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discounted EARLY registration ends Dec 31, 2014
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Metabolic Modeling Tutorial
discounted EARLY registration ends Dec 31, 2014
BioCyc websites down
12/28 - 12/31
for maintenance.
Metabolic Modeling Tutorial
discounted EARLY registration ends Dec 31, 2014
BioCyc websites down
12/28 - 12/31
for maintenance.
Metabolic Modeling Tutorial
discounted EARLY registration ends Dec 31, 2014
BioCyc websites down
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MetaCyc Enzyme: hydroxymethylpyrimidine kinase / phosphohydroxymethylpyrimidine kinase

Gene: thiD Accession Numbers: G7135 (MetaCyc), b2103, ECK2096

Synonyms: thiN, thiA, thiJ, hydroxymethylpyrimidine kinase 2

Species: Escherichia coli K-12 substr. MG1655

Subunit composition of hydroxymethylpyrimidine kinase / phosphohydroxymethylpyrimidine kinase = [ThiD]4

Summary:
Hydroxymethylpyrimidine (HMP) kinase is involved in the biosynthesis of thiamine phosphate. This enzyme catalyzes the conversion of hydroxymethylpyrimidine to its monophosphate (HMP-P) in the presence of ATP. Subsequently, this enzyme catalyzes the conversion of HMP-P to hydroxymethylpyrimidine pyrophosphate (HMP-PP). Therefore, HMP kinase is a bifunctional enzyme catalyzing both HMP kinase and HMP-P kinase reactions. [Mizote89, Mizote99, Reddick98]

There are two HMP kinases in E. coli, the HMP kinase described above is encoded by the thiD gene and the other HMP kinase, also referred to as pyridoxal or pyridoxamine kinase (PdxK), is encoded by the pdxK gene product. Mutations in both genes in the same cell resulted in the complete loss of HMP kinase activity [Mizote96].

Under anaerobiosis, FNR represses thiD gene expression, but it is not known if this regulation is direct or indirect [Salmon03].

Locations: cytosol

Map Position: [2,181,738 <- 2,182,538]

Molecular Weight of Polypeptide: 28.634 kD (from nucleotide sequence), 43.0 kD (experimental) [Mizote89 ]

Unification Links: ASAP:ABE-0006958 , DIP:DIP-6867N , EchoBASE:EB3821 , EcoGene:EG14068 , EcoGene:EG20225 , EcoliWiki:b2103 , ModBase:P76422 , OU-Microarray:b2103 , PortEco:thiD , PR:PRO_000024053 , Pride:P76422 , Protein Model Portal:P76422 , RefSeq:NP_416606 , RegulonDB:G7135 , SMR:P76422 , String:511145.b2103 , Swiss-Model:P76422 , UniProt:P76422

Relationship Links: InterPro:IN-FAMILY:IPR004399 , InterPro:IN-FAMILY:IPR013749 , Pfam:IN-FAMILY:PF08543

Gene-Reaction Schematic: ?

GO Terms:

Biological Process: GO:0009228 - thiamine biosynthetic process Inferred from experiment Inferred by computational analysis [UniProtGOA11a, GOA01a, Mizote99]
GO:0009229 - thiamine diphosphate biosynthetic process Inferred from experiment Inferred by computational analysis [UniProtGOA12, Mizote99]
GO:0016310 - phosphorylation Inferred from experiment Inferred by computational analysis [UniProtGOA11a, Mizote89]
Molecular Function: GO:0008902 - hydroxymethylpyrimidine kinase activity Inferred from experiment Inferred by computational analysis [GOA01, Mizote89]
GO:0000166 - nucleotide binding Inferred by computational analysis [UniProtGOA11a]
GO:0005524 - ATP binding Inferred by computational analysis [UniProtGOA11a]
GO:0008972 - phosphomethylpyrimidine kinase activity Inferred by computational analysis [GOA01, GOA01a]
GO:0016301 - kinase activity Inferred by computational analysis [UniProtGOA11a]
GO:0016740 - transferase activity Inferred by computational analysis [UniProtGOA11a]
Cellular Component: GO:0005829 - cytosol Inferred from experiment Inferred by computational analysis [DiazMejia09, Ishihama08, LopezCampistrou05]

MultiFun Terms: metabolism biosynthesis of building blocks cofactors, small molecule carriers thiamin

Credits:
Imported from EcoCyc 16-Sep-2014 by Paley S , SRI International


Enzymatic reaction of: hydroxymethylpyrimidine kinase

Synonyms: ATP:4-amino-5-hydroxymethyl-2-methylpyrimidine 5-phosphotransferase, HMP kinase

EC Number: 2.7.1.49

ATP + hydroxymethylpyrimidine <=> ADP + 4-amino-2-methyl-5-phosphomethylpyrimidine + H+

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the Enzyme Commission system.

The reaction is favored in the direction shown.

In Pathways: thiamin salvage II , hydroxymethylpyrimidine salvage

Credits:
Imported from EcoCyc 16-Sep-2014 by Paley S , SRI International

Inhibitors (Competitive): pyridoxine (Kic = 2.7µM) [Mizote89]

Kinetic Parameters:

Substrate
Km (μM)
Citations
hydroxymethylpyrimidine
66.0
[Mizote89]

pH(opt): 6.0 [Mizote89]


Enzymatic reaction of: phosphohydroxymethylpyrimidine kinase

Synonyms: ATP:4-amino-2methyl-5-phosphomethylpyrimidine phosphotransferase, 4-amino-5-hydroxymethyl-2-methylpyrimidine phosphate kinase, HMP-P kinase

EC Number: 2.7.4.7

4-amino-2-methyl-5-phosphomethylpyrimidine + ATP <=> 4-amino-2-methyl-5-diphosphomethylpyrimidine + ADP

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the Enzyme Commission system.

The reaction is favored in the direction shown.

In Pathways: superpathway of thiamin diphosphate biosynthesis I , thiamin salvage II , 4-amino-2-methyl-5-diphosphomethylpyrimidine biosynthesis , hydroxymethylpyrimidine salvage

Credits:
Imported from EcoCyc 16-Sep-2014 by Paley S , SRI International


Sequence Features

Feature Class Location Citations Comment
Amino-Acid-Sites-That-Bind 44
[UniProt10]
UniProt: Substrate; Non-Experimental Qualifier: by similarity;

History:
3/2/1998 (pkarp) Merged genes G193/EG20225 and G7135/thiD
Markus Krummenacker on Tue Oct 14, 1997:
Gene object created from Blattner lab Genbank (v. M52) entry.


References

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

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."

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

LopezCampistrou05: Lopez-Campistrous A, Semchuk P, Burke L, Palmer-Stone T, Brokx SJ, Broderick G, Bottorff D, Bolch S, Weiner JH, Ellison MJ (2005). "Localization, annotation, and comparison of the Escherichia coli K-12 proteome under two states of growth." Mol Cell Proteomics 4(8);1205-9. PMID: 15911532

Mizote89: Mizote T, Nakayama H (1989). "Purification and properties of hydroxymethylpyrimidine kinase from Escherichia coli." Biochim Biophys Acta 1989;991(1);109-13. PMID: 2540841

Mizote96: Mizote T, Tsuda M, Nakazawa T, Nakayama H (1996). "The thiJ locus and its relation to phosphorylation of hydroxymethylpyrimidine in Escherichia coli." Microbiology 1996;142 ( Pt 10);2969-74. PMID: 8885414

Mizote99: Mizote T, Tsuda M, Smith DD, Nakayama H, Nakazawa T (1999). "Cloning and characterization of the thiD/J gene of Escherichia coli encoding a thiamin-synthesizing bifunctional enzyme, hydroxymethylpyrimidine kinase/phosphomethylpyrimidine kinase." Microbiology 1999;145 ( Pt 2);495-501. PMID: 10075431

Reddick98: Reddick JJ, Kinsland C, Nicewonger R, Christian T, Downs DM, Winkler ME, Begley TP "Overexpression, purification and characterization of two pyrimidine kinases involved in the biosynthesis of thiamin: 4-amino-5-hydroxymethyl-2-methylpyrimidine kinase and 4-amino-5-hydroxymethyl-2-methylpyrimidine phosphate kinase." Tetrahedron 54:15983-15991 (1998).

Salmon03: Salmon K, Hung SP, Mekjian K, Baldi P, Hatfield GW, Gunsalus RP (2003). "Global gene expression profiling in Escherichia coli K12. The effects of oxygen availability and FNR." J Biol Chem 278(32);29837-55. PMID: 12754220

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

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

UniProtGOA12: UniProt-GOA (2012). "Gene Ontology annotation based on UniPathway vocabulary mapping."


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 SRI International Pathway Tools version 18.5 on Sat Dec 20, 2014, BIOCYC13B.