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Information on EC 2.7.7.15 - choline-phosphate cytidylyltransferase and Organism(s) Homo sapiens
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2.7.7.15 choline-phosphate cytidylyltransferaseSpecify your search results
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- 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: Homo sapiens
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
-
-
-
-
CCT-alpha
CCTalpha
CDP-choline pyrophosphorylase
-
-
-
-
CDP-choline synthetase
-
-
-
-
choline phosphate cytidylyltransferase
-
-
-
-
CTP-phosphocholine cytidylyltransferase
-
-
-
-
CTP:cholinephosphate cytidylyltransferase
-
-
-
-
CTP:phosphocholine cytidylyltransferase
CTP:phosphorylcholine cytidylyltransferase
-
-
-
-
cytidine diphosphocholine pyrophosphorylase
-
-
-
-
cytidylyltransferase, choline phosphate
-
-
-
-
phosphocholine cytidylyltransferase
-
-
-
-
phosphorylcholine cytidylyltransferase
-
-
-
-
phosphorylcholine transferase
-
-
-
-
phosphorylcholine:CTP cytidylyltransferase
-
-
-
-
CTP:phosphocholine cytidylyltransferase
-
-
-
-
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
CTP + choline phosphate
diphosphate + CDPcholine
-
-
-
-
?
CTP + choline phosphate
diphosphate + CDP-choline
-
rate limiting enzyme for the synthesis of phosphatidylcholine, inhibition of CCT triggers apoptosis
-
-
?
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
CTP + choline phosphate
diphosphate + CDP-choline
-
rate limiting enzyme for the synthesis of phosphatidylcholine, inhibition of CCT triggers apoptosis
-
-
?
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
lysophosphatidylcholine
-
generated as a consequence of the activation of cytosolic phospholipase A2 by protein kinase C-alpha and p38 mitogen-activated protein kinase
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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
-
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
nuclear membrane association of CCTa induced by oleate loading is linked to dephosphorylation of S319
additional information
-
immunohistochemic analysis of enzyme subcellular localization, overview
-
-
reversibly translocates to nuclear tubules projecting from the nucleoplasmic reticulum in response to oleate
-
CCT-alpha forms intranuclear foci that colocalise with invaginations in prelamin-A-accumulating cells, overview
-
lipid activation of the enzyme results in its translocation to the nuclear envelope and expansion of an intranuclear membrane network termed the nucleoplasmic reticulum by a mechanism involving membrane deformation
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
metabolism
CTP:phosphocholine cytidylyltransferase is the key regulatory enzyme in phosphatidylcholine synthesis
physiological function
malfunction
-
acute prelamin A accumulation after reduction of the activity of the ZMPSTE24 endoprotease by siRNA knockdown, results in the generation of a complex nucleoplasmic reticulum that depends for its formation on the CTP:phosphocholinecytidylyltransferase-a, this structure can form during interphase, confirming that it is independent of mitosis and therefore not a consequence of disordered nuclear envelope assembly
malfunction
mutations in the gene encoding CTP:phosphocholine cytidylyltransferase (PCYT1A) cause three distinct pathologies in humans: lipodystrophy, spondylometaphyseal dysplasia with cone-rod dystrophy (SMD-CRD), and isolated retinal dystrophy
physiological function
-
CTP:phosphocholine cytidylyltransferase alpha is a nuclear enzyme that catalyzes the rate-limiting step in the CDP-choline pathway for phosphatidylcholine synthesis. The enzyme is not involved in the Hutchinson-Gilford progeria syndrome, overview
physiological function
-
nucleoplasmic reticulum development seems dependent on the enzyme CTP:phosphocholine-cytidylyltransferase-alpha, which is responsible for phosphatidylcholine synthesis for the biosynthesis and curvature of membranes, but nucleoplasmic reticulum development is independent of mitosis. Colocalisation of prelamin A and lamin B1 with a developing nucleoplasmic reticulum is dependent on CTP:phosphocholine-cytidylyltransferase-alpha
physiological function
CTP:phosphocholine cytidylyltransferase-alpha (CCTalpha) and CCTbeta catalyze the rate limiting step in phosphatidylcholine biosynthesis
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_HUMAN
367
0
41731
Swiss-Prot
other Location (Reliability: 3)
PCY1B_HUMAN
369
0
41940
Swiss-Prot
other Location (Reliability: 1)
C9J2E1_HUMAN
212
0
24006
TrEMBL
other Location (Reliability: 3)
C9JEJ2_HUMAN
380
0
43264
TrEMBL
other Location (Reliability: 3)
C9J050_HUMAN
293
0
33711
TrEMBL
other Location (Reliability: 3)
C9JPY0_HUMAN
133
0
14867
TrEMBL
other Location (Reliability: 3)
C9JVS0_HUMAN
115
0
12655
TrEMBL
other Location (Reliability: 3)
H7C1T3_HUMAN
201
0
22779
TrEMBL
other Location (Reliability: 5)
F8WAZ5_HUMAN
134
0
14733
TrEMBL
other Location (Reliability: 3)
B4E322_HUMAN
328
0
37368
TrEMBL
other Location (Reliability: 3)
B2R8P1_HUMAN
367
0
41757
TrEMBL
other Location (Reliability: 3)
H7BZN1_HUMAN
137
0
15769
TrEMBL
other Location (Reliability: 1)
D3DXB2_HUMAN
267
0
30040
TrEMBL
other Location (Reliability: 3)
F2Z2B1_HUMAN
177
0
20277
TrEMBL
other Location (Reliability: 1)
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
phosphoprotein
phosphoprotein
-
phosphorylation reduces membrane binding and therefore decreases activity
phosphoprotein
oleate treatment of cultured cells triggers CCTalpha translocation to the nuclear envelope and nuclear lipid droplets and rapid dephosphorylation of pS319. Removal of oleate leads to dissociation of CCTalpha from the nuclear envelope and increased phosphorylation of S319. Choline depletion of cells causes CCTalpha translocation to the nuclear envelope and S319 dephosphorylation. Y359 and S362 are constitutively phosphorylated during oleate addition and removal. The P-domain undergoes negative charge polarization due to dephosphorylation of S319 and possibly other proline-directed sites and retention of Y359 and S362 phosphorylation. Dephosphorylation of S319 and S315 is involved in CCTalpha recruitment to nuclear membranes
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
A93T
moderate solubility, but impaired catalytic activity and thermal destabilization. Mutation causes retinal dystrophy
A99T
moderate solubility, but impaired catalytic activity and thermal destabilization. Mutation causes spondylometaphyseal dysplasia
A99V
moderate solubility, but impaired catalytic activity and thermal destabilization. Mutation causes spondylometaphyseal dysplasia
E129K
moderate solubility, but impaired catalytic activity and thermal destabilization. Mutation causes spondylometaphyseal dysplasia
E280del
a single amino acid deletion in the autoinhibitory helix increases the constitutive (lipid-independent) enzyme activity x024fold. E280del enhances the response of the enzyme to anionic lipid vesicles 4fold. Mutation causes lipodystrophy in heterozygous status. Mutation causes lipodystrophy
F191L
severely reduced expression levels, suggesting aggregation and potential degradation of misfolded protein. Mutation causes spondylometaphyseal dysplasia
P150A
missense variant in the catalytic domain, low solubility linked to reduced activity in cell lysates, consistent with aberrant folding and aggregation. Mutation causes spondylometaphyseal dysplasia with cone-rod dystrophy
R223S
mutation in a signal-transducing linker between the catalytic and membrane-binding domains, impaired enzymatic activity without fold-destabilization. Mutation causes spondylometaphyseal dysplasia
R283stop
severely reduced expression levels, suggesting aggregation and potential degradation of misfolded protein. Mutation causes spondylometaphyseal dysplasia
S114T
severely reduced expression levels, suggesting aggregation and potential degradation of misfolded protein. Mutation causes spondylometaphyseal dysplasia
S333L.fs164
severely reduced expression levels, suggesting aggregation and potential degradation of misfolded protein. Mutation causes lipodystrophy
V142M
missense variant in the catalytic domain, low solubility linked to reduced activity in cell lysates, consistent with aberrant folding and aggregation. Mutation causes lipodystrophy in heterozygous status
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
54.5
Tm-value for wild-type enzyme isolated from the particulate fraction after denaturation and renaturation
55
Tm-value for wild-type enzyme purified in native form from the soluble fraction of COS cells
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expression in COS-1 cells, which have very low endogenous CTP:phosphocholine cytidylyltransferase activity
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
diagnostics
CCT-alpha status is not predictive of outcome of neoadjuvant cisplatin-based chemotherapy response in patients with T2-T4 bladder cancer. In the control group with cystectomy only it has prognostic value
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Hunt, A.N.; Postle, A.D.
Dye-affinity chromatography of CTP:cholinephosphate cytidylyltransferase
Biochem. Soc. Trans.
14
1279-1281
1986
Homo sapiens
-
Weinhold, P.A.; Rounsifer, M.E.; Charles, L.; Feldman, D.A.
Characterization of cytosolic forms of CTP:choline-phosphate cytidylyltransferase in lung, isolated alveolar type II cells, A549 cell and Hep G2 cells
Biochim. Biophys. Acta
1006
299-310
1989
Homo sapiens, Rattus norvegicus
Awasthi, S.; Vivekananda, J.; Awasthi, V.; Smith, D.; King, R.J.
CTP:phosphocholine cytidylyltransferase inhibition by ceramide via PKC-a, p38 MAPK, cPLA2, and 5-lipoxygenase
Am. J. Physiol.
281
L108-L118
2001
Homo sapiens
Lykidis, A.; Baburina, I.; Jackowski, S.
Distribution of CTP:phosphocholine cytidylyltransferase (CCT) isoforms. Identification of a new CCTb splice variant
J. Biol. Chem.
274
26992-27001
1999
Homo sapiens
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
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
Gehrig, K.; Cornell, R.B.; Ridgway, N.D.
Expansion of the nucleoplasmic reticulum requires the coordinated activity of lamins and CTP:phosphocholine cytidylyltransferase alpha
Mol. Biol. Cell
19
237-247
2008
Homo sapiens
Gehrig, K.; Ridgway, N.
CTP:phosphocholine cytidylyltransferase alpha (CCTalpha) and lamins alter nuclear membrane structure without affecting phosphatidylcholine synthesis
Biochim. Biophys. Acta
1811
377-385
2011
Cricetulus griseus, Homo sapiens
Goulbourne, C.N.; Malhas, A.N.; Vaux, D.J.
The induction of a nucleoplasmic reticulum by prelamin A accumulation requires CTP:phosphocholine cytidylyltransferase-alpha
J. Cell Sci.
124
4253-4266
2011
Homo sapiens
Cornell, R.B.; Taneva, S.G.; Dennis, M.K.; Tse, R.; Dhillon, R.K.; Lee, J.
Disease-linked mutations in the phosphatidylcholine regulatory enzyme CCTalpha impair enzymatic activity and fold stability
J. Biol. Chem.
294
1490-1501
2019
Homo sapiens (P49585), Homo sapiens
Yue, L.; McPhee, M.J.; Gonzalez, K.; Charman, M.; Lee, J.; Thompson, J.; Winkler, D.F.H.; Cornell, R.B.; Pelech, S.; Ridgway, N.D.
Differential dephosphorylation of CTP phosphocholine cytidylyltransferase upon translocation to nuclear membranes and lipid droplets
Mol. Biol. Cell
31
1047-1059
2020
Homo sapiens (P49585)
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