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Information on EC 1.5.8.3 - sarcosine dehydrogenase and Organism(s) Homo sapiens

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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).
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Homo sapiens
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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, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
monomethylglycine dehydrogenase
-
-
-
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sarcosine N-demethylase
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-
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sarcosine:(acceptor) oxidoreductase (demethylating)
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-
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sarcosine:electron-transfer flavoprotein oxidoreductase (demethylating)
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-
-
-
SARDH
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
oxidation
-
-
-
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oxidative demethylation
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-
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redox reaction
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-
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reduction
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PATHWAY SOURCE
PATHWAYS
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-, -, -
SYSTEMATIC NAME
IUBMB Comments
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).
CAS REGISTRY NUMBER
COMMENTARY hide
37228-65-2
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SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
sarcosine + acceptor + H2O
glycine + formaldehyde + reduced acceptor
show the reaction diagram
-
acceptors: 2,6-dichlorophenolindophenol, phenazine methosulfate
-
?
sarcosine + H2O + electron-transfer flavoprotein
glycine + formaldehyde + reduced electron-transfer flavoprotein
show the reaction diagram
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-
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
sarcosine + acceptor + H2O
glycine + formaldehyde + reduced acceptor
show the reaction diagram
-
acceptors: 2,6-dichlorophenolindophenol, phenazine methosulfate
-
?
sarcosine + H2O + electron-transfer flavoprotein
glycine + formaldehyde + reduced electron-transfer flavoprotein
show the reaction diagram
-
-
-
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
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
tetrahydrofolate
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-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
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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ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
renal carcinoma cell
Manually annotated by BRENDA team
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adult and fetal
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
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
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION?
SARDH_HUMAN
918
0
101037
Swiss-Prot
Mitochondrion (Reliability: 1)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
99505
-
1 * 99505
99510
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including covalently bound FAD
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
monomer
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1 * 99505
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expression of Myc- and His-tagged enzyme in HEK-293T cells, co-exxpression with TMEFF2, phenotype, overview
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EXPRESSION
ORGANISM
UNIPROT
LITERATURE
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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APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
medicine
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Eschenbrenner, M.; Schuman Jorns, M.
Cloning and mapping of the cDNA for human sarcosine dehydrogenase, a flavoenzyme defective in patients with sarcosinemia
Genomics
59
300-308
1999
Homo sapiens
Manually annotated by BRENDA team
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
Manually annotated by BRENDA team
Kim, H.; Lee, Y.; Koo, J.
Expression of sarcosine-metabolizing enzymes in thyroid cancer
Int. J. Clin. Exp. Pathol.
9
7132-7139
2016
Homo sapiens
-
Manually annotated by BRENDA team
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
11
e0165830
2016
Homo sapiens
Manually annotated by BRENDA team
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
73
1561-1575
2013
Homo sapiens
Manually annotated by BRENDA team
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
Manually annotated by BRENDA team