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Serine hydroxymethyltransferase 2

GlyA, SHMT2
This gene encodes the mitochondrial form of a pyridoxal phosphate-dependent enzyme that catalyzes the reversible reaction of serine and tetrahydrofolate to glycine and 5,10-methylene tetrahydrofolate. The encoded product is primarily responsible for glycine synthesis. The activity of the encoded protein has been suggested to be the primary source of intracellular glycine. The gene which encodes the cytosolic form of this enzyme is located on chromosome 17. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2009] (from NCBI)
Top mentioned proteins: Glycine Hydroxymethyltransferase, CAN, ACID, CD34, HAD
Papers on GlyA
A pyrazolopyran derivative preferentially inhibits the activity of human cytosolic hydroxymethyltransferase and induces cell death in lung cancer cells.
New
Cutruzzolà et al., Roma, Italy. In Oncotarget, Jan 2016
UNASSIGNED: Serine hydroxymethyltransferase (SHMT) is a central enzyme in the metabolic reprogramming of cancer cells, providing activated one-carbon units in the serine-glycine one-carbon metabolism.
miR-615-5p prevents proliferation and migration through negatively regulating serine hydromethyltransferase 2 (SHMT2) in hepatocellular carcinoma.
New
Liang et al., Nanjing, China. In Tumour Biol, Jan 2016
Here, in our present study, to investigate the mechanism of miR-615-5p, bioinformatic prediction and luciferase reporter assay were employed to ascertain the downstream target of miR-615-5p finding that the serine hydromethyltransferase 2 (SHMT2) was the direct downstream target.
NRF2 regulates serine biosynthesis in non-small cell lung cancer.
New
Impact
Cantley et al., New York City, United States. In Nat Genet, Dec 2015
We found that NRF2 controls the expression of the key serine/glycine biosynthesis enzyme genes PHGDH, PSAT1 and SHMT2 via ATF4 to support glutathione and nucleotide production.
Higher-Order Assembly of BRCC36-KIAA0157 Is Required for DUB Activity and Biological Function.
New
Sicheri et al., Toronto, Canada. In Mol Cell, Oct 2015
Higher-order association of BRCC36 and KIAA0157 into a dimer of heterodimers (super dimers) was required for DUB activity and interaction with targeting proteins SHMT2 and RAP80.
SHMT2 drives glioma cell survival in ischaemia but imposes a dependence on glycine clearance.
New
Impact
Sabatini et al., Cambridge, United States. In Nature, May 2015
In human glioblastoma multiforme, mitochondrial serine hydroxymethyltransferase (SHMT2) and glycine decarboxylase (GLDC) are highly expressed in the pseudopalisading cells that surround necrotic foci.
How pyridoxal 5'-phosphate differentially regulates human cytosolic and mitochondrial serine hydroxymethyltransferase oligomeric state.
New
Cutruzzolà et al., Roma, Italy. In Febs J, Apr 2015
Given its central role in serine metabolism, serine hydroxymethyltransferase (SHMT), a pyridoxal 5'-phosphate (PLP)-dependent enzyme, is an attractive target for tumour chemotherapy.
Involvement of the strychnine-sensitive glycine receptor in the anxiolytic effects of GlyT1 inhibitors on maternal separation-induced ultrasonic vocalization in rat pups.
New
Asada et al., Tsukuba, Japan. In Eur J Pharmacol, Feb 2015
There are two types of glycine receptor: the strychnine-sensitive glycine receptor (GlyA) and the strychnine-insensitive glycine receptor (GlyB); however, which receptor is the main contributor to the anxiolytic actions of GlyT1 inhibitors is yet to be determined.
The differentiation of human multipotent adult progenitor cells into hepatocyte-like cells induced by coculture with human hepatocyte line L02.
Hu et al., Fuzhou, China. In Ann Surg Treat Res, 2015
METHODS: hMAPCs were isolated by magnetic activated cell sorting (MACS) depletion selection using CD45 and GlyA microbeads.
2-Aminoacrylate Stress Induces a Context-Dependent Glycine Requirement in ridA Strains of Salmonella enterica.
Downs et al., Athens, United States. In J Bacteriol, 2014
Previous work showed that 2AA accumulation in ridA strains of Salmonella enterica led to the inactivation of multiple target enzymes, including serine hydroxymethyltransferase (GlyA).
Epigenetic regulation of the nuclear-coded GCAT and SHMT2 genes confers human age-associated mitochondrial respiration defects.
Hayashi et al., Tsukuba, Japan. In Sci Rep, 2014
Age-associated accumulation of somatic mutations in mitochondrial DNA (mtDNA) has been proposed to be responsible for the age-associated mitochondrial respiration defects found in elderly human subjects.
Autism and Intellectual Disability-Associated KIRREL3 Interacts with Neuronal Proteins MAP1B and MYO16 with Potential Roles in Neurodevelopment.
Srivastava et al., Greenwood, United States. In Plos One, 2014
Using a yeast two-hybrid screen, we found that the KIRREL3 extracellular domain interacts with brain expressed proteins MAP1B and MYO16 and its intracellular domain can potentially interact with ATP1B1, UFC1, and SHMT2.
Positive correlation between expression level of mitochondrial serine hydroxymethyltransferase and breast cancer grade.
Yin, Ningbo, China. In Onco Targets Ther, 2014
Although the mitochondrial isoform of SHMT (SHMT2) has been proven to be a crucial factor in the serine/glycine metabolism in several cancer cell types, the expression pattern of SHMT2 and the correlation of expression level of SHMT2 and other clinicopathological parameters in clinical breast cancer remain to be explored.
Bioinformatics analysis of the serine and glycine pathway in cancer cells.
Amelio et al., Roma, Italy. In Oncotarget, 2014
Employing 3 subsequent enzymes, phosphoglycerate dehydrogenase (PHGDH), phosphoserine phosphatase (PSPH), phosphoserine aminotransferase 1 (PSAT1), 3-phosphoglycerate from glycolysis can be converted in serine, which in turn can by converted in glycine by serine methyl transferase (SHMT).
SHMT1 knockdown induces apoptosis in lung cancer cells by causing uracil misincorporation.
Cutruzzolà et al., Roma, Italy. In Cell Death Dis, 2013
While the mitochondrial isoform of SHMT (SHMT2) has recently been identified as an important player in the control of cell proliferation in several cancer types and as a hot target for anticancer therapies, the role of the cytoplasmic isoform (SHMT1) in cancerogenesis is currently less defined.
Serine hydroxymethyltransferase 1 and 2: gene sequence variation and functional genomic characterization.
GeneRIF
Weinshilboum et al., Rochester, United States. In J Neurochem, 2012
The present study not only describes individual genetic variation that directly affects SHMT1 and SHMT2 activity, but provided insight into the overall regulation of the Folate and Methionine Cycles.
Vitamin B6 deficiency, genome instability and cancer.
Review
Lu et al., Kunming, China. In Asian Pac J Cancer Prev, 2011
It comprises a group of three related 3-hydroxy-2-methyl-pyrimidine derivatives: pyridoxine (PN), pyridoxal (PL), pyridoxamine (PM) and their phosphorylated derivatives [pyridoxal 5'-phosphate (PLP) and pyridoxamine 5'-phosphate (PMP)], In the folate metabolism pathway, PLP is a cofactor for the mitochondrial and cytoplasmic isozymes of serine hydroxymethyltransferase (SHMT2 and SHMT1), the P-protein of the glycine cleavage system, cystathionine β-synthase (CBS) and γ-cystathionase, and betaine hydroxymethyltransferase (BHMT), all of which contribute to homocysteine metabolism either through folate- mediated one-carbon metabolism or the transsulfuration pathway.
SHMT1 and SHMT2 are functionally redundant in nuclear de novo thymidylate biosynthesis.
GeneRIF
Stover et al., Ithaca, United States. In Plos One, 2008
SHMT1 and SHMT2 are functionally redundant in nuclear de novo thymidylate biosynthesis
Molecular cloning, characterization and alternative splicing of the human cytoplasmic serine hydroxymethyltransferase gene.
GeneRIF
Stover et al., Ithaca, United States. In Gene, 1998
This paper compares the mitochondrial and cytoplasmic forms of this enzyme and suggests that the two genes are a result of a single gene duplication.
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