Any feedback?
Information on EC 3.5.4.12 - dCMP deaminase and Organism(s) Homo sapiens
for references in articles please use BRENDA:EC3.5.4.12Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
EC Tree
3.5.4.12 dCMP deaminaseIUBMB Comments
Also acts on some 5-substituted dCMPs.
Specify your search results
Word Map
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
dcmp deaminase, deoxycytidylate deaminase, st2 protein, dcmpd, dcmpase, deoxycytidine monophosphate deaminase, dcmp aminohydrolase, deoxycytidylate aminohydrolase, t4-dcmp deaminase, dcmp-aminohydrolase, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
dCMP deaminase
dCMP-aminohydrolase
-
-
-
-
dCMPase
-
-
-
-
dCMPD
deaminase, deoxycytidylate
-
-
-
-
deoxy-CMP-deaminase
-
-
-
-
deoxycytidine monophosphate deaminase
deoxycytidine nucleotide deaminase
-
-
-
-
deoxycytidine-5'-monophosphate aminohydrolase
-
-
-
-
deoxycytidine-5'-phosphate deaminase
-
-
-
-
deoxycytidylate aminohydrolase
-
-
-
-
deoxycytidylate deaminase
dCMP deaminase
-
-
-
-
dCMPD
-
-
-
-
deoxycytidine monophosphate deaminase
-
-
-
-
deoxycytidylate deaminase
-
-
-
-
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
dCMP + H2O = dUMP + NH3
regulation, allosteric end-product regulation
-
dCMP + H2O = dUMP + NH3
most dramatic allosteric response at substrate levels 0.1 mM dCMP or less
-
dCMP + H2O = dUMP + NH3
highly regulated allosteric enzyme
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
hydrolysis of amidines
-
-
-
-
SYSTEMATIC NAME
IUBMB Comments
dCMP aminohydrolase
Also acts on some 5-substituted dCMPs.
CAS REGISTRY NUMBER
COMMENTARY
9026-92-0
-
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
5-hydroxymethyl-dCMP + H2O
5-hydroxymethyl-dUMP + NH3
-
HeLa cells, good substrate
-
-
?
beta-D-2',2'-difluorodeoxycytidine + H2O
beta-D-2',2'-difluorodeoxyuridine + NH3
-
-
-
-
?
5-Hg-dCMP + H2O
5-Hg-dUMP + NH3
-
very poor substrate in the absence of mercaptoethanol
-
-
?
5-Hg-dCMP + H2O
5-Hg-dUMP + NH3
-
deamination activated by dTTP and inhibited by dCTP
-
-
?
5-Hg-dCMP + H2O
5-Hg-dUMP + NH3
-
5-mercury derivative of dCMP only in the presence of an excess of mercaptoethanol
-
-
?
CMP + H2O
UMP + NH3
-
HeLa cells, at 1 mM, in presence and absence of dCTP and Mg2+: not a substrate
-
-
?
dCMP + H2O
dUMP + NH3
-
most dramatic allosteric response at substrate levels 0.1 mM dCMP or less
-
?
dCMP + H2O
dUMP + NH3
-
enzyme contributes formation of DNA by providing dUMP as substrate for thymidylate synthase. Potential role in cell division
-
?
dCMP + H2O
dUMP + NH3
-
providing an adequate supply of dUMP for formation of dTMP, via dTMP synthase a crucial intermediate for synthesis of DNA
-
-
?
dCMP + H2O
dUMP + NH3
-
key enzyme in pyrimidine deoxyribonucleotide metabolism, catalyzing the rate-limiting step, plays an important role in providing a balanced supply of dCTP and dTTP for DNA synthesis
-
?
dCMP + H2O
dUMP + NH3
-
important role in regulation of intracellular TTP levels
-
-
ir
dCMP + H2O
dUMP + NH3
-
importance in the generation of dUMP, precursor for synthesis of thymidine nucleotides
-
-
?
dCMP + H2O
dUMP + NH3
-
enzyme is major source of mammalian cell dUMP pool and regulates the synthesis of TMP
-
-
ir
dCMP + H2O
dUMP + NH3
-
the enzyme is important in the de novo synthesis of thymidine nucleotides, and may also be involved in the metabolism of anticancer agents
-
-
?
dCMP + H2O
dUMP + NH3
-
the enzyme plays a key role in the thymidylate synthase, pathway overview
-
-
?
additional information
?
-
-
HeLa cells, no activity with CDP at 1 mM, in presence and absence of dCTP and Mg2+
-
-
?
additional information
?
-
-
enzyme is involved in elimination of some dCyd analogues, such as 2',2'-difluorodeoxycytidine, fluoro-dCyd, and ara-C, from tissues or cultured cells
-
-
?
additional information
?
-
-
the enzyme also performs 5-methylcytidyl-DNA deaminase activity but to a lesser extent, deamination pathway, overview
-
-
?
additional information
?
-
-
the human cytomegalovirus requires the cellular host dCMP deaminase for replication in quiescent cells, overview
-
-
?
additional information
?
-
-
substrate specificity with deoxycytidine analogue monophosphates, overview
-
-
?
additional information
?
-
-
the enzyme also performs 5-methylcytidyl-DNA deaminase activity but to a lesser extent, substrate specificity, overview
-
-
?
additional information
?
-
-
cytidine monophosphate is not a good substrate for dCMPD. Monophosphates of deoxycytidine analogs nucleosides in the L-conformation (e.g. apricitabine, lamivudine, and emtricitabine) and dideoxycytidine do not act as substrates of dCMPD
-
-
?
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
dCMP + H2O
dUMP + NH3
-
enzyme contributes formation of DNA by providing dUMP as substrate for thymidylate synthase. Potential role in cell division
-
?
dCMP + H2O
dUMP + NH3
-
providing an adequate supply of dUMP for formation of dTMP, via dTMP synthase a crucial intermediate for synthesis of DNA
-
-
?
dCMP + H2O
dUMP + NH3
-
key enzyme in pyrimidine deoxyribonucleotide metabolism, catalyzing the rate-limiting step, plays an important role in providing a balanced supply of dCTP and dTTP for DNA synthesis
-
?
dCMP + H2O
dUMP + NH3
-
important role in regulation of intracellular TTP levels
-
-
ir
dCMP + H2O
dUMP + NH3
-
importance in the generation of dUMP, precursor for synthesis of thymidine nucleotides
-
-
?
dCMP + H2O
dUMP + NH3
-
enzyme is major source of mammalian cell dUMP pool and regulates the synthesis of TMP
-
-
ir
dCMP + H2O
dUMP + NH3
-
the enzyme is important in the de novo synthesis of thymidine nucleotides, and may also be involved in the metabolism of anticancer agents
-
-
?
dCMP + H2O
dUMP + NH3
-
the enzyme plays a key role in the thymidylate synthase, pathway overview
-
-
?
additional information
?
-
-
enzyme is involved in elimination of some dCyd analogues, such as 2',2'-difluorodeoxycytidine, fluoro-dCyd, and ara-C, from tissues or cultured cells
-
-
?
additional information
?
-
-
the enzyme also performs 5-methylcytidyl-DNA deaminase activity but to a lesser extent, deamination pathway, overview
-
-
?
additional information
?
-
-
the human cytomegalovirus requires the cellular host dCMP deaminase for replication in quiescent cells, overview
-
-
?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Ca2+
Co2+
-
divalent cations not necessary to improve activity, activation by dCTP and inhibition by dTTP both show an absolute requirement for a divalent cation. Mg2+, Ca2+ and Mn2+ almost equally effective in promoting activation by dCTP, Cu2+, Zn2+, and Co2+ are ineffective
divalent cations
-
divalent cations not necessary to improve activity, activation by dCTP and inhibition by dTTP both show an absolute requirement for a divalent cation. Mg2+, Ca2+ and Mn2+ almost equally effective in promoting activation by dCTP, Cu2+, Zn2+, and Co2+ are ineffective
Mg2+
Mn2+
Zn2+
-
divalent cations not necessary to improve activity, activation by dCTP and inhibition by dTTP both show an absolute requirement for a divalent cation. Mg2+, Ca2+ and Mn2+ almost equally effective in promoting activation by dCTP, Cu2+, Zn2+, and Co2+ are ineffective
additional information
Ca2+
-
divalent cations not necessary to improve activity, activation by dCTP and inhibition by dTTP both show an absolute requirement for a divalent cation. Mg2+, Ca2+ and Mn2+ almost equally effective in promoting activation by dCTP, Cu2+, Zn2+, and Co2+ are ineffective
Ca2+
-
activation of enzyme by dCTP or inhibition by TTP has absolute requirement for the presence of a divalent cation. Mg2+, Ca2+ and Mn2+ are equally effective cations for enzyme activation by dCTP, Mn2+ and Ca2+ are more effective than Mg2+ in enzyme inhibition by TTP
Mg2+
-
divalent cations not necessary to improve activity, activation by dCTP and inhibition by dTTP both show an absolute requirement for a divalent cation. Mg2+, Ca2+ and Mn2+ almost equally effective in promoting activation by dCTP, Cu2+, Zn2+, and Co2+ are ineffective
Mg2+
-
activation of enzyme by dCTP or inhibition by TTP has absolute requirement for the presence of a divalent cation. Mg2+, Ca2+ and Mn2+ are equally effective cations for enzyme activation by dCTP, Mn2+ and Ca2+ are more effective than Mg2+ in enzyme inhibition by TTP
Mn2+
-
divalent cations not necessary to improve activity, activation by dCTP and inhibition by dTTP both show an absolute requirement for a divalent cation. Mg2+, Ca2+ and Mn2+ almost equally effective in promoting activation by dCTP, Cu2+, Zn2+, and Co2+ are ineffective
Mn2+
-
activation of enzyme by dCTP or inhibition by TTP has absolute requirement for the presence of a divalent cation. Mg2+, Ca2+ and Mn2+ are equally effective cations for enzyme activation by dCTP, Mn2+ and Ca2+ are more effective than Mg2+ in enzyme inhibition by TTP
additional information
-
divalent cations not necessary to improve activity, activation by dCTP and inhibition by dTTP both show an absolute requirement for a divalent cation. Mg2+, Ca2+ and Mn2+ almost equally effective in promoting activation by dCTP, Cu2+, Zn2+, and Co2+ are ineffective
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
2',2'-difluorodeoxycytidine
-
high cellular nucleotide levels: inhibition: Concentration-dependent inhibition; inhibition by nucleotides of 2',2'-difluorodeoxycytidine, dual mechanism of inhibition
2'-beta-D-deoxyribose-pyrimidin-2-one 5'-phosphate
-
competitive inhibition, Ki: 0.000012 mM
5-Hg-dCMP
-
potent inhibitor, in the absence of 2-mercaptoethanol, 0.00024 mM: 37% inhibition, 0.0024 mM: 70% inhibition
D-beta-2'-fluoro-5-methyl-arabinofuranosyluracil monophosphate
-
no inhibition by L-beta-2'-fluoro-5-methyl-arabinofuranosyluracil monophosphate
dCTP
-
allosteric activator, 12fold, for aminohydrolysis of dCMP, inhibitor, 50% inhibition, for substrate: 5-Hg-dCMP in the presence of mercaptoethanol, dCMP-Hg-S-CH2-CH2-OH
Hg(CH3COO)2
-
Hg(acetate)2; mercuroacetate, potent inhibitor, 0.0002 mM: 26% inhibition, 0.001 mM: 40% inhibition
dTTP
-
0.0015 mM: 50% inhibition. dTTP inhibition reversed by dCTP; allosteric inhibitor
TTP
-
activating enzyme up to 1.7fold at concentration of 0.00025 mM, but inhibiting at higher concentration, 0.015 mM: 85% inhibition; inhibition by TTP has absolute requirement for the presence of a divalent cation, Mn2+ and Ca2+ are more effective than Mg2+ in the inhibition of enzyme activity by TTP; TTP inhibition partially reversed by dCTP
additional information
-
little or no inhibition by 3,4,5,6-tetrahydrouridine; mechanism of inhibition
-
additional information
-
inhibitory potency of pyrimidine phosphate analogues, overview
-
additional information
-
monophosphates of deoxycytidine analogs nucleosides in the L-conformation (e.g. apricitabine, lamivudine, and emtricitabine) and dideoxycytidine do not act as inhibitors of dCMPD
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
1-beta-D-arabinofuranosylcytosine 5'-triphosphate
-
low activation, allosteric activator
dTTP
-
allosteric inhibitor, 100% inhibition, for substrate dCMP, becomes activator, 2.5fold, for mercury substrate: 5-Hg-dCMP in the presence of mercaptoethanol, dCMP-Hg-S-CH2-CH2-OH, at relatively high, 1 to 2 mM, dCMP-Hg-S-CH2-CH2-OH concentration
TTP
-
activating enzyme up to 1.7fold at concentration of 0.00025 mM, but inhibiting at higher concentration, 0.015 mM: 85% inhibition
dCTP
-
activation by dCTP has absolute requirement for the presence of a divalent cation, Mg2+, Ca2+ and Mn2+ are equally effective cations for enzyme activation by dCTP
additional information
-
infection with the human cytomegalovirus upregulates the enzyme involved in thymidylate synthesis especially the dCMP deaminase, but not the dUTPase, overview
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
30
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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). DCTD_HUMAN
178
0
20016
Swiss-Prot
other Location (Reliability: 2)
PDB
SCOP
CATH
UNIPROT
ORGANISM
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
20000
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
hexamer
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
ethyleneglycol prevents protein denaturation during freezing in the presence of 2-mercaptoethanol
-
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-20°C, 10-20% ethyleneglycol, 0.01 mM dCTP, 1 mM MgCl2, 20 mM 2-mercaptoethanol and 0.05% Triton X-100, 1 year, no loss in activity
-
-50°C, 0.05 mM dCTP, 1 mM MgCl2 or 2 mM dithiothreitol, 18 h, 40% activity lost
-
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
native enzyme from sperm cells by ion exchange chromatography and preparative SDS-PAGE
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
-
associated mainly with dividing tissues, potential diagnostic tool for various disease states in which enzyme is elevated
pharmacology
pharmacology
-
elevated level of dCMPase in transformed cells and tumors: enzyme may represent another important target for cancer chemotherapy
pharmacology
-
enzyme might be a reasonable target for chemotherapeutic agents directed against parasitic as well as neoplastic diseases by limiting the synthesis of dUMP, particularly when used in combination with inhibitors of dTMP synthase or other purine and pyrimidine inhibitors of DNA synthesis
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Ellims, P.H.; Kao, A.Y.; Chabner, B.A.
Deoxycytidylate deaminase. Purification and some properties of the enzyme isolated from human spleen
J. Biol. Chem.
256
6335-6340
1981
Homo sapiens
Xu, Y.Z.; Plunkett, W.
Modulation of deoxycytidylate deaminase in intact human leukemia cells. Action of 2',2'-difluorodeoxycytidine
Biochem. Pharmacol.
44
1819-1827
1992
Homo sapiens
Moore, J.T.; Ciesla, J.M.; Changchien, L.M.; Maley, G.F.; Maley, F.
Identification of a site necessary for allosteric regulation in T4-phage deoxycytidylate deaminase
Biochemistry
33
2104-2112
1994
Tequatrovirus T4, Homo sapiens
Maley, G.F.; Lobo, A.P.; Maley, F.
Properties of an affinity-column-purified human deoxycytidylate deaminase
Biochim. Biophys. Acta
1162
161-170
1993
Homo sapiens
Riva, C.M.; Barra, Y.; Cano, J.P.; Tubiana, N.; Lejeune, C.; Merlin, M.; de Sousa, G.; Carcassonne, Y.; Kreis, W.; Lovecchio, J.; Rottachi, C.; Rustum, Y.M.
Correlation between deoxycytidine kinase and deaminase activities and response to therapy with ARA-C
J. Cell. Pharmacol.
1
79-85
1990
Homo sapiens
-
Maley, F.; Maley, G.F.
A tale of two enzymes, deoxycytidylate deaminase and thymidylate synthase
Prog. Nucleic Acid Res. Mol. Biol.
39
49-80
1990
Bacillus subtilis, Betapolyomavirus macacae, Echinoidea, Enterobacteria phage T6, Equus asinus, Escherichia phage T2, Gallus gallus, Herpes simplex virus, Homo sapiens, no activity in Escherichia coli, no activity in Salmonella typhimurium, Polyomavirus sp., Rattus norvegicus, Saccharomyces cerevisiae, Tequatrovirus T4
Jost, J.P.; Thiry, S.; Siegmann, M.
5-Methyldeoxycytidine monophosphate deaminase and 5-methylcytidyl-DNA deaminase activities are present in human mature sperm cells
FEBS Lett.
519
128-134
2002
Homo sapiens
Gribaudo, G.; Riera, L.; Caposio, P.; Maley, F.; Landolfo, S.
Human cytomegalovirus requires cellular deoxycytidylate deaminase for replication in quiescent cells
J. Gen. Virol.
84
1437-1441
2003
Homo sapiens
Liou, J.Y.; Krishnan, P.; Hsieh, C.C.; Dutschman, G.E.; Cheng, Y.C.
Assessment of the effect of phosphorylated metabolites of anti-human immunodeficiency virus and anti-hepatitis B virus pyrimidine analogs on the behavior of human deoxycytidylate deaminase
Mol. Pharmacol.
63
105-110
2003
Homo sapiens
Li, L.S.; Morales, J.C.; Veigl, M.; Sedwick, D.; Greer, S.; Meyers, M.; Wagner, M.; Fishel, R.; Boothman, D.A.
DNA mismatch repair (MMR)-dependent 5-fluorouracil cytotoxicity and the potential for new therapeutic targets
Br. J. Pharmacol.
158
679-692
2009
Homo sapiens
EXTERNAL LINKS (specific for EC-Number 3.5.4.12)
Use of this online version of BRENDA is free under the CC BY 4.0 license. See terms of use for full details.
Release 2023.1 (January 2023)
Legal
Curated at
Member of
