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Information on EC 2.7.7.15 - choline-phosphate cytidylyltransferase and Organism(s) Mus musculus and UniProt Accession P49586
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2.7.7.15 choline-phosphate cytidylyltransferaseSpecify your search results
Word Map
- 2.7.7.15
- phosphatidylcholine
- phospholipid
- phosphatidylethanolamine
- surfactant
- fetal
- diacylglycerol
- phospholipase
-
ptdcho
- alveolar
-
cholinephosphotransferase
- oleate
- phosphatidylglycerol
-
amphipathic
-
membrane-binding
- n-methyltransferase
-
disaturated
- lysophosphatidylcholine
- phosphatidate
-
3hcholine
-
vance
-
kennedy
-
cytidyltransferase
- 1,2-diacylglycerols
- phosphoethanolamine
-
3hglycerol
-
amphitropic
-
l-forms
-
methyl-14ccholine
- hexadecylphosphocholine
- analysis
- diagnostics
-
choline-deficient
- cdpcholine
-
methyl-3hcholine
-
2.7.8.2
-
14ccholine
-
ctp:phosphoethanolamine
-
choline-containing
- cdp-ethanolamine
- medicine
The taxonomic range for the selected organisms is: Mus musculus
The enzyme appears in selected viruses and cellular organisms
The enzyme appears in selected viruses and cellular organisms
Synonyms
ctp:phosphocholine cytidylyltransferase, cctalpha, ctalpha, phosphocholine cytidylyltransferase, pcyt1a, cholinephosphate cytidylyltransferase, cctbeta, choline-phosphate cytidylyltransferase, ctp:phosphocholine cytidylyltransferase alpha, ctp:choline-phosphate cytidylyltransferase, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
CCT
CCTalpha
CCTbeta2
CCTbeta3
CDP-choline pyrophosphorylase
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-
-
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CDP-choline synthetase
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-
-
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choline phosphate cytidylyltransferase
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-
-
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CTP-phosphocholine cytidylyltransferase
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-
-
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CTP:cholinephosphate cytidylyltransferase
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-
-
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CTP:phosphocholine cytidylyltransferase
CTP:phosphorylcholine cytidylyltransferase
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-
-
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cytidine diphosphocholine pyrophosphorylase
-
-
-
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cytidylyltransferase, choline phosphate
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-
-
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phosphocholine cytidylyltransferase
-
-
-
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phosphorylcholine cytidylyltransferase
-
-
-
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phosphorylcholine transferase
-
-
-
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phosphorylcholine:CTP cytidylyltransferase
-
-
-
-
additional information
CCT
-
-
-
-
CTP:phosphocholine cytidylyltransferase
-
-
-
-
additional information
-
different isoforms, CCTalpha and CCTbeta 2 and -3, CCTbeta 1 is not found in mice
additional information
-
four isoforms, CCTalpha ubiquitously expressed, whereas CCTbeta 1,-2, and -3 restricted in distribution
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
nucleotidyl group transfer
-
-
-
-
PATHWAY SOURCE
PATHWAYS
-
-, -, -, -, -, -
SYSTEMATIC NAME
IUBMB Comments
CTP:choline-phosphate cytidylyltransferase
-
CAS REGISTRY NUMBER
COMMENTARY
9026-34-0
-
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
additional information
?
-
-
key regulatory enzyme in the CDP-choline pathway for the biosynthesis of phosphatidylcholine, hepatic phosphatidylcholine biosynthesis is an important regulator of plasma high density lipoprotein
-
-
?
CTP + choline phosphate
diphosphate + CDP-choline
-
-
-
-
?
CTP + choline phosphate
diphosphate + CDP-choline
-
rate limiting enzyme for the synthesis of phosphatidylcholine
-
-
?
CTP + choline phosphate
diphosphate + CDP-choline
-
rate limiting enzyme for the synthesis of phosphatidylcholine, inhibition of CCT triggers apoptosis, disruption of CCTbeta leads to gonadal dysfunction and reduced fertility
-
-
?
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
?
-
-
key regulatory enzyme in the CDP-choline pathway for the biosynthesis of phosphatidylcholine, hepatic phosphatidylcholine biosynthesis is an important regulator of plasma high density lipoprotein
-
-
?
CTP + choline phosphate
diphosphate + CDP-choline
-
rate limiting enzyme for the synthesis of phosphatidylcholine
-
-
?
CTP + choline phosphate
diphosphate + CDP-choline
-
rate limiting enzyme for the synthesis of phosphatidylcholine, inhibition of CCT triggers apoptosis, disruption of CCTbeta leads to gonadal dysfunction and reduced fertility
-
-
?
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphatidylcholine
-
ET-18-OCH3, non-hydrolyzable lysophosphatidylcholine analog, competitive with respect to the lipid activator
calpain
-
calpain degrades CCTalpha, 0.6 pmol of calpain effectively cleaves 80% of purified CCTalpha (0.7 pmol) in the absence of calmodulin
-
lysophosphatidylcholine
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competitive with respect to the lipid activator, 50% inhibition at 0.025 mM in the presence of phosphatidylcholine/oleic acid
oxidized low density lipoprotein
-
40% inhibition by increase of enzyme degradation
-
oxidized low density lipoprotein
-
75% inhibition by increase of enzyme degradation
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
activator protein-1
-
potential regulator of CCTbeta2 expression in neuronal cells
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conduritol-B-epoxide
-
treatment of macrophages with 0.5 mM conduritol-B-epoxide results in elevated activity of CCT
Lipids
-
regulation of activity by reversible association with membrane lipids
-
retinoblastoma protein
-
regulates CTalpha expression by different mechanisms depending on the phase of the cell cycle, the regulation of CTalpha expression requires both the Sp1 and the retinoblastoma control elements
-
Sp1
-
Sp1 stimulates CTalpha transcription, and Sp1-mediated transcription is stimulated by the retinoblastoma protein
-
additional information
probucol does not have any diret stimulatory effect on CCT
-
additional information
probucol does not have any diret stimulatory effect on CCT
-
additional information
probucol does not have any diret stimulatory effect on CCT
-
additional information
probucol does not have any diret stimulatory effect on CCT
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
Cortical, primary sympathetic and cultured primary, isozyme CTbeta2 mRNA and protein are abundant in distal axons of mouse sympathetic neurons, whereas isozyme CTalpha mRNA and protein are not detected
-
BAC1.2F5 cell line, SCF-1-dependent clone derived from the BAC1 line which originated from transfection of splenic adherent cells with SV40
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
CTP:phosphocholine cytidylyltransferase binds stably and via its amphipatic alpha helix to lipid droplet surface during surface expansion, which is essential for the lipid droplet. It is the only enzyme of the phosphatidylecholine synthesis Kennedy pathway that localizes in the lipid droplets
additional information
additional information
-
CCT1 Is mobile and shuttles between nucleus and cytosol before oleate loading. CCT1 targets to lipid droplets after an initial delay and relocalizes to the nucleus when oleate is removed. CCT1 is targeted to lipid droplets when phosphatidylcholine levels are inadequate
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GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
drug target
-
CTP:phosphocholine cytidylyltransferase beta3 (CCTbeta3) may be targeted to suppress prolonged autophagy in cancer cells in vivo
malfunction
-
isozyme CTbeta2 deficiency in distal axons reduces the incorporation of choline into by 95% whereas phosphatidylcholine synthesis in cell bodies/proximal axons is unaltered. Brains of mice lacking CTbeta2 have normal phosphatidylethanolamine content despite having 35% lower enzyme activity than wild-type brains. Axon branching, but not axon extension, is impaired in CTbeta2-deficient neurons. Phenotypes, overview
metabolism
-
the enzyme catalyzes a step in the Kennedy pathway for phosphatidylecholine synthesis, overview
physiological function
physiological function
-
importance of isozyme CTbeta2 for phosphatidylcholine synthesis as well as for axon formation, growth and branching of primary sympathetic neurons
physiological function
-
phosphatidylcholine acts as a surfactant to prevent lipid droplet coalescence, which otherwise yields large, lipolysis-resistant lipid droplets and triglyceride accumulation. The need for additional phosphatidylecholine to coat the enlarging surface during lipid droplet expansion is provided by the Kennedy pathway, which is activated by reversible targeting of the rate-limiting enzyme, CTP:phosphocholine cytidylyltransferase, to growing lipid droplet surfaces. CCT1 regulates lipid droplet size and triacylgylceride storage in vivo
physiological function
-
phosphatidylcholine synthesis through CCTbeta3 (CTP:phosphocholine cytidylyltransferase beta3) activation on lipid droplets is crucial for sustaining autophagy and long-term cell survival
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). PCY1A_MOUSE
367
0
41667
Swiss-Prot
other Location (Reliability: 3)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
phosphoprotein
phosphoprotein
-
16 serine and 2 tyrosine residues available for phosphorylation, phosphorylation is associated with decreased membrane binding and therefore, decreased activity
phosphoprotein
-
phosphorylation reduces membrane binding and therefore decreases activity
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
K238R/K239R/Y240F
-
increased resistance to calpain cleavage, resistance to enzyme degradation by oxidized low density lipoprotein
Q243A
-
the mutation results in loss of calmodulin binding and leads to complete calpain resistance in vitro and in vivo
additional information
additional information
-
deletion of CCTalpha beginning at embryonic day 7.5 does not restrict lung development but results in severe respiratory failure at birth
additional information
loss of the CCTbeta2 isoform expression in mice results in gonadal dysfunction
additional information
loss of the CCTbeta2 isoform expression in mice results in gonadal dysfunction
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
in cultured primary neurons nerve growth factor increases the amount of isozyme CTbeta2, but not CTalpha, mRNA and protein
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Boggs, K.P.; Rock, C.O.; Jackowski, S.
Lysophosphatidylcholine and 1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine inhibit the CDP-choline pathway of phosphatidylcholine synthesis at the CTP:phosphocholine cytidylyltransferase step
J. Biol. Chem.
270
7757-7764
1995
Mus musculus
Ridsdale, R.; Tseu, I.; Wang, J.; Post, M.
CTP:phosphocholine cytidylyltransferase a is a cytosolic protein in pulmonary epithelial cells and tissues
J. Biol. Chem.
276
49148-49155
2001
Mus musculus, Rattus norvegicus
Zhou, J.; Ryan, A.J.; Medh, J.; Mallampalli, R.K.
Oxidized lipoproteins inhibit surfactant phosphatidylcholine synthesis via calpain-mediated Cleavage of CTP:phosphocholine cytidylyltransferase
J. Biol. Chem.
278
37032-37040
2003
Mus musculus, Rattus norvegicus
Ryan, A.J.; Fisher, K.; Thomas, C.P.; Mallampalli, R.K.
Transcriptional repression of the CTP:phosphocholine cytidylyltransferase gene by sphingosine
Biochem. J.
382
741-750
2004
Mus musculus, Rattus norvegicus
Ridsdale, R.; Tseu, I.; Roth-Kleiner, M.; Wang, J.; Post, M.
Increased phosphatidylcholine production but disrupted glycogen metabolism in fetal type II cells of mice that overexpress CTP:phosphocholine cytidylyltransferase
J. Biol. Chem.
279
55946-55957
2004
Mus musculus, Rattus norvegicus
Jackowski, S.; Fagone, P.
CTP:phosphocholine cytidylyltransferase: Paving the way from gene to membrane
J. Biol. Chem.
280
853-856
2005
Arabidopsis thaliana, Homo sapiens, Mus musculus
Gunter, C.; Frank, M.; Tian, Y.; Murti, K.G.; Rehg, J.E.; Jackowski, S.
Probucol therapy overcomes the reproductive defect in CTP: phosphocholine cytidylyltransferase beta2 knockout mice
Biochim. Biophys. Acta
1771
845-852
2007
Mus musculus (P49586), Mus musculus (Q811Q9)
Marcucci, H.; Elena, C.; Gilardoni, P.; Banchio, C.
Characterization of the murine CTP:phosphocholine cytidylyltransferase beta gene promoter
Biochim. Biophys. Acta
1781
254-262
2008
Mus musculus
Kacher, Y.; Golan, A.; Pewzner-Jung, Y.; Futerman, A.H.
Changes in macrophage morphology in a Gaucher disease model are dependent on CTP:phosphocholine cytidylyltransferase alpha
Blood Cells Mol. Dis.
39
124-129
2007
Homo sapiens, Mus musculus
Banchio, C.; Lingrell, S.; Vance, D.E.
Sp-1 binds promoter elements that are regulated by retinoblastoma and regulate CTP:phosphocholine cytidylyltransferase-alpha transcription
J. Biol. Chem.
282
14827-14835
2007
Mus musculus
Chen, B.B.; Mallampalli, R.K.
Calmodulin binds and stabilizes the regulatory enzyme, CTP:phosphocholine cytidylyltransferase
J. Biol. Chem.
282
33494-33506
2007
Mus musculus
Jacobs, R.L.; Lingrell, S.; Zhao, Y.; Francis, G.A.; Vance, D.E.
Hepatic CTP:phosphocholine cytidylyltransferase-alpha is a critical predictor of plasma high density lipoprotein and very low density lipoprotein
J. Biol. Chem.
283
2147-2155
2008
Mus musculus
Tian, Y.; Zhou, R.; Rehg, J.E.; Jackowski, S.
Role of phosphocholine cytidylyltransferase alpha in lung development
Mol. Cell. Biol.
27
975-982
2007
Mus musculus
Okamura, K.; Yamashita, S.; Ando, H.; Horibata, Y.; Aoyama, C.; Takagishi, K.; Izumi, T.; Vance, D.E.; Sugimoto, H.
Identification of nuclear localization and nuclear export signals in Ets2, and the transcriptional regulation of Ets2 and CTP:phosphocholine cytidylyltransferase alpha in tetradecanoyl-13-acetate or macrophage-colony stimulating factor stimulated RAW264 cells
Biochim. Biophys. Acta
1791
173-182
2009
Mus musculus
Fagone, P.; Gunter, C.; Sage, C.R.; Gunn, K.E.; Brewer, J.W.; Jackowski, S.
CTP:phosphocholine cytidylyltransferase alpha is required for B-cell proliferation and class switch recombination
J. Biol. Chem.
284
6847-6854
2009
Mus musculus
Strakova, J.; Demizieux, L.; Campenot, R.B.; Vance, D.E.; Vance, J.E.
Involvement of cin axonal phosphatidylcholine synthesis and branching of neurons
Biochim. Biophys. Acta
1811
617-625
2011
Mus musculus, Rattus norvegicus, Rattus norvegicus Sprague-Dawley
Krahmer, N.; Guo, Y.; Wilfling, F.; Hilger, M.; Lingrell, S.; Heger, K.; Newman, H.W.; Schmidt-Supprian, M.; Vance, D.E.; Mann, M.; Farese, R.V.; Walther, T.C.
Phosphatidylcholine synthesis for lipid droplet expansion is mediated by localized activation of CTP:phosphocholine cytidylyltransferase
Cell Metab.
14
504-515
2011
Drosophila melanogaster, Mus musculus
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