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Gene Symbol |
SET |
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Aliases |
2PP2A, I2PP2A, IGAAD, IPP2A2, MRD58, PHAPII, TAF-I, TAF-IBETA |
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Entrez Gene ID |
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Gene Name |
SET nuclear proto-oncogene |
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Chromosomal Location |
9q34.11 |
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HGNC ID |
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Summary |
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]
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RefSeq DNA |
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RefSeq mRNA |
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e!Ensembl
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Gene Ontology (GO)
| GO ID |
Ontology |
Function |
Evidence |
Reference |
| GO:0006260 |
Biological process |
DNA replication |
TAS |
7753797 |
| GO:0006337 |
Biological process |
Nucleosome disassembly |
TAS |
11555662 |
| GO:0035067 |
Biological process |
Negative regulation of histone acetylation |
TAS |
11555662 |
| GO:0043524 |
Biological process |
Negative regulation of neuron apoptotic process |
IGI |
18374643 |
| GO:0045892 |
Biological process |
Negative regulation of transcription, DNA-templated |
IDA |
19343227 |
| GO:0005634 |
Cellular component |
Nucleus |
HDA |
16791210 |
| GO:0005634 |
Cellular component |
Nucleus |
IDA |
11555662 |
| GO:0005634 |
Cellular component |
Nucleus |
TAS |
18374643 |
| GO:0005737 |
Cellular component |
Cytoplasm |
IDA |
11909973, 12524539 |
| GO:0005783 |
Cellular component |
Endoplasmic reticulum |
IDA |
11555662, 12524539 |
| GO:0032991 |
Cellular component |
Protein-containing complex |
IDA |
11909973 |
| GO:0048471 |
Cellular component |
Perinuclear region of cytoplasm |
IDA |
11555662, 12524539 |
| GO:0004864 |
Molecular function |
Protein phosphatase inhibitor activity |
TAS |
8626647 |
| GO:0005515 |
Molecular function |
Protein binding |
IPI |
11909973, 16189514, 17245428, 17318177, 19343227, 20195357, 21988832, 23195690, 24983498, 25416956 |
| GO:0019888 |
Molecular function |
Protein phosphatase regulator activity |
TAS |
11555662 |
| GO:0042393 |
Molecular function |
Histone binding |
TAS |
11555662 |
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| Protein Information |
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Protein Name |
Protein SET, HLA-DR-associated protein II, SET nuclear oncogene, SET translocation (myeloid leukemia-associated), Template-Activating Factor-I, chromatin remodelling factor, chromatin remodelling factor, inhibitor of granzyme A-activated DNase, inhibitor-2 of protein phosphatase-2A, phosphatase 2A inhibitor I2PP2A, protein phosphatase type 2A inhibitor |
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Function |
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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. |
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UniProt |
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PDB |
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Interactions |
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| STRING |
MINT |
IntAct |
| ENSP00000264634 |
P41221 |
P41221 |
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View interactions
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Associated Diseases
| Disease group | Disease Name | References |
| Endocrine System Diseases |
| PCOS |
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| Neoplasms |
| Medulloblastoma |
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References |
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| Jiang Shi-Wen, Xu Siliang, Chen Haibin, Liu Xiaoqiang, Tang Zuoqing, Cui Yugui, Liu Jiayin |
| Department of Obstetrics and Gynecology, The Second Affiliated Hospital, Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, China; Department of Biomedical Science, Mercer University School of Medicine, Savannah, GA, USA. Electronic address: jiang_s@mercer.edu.| Department of Biomedical Science, Mercer University School of Medicine, Savannah, GA, USA; The State Key Laboratory of Reproductive Medicine, Clinical Center of Reproductive Medicine, First Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu 210029, China.| Department of Histology and Embryology, Shantou University Medical College, Shantou, Guangdong 515000, China.| The Third People's Hospital of Qingdao, Department of Obstetrics and Gynecology, Qingdao, Shandong 266041, China; Department of Medical Genetics and Developmental Biology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China.| Department of Medical Genetics, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China.| The State Key Laboratory of Reproductive Medicine, Clinical Center of Reproductive Medicine, First Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu 210029, China.| The State Key Laboratory of Reproductive Medicine, Clinical Center of Reproductive Medicine, First Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu 210029, China. Electronic address: jyliu_nj@126.com. |
| Clin Chim Acta. 2017 Jan;464:155-159. doi: 10.1016/j.cca.2016.11.010. Epub 2016 |
Abstract
SET (SE translocation, SET), a constitutive inhibitor of protein phosphatase 2A (PP2A), is a multifunctional oncoprotein involved in DNA replication, histone modification, nucleosome assembly, gene transcription and cell proliferation. It is widely expressed in human tissues including the gonadal system and brain. Intensive studies have shown that overexpressed SET plays an important role in the development of Alzheimer's disease (AD), and may also contribute to the malignant transformation of breast and ovarian cancers. Recent studies indicated that through interaction with PP2A, SET may upregulate androgen biosynthesis and contribute to hyperandrogenism in polycystic ovary syndrome (PCOS) patients. This review article summarizes data concerning the SET expression in ovaries from PCOS and normal women, and analyzes the role/regulatory mechanism of SET for androgen biosynthesis in PCOS, as well as the significance of this action in the development of PCOS. The potential value of SET-triggered pathway as a therapeutic target and the application of anti-SET reagents for treating hyperandrogenism in PCOS patients are also discussed. |
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