Human Gene SET (ENST00000409104.7) from GENCODE V44
Description: Homo sapiens SET nuclear proto-oncogene (SET), transcript variant 3, mRNA. (from RefSeq NM_001248000) RefSeq Summary (NM_001248000): 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]. Sequence Note: This RefSeq record was created from transcript and genomic sequence data to make the sequence consistent with the reference genome assembly. The genomic coordinates used for the transcript record were based on transcript alignments. Gencode Transcript: ENST00000409104.7 Gencode Gene: ENSG00000119335.18 Transcript (Including UTRs) Position: hg38 chr9:128,685,083-128,694,734 Size: 9,652 Total Exon Count: 8 Strand: + Coding Region Position: hg38 chr9:128,685,168-128,694,664 Size: 9,497 Coding Exon Count: 8
ID:SET_HUMAN DESCRIPTION: RecName: Full=Protein SET; AltName: Full=HLA-DR-associated protein II; AltName: Full=Inhibitor of granzyme A-activated DNase; Short=IGAAD; AltName: Full=PHAPII; AltName: Full=Phosphatase 2A inhibitor I2PP2A; Short=I-2PP2A; AltName: Full=Template-activating factor I; Short=TAF-I; 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. Isoform 1 and isoform 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, which also contains ANP32A, APEX1, HMGB2 and NME1, but not NME2. Within this complex, directly interacts with NME1 and with HMGB2. Interacts with SETBP1. Interacts with SGOL1. Interacts with APBB1. INTERACTION: Q00987:MDM2; NbExp=2; IntAct=EBI-1053182, EBI-389668; P10644:PRKAR1A; NbExp=2; IntAct=EBI-1053182, EBI-476431; SUBCELLULAR LOCATION: Cytoplasm, cytosol. Endoplasmic reticulum. Nucleus, nucleoplasm. Note=In the cytoplasm, found both in the cytosol and associated with the endoplasmic reticulum. Following CTL attack, 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. The SET complex is associated with the endoplasmic reticulum. TISSUE SPECIFICITY: 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 Thr-23. 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). DISEASE: 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. SIMILARITY: Belongs to the nucleosome assembly protein (NAP) family. WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/SETID42272ch9q34.html";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on Q01105
Front
Top
Side
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.
Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.