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Escherichia coli K-12 substr. MG1655 Polypeptide: NADH-dependent dihydropyrimidine dehydrogenase subunit



Gene: preA Accession Numbers: EG11289 (EcoCyc), b2147, ECK2140

Synonyms: yeiA

Regulation Summary Diagram: ?

Component of: NAD-dependent dihydropyrimidine dehydrogenase (summary available)

Summary:
Based on sequence similarity, PreA was predicted to be a dihydrothymine/dihydropyrimidine dehydrogenase [Reed03, Serres01]. PreA has similarity to the C-terminal half of mammalian dihydropyrimidine dehydrogenase [Hidese11].

PreA was shown to be in a complex with PreT [Lasserre06, Mihara08] and is required for swarming motility [Inoue07].

Locations: cytosol

Map Position: [2,233,287 -> 2,234,522] (48.13 centisomes)
Length: 1236 bp / 411 aa

Molecular Weight of Polypeptide: 45.069 kD (from nucleotide sequence)

Unification Links: ASAP:ABE-0007098 , DIP:DIP-11915N , EchoBASE:EB1266 , EcoGene:EG11289 , EcoliWiki:b2147 , ModBase:P25889 , OU-Microarray:b2147 , PortEco:yeiA , Protein Model Portal:P25889 , RefSeq:NP_416652 , RegulonDB:EG11289 , SMR:P25889 , String:511145.b2147 , UniProt:P25889

Relationship Links: InterPro:IN-FAMILY:IPR005720 , InterPro:IN-FAMILY:IPR012135 , InterPro:IN-FAMILY:IPR013785 , InterPro:IN-FAMILY:IPR017896 , InterPro:IN-FAMILY:IPR017900 , Pfam:IN-FAMILY:PF01180 , Prosite:IN-FAMILY:PS00198 , Prosite:IN-FAMILY:PS51379

In Paralogous Gene Group: 228 (2 members)

Gene-Reaction Schematic: ?

Genetic Regulation Schematic: ?

GO Terms:

Biological Process: GO:0006208 - pyrimidine nucleobase catabolic process Inferred from experiment [Hidese11]
GO:0006928 - cellular component movement Inferred from experiment [Inoue07]
GO:0006222 - UMP biosynthetic process Inferred by computational analysis [GOA01]
GO:0008152 - metabolic process Inferred by computational analysis [Serres01]
GO:0055114 - oxidation-reduction process Inferred by computational analysis [UniProtGOA11, GOA01]
Molecular Function: GO:0003954 - NADH dehydrogenase activity Inferred from experiment [Hidese11]
GO:0005515 - protein binding Inferred from experiment [Lasserre06, Mihara08]
GO:0051536 - iron-sulfur cluster binding Inferred from experiment Inferred by computational analysis [UniProtGOA11, GOA01, Mihara08]
GO:0003824 - catalytic activity Inferred by computational analysis [GOA01]
GO:0004152 - dihydroorotate dehydrogenase activity Inferred by computational analysis [GOA01]
GO:0004159 - dihydrouracil dehydrogenase (NAD+) activity Inferred by computational analysis [GOA01a, Reed03]
GO:0016491 - oxidoreductase activity Inferred by computational analysis [UniProtGOA11]
GO:0046872 - metal ion binding Inferred by computational analysis [UniProtGOA11]
GO:0051539 - 4 iron, 4 sulfur cluster binding Inferred by computational analysis [UniProtGOA11]
Cellular Component: GO:0005737 - cytoplasm Inferred by computational analysis [GOA01]
GO:0005829 - cytosol Inferred by computational analysis [DiazMejia09]

MultiFun Terms: metabolism

Essentiality data for preA knockouts: ?

Growth Medium Growth? T (°C) O2 pH Osm/L Growth Observations
LB enriched Yes 37 Aerobic 6.95   Yes [Gerdes03, Comment 1]
LB Lennox Yes 37 Aerobic 7   Yes [Baba06, Comment 2]
M9 medium with 1% glycerol Yes 37 Aerobic 7.2 0.35 Yes [Joyce06, Comment 3]
MOPS medium with 0.4% glucose Yes 37 Aerobic 7.2 0.22 Yes [Baba06, Comment 2]

Credits:
Last-Curated ? 20-Mar-2009 by Keseler I , SRI International


Subunit of: NAD-dependent dihydropyrimidine dehydrogenase

Subunit composition of NAD-dependent dihydropyrimidine dehydrogenase = [PreT]2[PreA]2
         NADH-dependent dihydropyrimidine dehydrogenase subunit = PreT (summary available)
         NADH-dependent dihydropyrimidine dehydrogenase subunit = PreA (summary available)

Summary:
The purified and reconstituted PreA/PreT complex was shown to have NAD-dependent dihydropyrimidine dehydrogenase activity [Mihara08, Hidese11]. The enzyme appears to produce dihydrouracil during exponential growth and during stationary phase convert it back to uracil, which can be incorporated into nucleic acids [Hidese11].

A preTA-deficient mutant has no growth defect in LB medium, but it is not producing dihydrouracil [Hidese11].

GO Terms:

Molecular Function: GO:0004159 - dihydrouracil dehydrogenase (NAD+) activity Inferred from experiment [Hidese11, Mihara08]

Credits:
Created 19-Mar-2009 by Keseler I , SRI International
Last-Curated ? 05-Jan-2011 by Keseler I , SRI International


Enzymatic reaction of: dihydropyrimidine dehydrogenase

Synonyms: dihydrouracil dehydrogenase (NAD+), 5,6-dihydrouracil:NAD+ 5-oxidoreductase, DPD

EC Number: 1.3.1.1

5,6-dihydrouracil + NAD+ <=> uracil + NADH + 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.

This reaction is reversible. [Hidese11]

Alternative Substrates for uracil: 5-fluorouracil [Hidese11 ]

Summary:
NADP+ can not substitute for NAD+ [Mihara08].

Km for uracil was measured at pH 6.0, while the Km for 5.6-dihydrouracil was measured at pH 11.0 [Hidese11].

Kinetic Parameters:

Substrate
Km (μM)
Citations
uracil
38.0
[Hidese11]
5,6-dihydrouracil
160.0
[Hidese11]


Enzymatic reaction of: dihydropyrimidine dehydrogenase

Synonyms: dihydrothymine dehydrogenase (NAD+)

EC Number: 1.3.1.1

5,6-dihydrothymine + NAD+ <=> thymine + NADH + 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.

This reaction is reversible. [Hidese11]

Summary:
Km for thymine was measured at pH 6.0, while the Km for 5.6-dihydrothymine was measured at pH 11.0 [Hidese11].

Kinetic Parameters:

Substrate
Km (μM)
Citations
5,6-dihydrothymine
130.0
[Hidese11]
thymine
87.0
[Hidese11]


Sequence Features

Feature Class Location Citations Comment
Amino-Acid-Sites-That-Bind 76
[UniProt12a]
UniProt: Substrate; Non-Experimental Qualifier: by similarity.
Protein-Segment 134 -> 136
[UniProt12a]
UniProt: Substrate binding; Sequence Annotation Type: region of interest; Non-Experimental Qualifier: by similarity.
Active-Site 137
[UniProt11a]
UniProt: Nucleophile; Non-Experimental Qualifier: by similarity.
Protein-Segment 201 -> 202
[UniProt12a]
UniProt: Substrate binding; Sequence Annotation Type: region of interest; Non-Experimental Qualifier: by similarity.
Conserved-Region 335 -> 367
[UniProt09]
UniProt: 4Fe-4S ferredoxin-type 1;
Metal-Binding-Site 344
[UniProt10]
UniProt: Iron-sulfur 1 (4Fe-4S); Non-Experimental Qualifier: potential;
Metal-Binding-Site 347
[UniProt10]
UniProt: Iron-sulfur 1 (4Fe-4S); Non-Experimental Qualifier: potential;
Metal-Binding-Site 350
[UniProt10]
UniProt: Iron-sulfur 1 (4Fe-4S); Non-Experimental Qualifier: potential;
Metal-Binding-Site 354
[UniProt10]
UniProt: Iron-sulfur 2 (4Fe-4S); Non-Experimental Qualifier: potential;
Conserved-Region 369 -> 398
[UniProt09]
UniProt: 4Fe-4S ferredoxin-type 2;
Metal-Binding-Site 378
[UniProt10]
UniProt: Iron-sulfur 2 (4Fe-4S); Non-Experimental Qualifier: potential;
Metal-Binding-Site 381
[UniProt10]
UniProt: Iron-sulfur 2 (4Fe-4S); Non-Experimental Qualifier: potential;
Metal-Binding-Site 384
[UniProt10]
UniProt: Iron-sulfur 2 (4Fe-4S); Non-Experimental Qualifier: potential;
Metal-Binding-Site 388
[UniProt10]
UniProt: Iron-sulfur 1 (4Fe-4S); Non-Experimental Qualifier: potential;
Sequence-Conflict 389 -> 411
[Hogg91, UniProt10a]
Alternate sequence: PVGCIELGEVKFKKGEKEHPVTL → RWVVLSSGK; UniProt: (in Ref. 3; M59444);


Gene Local Context (not to scale): ?

Transcription Unit:

Notes:

History:
Peter D. Karp on Wed Jan 18, 2006:
Gene left-end position adjusted based on analysis performed in the 2005 E. coli annotation update [Riley06 ].
10/20/97 Gene b2147 from Blattner lab Genbank (v. M52) entry merged into EcoCyc gene EG11289; 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

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

Gerdes03: Gerdes SY, Scholle MD, Campbell JW, Balazsi G, Ravasz E, Daugherty MD, Somera AL, Kyrpides NC, Anderson I, Gelfand MS, Bhattacharya A, Kapatral V, D'Souza M, Baev MV, Grechkin Y, Mseeh F, Fonstein MY, Overbeek R, Barabasi AL, Oltvai ZN, Osterman AL (2003). "Experimental determination and system level analysis of essential genes in Escherichia coli MG1655." J Bacteriol 185(19);5673-84. PMID: 13129938

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.

Hidese11: Hidese R, Mihara H, Kurihara T, Esaki N (2011). "Escherichia coli dihydropyrimidine dehydrogenase is a novel NAD-dependent heterotetramer essential for the production of 5,6-dihydrouracil." J Bacteriol 193(4);989-93. PMID: 21169495

Hogg91: Hogg RW, Voelker C, Von Carlowitz I (1991). "Nucleotide sequence and analysis of the mgl operon of Escherichia coli K12." Mol Gen Genet 229(3);453-9. PMID: 1719366

Inoue07: Inoue T, Shingaki R, Hirose S, Waki K, Mori H, Fukui K (2007). "Genome-wide screening of genes required for swarming motility in Escherichia coli K-12." J Bacteriol 189(3);950-7. PMID: 17122336

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

Lasserre06: Lasserre JP, Beyne E, Pyndiah S, Lapaillerie D, Claverol S, Bonneu M (2006). "A complexomic study of Escherichia coli using two-dimensional blue native/SDS polyacrylamide gel electrophoresis." Electrophoresis 27(16);3306-21. PMID: 16858726

Mihara08: Mihara H, Hidese R, Yamane M, Kurihara T, Esaki N (2008). "The iscS gene deficiency affects the expression of pyrimidine metabolism genes." Biochem Biophys Res Commun 372(3);407-11. PMID: 18482579

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

Riley06: Riley M, Abe T, Arnaud MB, Berlyn MK, Blattner FR, Chaudhuri RR, Glasner JD, Horiuchi T, Keseler IM, Kosuge T, Mori H, Perna NT, Plunkett G, Rudd KE, Serres MH, Thomas GH, Thomson NR, Wishart D, Wanner BL (2006). "Escherichia coli K-12: a cooperatively developed annotation snapshot--2005." Nucleic Acids Res 34(1);1-9. PMID: 16397293

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

UniProt09: UniProt Consortium (2009). "UniProt version 15.8 released on 2009-10-01 00:00:00." Database.

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

UniProt10a: UniProt Consortium (2010). "UniProt version 2010-11 released on 2010-11-02 00:00:00." Database.

UniProt11a: UniProt Consortium (2011). "UniProt version 2011-06 released on 2011-06-30 00:00:00." Database.

UniProt12a: UniProt Consortium (2012). "UniProt version 2012-09 released on 2012-09-12 00:00:00." Database.

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

Other References Related to Gene Regulation

MendozaVargas09: Mendoza-Vargas A, Olvera L, Olvera M, Grande R, Vega-Alvarado L, Taboada B, Jimenez-Jacinto V, Salgado H, Juarez K, Contreras-Moreira B, Huerta AM, Collado-Vides J, Morett E (2009). "Genome-wide identification of transcription start sites, promoters and transcription factor binding sites in E. coli." PLoS One 4(10);e7526. PMID: 19838305


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, biocyc13.