Metabolic Modeling Tutorial
discounted EARLY registration ends Dec 31, 2014
Metabolic Modeling Tutorial
discounted EARLY registration ends Dec 31, 2014
Metabolic Modeling Tutorial
discounted EARLY registration ends Dec 31, 2014
Metabolic Modeling Tutorial
discounted EARLY registration ends Dec 31, 2014
Metabolic Modeling Tutorial
discounted EARLY registration ends Dec 31, 2014
twitter

Escherichia coli K-12 substr. MG1655 Enzyme: thymidine kinase / deoxyuridine kinase



Gene: tdk Accession Numbers: EG10994 (EcoCyc), b1238, ECK1233

Regulation Summary Diagram: ?

Summary:
Early studies of the enzyme indicated that in the presence of an activator or an inhibitor deoxynucleotide the enzyme dimerizes. Dimerization accounts for the regulatory properties of the enzyme, which has either an active or inactive conformation, depending upon which effector nucleotide interacts with it. [Iwatsuki67, Chen78]

Locations: cytosol

Map Position: [1,292,750 -> 1,293,367] (27.86 centisomes)
Length: 618 bp / 205 aa

Molecular Weight of Polypeptide: 23.457 kD (from nucleotide sequence)

pI: 6.34

Unification Links: ASAP:ABE-0004157 , CGSC:120 , EchoBASE:EB0987 , EcoGene:EG10994 , EcoliWiki:b1238 , OU-Microarray:b1238 , PortEco:tdk , PR:PRO_000024045 , Protein Model Portal:P23331 , RefSeq:NP_415754 , RegulonDB:EG10994 , SMR:P23331 , String:511145.b1238 , UniProt:P23331

Relationship Links: InterPro:IN-FAMILY:IPR001267 , InterPro:IN-FAMILY:IPR020633 , InterPro:IN-FAMILY:IPR020634 , InterPro:IN-FAMILY:IPR027417 , Panther:IN-FAMILY:PTHR11441 , Pfam:IN-FAMILY:PF00265 , Prosite:IN-FAMILY:PS00603

Gene-Reaction Schematic: ?

GO Terms:

Biological Process: GO:0006259 - DNA metabolic process Inferred from experiment Inferred by computational analysis [GOA06, GOA01, Okazaki64a]
GO:0009157 - deoxyribonucleoside monophosphate biosynthetic process Inferred by computational analysis Inferred from experiment [Okazaki64a, GOA06, GOA01a, GOA01]
GO:0006260 - DNA replication Inferred by computational analysis [UniProtGOA11]
GO:0008152 - metabolic process Inferred by computational analysis [UniProtGOA11]
GO:0016310 - phosphorylation Inferred by computational analysis [UniProtGOA11]
Molecular Function: GO:0004797 - thymidine kinase activity Inferred from experiment Inferred by computational analysis [GOA06, GOA01a, GOA01, Okazaki64a]
GO:0000166 - nucleotide binding Inferred by computational analysis [UniProtGOA11]
GO:0003824 - catalytic activity Inferred by computational analysis [UniProtGOA11]
GO:0005524 - ATP binding Inferred by computational analysis [UniProtGOA11, GOA06, GOA01]
GO:0008270 - zinc ion binding Inferred by computational analysis [GOA06]
GO:0016301 - kinase activity Inferred by computational analysis [UniProtGOA11]
GO:0016740 - transferase activity Inferred by computational analysis [UniProtGOA11]
GO:0046872 - metal ion binding Inferred by computational analysis [UniProtGOA11]
Cellular Component: GO:0005829 - cytosol Inferred from experiment Inferred by computational analysis [DiazMejia09, Ishihama08]
GO:0005737 - cytoplasm Inferred by computational analysis [UniProtGOA11a, UniProtGOA11, GOA06]

MultiFun Terms: metabolism central intermediary metabolism nucleotide and nucleoside conversions

Essentiality data for tdk knockouts: ?

Growth Medium Growth? T (°C) O2 pH Osm/L Growth Observations
LB Lennox Yes 37 Aerobic 7   Yes [Baba06, Comment 1]
M9 medium with 1% glycerol Yes 37 Aerobic 7.2 0.35 Yes [Joyce06, Comment 2]
MOPS medium with 0.4% glucose Yes 37 Aerobic 7.2 0.22 Yes [Baba06, Comment 1]
Yes [Feist07, Comment 3]

Enzymatic reaction of: thymidine kinase

Synonyms: ATP:thymidine 5'-phosphotransferase, deoxythymidine kinase, TK, dTKinase

EC Number: 2.7.1.21/2.7.1.145

thymidine + ATP <=> dTMP + ADP + H+

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the direction of enzyme catalysis.

The reaction is irreversible in the direction shown.

Alternative Substrates for ATP [Chen78 , Okazaki64a ]: ITP , GTP , dCTP , dATP , dGTP

Alternative Substrates for thymidine [Chen78 , Okazaki64a ]: a 5-halogenated analog , 5-mercaptodeoxyuridine , 2'-deoxyuridine

In Pathways: salvage pathways of pyrimidine deoxyribonucleotides

Cofactors or Prosthetic Groups: Mg2+ [Comment 4]

Activators (Allosteric): hydroxymethyl-dCTP [Iwatsuki67, Chen78] , hydroxymethyl-dCDP [Iwatsuki67, Chen78] , 5-bromo-dCTP [Iwatsuki67, Chen78] , 5-iodo-dCTP [Iwatsuki67, Chen78] , ATP [Iwatsuki67, Chen78, Comment 5] , GDP [Iwatsuki67, Chen78] , dGDP [Iwatsuki67, Chen78] , dADP [Iwatsuki67, Chen78] , GTP [Iwatsuki67, Chen78] , dCDP [Iwatsuki67, Chen78] , dGTP [Iwatsuki67, Chen78] , dATP [Iwatsuki67, Chen78] , dCTP [Iwatsuki67, Chen78]

Inhibitors (Competitive): dTTP [Okazaki64a, Chen78, Iwatsuki67, Comment 6]

Primary Physiological Regulators of Enzyme Activity: dCTP , dTTP


Enzymatic reaction of: deoxyuridine kinase

EC Number: 2.7.1.21/2.7.1.145

2'-deoxyuridine + ATP <=> dUMP + ADP + H+

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the direction of enzyme catalysis.

The reaction is irreversible in the direction shown.

In Pathways: salvage pathways of pyrimidine deoxyribonucleotides


Sequence Features

Feature Class Location Citations Comment
Nucleotide-Phosphate-Binding-Region 9 -> 16
[UniProt10]
UniProt: ATP; Non-Experimental Qualifier: probable;
Nucleotide-Phosphate-Binding-Region 87 -> 90
[UniProt10b]
UniProt: ATP; Non-Experimental Qualifier: by similarity;
Active-Site 88
[UniProt10b]
UniProt: Proton acceptor; Non-Experimental Qualifier: potential;
Metal-Binding-Site 145
[UniProt10b]
UniProt: Zinc; Non-Experimental Qualifier: by similarity;
Metal-Binding-Site 147
[UniProt10b]
UniProt: Zinc; Non-Experimental Qualifier: by similarity;
Metal-Binding-Site 182
[UniProt10b]
UniProt: Zinc; Non-Experimental Qualifier: by similarity;
Metal-Binding-Site 185
[UniProt10b]
UniProt: Zinc; Non-Experimental Qualifier: by similarity;


Gene Local Context (not to scale): ?

Transcription Unit:

Notes:

History:
10/20/97 Gene b1238 from Blattner lab Genbank (v. M52) entry merged into EcoCyc gene EG10994; confirmed by SwissProt match.


References

Baba06: Baba T, Ara T, Hasegawa M, Takai Y, Okumura Y, Baba M, Datsenko KA, Tomita M, Wanner BL, Mori H (2006). "Construction of Escherichia coli K-12 in-frame, single-gene knockout mutants: the Keio collection." Mol Syst Biol 2;2006.0008. PMID: 16738554

Chen78: Chen MS, Prusoff WH (1978). "Thymidine kinase from Escherichia coli." Methods Enzymol 1978;51;354-60. PMID: 357898

DiazMejia09: Diaz-Mejia JJ, Babu M, Emili A (2009). "Computational and experimental approaches to chart the Escherichia coli cell-envelope-associated proteome and interactome." FEMS Microbiol Rev 33(1);66-97. PMID: 19054114

Feist07: Feist AM, Henry CS, Reed JL, Krummenacker M, Joyce AR, Karp PD, Broadbelt LJ, Hatzimanikatis V, Palsson BO (2007). "A genome-scale metabolic reconstruction for Escherichia coli K-12 MG1655 that accounts for 1260 ORFs and thermodynamic information." Mol Syst Biol 3;121. PMID: 17593909

GOA01: GOA, DDB, FB, MGI, ZFIN (2001). "Gene Ontology annotation through association of InterPro records with GO terms."

GOA01a: GOA, MGI (2001). "Gene Ontology annotation based on Enzyme Commission mapping." Genomics 74;121-128.

GOA06: GOA, SIB (2006). "Electronic Gene Ontology annotations created by transferring manual GO annotations between orthologous microbial proteins."

Ishihama08: Ishihama Y, Schmidt T, Rappsilber J, Mann M, Hartl FU, Kerner MJ, Frishman D (2008). "Protein abundance profiling of the Escherichia coli cytosol." BMC Genomics 9;102. PMID: 18304323

Iwatsuki67: Iwatsuki N, Okazaki R (1967). "Mechanism of regulation of deoxythymidine kinase of Escherichia coli. I. Effect of regulatory deoxynucleotides on the state of aggregation of the enzyme." J Mol Biol 1967;29(1);139-54. PMID: 4861610

Joyce06: Joyce AR, Reed JL, White A, Edwards R, Osterman A, Baba T, Mori H, Lesely SA, Palsson BO, Agarwalla S (2006). "Experimental and computational assessment of conditionally essential genes in Escherichia coli." J Bacteriol 188(23);8259-71. PMID: 17012394

Okazaki64a: Okazaki R, Kornberg A (1964). "Deoxythymidine Kinase of Escherichia coli I. Purification and some properties of the enzyme." J Biol Chem 1964;239(1):269-274. PMID: 14114853

Okazaki64b: Okazaki R, Kornberg A "Deoxythymidine Kinase of Escherichia coli II. Kinetics and feedback control." J Biol Chem 1964;239(1):275-284.

UniProt10: UniProt Consortium (2010). "UniProt version 2010-07 released on 2010-06-15 00:00:00." Database.

UniProt10b: UniProt Consortium (2010). "UniProt version 2010-12 released on 2010-12-01 00:00:00." Database.

UniProtGOA11: UniProt-GOA (2011). "Gene Ontology annotation based on manual assignment of UniProtKB keywords in UniProtKB/Swiss-Prot entries."

UniProtGOA11a: UniProt-GOA (2011). "Gene Ontology annotation based on the manual assignment of UniProtKB Subcellular Location terms in UniProtKB/Swiss-Prot entries."

Other References Related to Gene Regulation

Oberto10: Oberto J (2010). "FITBAR: a web tool for the robust prediction of prokaryotic regulons." BMC Bioinformatics 11;554. PMID: 21070640


Report Errors or Provide Feedback
Please cite the following article in publications resulting from the use of EcoCyc: Nucleic Acids Research 41:D605-12 2013
Page generated by SRI International Pathway Tools version 18.5 on Fri Nov 28, 2014, biocyc14.