PubMed:12628186, ECO:0000269|PubMed:16818237}.
PtmIsoform 2 is phosphorylated on Ser-15 and Thr-23. {ECO:0000269|PubMed:17081983, ECO:0000269|PubMed:17924679, ECO:0000269|PubMed:20068231}.
PtmN-terminus of isoform 1 is methylated by METTL11A/NTM1. Mainly trimethylated (By similarity). {ECO:0000250}.
PtmSome 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). {ECO:0000250}.
SimilarityBelongs to the nucleosome assembly protein (NAP) family. {ECO:0000305}.
Subcellular LocationCytoplasm, 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.
SubunitHeadphone-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, SGOL1. {ECO:0000269|PubMed:11231286, ECO:0000269|PubMed:11555662, ECO:0000269|PubMed:11909973, ECO:0000269|PubMed:12628186, ECO:0000269|PubMed:16541025, ECO:0000269|PubMed:16818237, ECO:0000269|PubMed:17360516, ECO:0000269|PubMed:19343227}.
Tissue SpecificityWidely expressed. Low levels in quiescent cells during serum starvation, contact inhibition or differentiation. Highly expressed in Wilms' tumor.
Web ResourceName=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/SETID42272ch9q34.html";
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