Property Summary

NCBI Gene PubMed Count 29
PubMed Score 115.12
PubTator Score 32.73

Knowledge Summary

Patent

No data available

TINX Plot

  Disease (3)

Disease Target Count P-value
osteosarcoma 7933 6.5e-04
gastric carcinoma 832 1.1e-02
Disease Target Count Z-score Confidence
Cancer 2346 3.31 1.7
Disease Target Count Z-score Confidence
diabetes mellitus 1663 3.453 1.7
Obesity 616 3.054 1.5
Metabolic syndrome X 155 3.051 1.5

Expression

  Differential Expression (2)

Disease log2 FC p
osteosarcoma -1.070 6.5e-04
gastric carcinoma -1.200 1.1e-02

Protein-protein Interaction (2)

Gene RIF (17)

PMID Text
26775843 Thus, these results suggest that SIRT4 has essential roles in stress resistance and may be an important therapeutic target for cancer treatment.
26086877 SIRT4 has a tumour-suppressive function and may serve as a novel therapeutic target in colorectal cancer.
26054687 SIRT4 behaves as a tumor suppressor at the human tissue protein level.
25633289 C-terminal-binding protein (CtBP) was found to have an essential role in promoting glutaminolysis by directly repressing the expression of SIRT4.
25525879 Until now, a mammalian cellular lipoamidase has not been characterized; this study discovered that SIRT4 can function with this enzymatic capacity in the mitochondria, and that PDH is a biological substrate; compared to its catalytic efficiency for deacetylation, SIRT4 exhibits far superior enzymatic activity for lipoyl- and biotinyl-lysine modifications.
25466907 Serum Sirt4 was inversely related to anthropometric and metabolic parameters and positively related to peak GH and IGF-1.
25361925 This study demonstrated that SIRT4 upregulation in the liver of non-alcoholic fatty liver disease patients.
25331589 Overexpression of SIRT4 attenuated inflammation mediators in umbilical vein endothelial cells.
25165814 Results show that mitochondrial sirtuins SIRT3, SIRT4, and SIRT5 can promote increased mitochondrial respiration and cellular metabolism and respond to excess glucose by inducing a coordinated increase of glycolysis and respiration.
25045415 The present study shows low circulating levels of SIRT4 in obese patients with nonalcoholic fatty liver disease.
24368766 these results highlight the tumor-suppressive role of SIRT4 in Myc-induced B cell lymphoma and suggest that SIRT4 may be a potential target against Myc-induced and/or glutamine-dependent cancers.
24296486 regulates ATP levels via ANT2 and a feedback loop involving AMPK
23663782 Study shows that mTORC1 promotes glutamine anaplerosis by activating glutamate dehydrogenase (GDH). This regulation requires transcriptional repression of SIRT4, the mitochondrial-localized sirtuin that inhibits GDH. Mechanistically, mTORC1 represses SIRT4 by promoting the proteasome-mediated destabilization of cAMP-responsive element binding 2.
23044393 Sirt-4 modulates sensitivity to mitochondrial permeability transition pore (PTP) onset induced by calcium and the oxidative cross linking reagent phenylarsine oxide, and PTP dependent cytotoxicity brought about by TNF or doxorubicin.
21556116 there is a negative correlation between SIRTs 1 and 4 and fasting plasma glucose, a positive correlation between SIRT4 mRNA levels and triglyceride/lipoprotein a levels, and a negative correlation between SIRT4 mRNA levels and HDL
19209188 Meta-analysis of gene-disease association. (HuGE Navigator)
17715127 mitochondrial SIRT4 has a role in the regulation of insulin secretion

AA Sequence

MKMSFALTFRSAKGRWIANPSQPCSKASIGLFVPASPPLDPEKVKELQRFITLSKRLLVMTGAGISTESG      1 - 70
IPDYRSEKVGLYARTDRRPIQHGDFVRSAPIRQRYWARNFVGWPQFSSHQPNPAHWALSTWEKLGKLYWL     71 - 140
VTQNVDALHTKAGSRRLTELHGCMDRVLCLDCGEQTPRGVLQERFQVLNPTWSAEAHGLAPDGDVFLSEE    141 - 210
QVRSFQVPTCVQCGGHLKPDVVFFGDTVNPDKVDFVHKRVKEADSLLVVGSSLQVYSGYRFILTAWEKKL    211 - 280
PIAILNIGPTRSDDLACLKLNSRCGELLPLIDPC                                        281 - 314
//

Text Mined References (30)

PMID Year Title
26775843 2016 SIRT4 regulates cancer cell survival and growth after stress.
26086877 2015 Tumour-suppressive function of SIRT4 in human colorectal cancer.
26054687 2015 Sirtuin-4 (SIRT4) is downregulated and associated with some clinicopathological features in gastric adenocarcinoma.
25633289 2015 CtBP maintains cancer cell growth and metabolic homeostasis via regulating SIRT4.
25525879 2014 Sirtuin 4 is a lipoamidase regulating pyruvate dehydrogenase complex activity.
25466907 2015 Preliminary data on the relationship between circulating levels of Sirtuin 4, anthropometric and metabolic parameters in obese subjects according to growth hormone/insulin-like growth factor-1 status.
25361925 2014 Direct evidence of sirtuin downregulation in the liver of non-alcoholic fatty liver disease patients.
25331589 2015 SIRT4 Suppresses Inflammatory Responses in Human Umbilical Vein Endothelial Cells.
25165814 2014 Overexpression of mitochondrial sirtuins alters glycolysis and mitochondrial function in HEK293 cells.
25045415 2014 Circulating levels of sirtuin 4, a potential marker of oxidative metabolism, related to coronary artery disease in obese patients suffering from NAFLD, with normal or slightly increased liver enzymes.
24368766 2014 SIRT4 protein suppresses tumor formation in genetic models of Myc-induced B cell lymphoma.
24296486 2013 SIRT4 regulates ATP homeostasis and mediates a retrograde signaling via AMPK.
24043310 2013 SIRT4 represses peroxisome proliferator-activated receptor ? activity to suppress hepatic fat oxidation.
23663782 2013 The mTORC1 pathway stimulates glutamine metabolism and cell proliferation by repressing SIRT4.
23562301 2013 SIRT4 has tumor-suppressive activity and regulates the cellular metabolic response to DNA damage by inhibiting mitochondrial glutamine metabolism.
23044393 2013 Sirtuin-4 modulates sensitivity to induction of the mitochondrial permeability transition pore.
21556116 2011 The expression of Sirtuins 1 and 4 in peripheral blood leukocytes from patients with type 2 diabetes.
19209188 2009 Genetic association analysis of 13 nuclear-encoded mitochondrial candidate genes with type II diabetes mellitus: the DAMAGE study.
17715127 2007 Regulation of insulin secretion by SIRT4, a mitochondrial ADP-ribosyltransferase.
17456799 2007 Sirtuin functions in health and disease.
16959573 2006 SIRT4 inhibits glutamate dehydrogenase and opposes the effects of calorie restriction in pancreatic beta cells.
16541075 2006 The finished DNA sequence of human chromosome 12.
16079181 2005 Evolutionarily conserved and nonconserved cellular localizations and functions of human SIRT proteins.
15489334 2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
15342556 2004 Sequence comparison of human and mouse genes reveals a homologous block structure in the promoter regions.
15122253 2004 Hot-spot residue in small heat-shock protein 22 causes distal motor neuropathy.
12477932 2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.
10873683 2000 Phylogenetic classification of prokaryotic and eukaryotic Sir2-like proteins.
10381378 1999 Characterization of five human cDNAs with homology to the yeast SIR2 gene: Sir2-like proteins (sirtuins) metabolize NAD and may have protein ADP-ribosyltransferase activity.
9847074 1998 Toward a complete human genome sequence.