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Information on EC 2.7.7.14 - ethanolamine-phosphate cytidylyltransferase and Organism(s) Homo sapiens and UniProt Accession Q99447
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2.7.7.14 ethanolamine-phosphate cytidylyltransferaseSpecify your search results
Word Map
- 2.7.7.14
- phosphatidylethanolamine
- phospholipid
- cdp-ethanolamine
- diacylglycerols
-
kennedy
- cdp-choline
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ctp:phosphocholine
- phosphocholine
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3hethanolamine
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ptdetn
- ethanolaminephosphotransferase
-
14cethanolamine
- drug development
The taxonomic range for the selected organisms is: Homo sapiens
The enzyme appears in selected viruses and cellular organisms
The enzyme appears in selected viruses and cellular organisms
Synonyms
pcyt2, ctp:phosphoethanolamine cytidylyltransferase, pect1, phosphoethanolamine cytidylyltransferase, ethanolamine-phosphate cytidylyltransferase, ctp:ethanolaminephosphate cytidylyltransferase, ctp:phosphoethanolamine cytidylyltransferase gene, pcyt2beta, pcyt2alpha, ctp-phosphoethanolamine cytidylyltransferase, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
CTP-phosphoethanolamine cytidylyltransferase
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cytidylyltransferase, ethanolamine phosphate
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ET
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ethanolamine phosphate cytidylyltransferase
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phosphoethanolamine cytidylyltransferase
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phosphorylethanolamine transferase
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
nucleotidyl group transfer
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PATHWAY SOURCE
PATHWAYS
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-, -
SYSTEMATIC NAME
IUBMB Comments
CTP:ethanolamine-phosphate cytidylyltransferase
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CAS REGISTRY NUMBER
COMMENTARY
9026-33-9
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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
CTP + ethanolamine phosphate
diphosphate + CDP-ethanolamine
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?
additional information
?
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catalytic reaction of ECT obeys Michaelis-Menten kinetics with respect to both CTP and phosphoethanolamine
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?
additional information
?
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catalytic reaction of ECT obeys Michaelis-Menten kinetics with respect to both CTP and phosphoethanolamine
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?
additional information
?
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uses N-methylated derivatives of ethanolamine phosphate less efficiently and does not react with phosphocholine
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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
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
early growth response protein 1
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important transcriptional stimulator of gene expression
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additional information
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does not require the presence of exogenous lipids for optimal activity
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE 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
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associated with the membranes of the rough endoplasmic reticulum
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
metabolism
rate-limiting enzyme in mammalian phosphatidylethanolamine biosynthesis
physiological function
enzyme is composed of two tandem cytidylyltransferase domains. The histidines, especially the first histidine, in the CTP-binding motif HxGH in the N-terminal CT domain are critical for its catalytic activity in vitro, while those in the C-terminal CT domain are not. Overexpression of the wild-type mutants containing amino acid substitutions in the HxGH motif in the C-terminal CT domain suppresses the growth defect of the Saccharomyces cerevisiae mutant of ECT1 in the absence of a phosphatidylethanolamine supply via the decarboxylation of phosphatidylserine, but overexpression of ECT mutants of the N-terminal CT domain does not
metabolism
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the enzyme is important and the main regulatory enzyme in de novo production of phosphatidylethanolamine via the CDP-ethanolamine Kennedy pathway, overview. Pcyt2 gene is a target of liver X receptor
physiological function
additional information
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both isoforms are unique cytidylyltransferases, containing two CTP binding HXGH motifs and large repetitive sequences within the N- and C-domains made by gene duplication. Overexpression of Pcyt2 increases the level of CDP-ethanolamine, but phosphatidylethanolamine content remains unchanged since no adequate diacylglacerol is present
physiological function
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serum-deficient MCF-7 cells adapt to stress conditions by increasing synthesis and content of phosphatidylethanolamine and diacylglycerol. The biosynthesis of phosphatidylethanolamine from diacylglycerol and ethanolamine is regulated at the level of formation of CDP-ethanolamine, the metabolic step catalyzed by Pcyt2. The catalytic activity of Pcyt2 is elevated 2-3fold, yet the enzyme remains rate-limiting in serum-deficient cells. The mRNA levels of two splice variants, Pcyt2alpha and Pcyt2beta, are 1.5-3fold higher in deficient cells. Elevated diacylglycerol formation and the increased activity of the rate-regulatory enzyme Pcyt2 are critical modulators of the phosphatidylethanolamine Kennedy pathway, and total phosphatidylethanolamine content in serum-deprived breast cancer cells
physiological function
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the enzyme is important in de novo production of phosphatidylethanolamine, which is the most abundant lipid on the cytoplasmic layer of cellular membranes, with significant roles in cellular processes such as membrane fusion, cell cycle, autophagy, and apoptosis. Transcriptional regulation of Pcyt2, and Pcyt2 expression in the metabolic syndrome and related disorders, overview. Function of Pcyt2 in cancer cell growth, and Pcyt2 expression in lipid-related disorders and cancer, detailed overview. Phosphatidylethanolamine is the precursor of the ethanolamine phosphoglycerol moiety bound to eukaryotic elongation factor 1A, which plays a crucial role in binding aminoacyl-tRNAs during protein synthesis, the upregulation of Pcyt2 expression in methotrexate-resistant HT-29 cells may be important for the production of phosphoethanolamine as a precursor of ethanolamine-phosphoglycerol moiety bound to eEF1A
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). PCY2_HUMAN
389
0
43835
Swiss-Prot
other Location (Reliability: 5)
PDB
SCOP
CATH
UNIPROT
ORGANISM
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
phosphoprotein
splice variant Pcyt2beta is specifically phosphorylated at the end of the first cytidylyltransferase domain. Splice variant Pcyt2alpha is phosphorylated within the alpha-specific motif that is spliced out in Pcyt2beta and on two protein kinase C consensus serine residues, Ser215 and Ser223. Single and double mutations of protein kinase C consensus sites reduce Pcyt2alpha phosphorylation, activity, and phosphatidylethanolamine synthesis by 50-90%. The phosphorylation and activity of endogenous Pcyt2 are dramatically increased with phorbol esters and reduced by specific protein kinase C inhibitors. In vitro translated Pcyt2 is phosphorylated by protein kinase Calpha, protein kinase CbetaI, and protein kinase CbetaII. The phosphorylated sites cluster within and flanking the central linker region that connects the two catalytic domains and is a regulatory segment not present in other cytidylyltransferases
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
H226A
mutation in histidine residue in the HxGH motif of the C-terminal CT domain. Decrease in activity
H229A
mutation in histidine residue in the HxGH motif of the N-terminal CT domain. Activity similar to wild-type activity
H35A
mutation in histidine residue in the HxGH motif of the N-terminal CT domain. Complete loss of activity
H38A
mutation in histidine residue in the HxGH motif of the N-terminal CT domain. Strong decrease in activity
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
Pcyt2, two splicing isozymes Pcyt2alpha and Pcyt2beta, DNA and amino acid sequence and promoter determination and analysis, human Pcyt2, cDNA isolated from glioblastoma cells, is able to restore the synthesis of CDP-ethanolamine as well as the formation of PE in the enzyme-deficient yeast mutant. Transcriptional regulation of Pcyt2, overview
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EXPRESSION
ORGANISM
UNIPROT
LITERATURE
increased Pcyt2 mRNA levels after serum starvation are suppressed by 25-hydroxycholesterol. The suppressive effect of 25-hydroxycholesterol on mRNA transcription is ameliorated by trichostatin A. Anacardic acid, 25-hydroxycholesterol and 24(S)-hydroxycholesterol suppress the transcription by inhibiting H3K27 acetylation in the promoter. 27-Hydroxycholesterol, 22(S)-hydroxycholesterol and 22(R)-hydroxycholesterol suppress the transcription
25-hydroxycholesterol, an endogenous activator of liver X receptor, and the liver X receptor synthetic agonist TO901317 both significantly reduce the biosynthesis of phosphatidylethanolamine via the CDP-ethanolamine Kennedy pathway by inhibiting the promoter function and expression of Pcyt2 in human MCF-7 cells. The enzyme is downregulated in insulin-resistant muscle
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liver X receptor, LXR, can modulate and activate promoter activity and transcription of Pcyt2. Pcyt2 is upregulated in methotrexate-resistant HT-29 cells in comparison to a methotrexate-sensitive colon cancer cell line
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REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Bakovic, M.; Fullerton, M.D.; Michel, V.
Metabolic and molecular aspects of ethanolamine phospholipid biosynthesis: the role of CTP:phosphoethanolamine cytidylyltransferase (Pcyt2)
Biochem. Cell Biol.
85
283-300
2007
Homo sapiens, Mus musculus (Q922E4), Mus musculus, Rattus norvegicus, Saccharomyces cerevisiae
Zhu, L.; Johnson, C.; Bakovic, M.
Stimulation of the human CTP:phosphoethanolamine cytidylyltransferase gene by early growth response protein 1
J. Lipid Res.
49
2197-2211
2008
Homo sapiens
Ando, H.; Horibata, Y.; Yamashita, S.; Oyama, T.; Sugimoto, H.
Low-density lipoprotein and oxysterols suppress the transcription of CTP:Phosphoethanolamine cytidylyltransferase in vitro
Biochim. Biophys. Acta
1801
487-495
2010
Homo sapiens, Mus musculus
Zhu, L.; Bakovic, M.
Breast cancer cells adapt to metabolic stress by increasing ethanolamine phospholipid synthesis and CTP:ethanolaminephosphate cytidylyltransferase-Pcyt2 activity
Biochem. Cell Biol.
90
188-199
2012
Homo sapiens
Pavlovic, Z.; Bakovic, M.
Regulation of phosphatidylethanolamine homeostasis - the critical role of CTP:phosphoethanolamine cytidylyltransferase (Pcyt2)
Int. J. Mol. Sci.
14
2529-2550
2013
Homo sapiens, Mus musculus, Mus musculus C57BL/6, Plasmodium berghei, Rattus norvegicus, Rattus norvegicus Wistar, Saccharomyces cerevisiae, Trypanosoma brucei
Tian, S.; Ohtsuka, J.; Wang, S.; Nagata, K.; Tanokura, M.; Ohta, A.; Horiuchi, H.; Fukuda, R.
Human CTP:phosphoethanolamine cytidylyltransferase: enzymatic properties and unequal catalytic roles of CTP-binding motifs in two cytidylyltransferase domains
Biochem. Biophys. Res. Commun.
449
26-31
2014
Homo sapiens (Q99447), Homo sapiens
Pavlovic, Z.; Zhu, L.; Pereira, L.; Singh, R.; Cornel, R.; Bakovic, M.
Isoform-specific and protein kinase C-mediated regulation of CTP:phosphoethanolamine cytidylyltransferase phosphorylation
J. Biol. Chem.
289
9053-9064
2014
Homo sapiens (Q99447), Homo sapiens
Ando, H.; Horibata, Y.; Aoyama, C.; Shimizu, H.; Shinohara, Y.; Yamashita, S.; Sugimoto, H.
Side-chain oxysterols suppress the transcription of CTP phosphoethanolamine cytidylyltransferase and 3-hydroxy-3-methylglutaryl-CoA reductase by inhibiting the interaction of p300 and NF-Y, and H3K27 acetylation
J. Steroid Biochem. Mol. Biol.
195
105482
2019
Mus musculus (Q922E4), Homo sapiens (Q99447)
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