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 

Page IndexSequence and LinksUniProtKB CommentsPrimersMalaCardsCTD
RNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther SpeciesGO Annotations
mRNA DescriptionsPathwaysOther NamesMethods
Data last updated at UCSC: 2023-08-18 00:09:47

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr9:128,685,083-128,694,734)mRNA (may differ from genome)Protein (268 aa)
Gene SorterGenome BrowserOther Species FASTAGene interactionsTable SchemaAlphaFold
BioGPSEnsemblEntrez GeneExonPrimerGencodeGeneCards
HGNCLynxMalacardsMGIneXtProtOMIM
PubMedReactomeUniProtKBWikipediaBioGrid CRISPR DB

-  Comments and Description Text from UniProtKB
  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";

-  Primer design for this transcript
 

Primer3Plus can design qPCR Primers that straddle exon-exon-junctions, which amplify only cDNA, not genomic DNA.
Click here to load the transcript sequence and exon structure into Primer3Plus

Exonprimer can design one pair of Sanger sequencing primers around every exon, located in non-genic sequence.
Click here to open Exonprimer with this transcript

To design primers for a non-coding sequence, zoom to a region of interest and select from the drop-down menu: View > In External Tools > Primer3


-  MalaCards Disease Associations
  MalaCards Gene Search: SET
Diseases sorted by gene-association score: leukemia, acute myeloid (4), leukoencephalopathy with vanishing white matter (1)

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 147.68 RPKM in Cells - EBV-transformed lymphocytes
Total median expression: 2482.49 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -25.9085-0.305 Picture PostScript Text
3' UTR -9.8070-0.140 Picture PostScript Text

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.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR002164 - NAP_family

Pfam Domains:
PF00956 - Nucleosome assembly protein (NAP)

Protein Data Bank (PDB) 3-D Structure
MuPIT help
2E50 - X-ray MuPIT


ModBase Predicted Comparative 3D Structure on Q01105
FrontTopSide
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.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
Genome BrowserGenome BrowserNo orthologNo orthologGenome BrowserNo ortholog
Gene Details     
Gene Sorter     
MGIRGD  WormBase 
Protein SequenceProtein Sequence  Protein Sequence 
AlignmentAlignment  Alignment 

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0003677 DNA binding
GO:0004864 protein phosphatase inhibitor activity
GO:0005515 protein binding
GO:0019888 protein phosphatase regulator activity
GO:0042393 histone binding

Biological Process:
GO:0006260 DNA replication
GO:0006334 nucleosome assembly
GO:0006337 nucleosome disassembly
GO:0016032 viral process
GO:0032515 negative regulation of phosphoprotein phosphatase activity
GO:0035067 negative regulation of histone acetylation
GO:0043488 regulation of mRNA stability
GO:0043524 negative regulation of neuron apoptotic process
GO:0043666 regulation of phosphoprotein phosphatase activity
GO:0045892 negative regulation of transcription, DNA-templated

Cellular Component:
GO:0005634 nucleus
GO:0005654 nucleoplasm
GO:0005737 cytoplasm
GO:0005783 endoplasmic reticulum
GO:0005811 lipid particle
GO:0005829 cytosol
GO:0032991 macromolecular complex
GO:0048471 perinuclear region of cytoplasm


-  Descriptions from all associated GenBank mRNAs
  AK300794 - Homo sapiens cDNA FLJ51749 complete cds, highly similar to Protein SET.
D45198 - Homo sapiens set mRNA for template acyivating factor-I alpha, complete cds.
AB464200 - Synthetic construct DNA, clone: pF1KB6336, Homo sapiens SET gene for SET translocation, without stop codon, in Flexi system.
AM393022 - Synthetic construct Homo sapiens clone IMAGE:100002298 for hypothetical protein (SET gene).
JF729356 - Homo sapiens SET mRNA, complete cds.
BC056245 - Homo sapiens cDNA clone IMAGE:6698185, partial cds.
AK223556 - Homo sapiens mRNA for SET translocation (myeloid leukemia-associated) variant, clone: FCC127D11.
BC014567 - Homo sapiens cDNA clone IMAGE:3010577, containing frame-shift errors.
AK315313 - Homo sapiens cDNA, FLJ96345, Homo sapiens SET translocation (myeloid leukemia-associated) (SET),mRNA.
BC032749 - Homo sapiens SET nuclear oncogene, mRNA (cDNA clone MGC:45315 IMAGE:5587291), complete cds.
X75091 - H.sapiens mRNA for HLA-DR associated protein II (PHAPII).
EF534308 - Homo sapiens SET mRNA, complete cds.
AM392720 - Synthetic construct Homo sapiens clone IMAGE:100002122 for hypothetical protein (SET gene).
AM392742 - Synthetic construct Homo sapiens clone IMAGE:100002121 for hypothetical protein (SET gene).
AM393175 - Synthetic construct Homo sapiens clone IMAGE:100002126 for hypothetical protein (SET gene).
AM393446 - Synthetic construct Homo sapiens clone IMAGE:100002125 for hypothetical protein (SET gene).
DQ894408 - Synthetic construct Homo sapiens clone IMAGE:100008868; FLH170300.01L; RZPDo839D1297D SET translocation (myeloid leukemia-associated) (SET) gene, encodes complete protein.
EU176263 - Synthetic construct Homo sapiens clone IMAGE:100006375; FLH170307.01X; RZPDo839D10250D SET translocation (myeloid leukemia-associated) (SET) gene, encodes complete protein.
CU689520 - Synthetic construct Homo sapiens gateway clone IMAGE:100016619 5' read SET mRNA.
KJ892125 - Synthetic construct Homo sapiens clone ccsbBroadEn_01519 SET gene, encodes complete protein.
M93651 - Human set gene, complete cds.
CR542050 - Homo sapiens full open reading frame cDNA clone RZPDo834A0736D for gene SET, SET translocation (myeloid leukemia-associated); complete cds, without stopcodon.
AY349172 - Homo sapiens inhibitor-2 of protein phosphatase-2A mRNA, complete cds.
U51924 - Human phosphatase 2A inhibitor I2PP2A mRNA, complete cds.
CR536543 - Homo sapiens full open reading frame cDNA clone RZPDo834H0620D for gene SET, SET translocation (myeloid leukemia-associated); complete cds, incl. stopcodon.
AK300609 - Homo sapiens cDNA FLJ59759 complete cds, highly similar to Protein SET.
AK311346 - Homo sapiens cDNA, FLJ18388.
LF358860 - JP 2014500723-A/166363: Polycomb-Associated Non-Coding RNAs.
MA594437 - JP 2018138019-A/166363: Polycomb-Associated Non-Coding RNAs.
LF358859 - JP 2014500723-A/166362: Polycomb-Associated Non-Coding RNAs.
MA594436 - JP 2018138019-A/166362: Polycomb-Associated Non-Coding RNAs.
JD073747 - Sequence 54771 from Patent EP1572962.
LF358858 - JP 2014500723-A/166361: Polycomb-Associated Non-Coding RNAs.
MA594435 - JP 2018138019-A/166361: Polycomb-Associated Non-Coding RNAs.
JD309052 - Sequence 290076 from Patent EP1572962.
JD267851 - Sequence 248875 from Patent EP1572962.
JD471200 - Sequence 452224 from Patent EP1572962.
JD073880 - Sequence 54904 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  BioCarta from NCI Cancer Genome Anatomy Project
h_setPathway - Granzyme A mediated Apoptosis Pathway

Reactome (by CSHL, EBI, and GO)

Protein Q01105 (Reactome details) participates in the following event(s):

R-HSA-450387 HuR binds the CRM1 nuclear export machinery
R-HSA-2429719 MCPH1 sequesters condensin II
R-HSA-450520 HuR (ELAVL1) binds and stabilizes mRNA
R-HSA-2299718 Condensation of Prophase Chromosomes
R-HSA-450531 Regulation of mRNA stability by proteins that bind AU-rich elements
R-HSA-68875 Mitotic Prophase
R-HSA-8953854 Metabolism of RNA
R-HSA-68886 M Phase
R-HSA-69278 Cell Cycle (Mitotic)
R-HSA-1640170 Cell Cycle

-  Other Names for This Gene
  Alternate Gene Symbols: A5A5H4, ENST00000409104.1, ENST00000409104.2, ENST00000409104.3, ENST00000409104.4, ENST00000409104.5, ENST00000409104.6, NM_001248000, Q01105, Q15541, Q5VXV1, Q6FHZ5, SET_HUMAN, uc022bol.1, uc022bol.2
UCSC ID: ENST00000409104.7
RefSeq Accession: NM_001248000
Protein: Q01105 (aka SET_HUMAN)
CCDS: CCDS59149.1

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.