Updated BioCyc iOS App now
available in iTunes store
Updated BioCyc iOS App now
available in iTunes store
Updated BioCyc iOS App now
available in iTunes store
Updated BioCyc iOS App now
available in iTunes store
Updated BioCyc iOS App now
available in iTunes store
twitter

MetaCyc Enzyme: NAD kinase

Gene: nadK Accession Numbers: EG12192 (MetaCyc), b2615, ECK2611

Synonyms: yfjE, yfjB

Species: Escherichia coli K-12 substr. MG1655

Subunit composition of NAD kinase = [NadK]6
         NAD kinase monomer = NadK

Summary:
NAD kinase appears to be an allosteric enzyme, with activity tightly coupled to the NADPH/NADP+ and NADH/NAD+ ratios present in the cell. That suggests that NAD kinase may play an important role in the regulation of NADP turnover and size of the NADP pool [Zerez87, Kawai01a].

nadK is likely essential for growth [Gerdes02, Baba06].

Site-directed mutagenesis studies of the E. coli enzyme showed that a R175G mutation relaxed the strict NAD substrate specificity of the enzyme, resulting in a low level of ATP-dependent NADH kinase activity [Mori05].

Structure-function relationships in NAD kinases from archaea, bacteria (including E. coli) and eukaryotes have been reviewed [Magni06, Kawai08, Shi09].

Locations: cytosol

Map Position: [2,748,853 -> 2,749,731]

Molecular Weight of Polypeptide: 32.566 kD (from nucleotide sequence), 30 kD (experimental) [Kawai01a]

Molecular Weight of Multimer: 180.0 kD (experimental) [Kawai01a]

Unification Links: ASAP:ABE-0008603, DIP:DIP-48103N, EchoBASE:EB2109, EcoGene:EG12192, EcoliWiki:b2615, OU-Microarray:b2615, PortEco:nadK, Pride:P0A7B3, Protein Model Portal:P0A7B3, RefSeq:NP_417105, RegulonDB:EG12192, SMR:P0A7B3, String:511145.b2615, Swiss-Model:P0A7B3, UniProt:P0A7B3

Relationship Links: InterPro:IN-FAMILY:IPR002504, InterPro:IN-FAMILY:IPR016064, InterPro:IN-FAMILY:IPR017437, InterPro:IN-FAMILY:IPR017438, Panther:IN-FAMILY:PTHR20275, Pfam:IN-FAMILY:PF01513

Gene-Reaction Schematic

Gene-Reaction Schematic


GO Terms:
Biological Process:
Inferred from experimentInferred by computational analysisGO:0006741 - NADP biosynthetic process [GOA06, GOA01a, Kawai01a]
Inferred by computational analysisGO:0008152 - metabolic process [GOA01a]
Inferred by computational analysisGO:0016310 - phosphorylation [UniProtGOA11a]
Inferred by computational analysisGO:0019674 - NAD metabolic process [GOA01a]
Molecular Function:
Inferred from experimentInferred by computational analysisGO:0003951 - NAD+ kinase activity [GOA06, GOA01, GOA01a, Kawai01a]
Inferred from experimentInferred by computational analysisGO:0005524 - ATP binding [UniProtGOA11a, Mori05]
Inferred from experimentGO:0042802 - identical protein binding [Kawai01a]
Inferred from experimentGO:0051287 - NAD binding [Mori05]
Inferred by computational analysisGO:0000166 - nucleotide binding [UniProtGOA11a]
Inferred by computational analysisGO:0016301 - kinase activity [UniProtGOA11a]
Inferred by computational analysisGO:0016740 - transferase activity [UniProtGOA11a]
Inferred by computational analysisGO:0046872 - metal ion binding [GOA06]
Cellular Component:
Inferred from experimentInferred by computational analysisGO:0005829 - cytosol [DiazMejia09, Watt07]
Inferred by computational analysisGO:0005737 - cytoplasm [UniProtGOA11, UniProtGOA11a, GOA06]

MultiFun Terms: metabolismbiosynthesis of building blockscofactors, small molecule carriersnicotinamide adenine dinucleotide

Credits:
Imported from EcoCyc 30-Sep-2015 by Paley S, SRI International


Enzymatic reaction of: NAD kinase

Inferred by computational analysisInferred from experiment

Synonyms: ATP:NAD+ 2'-phosphotransferase, ATP-NAD kinase

EC Number: 2.7.1.23

ATP + NAD+ → ADP + NADP+ + H+

The direction shown, i.e. which substrates are on the left and right sides, is in accordance with the Enzyme Commission system.

The reaction is favored in the direction shown.

Alternative Substrates for ATP: dTTP [Kawai01a ], GTP [Kawai01a ], dATP [Kawai01a ], UTP [Kawai01a ], CTP [Kawai01a ]

In Pathways: NAD phosphorylation and transhydrogenation, NAD phosphorylation and dephosphorylation

Credits:
Imported from EcoCyc 30-Sep-2015 by Paley S, SRI International

Summary:
The enzyme catalyzes the ATP-dependent phosphorylation of NAD+ and has strict substrate specificity for NAD+ [Mori05].

Cofactors or Prosthetic Groups: Mg2+ [Kawai01a, Zerez87]

Inhibitors (Allosteric): NADH [Kawai01a, Zerez87], NADPH [Kawai01a, Zerez87]

Primary Physiological Regulators of Enzyme Activity: NADH, NADPH

Kinetic Parameters:
Substrate Km (μM) kcat (sec-1) kcat/Km (sec-1 μM-1) Citations
ATP 230.0 [Mori05, BRENDA14]
ATP 2500.0 55.0 0.022 [Kawai01a, BRENDA14]
NAD+ 1850.0 [Mori05, BRENDA14]
NAD+ 2000.0 125.0 0.062 [Kawai01a]

T(opt): 60 °C [BRENDA14, Kawai01a]

pH(opt): 7.5 [Kawai01a]


Sequence Features

Feature Class Location Attached Group Citations Comment
Active-Site 73  
Inferred by computational analysis[UniProt15]
UniProt: Proton acceptor.
Nucleotide-Phosphate-Binding-Region 73 -> 74 NAD+
Inferred by computational analysis[UniProt15]
UniProt: NAD.
Nucleotide-Phosphate-Binding-Region 147 -> 148 NAD+
Inferred by computational analysis[UniProt15]
UniProt: NAD.
Amino-Acid-Sites-That-Bind 158  
Inferred by computational analysis[UniProt15]
UniProt: NAD.
Mutagenesis-Variant 175  
Inferred from experiment[Mori05]
Inferred from experiment[Mori05]
Inferred from experiment[Mori05]
E, I or K: Does not exhibit NADH kinase activity in addition to NAD kinase activity.
H, Q or T: Exhibits NADH kinase activity in addition to NAD kinase activity.
G: Exhibits NADH kinase activity in addition to NAD kinase activity. Reduces the Vmax of the NAD kinase activity.
Amino-Acid-Sites-That-Bind 175  
Inferred by computational analysis[UniProt15]
UniProt: NAD.
Amino-Acid-Sites-That-Bind 177  
Inferred by computational analysis[UniProt15]
UniProt: NAD.
Amino-Acid-Sites-That-Bind 185  
Inferred by computational analysis[UniProt15]
UniProt: NAD; via carbonyl oxygen.
Nucleotide-Phosphate-Binding-Region 188 -> 193 NAD+
Inferred by computational analysis[UniProt15]
UniProt: NAD.
Amino-Acid-Sites-That-Bind 247  
Inferred by computational analysis[UniProt15]
UniProt: NAD.

History:
Peter D. Karp on Thu Jan 16, 2003:
Predicted gene function revised as a result of E. coli genome reannotation by Serres et al. [Serres01].
10/20/97 Gene b2615 from Blattner lab Genbank (v. M52) entry merged into EcoCyc gene EG12192; 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

BRENDA14: BRENDA team (2014). Imported from BRENDA version existing on Aug 2014.

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

Gerdes02: Gerdes SY, Scholle MD, D'Souza M, Bernal A, Baev MV, Farrell M, Kurnasov OV, Daugherty MD, Mseeh F, Polanuyer BM, Campbell JW, Anantha S, Shatalin KY, Chowdhury SA, Fonstein MY, Osterman AL (2002). "From genetic footprinting to antimicrobial drug targets: examples in cofactor biosynthetic pathways." J Bacteriol 184(16);4555-72. PMID: 12142426

GOA01: GOA, MGI (2001). "Gene Ontology annotation based on Enzyme Commission mapping." Genomics 74;121-128.

GOA01a: GOA, DDB, FB, MGI, ZFIN (2001). "Gene Ontology annotation through association of InterPro records with GO terms."

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

Imsande62: Imsande J, Pardee AB (1962). "Regulation of pyridine nucleotide biosynthesis in Escherichia coli." J Biol Chem 237(4):1305-8.

Kawai01a: Kawai S, Mori S, Mukai T, Hashimoto W, Murata K (2001). "Molecular characterization of Escherichia coli NAD kinase." Eur J Biochem 268(15);4359-65. PMID: 11488932

Kawai08: Kawai S, Murata K (2008). "Structure and function of NAD kinase and NADP phosphatase: key enzymes that regulate the intracellular balance of NAD(H) and NADP(H)." Biosci Biotechnol Biochem 72(4);919-30. PMID: 18391451

Magni06: Magni G, Orsomando G, Raffaelli N (2006). "Structural and functional properties of NAD kinase, a key enzyme in NADP biosynthesis." Mini Rev Med Chem 6(7);739-46. PMID: 16842123

Mori05: Mori S, Kawai S, Shi F, Mikami B, Murata K (2005). "Molecular conversion of NAD kinase to NADH kinase through single amino acid residue substitution." J Biol Chem 280(25);24104-12. PMID: 15855156

Reed03: Reed JL, Vo TD, Schilling CH, Palsson BO (2003). "An expanded genome-scale model of Escherichia coli K-12 (iJR904 GSM/GPR)." Genome Biol 4(9);R54. PMID: 12952533

Serres01: Serres MH, Gopal S, Nahum LA, Liang P, Gaasterland T, Riley M (2001). "A functional update of the Escherichia coli K-12 genome." Genome Biol 2(9);RESEARCH0035. PMID: 11574054

Shi09: Shi F, Li Y, Wang X (2009). "Molecular properties, functions, and potential applications of NAD kinases." Acta Biochim Biophys Sin (Shanghai) 41(5);352-61. PMID: 19430699

UniProt15: UniProt Consortium (2015). "UniProt version 2015-08 released on 2015-07-22." Database.

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

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

Watt07: Watt RM, Wang J, Leong M, Kung HF, Cheah KS, Liu D, Danchin A, Huang JD (2007). "Visualizing the proteome of Escherichia coli: an efficient and versatile method for labeling chromosomal coding DNA sequences (CDSs) with fluorescent protein genes." Nucleic Acids Res 35(6);e37. PMID: 17272300

Zerez87: Zerez CR, Moul DE, Gomez EG, Lopez VM, Andreoli AJ (1987). "Negative modulation of Escherichia coli NAD kinase by NADPH and NADH." J Bacteriol 1987;169(1);184-8. PMID: 3025169


Report Errors or Provide Feedback
Please cite the following article in publications resulting from the use of MetaCyc: Caspi et al, Nucleic Acids Research 42:D459-D471 2014
Page generated by Pathway Tools version 19.5 (software by SRI International) on Sun May 1, 2016, biocyc11.