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EC Tree
IUBMB Comments A flavoprotein (FMN) found in eukaryotes. In the absence of tetrahydrofolate the enzyme produces formaldehyde. cf. EC 1.5.3.1, sarcosine oxidase (formaldehyde-forming), and EC 1.5.3.24, sarcosine oxidase (5,10-methylenetetrahydrofolate-forming).
The taxonomic range for the selected organisms is: Homo sapiens The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
Synonyms
sarcosine dehydrogenase, sardh,
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monomethylglycine dehydrogenase
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sarcosine N-demethylase
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sarcosine:(acceptor) oxidoreductase (demethylating)
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sarcosine:electron-transfer flavoprotein oxidoreductase (demethylating)
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SARDH
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oxidative demethylation
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sarcosine, 5,6,7,8-tetrahydrofolate:electron-transferflavoprotein oxidoreductase (demethylating,5,10-methylenetetrahydrofolate-forming)
A flavoprotein (FMN) found in eukaryotes. In the absence of tetrahydrofolate the enzyme produces formaldehyde. cf. EC 1.5.3.1, sarcosine oxidase (formaldehyde-forming), and EC 1.5.3.24, sarcosine oxidase (5,10-methylenetetrahydrofolate-forming).
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sarcosine + acceptor + H2O
glycine + formaldehyde + reduced acceptor
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acceptors: 2,6-dichlorophenolindophenol, phenazine methosulfate
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sarcosine + H2O + electron-transfer flavoprotein
glycine + formaldehyde + reduced electron-transfer flavoprotein
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sarcosine + acceptor + H2O
glycine + formaldehyde + reduced acceptor
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acceptors: 2,6-dichlorophenolindophenol, phenazine methosulfate
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sarcosine + H2O + electron-transfer flavoprotein
glycine + formaldehyde + reduced electron-transfer flavoprotein
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electron transferring flavoprotein
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FAD
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covalent bound FAD linked via 8a-position of the isoalloxazin ring to the imidazole N(3) of a histidine residue, structural homology between the amino acid sequence of the flavin-peptides
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TMEFF2
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i.e. full-length follistatin motifs 2, the enzyme interacts with the full-length follistatin motifs 2, TMEFF2. TMEFF2 has a dual mode of action. The ectodomain does not bind to SARDH. Ectopic expression of wild-type full-length TMEFF2 inhibits soft agar colony formation, cellular invasion, and migration and increases cellular sensitivity to apoptosis. Expression of the full-length TMEFF2 but not the ectodomain results in a decreased level of sarcosine in the cells
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Brain Neoplasms
Expression of sarcosine metabolism-related proteins according to metastatic site in breast cancer.
Breast Neoplasms
Expression of sarcosine metabolism-related proteins according to metastatic site in breast cancer.
Breast Neoplasms
Implications of differences in expression of sarcosine metabolism-related proteins according to the molecular subtype of breast cancer.
Carcinoma
DNA methylation of sarcosine dehydrogenase (SARDH) loci as a prognosticator for renal cell carcinoma.
Carcinoma, Renal Cell
DNA methylation of sarcosine dehydrogenase (SARDH) loci as a prognosticator for renal cell carcinoma.
Cardiomyopathy, Dilated
Anti-mitochondrial antibodies in patients with dilated cardiomyopathy (anti-M7) are directed against flavoenzymes with covalently bound FAD.
Colorectal Neoplasms
Alteration of the tumour suppressor SARDH in sporadic colorectal cancer: a functional and transcriptome profiling-based study.
Heart Diseases
Anti-mitochondrial antibodies (anti-M7) in heart diseases recognize epitopes on bacterial and mammalian sarcosine dehydrogenase.
Liver Neoplasms
Alteration of the tumour suppressor SARDH in sporadic colorectal cancer: a functional and transcriptome profiling-based study.
Lung Neoplasms
Alteration of the tumour suppressor SARDH in sporadic colorectal cancer: a functional and transcriptome profiling-based study.
Myocarditis
Anti-mitochondrial antibodies in patients with dilated cardiomyopathy (anti-M7) are directed against flavoenzymes with covalently bound FAD.
Neoplasm Metastasis
DNA methylation of sarcosine dehydrogenase (SARDH) loci as a prognosticator for renal cell carcinoma.
Neoplasm Metastasis
Expression of sarcosine metabolism-related proteins according to metastatic site in breast cancer.
Neoplasms
Alteration of the tumour suppressor SARDH in sporadic colorectal cancer: a functional and transcriptome profiling-based study.
Neoplasms
DNA methylation of sarcosine dehydrogenase (SARDH) loci as a prognosticator for renal cell carcinoma.
Neoplasms
Sarcosine Up-Regulates Expression of Genes Involved in Cell Cycle Progression of Metastatic Models of Prostate Cancer.
Neoplasms
The role of sarcosine metabolism in prostate cancer progression.
Neoplasms
The tumor suppressor activity of the transmembrane protein with epidermal growth factor and two follistatin motifs 2 (TMEFF2) correlates with its ability to modulate sarcosine levels.
Neoplasms
TMEFF2 and SARDH cooperate to modulate one-carbon metabolism and invasion of prostate cancer cells.
Pancreatic Neoplasms
Alteration of the tumour suppressor SARDH in sporadic colorectal cancer: a functional and transcriptome profiling-based study.
Prostatic Neoplasms
TMEFF2 and SARDH cooperate to modulate one-carbon metabolism and invasion of prostate cancer cells.
Respiratory Insufficiency
A young adult with sarcosinemia. No benefit from long duration treatment with memantine.
sarcosine dehydrogenase deficiency
Sarcosine dehydrogenase deficiency, the enzyme defect in hypersarcosinemia.
sarcosine dehydrogenase deficiency
[Sarcosine dehydrogenase deficiency]
Spinal Dysraphism
An association study of 45 folate-related genes in spina bifida: Involvement of cubilin (CUBN) and tRNA aspartic acid methyltransferase 1 (TRDMT1).
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UniProt
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renal carcinoma cell
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adult and fetal
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adult and fetal
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malfunction
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reducing the expression of the enzyme promotes localization of TMEFF2 to the cytoskeleton and also results in increased cellular invasion in tumorigenesis
metabolism
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TMEFF2 interacts with SARDH and regulates the cellular levels of sarcosine. The tumor suppressor activity of TMEFF2 requires the cytoplasmic/transmembrane portion of the protein and correlates with its ability to bind to SARDH and to modulate the level of sarcosine
additional information
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the enzyme interacts with the full-length follistatin motifs 2, TMEFF2. TMEFF2 has a dual mode of action. The ectodomain does not bind to SARDH. Ectopic expression of wild-type full-length TMEFF2 inhibits soft agar colony formation, cellular invasion, and migration and increases cellular sensitivity to apoptosis. Expression of the full-length TMEFF2 but not the ectodomain results in a decreased level of sarcosine in the cells
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SARDH_HUMAN
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101037
Swiss-Prot
Mitochondrion (Reliability: 1 )
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99510
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including covalently bound FAD
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expression of Myc- and His-tagged enzyme in HEK-293T cells, co-exxpression with TMEFF2, phenotype, overview
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overexpression of TMEFF2 activates the enzyme activity but does not affect its expression level
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sarcosine treatment results in significant increase in enzyme concentration
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medicine
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sarcosine dehydrogenase is defective in patient with sarcosinemia
medicine
kidney tumors with clinically aggressive features such as a high tumor stage, positive lymph nodes, distant metastases or a previously advanced tumor status exhibit significantly lower methylation of a locus in the SARDH gene. SARDH gene methylation is a significant prognostic factor for recurrence-free survival in renal cell carcinoma patients showing statistical independence from the clinical prognosticators, grade, stage and state of metastasis
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Eschenbrenner, M.; Schuman Jorns, M.
Cloning and mapping of the cDNA for human sarcosine dehydrogenase, a flavoenzyme defective in patients with sarcosinemia
Genomics
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300-308
1999
Homo sapiens
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Chen, X.; Overcash, R.; Green, T.; Hoffman, D.; Asch, A.S.; Ruiz-Echevarria, M.J.
The tumor suppressor activity of the transmembrane protein with epidermal growth factor and two follistatin motifs 2 (TMEFF2) correlates with its ability to modulate sarcosine levels
J. Biol. Chem.
286
16091-16100
2011
Homo sapiens
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Kim, H.; Lee, Y.; Koo, J.
Expression of sarcosine-metabolizing enzymes in thyroid cancer
Int. J. Clin. Exp. Pathol.
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7132-7139
2016
Homo sapiens
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Heger, Z.; Merlos Rodrigo, M.A.; Michalek, P.; Polanska, H.; Masarik, M.; Vit, V.; Plevova, M.; Pacik, D.; Eckschlager, T.; Stiborova, M.; Adam, V.
Sarcosine up-regulates expression of genes involved in cell cycle progression of metastatic models of prostate cancer
PLoS ONE
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e0165830
2016
Homo sapiens
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Green, T.; Chen, X.; Ryan, S.; Asch, A.S.; Ruiz-Echevarria, M.J.
TMEFF2 and SARDH cooperate to modulate one-carbon metabolism and invasion of prostate cancer cells
Prostate
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1561-1575
2013
Homo sapiens
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Mazdak, M.; Tezval, H.; Callauch, J.C.; Dubrowinskaja, N.; Peters, I.; Bokemeyer, C.; Hennenlotter, J.; Stenzl, A.; Kuczyk, M.A.; Serth, J.
DNA methylation of sarcosine dehydrogenase (SARDH) loci as a prognosticator for renal cell carcinoma
Oncol. Rep.
42
2159-2168
2019
Homo sapiens (Q9UL12), Homo sapiens
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