Escherichia coli K-12 substr. MG1655 Polypeptide: HPr

Gene: ptsH Accession Numbers: EG10788 (EcoCyc), b2415, ECK2410

Synonyms: ctr, hpr

Regulation Summary Diagram: ?

Regulation summary diagram for ptsH

Alternative forms of HPr: HPr - phosphorylated (summary available)

HPr (histidine protein) is one of two sugar-non-specific protein constituents of the phosphoenolpyruvate:sugar phosphotransferase system (PTSsugar). It accepts a phosphoryl group from phosphorylated Enzyme I (PtsI-P) and then transfers it to the EIIA domain of any one of the many sugar-specific enzymes (collectively known as Enzymes II) of the PTSsugar (reviewed in [Postma93]).

HPr is a small monomeric, single domain, protein that is relatively heat stable [Anderson71]. HPr is phosphorylated at the N-1 position of histidine residue 15 (His-15) [Anderson71, Rajagopal94]. Phosphorylated HPr transfers its phosphate to the active histidine of the sugar transporters of the PTSsugar. Solution structures of the complex between HPr and the N-terminal domain of Enzyme I [Garrett99], and between HPr and the EIIA domain/protein of the glucose-specific PTS [Wang00a], the mannitol PTS [Cornilescu02] and the mannose PTS [Williams05a] have been obtained. HPr uses a consensus surface to interact with the varying proteins of the PTSsugar [Wang00b].

In addition to its role as a phosphorelay protein of the PTSsugar, HPr may also function as a regulatory subunit of glycogen phosphorylase (GlgP) [Seok01]. Purified HPr binds to, and enhances the oligomeric associations of GlgP [Seok97]. Binding of purified HPr to GlgP in vitro decreases the Km of GlgP for glycogen 5-fold. Phosphorylated HPr has 4-fold higher affinity for GlgP than the unphosphorylated form, but does not appear to stimulate the activity of GlgP [Seok97].

Reviews: [Waygood98, Peterkofsky01]

Citations: [Kundig71, Reichenbach07, Koch96, Jia93, vanNuland92]

Gene Citations: [Ryu95, De88, Saffen87]

Locations: cytosol

Map Position: [2,531,786 -> 2,532,043] (54.57 centisomes, 196°)
Length: 258 bp / 85 aa

Molecular Weight of Polypeptide: 9.119 kD (from nucleotide sequence)

Unification Links: ASAP:ABE-0007962 , CGSC:348 , DIP:DIP-35731N , EchoBASE:EB0781 , EcoGene:EG10788 , EcoliWiki:b2415 , Mint:MINT-8085981 , ModBase:P0AA04 , OU-Microarray:b2415 , PortEco:ptsH , PR:PRO_000023632 , Pride:P0AA04 , Protein Model Portal:P0AA04 , RefSeq:NP_416910 , RegulonDB:EG10788 , SMR:P0AA04 , String:511145.b2415 , UniProt:P0AA04

Relationship Links: InterPro:IN-FAMILY:IPR000032 , InterPro:IN-FAMILY:IPR001020 , InterPro:IN-FAMILY:IPR002114 , PDB:Structure:1CM2 , PDB:Structure:1CM3 , PDB:Structure:1GGR , PDB:Structure:1HDN , PDB:Structure:1J6T , PDB:Structure:1OPD , PDB:Structure:1PFH , PDB:Structure:1POH , PDB:Structure:1VRC , PDB:Structure:2JEL , PDB:Structure:2LRK , PDB:Structure:2LRL , PDB:Structure:2XDF , PDB:Structure:3CCD , PDB:Structure:3EZA , PDB:Structure:3EZB , PDB:Structure:3EZE , Pfam:IN-FAMILY:PF00381 , Prints:IN-FAMILY:PR00107 , Prosite:IN-FAMILY:PS00369 , Prosite:IN-FAMILY:PS00589 , Prosite:IN-FAMILY:PS51350

In Reactions of unknown directionality:

Not in pathways:
BglG + HPr-Phis15 = HPr + BglG-Phis208
PtsI-Phis189 + HPr = HPr-Phis15 + PtsI

In Transport reactions:
HPr-Phis15 + N-acetyl-β-D-glucosamine[periplasmic space]N-acetyl-D-glucosamine 6-phosphate[cytosol] + HPr ,
N-acetyl-β-D-mannosamine[periplasmic space] + HPr-Phis15N-acetyl-D-mannosamine 6-phosphate[cytosol] + HPr ,
HPr-Phis15 + β-D-cellobiose[periplasmic space] → β-D-cellobiose 6'-phosphate[cytosol] + HPr ,
arbutin[periplasmic space] + HPr-Phis15 → arbutin-6-phosphate[cytosol] + HPr ,
methyl β-D-glucoside[periplasmic space] + HPr-Phis15 → methyl β-D-glucoside 6-phosphate[cytosol] + HPr ,
β-D-fructofuranose[periplasmic space] + HPr-Phis15 → β-D-fructofuranose 6-phosphate[cytosol] + HPr ,
α-D-mannose[periplasmic space] + HPr-Phis15 → α-D-mannose 6-phosphate[cytosol] + HPr ,
methyl α-D-glucoside[periplasmic space] + HPr-Phis15HPr + methyl α-D-glucoside 6-phosphate[cytosol] ,
HPr-Phis15 + β-D-glucopyranose[periplasmic space] → β-D-glucose 6-phosphate[cytosol] + HPr ,
HPr-Phis15 + L-ascorbate[periplasmic space] → L-ascorbate 6-phosphate[cytosol] + HPr ,
HPr-Phis15 + 2-O-α-mannosyl-D-glycerate[periplasmic space] → 2-O-(6-phospho-α-D-mannosyl)-D-glycerate[cytosol] + HPr ,
HPr-Phis15 + α,α-trehalose[periplasmic space] → α,α-trehalose 6-phosphate[cytosol] + HPr ,
HPr-Phis15 + salicin[periplasmic space] → salicin 6-phosphate[cytosol] + HPr ,
HPr-Phis15 + D-mannitol[periplasmic space] → D-mannitol 1-phosphate[cytosol] + HPr ,
HPr-Phis15 + D-glucosamine[periplasmic space] → D-glucosamine 6-phosphate[cytosol] + HPr ,
HPr-Phis15 + N-acetylmuramate[periplasmic space]N-acetyl-β-muramate 6-phosphate[cytosol] + HPr ,
HPr-Phis15 + N,N'-diacetylchitobiose[periplasmic space]N,N'-diacetylchitobiose 6'-phosphate[cytosol] + HPr ,
HPr-Phis15 + galactitol[periplasmic space] → galactitol 1-phosphate[cytosol] + HPr ,
2-deoxy-D-glucose[periplasmic space] + HPr-Phis15 → 2-deoxy-D-glucose 6-phosphate[cytosol] + HPr ,
HPr-Phis15 + D-sorbitol[periplasmic space] → D-sorbitol 6-phosphate[cytosol] + HPr

Genetic Regulation Schematic: ?

Genetic regulation schematic for ptsH

GO Terms:

Biological Process: GO:0009401 - phosphoenolpyruvate-dependent sugar phosphotransferase system Inferred from experiment Inferred by computational analysis [UniProtGOA11a, Kundig71]
GO:0043085 - positive regulation of catalytic activity Inferred from experiment [Seok97]
GO:0045819 - positive regulation of glycogen catabolic process Inferred from experiment [Seok97]
GO:0006468 - protein phosphorylation Inferred by computational analysis [UniProtGOA11a]
GO:0006810 - transport Inferred by computational analysis [UniProtGOA11a]
GO:0008643 - carbohydrate transport Inferred by computational analysis [UniProtGOA11a]
GO:0016310 - phosphorylation Inferred by computational analysis [UniProtGOA11a]
Molecular Function: GO:0005515 - protein binding Inferred from experiment [Wang00a, Garrett97, Yu12a, Lopian10]
GO:0008047 - enzyme activator activity Inferred from experiment [Seok97]
GO:0008965 - phosphoenolpyruvate-protein phosphotransferase activity Inferred from experiment [Kundig71]
GO:0016301 - kinase activity Inferred from experiment Inferred by computational analysis [UniProtGOA11a, Anderson71]
GO:0004674 - protein serine/threonine 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]
GO:0019197 - phosphoenolpyruvate-dependent sugar phosphotransferase complex Inferred from experiment [Kundig71]
GO:0005737 - cytoplasm Inferred by computational analysis [UniProtGOA11, UniProtGOA11a]

MultiFun Terms: metabolism carbon utilization carbon compounds
transport Accessory Factors Involved in Transport

Essentiality data for ptsH 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 Indeterminate 37 Aerobic 7.2 0.22 Yes [Baba06, Comment 2]
No [Feist07, Comment 4]

Last-Curated ? 07-Jul-2011 by Mackie A , Macquarie University

Sequence Features

Protein sequence of HPr with features indicated

Feature Class Location Citations Comment State
Conserved-Region 1 -> 85
UniProt: HPr;
Active-Site 15
[vanDijk90, UniProt11a]
UniProt: Pros-phosphohistidine intermediate.
Phosphorylation-Modification 15
UniProt: Pros-phosphohistidine intermediate;

Gene Local Context (not to scale): ?

Gene local context diagram

Transcription Units:

Transcription-unit diagram

Transcription-unit diagram

Transcription-unit diagram

Transcription-unit diagram

Transcription-unit diagram

Transcription-unit diagram

Transcription-unit diagram


10/20/97 Gene b2415 from Blattner lab Genbank (v. M52) entry merged into EcoCyc gene EG10788; confirmed by SwissProt match.


Anderson71: Anderson B, Weigel N, Kundig W, Roseman S (1971). "Sugar transport. 3. Purification and properties of a phosphocarrier protein (HPr) of the phosphoenolpyruvate-dependent phosphotransferase system of Escherichia coli." J Biol Chem 246(22);7023-33. PMID: 4942330

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

Cornilescu02: Cornilescu G, Lee BR, Cornilescu CC, Wang G, Peterkofsky A, Clore GM (2002). "Solution structure of the phosphoryl transfer complex between the cytoplasmic A domain of the mannitol transporter IIMannitol and HPr of the Escherichia coli phosphotransferase system." J Biol Chem 277(44);42289-98. PMID: 12202490

De88: De Reuse H, Danchin A (1988). "The ptsH, ptsI, and crr genes of the Escherichia coli phosphoenolpyruvate-dependent phosphotransferase system: a complex operon with several modes of transcription." J Bacteriol 1988;170(9);3827-37. PMID: 2457575

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

Garrett97: Garrett DS, Seok YJ, Peterkofsky A, Clore GM, Gronenborn AM (1997). "Identification by NMR of the binding surface for the histidine-containing phosphocarrier protein HPr on the N-terminal domain of enzyme I of the Escherichia coli phosphotransferase system." Biochemistry 36(15);4393-8. PMID: 9109646

Garrett99: Garrett DS, Seok YJ, Peterkofsky A, Gronenborn AM, Clore GM (1999). "Solution structure of the 40,000 Mr phosphoryl transfer complex between the N-terminal domain of enzyme I and HPr." Nat Struct Biol 6(2);166-73. PMID: 10048929

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

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

Jia93: Jia Z, Quail JW, Waygood EB, Delbaere LT (1993). "The 2.0-A resolution structure of Escherichia coli histidine-containing phosphocarrier protein HPr. A redetermination." J Biol Chem 268(30);22490-501. PMID: 8226757

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

Koch96: Koch S, Sutrina SL, Wu LF, Reizer J, Schnetz K, Rak B, Saier MH (1996). "Identification of a site in the phosphocarrier protein, HPr, which influences its interactions with sugar permeases of the bacterial phosphotransferase system: kinetic analyses employing site-specific mutants." J Bacteriol 178(4);1126-33. PMID: 8576048

Kundig71: Kundig W, Roseman S (1971). "Sugar transport. I. Isolation of a phosphotransferase system from Escherichia coli." J Biol Chem 246(5);1393-406. PMID: 5545082

Lopian10: Lopian L, Elisha Y, Nussbaum-Shochat A, Amster-Choder O (2010). "Spatial and temporal organization of the E. coli PTS components." EMBO J 29(21);3630-45. PMID: 20924357

Peterkofsky01: Peterkofsky A, Wang G, Garrett DS, Lee BR, Seok YJ, Clore GM (2001). "Three-dimensional structures of protein-protein complexes in the E. coli PTS." J Mol Microbiol Biotechnol 3(3);347-54. PMID: 11361064

Postma93: Postma PW, Lengeler JW, Jacobson GR (1993). "Phosphoenolpyruvate:carbohydrate phosphotransferase systems of bacteria." Microbiol Rev 57(3);543-94. PMID: 8246840

Rajagopal94: Rajagopal P, Waygood EB, Klevit RE (1994). "Structural consequences of histidine phosphorylation: NMR characterization of the phosphohistidine form of histidine-containing protein from Bacillus subtilis and Escherichia coli." Biochemistry 33(51);15271-82. PMID: 7803390

Reichenbach07: Reichenbach B, Breustedt DA, Stulke J, Rak B, Gorke B (2007). "Genetic dissection of specificity determinants in the interaction of HPr with enzymes II of the bacterial phosphoenolpyruvate:sugar phosphotransferase system in Escherichia coli." J Bacteriol 189(13);4603-13. PMID: 17449611

Ryu95: Ryu S, Ramseier TM, Michotey V, Saier MH, Garges S (1995). "Effect of the FruR regulator on transcription of the pts operon in Escherichia coli." J Biol Chem 1995;270(6);2489-96. PMID: 7852310

Saffen87: Saffen DW, Presper KA, Doering TL, Roseman S (1987). "Sugar transport by the bacterial phosphotransferase system. Molecular cloning and structural analysis of the Escherichia coli ptsH, ptsI, and crr genes." J Biol Chem 262(33);16241-53. PMID: 2960675

Seok01: Seok YJ, Koo BM, Sondej M, Peterkofsky A (2001). "Regulation of E. coli glycogen phosphorylase activity by HPr." J Mol Microbiol Biotechnol 3(3);385-93. PMID: 11361069

Seok97: Seok YJ, Sondej M, Badawi P, Lewis MS, Briggs MC, Jaffe H, Peterkofsky A (1997). "High affinity binding and allosteric regulation of Escherichia coli glycogen phosphorylase by the histidine phosphocarrier protein, HPr." J Biol Chem 272(42);26511-21. PMID: 9334229

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

UniProt10: 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.

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."

vanDijk90: van Dijk AA, de Lange LC, Bachovchin WW, Robillard GT (1990). "Effect of phosphorylation on hydrogen-bonding interactions of the active site histidine of the phosphocarrier protein HPr of the phosphoenolpyruvate-dependent phosphotransferase system determined by 15N NMR spectroscopy." Biochemistry 29(35);8164-71. PMID: 2261470

vanNuland92: van Nuland NA, Grotzinger J, Dijkstra K, Scheek RM, Robillard GT (1992). "Determination of the three-dimensional solution structure of the histidine-containing phosphocarrier protein HPr from Escherichia coli using multidimensional NMR spectroscopy." Eur J Biochem 210(3);881-91. PMID: 1483471

Wang00a: Wang G, Louis JM, Sondej M, Seok YJ, Peterkofsky A, Clore GM (2000). "Solution structure of the phosphoryl transfer complex between the signal transducing proteins HPr and IIA(glucose) of the Escherichia coli phosphoenolpyruvate:sugar phosphotransferase system." EMBO J 19(21);5635-49. PMID: 11060015

Wang00b: Wang G, Sondej M, Garrett DS, Peterkofsky A, Clore GM (2000). "A common interface on histidine-containing phosphocarrier protein for interaction with its partner proteins." J Biol Chem 275(22);16401-3. PMID: 10764730

Waygood98: Waygood EB (1998). "The structure and function of HPr." Biochem Cell Biol 76(2-3);359-67. PMID: 9923705

Williams05a: Williams DC, Cai M, Suh JY, Peterkofsky A, Clore GM (2005). "Solution NMR structure of the 48-kDa IIAMannose-HPr complex of the Escherichia coli mannose phosphotransferase system." J Biol Chem 280(21);20775-84. PMID: 15788390

Yu12a: Yu TK, Yun YJ, Lee KO, Ahn KJ, Suh JY (2012). "Active site phosphoryl groups in the biphosphorylated phosphotransferase complex reveal dynamics in a millisecond time scale." FEBS Lett 586(10);1439-44. PMID: 22673508

Other References Related to Gene Regulation

De92: De Reuse H, Kolb A, Danchin A (1992). "Positive regulation of the expression of the Escherichia coli pts operon. Identification of the regulatory regions." J Mol Biol 1992;226(3);623-35. PMID: 1324322

Jeong04b: Jeong JY, Kim YJ, Cho N, Shin D, Nam TW, Ryu S, Seok YJ (2004). "Expression of ptsG Encoding the Major Glucose Transporter Is Regulated by ArcA in Escherichia coli." J Biol Chem 279(37);38513-8. PMID: 15252051

Kim99a: Kim SY, Nam TW, Shin D, Koo BM, Seok YJ, Ryu S (1999). "Purification of Mlc and analysis of its effects on the pts expression in Escherichia coli." J Biol Chem 1999;274(36);25398-402. PMID: 10464268

Kumar11: Kumar R, Shimizu K (2011). "Transcriptional regulation of main metabolic pathways of cyoA, cydB, fnr, and fur gene knockout Escherichia coli in C-limited and N-limited aerobic continuous cultures." Microb Cell Fact 10;3. PMID: 21272324

Marzan13: Marzan LW, Hasan CM, Shimizu K (2013). "Effect of acidic condition on the metabolic regulation of Escherichia coli and its phoB mutant." Arch Microbiol 195(3);161-71. PMID: 23274360

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

Plumbridge01: Plumbridge J (2001). "DNA binding sites for the Mlc and NagC proteins: regulation of nagE, encoding the N-acetylglucosamine-specific transporter in Escherichia coli." Nucleic Acids Res 29(2);506-14. PMID: 11139621

Plumbridge99a: Plumbridge J (1999). "Expression of the phosphotransferase system both mediates and is mediated by Mlc regulation in Escherichia coli." Mol Microbiol 33(2);260-73. PMID: 10411743

Ryu94: Ryu S, Garges S (1994). "Promoter switch in the Escherichia coli pts operon." J Biol Chem 269(7);4767-72. PMID: 8106445

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

Shimada11a: Shimada T, Yamamoto K, Ishihama A (2011). "Novel Members of the Cra Regulon Involved in Carbon Metabolism in Escherichia coli." J Bacteriol 193(3);649-59. PMID: 21115656

Shin08: Shin D, Cho N, Kim YJ, Seok YJ, Ryu S (2008). "Up-regulation of the cellular level of Escherichia coli PTS components by stabilizing reduced transcripts of the genes in response to the low oxygen level." Biochem Biophys Res Commun 370(4);609-12. PMID: 18402772

Tanaka99a: Tanaka Y, Kimata K, Inada T, Tagami H, Aiba H (1999). "Negative regulation of the pts operon by Mlc: mechanism underlying glucose induction in Escherichia coli." Genes Cells 4(7);391-9. PMID: 10469172

Zheng04: Zheng D, Constantinidou C, Hobman JL, Minchin SD (2004). "Identification of the CRP regulon using in vitro and in vivo transcriptional profiling." Nucleic Acids Res 32(19);5874-93. PMID: 15520470

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Please cite the following article in publications resulting from the use of EcoCyc: Nucleic Acids Research 41:D605-12 2013
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