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Information on EC 2.1.1.17 - phosphatidylethanolamine N-methyltransferase and Organism(s) Mus musculus and UniProt Accession Q61907
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EC Tree
2.1.1.17 phosphatidylethanolamine N-methyltransferaseSpecify your search results
Word Map
- 2.1.1.17
- phosphatidylcholine
- choline
- homocysteine
- cytidylyltransferase
- cdp-choline
- betaine
- s-adenosylhomocysteine
-
ctp:phosphocholine
- cdp-diacylglycerol
- phosphatidyl-n,n-dimethylethanolamine
- phosphatidyl-n-monomethylethanolamine
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choline-deficient
-
transmethylation
- n-methyltransferases
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kennedy
- adomet
-
vance
- phosphatidylmonomethylethanolamine
- medicine
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ptdcho
- analysis
- phosphatidyldimethylethanolamine
- mthfd1
-
remethylation
-
cholinephosphotransferase
-
adohcy
-
choline-supplemented
The taxonomic range for the selected organisms is: Mus musculus
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria, Archaea
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria, Archaea
Reaction Schemes
Synonyms
pemt, phosphatidylethanolamine n-methyltransferase, phosphatidylethanolamine methyltransferase, phospholipid n-methyltransferase, phosphatidylethanolamine-n-methyltransferase, pe n-mtase, pmtx1, pe-nmt, pmtx3, s-adenosyl-l-methionine:phosphatidylethanolamine n-methyltransferase, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
lipid methyl transferase
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LMTase
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methyltransferase, phosphatidylethanolamine
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PE N-MTase
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PEMT
phosphatidylethanolamine methyltransferase
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phosphatidylethanolamine-N-methylase
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phosphatidylethanolamine-S-adenosylmethionine methyltransferase
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PEMT
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
methyl group transfer
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PATHWAY SOURCE
PATHWAYS
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SYSTEMATIC NAME
IUBMB Comments
S-adenosyl-L-methionine:phosphatidylethanolamine N-methyltransferase
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CAS REGISTRY NUMBER
COMMENTARY
37256-91-0
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
2 S-adenosyl-L-methionine + phosphatidyl-N-methylethanolamine
2 S-adenosyl-L-homocysteine + phosphatidylcholine
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the transfer of a methyl group to phosphatidyl-N-methylethanolamine and phosphatidyl-N,N-dimethylethanolamine is catalyzed by a second enzyme
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-
?
S-adenosyl-L-methionine + phosphatidyl-N-methylethanolamine
S-adenosyl-L-homocysteine + phosphatidyl-N,N-dimethylethanolamine
S-adenosyl-L-methionine + phosphatidylethanolamine
S-adenosyl-L-homocysteine + phosphatidyl-N-methylethanolamine
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the transfer of a methyl group to monomethyl-N-phosphatidylcholine and dimethyl-N,N-phosphatidylcholine is catalyzed by a second enzyme
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-
?
S-adenosyl-L-methionine + phosphatidyl-N-methylethanolamine
S-adenosyl-L-homocysteine + phosphatidyl-N,N-dimethylethanolamine
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-
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?
S-adenosyl-L-methionine + phosphatidyl-N-methylethanolamine
S-adenosyl-L-homocysteine + phosphatidyl-N,N-dimethylethanolamine
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the transfer of a methyl group to phosphatidyl-N-methylethanolamine and phosphatidyl-N,N-dimethylethanolamine is catalyzed by a second enzyme
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?
additional information
?
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enzyme-mediated secretion of homocysteine correlates with the methyltransferase activity of the enzyme, independently of subcellular localization
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?
additional information
?
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phosphatidylethanolamine N-methyltransferase is the key enzyme for endogenous biosynthesis of phosphatidylcholine.
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?
additional information
?
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a striking gender-specific conservation of choline in female mice does not occur in male mice
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?
additional information
?
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physiological functions of phosphatidylcholine, mutational analysis, overview
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?
additional information
additional information
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Mdr2 (+/-) and Mdr2 (+/+) mice have similar S-adenosylmethionine levels at 0 and 7 days on methionine and choline deficient diet, Mdr2 (+/-) mice have significantly higher S-adenosylmethionine levels after 30 days on methionine and choline deficient diet (40.2 vs. 6.1 nmol/g).
S-adenosylhomocysteine levels are significantly lower in Mdr2 (+/-) compared to Mdr2 (+/+) mice at 0 days (33.4 vs. 41.9 nmol/g) and 7 days on methionine and choline deficient diet (16.0 vs. 42.9 nmol/g).
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?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
additional information
?
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enzyme-mediated secretion of homocysteine correlates with the methyltransferase activity of the enzyme, independently of subcellular localization
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-
?
additional information
?
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phosphatidylethanolamine N-methyltransferase is the key enzyme for endogenous biosynthesis of phosphatidylcholine.
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?
additional information
?
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a striking gender-specific conservation of choline in female mice does not occur in male mice
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?
additional information
?
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physiological functions of phosphatidylcholine, mutational analysis, overview
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?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
17-beta-estradiol induces the enzyme in hepatocytes
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
-
phosphatidylethanolamine N-methyltransferase activity is significantly lower in Mdr2 (+/-) compared to Mdr2 (+/+) mice: 1.20 nmol/mg/min vs. 1.98 nmol/mg/min. After 7 days on methionine and choline deficient diet enzyme activity is: Mdr2 (+/-) = 1.31 nmol/mg/min vs. Mdr2 (+/+) = 1.96 nmol/mg/min. After 30 days on methionine and choline deficient diet enzyme activity is: Mdr2 (+/-) = 1.60 nmol/mg/min vs. Mdr2 (+/+) = 1.99 nmol/mg/min
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
physiological function
malfunction
physiological function
a transgenic HO mouse model of classical homocystinuria exhibits only mild liver injury. Hepatic expression of PEMT in both the cystathionine beta-synthase-/- and HO models is post-translationally repressed with decreased levels of PEMT protein and activity that inversely correlates with the scale of liver injury. PEMT in HO mice is not further induced by increased homocysteine, methionine and S-adenosylhomocysteine or depletion of glutathione
physiological function
In chow-fed Pemt-/- mice, the hepatic phosphatidylcholine/phosphatidylethanolamine ratio in the ER is lower than in Pemt+/+ mice, and levels of ER stress markers, CHOP and BIP, are higher without activation of the unfolded protein response. In livers of high-fat-diet-fed Pemt-/- mice the ER has a lower phosphatidylcholine/phosphatidylethanolamine ratio, and exhibits more ER stress and unfolded protein response activation. The unfolded protein response is repressed in McArdle cells expressing PEMT compared with those lacking PEMT
physiological function
in Pemt-/- mice, treatment with vitamin E (0.5 g/kg) for 3 weeks improves very low-density lipoprotein-triglyceride secretion and normalizes cholesterol metabolism, but fails to reduce hepatic triglyceride content. Vitamin E treatment is able to reduce hepatic oxidative stress, inflammation and fibrosis. Pemt-/- mice fed a high-fat diet show abnormal ceramide metabolism, with elevation of ceramides and other sphingolipids and higher expression of mRNAs for acid ceramidase (Asah1) and ceramide kinase (Cerk)
malfunction
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PEMT deficiency reduces plasma homocysteine by 34% to 52% in mice deficient in both PEMT and low-density lipoprotein receptors, deletion of PEMT modestly reduces hepatic very low density lipoprotein secretion in low-density lipoprotein receptors knockout mice and alters the rate of very low density lipoprotein clearance from plasma
malfunction
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lack of PEMT decreases liver damage in Abcb4-/- mice caused by exposure of the liver to excess bile acids. PEMT deficiency affects intestinal Na+ absorption resulting in an impaired Na+ concentration gradient along the length of the small intestine and abnormal absorption of bile acids mediated by apical sodium-dependent bile acid transporter
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). PEMT_MOUSE
199
3
22579
Swiss-Prot
Secretory Pathway (Reliability: 3)
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
H196S
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protein is barely detectable due to poor expression or rapid degradation
K197S
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fails to localize to endoplasmic reticulum, but localize to Golgi apparatus, mutant is catalytically active
K197S/R198S
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fails to localize to endoplasmic reticulum, but localize to Golgi apparatus, mutant is catalytically active
additional information
additional information
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animals with homozygous disruption of enzyme gene, develop severe steatosis when fed a diet deficient in choline. Animals have substantially diminished concentrations of docosahexaenoic acid and arachidonic acid in plasma
additional information
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construction of Pemt-/- mice lacking all enzyme activity, but with no abnormal phenotype, normal hepatocyte morphology, normal plasma lipid levels, and no differences in bile composition compared to the wild-type mice, but the phenotype is altered after withdrawal of phosphatidylcholine and production of it, overview. In the liver-specific CTP:phosphocholine cytidylyltransferase alpha knock-out mice, PEMT activity is increased nearly 2fold above control levels. The double knockout mutant shows a dramatic decrease in hepatic phosphatidylcholine, overview
additional information
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enzyme-deficient female Pemt-/- mice maintain hepatic PC/total choline levels during the first day of choline deprivation and escaped liver damage whereas male Pemt-/- mice do not, plasma phosphocholine levels in high-density lipoproteins are higher in male Pemt-/- mice than those in females before choline deprivation, overview
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
DNA and amino acid sequence determination and analysis including a estrogen response sequence, the PEMT gene has three unique transcription start sites, which are indicative of either multiple promoters and/or alternative splicing
the PEMT gene is localized to chromosome 11 and spans 25 kb with seven exons and six introns, expression analysis
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EXPRESSION
ORGANISM
UNIPROT
LITERATURE
PEMT mRNA and protein levels increase dramatically in 3T3-L1 cells upon differentiation to adipocytes. Expression is regulated through transcription factor Sp1
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APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
medicine
medicine
in Pemt-/- mice, treatment with vitamin E (0.5 g/kg) for 3 weeks improves very low-density lipoprotein-triglyceride secretion and normalizes cholesterol metabolism, but fails to reduce hepatic triglyceride content. Vitamin E treatment is able to reduce hepatic oxidative stress, inflammation and fibrosis. Pemt-/- mice fed a high-fat diet show abnormal ceramide metabolism, with elevation of ceramides and other sphingolipids and higher expression of mRNAs for acid ceramidase (Asah1) and ceramide kinase (Cerk)
medicine
PEMT deficiency reduces the phosphatidylcholine/phosphatidylethanolamine ratio in the ER and induces ER stress,which sensitizes the mice to high-fat-induced steatohepatitis
medicine
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animals with homozygous disruption of enzyme gene, develop severe steatosis when fed a diet deficient in choline. Animals have substantially diminished concentrations of docosahexaenoic acid and arachidonic acid in plasma
medicine
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inhibition of PEMT and/or reduction of intestinal sodium concentration may be helpful in attenuating liver damage and prolonging hepatic function in intrahepatic cholestasis
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Makishima, F.; Toyoshima, S.; Osawa, T.
Partial purification and characterization of phospholipid N-methyltransferases from murine thymocyte microsomes
Arch. Biochem. Biophys.
238
315-324
1985
Mus musculus
Shields, D.J.; Lingrell, S.; Agellon, L.B.; Brosnan, J.T.; Vance, D.E.
Localization-independent regulation of homocysteine secretion by phosphatidylethanolamine N-methyltransferase
J. Biol. Chem.
280
27339-27344
2005
Mus musculus
Watkins, S.M.; Zhu, X.; Zeisel, S.H.
Phosphatidylethanolamine-N-methyltransferase activity and dietary choline regulate liver-plasma lipid flux and essential fatty acid metabolism in mice
J. Nutr.
133
3386-3391
2003
Mus musculus
Zhu, X.; Zeisel, S.H.
Gene expression profiling in phosphatidylethanolamine N-methyltransferase knockout mice
Brain Res. Mol. Brain Res.
134
239-255
2005
Mus musculus
Igolnikov, A.C.; Green, R.M.
Mice heterozygous for the Mdr2 gene demonstrate decreased PEMT activity and diminished steatohepatitis on the MCD diet
J. Hepatol.
44
586-592
2006
Mus musculus
Li, Z.; Agellon, L.B.; Vance, D.E.
A role for high density lipoproteins in hepatic phosphatidylcholine homeostasis
Biochim. Biophys. Acta
1771
893-900
2007
Mus musculus
Resseguie, M.; Song, J.; Niculescu, M.D.; da Costa, K.; Randall, T.A.; Zeisel, S.H.
Phosphatidylethanolamine N-methyltransferase (PEMT) gene expression is induced by estrogen in human and mouse primary hepatocytes
FASEB J.
21
2622-2632
2007
Mus musculus (Q61907), Mus musculus, Homo sapiens (Q9UBM1), Homo sapiens
Vance, D.E.; Li, Z.; Jacobs, R.L.
Hepatic phosphatidylethanolamine N-methyltransferase, unexpected roles in animal biochemistry and physiology
J. Biol. Chem.
282
33237-33241
2007
Mus musculus
Zhao, Y.; Su, B.; Jacobs, R.L.; Kennedy, B.; Francis, G.A.; Waddington, E.; Brosnan, J.T.; Vance, J.E.; Vance, D.E.
Lack of phosphatidylethanolamine N-methyltransferase alters plasma VLDL phospholipids and attenuates atherosclerosis in mice
Arterioscler. Thromb. Vasc. Biol.
29
1349-1355
2009
Mus musculus
Li, Z.; Agellon, L.B.; Vance, D.E.
The role of phosphatidylethanolamine methyltransferase in a mouse model of intrahepatic cholestasis
Biochim. Biophys. Acta
1811
278-283
2011
Mus musculus
Cole, L.K.; Vance, D.E.
A role for Sp1 in transcriptional regulation of phosphatidylethanolamine N-methyltransferase in liver and 3T3-L1 adipocytes
J. Biol. Chem.
285
11880-11891
2010
Mus musculus
Gao, X.; van der Veen, J.N.; Vance, J.E.; Thiesen, A.; Vance, D.E.; Jacobs, R.L.
Lack of phosphatidylethanolamine N-methyltransferase alters hepatic phospholipid composition and induces endoplasmic reticulum stress
Biochim. Biophys. Acta
1852
2689-2699
2015
Mus musculus (Q61907), Mus musculus
Presa, N.; Clugston, R.D.; Lingrell, S.; Kelly, S.E.; Merrill, A.H.; Jana, S.; Kassiri, Z.; Gomez-Munoz, A.; Vance, D.E.; Jacobs, R.L.; van der Veen, J.N.
Vitamin E alleviates non-alcoholic fatty liver disease in phosphatidylethanolamine N-methyltransferase deficient mice
Biochim. Biophys. Acta
1865
14-25
2019
Mus musculus (Q61907)
Jacobs, R.L.; Jiang, H.; Kennelly, J.P.; Orlicky, D.J.; Allen, R.H.; Stabler, S.P.; Maclean, K.N.
Cystathionine beta-synthase deficiency alters hepatic phospholipid and choline metabolism Post-translational repression of phosphatidylethanolamine N-methyltransferase is a consequence rather than a cause of liver injury in homocystinuria
Mol. Genet. Metab.
120
325-336
2017
Mus musculus (Q61907), Mus musculus
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