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Escherichia coli K-12 substr. MG1655 Transporter: tripeptide / dipeptide:H+ symporter DtpA



Gene: dtpA Accession Numbers: G6877 (EcoCyc), b1634, ECK1630

Synonyms: ydgR, tppB, TppB peptide POT transporter

Regulation Summary Diagram: ?

Summary:
The DtpA protein (formerly TppB) is a member of the POT (proton-dependent oligopeptide transporter) family of peptide transporters [Paulsen94] also known as the PTR (peptide transport) family. DtpA is responsible for proton-dependent transport of di- and tripeptides as well as some structurally related peptidomimetics like B-lactam antibiotics [Weitz07, Harder08]. DtpA transports the tetrapeptide, tetraalanine in vitro [Prabhala14] however tetraalanine does not function as an inhibitor in competitive transport assays [Weitz07]. DtpA shows a preference for di- and tripeptides composed of L amino acids and for peptides containing a positively charged side chain in the N-terminal position [Harder08].

Transmission electron microscopy of solubilised DtpA suggests a monomeric crown-like structure with a pore of approximately 8 nm [Weitz07]. DtpA is predicted to contain 14 transmembrane regions with both termini located in the cytoplasm [Bippes13]. Characterisation of DtpA embedded in a lipid membrane indicates that the protein adopts two alternate conformational states defined largely by the stabilisation of transmembrane helix 2 (TMH2). Binding of an inhibitor molecule shifts the equilibrium between these two states towards the conformation containing a stabilised TMH2 [Bippes13].

dtpA was identified as a member of the OmpR regulon in a DNA microarray experiment [Oshima02]. dtpA expression is transcriptionally regulated by OmpR, but is not sensitive to changes in medium osmolarity [Goh04].

tpp: tripeptide permease
dtpA: dipeptide and tripeptide permease A

Citations: [Alves80, Goodell87, Smith90, Payne01, Smith99, Malle11]

Locations: inner membrane

Map Position: [1,710,793 -> 1,712,295] (36.87 centisomes)
Length: 1503 bp / 500 aa

Molecular Weight of Polypeptide: 53.991 kD (from nucleotide sequence), 39.0 kD (experimental) [Weitz07 ]

Unification Links: ASAP:ABE-0005469 , EchoBASE:EB3698 , EcoGene:EG13939 , EcoliWiki:b1634 , ModBase:P77304 , OU-Microarray:b1634 , PortEco:tppB , PR:PRO_000024094 , Protein Model Portal:P77304 , RefSeq:NP_416151 , RegulonDB:G6877 , SMR:P77304 , String:511145.b1634 , UniProt:P77304

Relationship Links: InterPro:IN-FAMILY:IPR000109 , InterPro:IN-FAMILY:IPR005279 , InterPro:IN-FAMILY:IPR016196 , InterPro:IN-FAMILY:IPR018456 , InterPro:IN-FAMILY:IPR020846 , InterPro:IN-FAMILY:IPR023517 , Panther:IN-FAMILY:PTHR11654 , Panther:IN-FAMILY:PTHR11654:SF6 , Pfam:IN-FAMILY:PF00854 , Prosite:IN-FAMILY:PS01022 , Prosite:IN-FAMILY:PS01023 , Prosite:IN-FAMILY:PS50850

Gene-Reaction Schematic: ?

Genetic Regulation Schematic: ?

GO Terms:

Biological Process: GO:0006857 - oligopeptide transport Inferred from experiment Inferred by computational analysis [GOA01a, Harder08]
GO:0035442 - dipeptide transmembrane transport Inferred from experiment [Harder08, Weitz07]
GO:0035443 - tripeptide transmembrane transport Inferred from experiment [Weitz07]
GO:0042891 - antibiotic transport Inferred from experiment [Harder08]
GO:1902600 - hydrogen ion transmembrane transport Inferred from experiment [Weitz07]
GO:0006810 - transport Inferred by computational analysis [UniProtGOA11a, GOA01a]
GO:0015031 - protein transport Inferred by computational analysis [UniProtGOA11a]
GO:0015833 - peptide transport Inferred by computational analysis [UniProtGOA11a, GOA01a]
GO:0042938 - dipeptide transport Inferred by computational analysis [GOA06]
GO:0042939 - tripeptide transport Inferred by computational analysis [GOA06]
Molecular Function: GO:0015078 - hydrogen ion transmembrane transporter activity Inferred from experiment [Weitz07, Harder08]
GO:0015293 - symporter activity Inferred from experiment [Harder08]
GO:0015333 - peptide:proton symporter activity Inferred from experiment Inferred by computational analysis [GOA06, Weitz07, Harder08]
GO:0042895 - antibiotic transporter activity Inferred from experiment [Harder08]
GO:0042937 - tripeptide transporter activity Inferred from experiment Inferred by computational analysis [GOA06, Weitz07]
GO:0071916 - dipeptide transmembrane transporter activity Inferred from experiment [Harder08, Weitz07]
GO:0005215 - transporter activity Inferred by computational analysis [GOA01a]
GO:0015197 - peptide transporter activity Inferred by computational analysis [GOA01a]
GO:0042936 - dipeptide transporter activity Inferred by computational analysis [GOA06]
Cellular Component: GO:0005886 - plasma membrane Inferred from experiment Inferred by computational analysis [UniProtGOA11, UniProtGOA11a, DiazMejia09, Zhang07, Daley05]
GO:0005887 - integral component of plasma membrane Inferred from experiment Inferred by computational analysis [GOA06, Bippes13, Weitz07]
GO:0016021 - integral component of membrane Inferred from experiment Inferred by computational analysis [UniProtGOA11a, Harder08]
GO:0016020 - membrane Inferred by computational analysis [UniProtGOA11a, GOA01a]

MultiFun Terms: cell structure membrane
transport Electrochemical potential driven transporters Porters (Uni-, Sym- and Antiporters)

Essentiality data for dtpA 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]

Credits:
Last-Curated ? 19-Feb-2014 by Mackie A , Macquarie University


Enzymatic reaction of: transport of a dipeptide (tripeptide / dipeptide:H+ symporter DtpA)

Summary:
DtpA transports glycyl-sarcosine with an apparent Km of 1mM [Harder08].


Enzymatic reaction of: transport of a tripeptide (tripeptide / dipeptide:H+ symporter DtpA)

Alternative Products for a tripeptide: 5-aminolevulinate [Weitz07 ] , glycylsarcosine [Weitz07 ] , a dipeptide [Weitz07 ] , cephalexin [Weitz07 ] , cephalexin [Weitz07 ] , val-FMDP [Marshall03 ] , tyr-FMDP [Marshall03 ] , phe-FMDP [Marshall03 ] , nva-FMDP [Marshall03 ] , met-FMDP [Marshall03 ] , nva-FMDB [Marshall03 ] , lysyl-Z-nitro-proline [Weitz07 ] , beta-alanyl-lysyl-AMCA [Weitz07 ] , cefadroxil [Weitz07 ] , alafosfalin [Weitz07 ] , cefuroxime [Weitz07 ] , cephradine [Weitz07 ] , cefamandole [Weitz07 ] , captopril [Weitz07 ] , enalapril [Weitz07 ]


Sequence Features

Feature Class Location Citations Comment
Transmembrane-Region 22 -> 44
[UniProt10]
UniProt: Helical;; Non-Experimental Qualifier: potential;
Transmembrane-Region 60 -> 80
[UniProt10a]
UniProt: Helical;; Non-Experimental Qualifier: potential;
Transmembrane-Region 90 -> 110
[UniProt10a]
UniProt: Helical;; Non-Experimental Qualifier: potential;
Transmembrane-Region 112 -> 132
[UniProt10a]
UniProt: Helical;; Non-Experimental Qualifier: potential;
Transmembrane-Region 154 -> 174
[UniProt10a]
UniProt: Helical;; Non-Experimental Qualifier: potential;
Transmembrane-Region 179 -> 199
[UniProt10a]
UniProt: Helical;; Non-Experimental Qualifier: potential;
Transmembrane-Region 220 -> 240
[UniProt10]
UniProt: Helical;; Non-Experimental Qualifier: potential;
Transmembrane-Region 247 -> 267
[UniProt10a]
UniProt: Helical;; Non-Experimental Qualifier: potential;
Transmembrane-Region 275 -> 295
[UniProt10a]
UniProt: Helical;; Non-Experimental Qualifier: potential;
Transmembrane-Region 321 -> 341
[UniProt10a]
UniProt: Helical;; Non-Experimental Qualifier: potential;
Transmembrane-Region 353 -> 373
[UniProt10a]
UniProt: Helical;; Non-Experimental Qualifier: potential;
Transmembrane-Region 379 -> 399
[UniProt10a]
UniProt: Helical;; Non-Experimental Qualifier: potential;
Transmembrane-Region 415 -> 435
[UniProt10a]
UniProt: Helical;; Non-Experimental Qualifier: potential;
Transmembrane-Region 460 -> 480
[UniProt10a]
UniProt: Helical;; Non-Experimental Qualifier: potential;


Gene Local Context (not to scale): ?

Transcription Unit:

Notes:

History:
Amanda Mackie on Wed Feb 19, 2014:
Gene name changed from tppA (tripeptide permease) to dptA (dipeptide and tripeptide permease) as a result of functional studies (PMID 18485005) - A. Mackie 20/2/2014
Markus Krummenacker on Tue Oct 14, 1997:
Gene object created from Blattner lab Genbank (v. M52) entry.


References

Alves80: Alves RA, Payne JW (1980). "The number and nature of the peptide-transport systems of Escherichia coli: characterization of specific transport mutants." Biochem Soc Trans 8(6);704-5. PMID: 7007121

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

Bippes13: Bippes CA, Ge L, Meury M, Harder D, Ucurum Z, Daniel H, Fotiadis D, Muller DJ (2013). "Peptide transporter DtpA has two alternate conformations, one of which is promoted by inhibitor binding." Proc Natl Acad Sci U S A 110(42);E3978-86. PMID: 24082128

Daley05: Daley DO, Rapp M, Granseth E, Melen K, Drew D, von Heijne G (2005). "Global topology analysis of the Escherichia coli inner membrane proteome." Science 308(5726);1321-3. PMID: 15919996

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

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."

Goh04: Goh EB, Siino DF, Igo MM (2004). "The Escherichia coli tppB (ydgR) gene represents a new class of OmpR-regulated genes." J Bacteriol 186(12);4019-24. PMID: 15175316

Goodell87: Goodell EW, Higgins CF (1987). "Uptake of cell wall peptides by Salmonella typhimurium and Escherichia coli." J Bacteriol 169(8);3861-5. PMID: 3301822

Harder08: Harder D, Stolz J, Casagrande F, Obrdlik P, Weitz D, Fotiadis D, Daniel H (2008). "DtpB (YhiP) and DtpA (TppB, YdgR) are prototypical proton-dependent peptide transporters of Escherichia coli." FEBS J 275(13):3290-8. PMID: 18485005

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

Malle11: Malle E, Zhou H, Neuhold J, Spitzenberger B, Klepsch F, Pollak T, Bergner O, Ecker GF, Stolt-Bergner PC (2011). "Random mutagenesis of the prokaryotic peptide transporter YdgR identifies potential periplasmic gating residues." J Biol Chem 286(26);23121-31. PMID: 21558271

Marshall03: Marshall NJ, Andruszkiewicz R, Gupta S, Milewski S, Payne JW (2003). "Structure-activity relationships for a series of peptidomimetic antimicrobial prodrugs containing glutamine analogues." J Antimicrob Chemother 51(4);821-31. PMID: 12654735

Oshima02: Oshima T, Aiba H, Masuda Y, Kanaya S, Sugiura M, Wanner BL, Mori H, Mizuno T (2002). "Transcriptome analysis of all two-component regulatory system mutants of Escherichia coli K-12." Mol Microbiol 46(1);281-91. PMID: 12366850

Paulsen94: Paulsen IT, Skurray RA (1994). "The POT family of transport proteins." Trends Biochem Sci 1994;19(10);404. PMID: 7817396

Payne01: Payne JW, Payne GM, Gupta S, Marshall NJ, Grail BM (2001). "Conformational limitations of glycylsarcosine as a prototypic substrate for peptide transporters." Biochim Biophys Acta 1514(1);65-75. PMID: 11513805

Prabhala14: Prabhala BK, Aduri NG, Jensen JM, Ernst HA, Iram N, Rahman M, Mirza O (2014). "New insights into the substrate specificities of proton-coupled oligopeptide transporters from E. coli by a pH sensitive assay." FEBS Lett 588(4);560-5. PMID: 24440353

Smith90: Smith MW, Payne JW (1990). "Simultaneous exploitation of different peptide permeases by combinations of synthetic peptide smugglins can lead to enhanced antibacterial activity." FEMS Microbiol Lett 58(3);311-6. PMID: 2227366

Smith99: Smith MW, Tyreman DR, Payne GM, Marshall NJ, Payne JW (1999). "Substrate specificity of the periplasmic dipeptide-binding protein from Escherichia coli: experimental basis for the design of peptide prodrugs." Microbiology 1999;145 ( Pt 10);2891-901. PMID: 10537211

UniProt10: UniProt Consortium (2010). "UniProt version 2010-11 released on 2010-11-02 00:00:00." Database.

UniProt10a: UniProt Consortium (2010). "UniProt version 2010-07 released on 2010-06-15 00:00:00." 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."

Weitz07: Weitz D, Harder D, Casagrande F, Fotiadis D, Obrdlik P, Kelety B, Daniel H (2007). "Functional and structural characterization of a prokaryotic peptide transporter with features similar to mammalian PEPT1." J Biol Chem 282(5);2832-9. PMID: 17158458

Zhang07: Zhang N, Chen R, Young N, Wishart D, Winter P, Weiner JH, Li L (2007). "Comparison of SDS- and methanol-assisted protein solubilization and digestion methods for Escherichia coli membrane proteome analysis by 2-D LC-MS/MS." Proteomics 7(4);484-93. PMID: 17309111

Other References Related to Gene Regulation

Raivio13: Raivio TL, Leblanc SK, Price NL (2013). "The Escherichia coli Cpx envelope stress response regulates genes of diverse function that impact antibiotic resistance and membrane integrity." J Bacteriol 195(12);2755-67. PMID: 23564175


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, biocyc12.