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Escherichia coli K-12 substr. MG1655 Enzyme: EfeB dimer

Gene: efeB Accession Numbers: EG11735 (EcoCyc), b1019, ECK1009

Synonyms: ycdB

Regulation Summary Diagram

Regulation summary diagram for efeB

Component of: EfeU/EfeO/EfeB ferrous iron transporter; cryptic (extended summary available)

Subunit composition of EfeB dimer = [EfeB]2
         heme-containing peroxidase/deferrochelatase = EfeB

EfeB is a heme-containing component of the cryptic EfeUOB ferrous iron transporter.

Due to the lack of an outer membrane receptor for heme, E. coli K-12 is unable to utilize heme as a source of iron [Sasarman68, McConville79b]. However, expression of the heme receptor protein HasR from Serratia marcescens enables utilization of heme as a source of iron. This requires the presence of either the Dpp dipeptide ABC transporter or of the EfeUO transporter, which is not functional in E. coli K-12 due to a frameshift mutation disrupting efeU. Similar to YfeX, the EfeB protein, although it is normally transported to the periplasm, is able to catalyze the cytoplasmic release of iron from hemin without destroying the tetrapyrrol ring [Letoffe09].

EfeB is a dimeric, non-covalently bound heme-containing peroxidase enzyme of the DyP-type peroxidase family, and is a substrate of the twin arginine translocation (Tat) system [Sturm06]. The Tat-system allows EfeB to assemble in the cytoplasm prior to transport [Sturm06]. The heme cofactor has been identified as FeIII-protoporphyrin IX [Sturm06].

EfeB may act to reduce Fe3+ to Fe2+ for transport or to oxidize Fe2+ during transport [Cao07]. EfeB exhibits guaiacol peroxidase activity at an optimum pH of about 4.0 and may function under acid-stress conditions [Sturm06].

The crystal structure of EfeB has been determined in the apo form to a resolution of 2.0 Å; crystals with bound haem were obtained and diffract to 2.9 Å [Cartron07].

A yfeX efeB double mutant in a HasR-expressing strain is unable to use heme as an external source of iron [Letoffe09].

Locations: cytosol, periplasmic space, cytosol

Map Position: [1,082,599 -> 1,083,870] (23.33 centisomes, 84°)
Length: 1272 bp / 423 aa

Molecular Weight of Polypeptide: 46.754 kD (from nucleotide sequence), 45.1 kD (experimental) [Sturm06]

Molecular Weight of Multimer: 89.9 kD (experimental) [Sturm06]

Unification Links: ASAP:ABE-0003451, EchoBASE:EB1686, EcoGene:EG11735, EcoliWiki:b1019, OU-Microarray:b1019, PortEco:efeB, Pride:P31545, Protein Model Portal:P31545, RefSeq:NP_415538, RegulonDB:EG11735, SMR:P31545, String:511145.b1019, UniProt:P31545

Relationship Links: InterPro:IN-FAMILY:IPR006311, InterPro:IN-FAMILY:IPR006313, InterPro:IN-FAMILY:IPR006314, InterPro:IN-FAMILY:IPR011008, PDB:Structure:2Y4D, PDB:Structure:2Y4E, PDB:Structure:2Y4F, Pfam:IN-FAMILY:PF04261, Prosite:IN-FAMILY:PS51318, Prosite:IN-FAMILY:PS51404

In Paralogous Gene Group: 242 (2 members)

Gene-Reaction Schematic

Gene-Reaction Schematic

GO Terms:
Biological Process:
Inferred from experimentGO:0006974 - cellular response to DNA damage stimulus [Khil02]
Inferred from experimentInferred by computational analysisGO:0015684 - ferrous iron transport [GOA01a, Cao07]
Inferred from experimentInferred by computational analysisGO:0033212 - iron assimilation [GOA01a, Letoffe09]
Inferred by computational analysisGO:0055114 - oxidation-reduction process [UniProtGOA11a, GOA01a]
Molecular Function:
Inferred from experimentInferred by computational analysisGO:0004601 - peroxidase activity [UniProtGOA11a, GOA01a, Sturm06]
Inferred from experimentGO:0016675 - oxidoreductase activity, acting on a heme group of donors [Sturm06]
Inferred from experimentInferred by computational analysisGO:0020037 - heme binding [GOA01a, Sturm06]
Inferred by computational analysisGO:0016491 - oxidoreductase activity [UniProtGOA11a]
Inferred by computational analysisGO:0046872 - metal ion binding [UniProtGOA11a]
Cellular Component:
Inferred from experimentGO:0005737 - cytoplasm [Letoffe09]
Inferred from experimentInferred by computational analysisGO:0042597 - periplasmic space [UniProtGOA11, UniProtGOA11a, Sturm06]
GO:0005829 - cytosol [Letoffe09]
GO:0030288 - outer membrane-bounded periplasmic space [Sturm06]

MultiFun Terms: transportAccessory Factors Involved in Transport

Essentiality data for efeB knockouts:

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

Last-Curated 31-Oct-2006 by Johnson A, TIGR
Revised 09-Jul-2009 by Mackie A, Macquarie University

Enzymatic reaction of: deferrochelatase (EfeB dimer)

Inferred from experiment

EC Number:

ferroheme b + 2 H+ → Fe2+ + protoporphyrin IX

The direction shown, i.e. which substrates are on the left and right sides, is in accordance with the direction of enzyme catalysis.

The reaction is physiologically favored in the direction shown.

Subunit of: EfeU/EfeO/EfeB ferrous iron transporter; cryptic

Subunit composition of EfeU/EfeO/EfeB ferrous iron transporter; cryptic = [EfeU_1][EfeO][EfeB]
         hypothetical protein of the OFeT transport family = EfeU_1 (summary available)
         conserved periplasmic protein = EfeO (summary available)
         heme-containing peroxidase/deferrochelatase = EfeB (extended summary available)

EfeUOB is a cryptic Fe2+ transporter responsible for uptake of ferrous iron under conditions of iron limitation and low pH. All three components are required for efficient Fe2+ transport when EfeUOB is activated.

The functional efeU (ycdN) gene in E. coli Nissle 1917 encodes the oxidase-dependent, OFeT family ferrous iron permease, EfeU, which is an integral inner membrane protein with seven transmembrane segments [Grosse06]. efeU in E. coli K-12 has been disrupted by a frameshift mutation leaving the efeU_1 and efeU_2 fragments nonfunctional [Grosse06].

EfeO is a monomeric protein which is transported to the periplasm with high efficiency [Sturm06]. The role of EfeO in Fe2+ transport is unknown [Cao07].

Deletion of efeU, efeO, or efeB did not result in any growth defects or other detectable phenotypes [Cao07]. Expression of the corrected EfeU protein in a strain lacking all other known iron transporters resulted in improved growth and increased iron uptake [Cao07, Grosse06]. Deletion of efeO or efeB caused a growth defect during iron limitation when corrected efeU is supplied [Cao07].

efeUOB is induced at low pH due to phosphorylation of the CpxR component of the CpxAR two-component response regulator [Stancik02, Maurer05a, Cao07]. Expression of efeUOB increased in response to iron-depleted conditions in a Fe2+-Fur-dependent manner as well as to increased Cu2+ as excess Cu2+ impedes iron entry into the cell [Cao07, Grosse06]. efeUOB is repressed by autoclaved stationary phase supernatant in DH5α [Ren04] and in an indirect response to expression of RhyB, which down-regulates iron-binding proteins and makes more Fe2+ available for Fur repression [Masse05]. Expression of EfeU decreased upon osmotic upshift [Weber02]. efeU_2 is also repressed under anaerobic conditions [Kang05]. efeB is repressed by luxS in W3110 [Wang05]. Expression increased in response to FlhD/FlhC and Aer in MC1000 and YK410 strains [Pruss03].

Citations: [Graubner07]

Created 05-Nov-2007 by Johnson A, JCVI

Sequence Features

Protein sequence of heme-containing peroxidase/deferrochelatase with features indicated

Feature Class Location Citations Comment
Signal-Sequence 1 -> 35
Chain 36 -> 423
Author statement[UniProt15]
UniProt: Deferrochelatase/peroxidase EfeB.
Pfam PF04261 61 -> 410
Inferred by computational analysis[Finn14]
Dyp_perox : Dyp-type peroxidase family
Protein-Segment 236 -> 238
Author statement[UniProt15]
UniProt: Heme binding; Sequence Annotation Type: region of interest.
Metal-Binding-Site 329
Author statement[UniProt15]
UniProt: Iron (heme proximal ligand); via tele nitrogen.
Protein-Segment 334 -> 336
Author statement[UniProt15]
UniProt: Heme binding; Sequence Annotation Type: region of interest.
Amino-Acid-Sites-That-Bind 347
Author statement[UniProt15]
UniProt: Heme.

Gene Local Context (not to scale -- see Genome Browser for correct scale)

Gene local context diagram

Transcription Unit

Transcription-unit diagram


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 b1019 from Blattner lab Genbank (v. M52) entry merged into EcoCyc gene EG11735; confirmed by SwissProt match.


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

Cao07: Cao J, Woodhall MR, Alvarez J, Cartron ML, Andrews SC (2007). "EfeUOB (YcdNOB) is a tripartite, acid-induced and CpxAR-regulated, low-pH Fe2+ transporter that is cryptic in Escherichia coli K-12 but functional in E. coli O157:H7." Mol Microbiol 65(4);857-75. PMID: 17627767

Cartron07: Cartron ML, Mitchell SA, Woodhall MR, Andrews SC, Watson KA (2007). "Preliminary X-ray diffraction analysis of YcdB from Escherichia coli: a novel haem-containing and Tat-secreted periplasmic protein with a potential role in iron transport." Acta Crystallogr Sect F Struct Biol Cryst Commun 63(Pt 1);37-41. PMID: 17183171

Finn14: Finn RD, Bateman A, Clements J, Coggill P, Eberhardt RY, Eddy SR, Heger A, Hetherington K, Holm L, Mistry J, Sonnhammer EL, Tate J, Punta M (2014). "Pfam: the protein families database." Nucleic Acids Res 42(Database issue);D222-30. PMID: 24288371

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

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

Graubner07: Graubner W, Schierhorn A, Bruser T (2007). "DnaK plays a pivotal role in Tat targeting of CueO and functions beside SlyD as a general Tat signal binding chaperone." J Biol Chem 282(10);7116-24. PMID: 17215254

Grosse06: Grosse C, Scherer J, Koch D, Otto M, Taudte N, Grass G (2006). "A new ferrous iron-uptake transporter, EfeU (YcdN), from Escherichia coli." Mol Microbiol 62(1);120-31. PMID: 16987175

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

Kang05: Kang Y, Weber KD, Qiu Y, Kiley PJ, Blattner FR (2005). "Genome-wide expression analysis indicates that FNR of Escherichia coli K-12 regulates a large number of genes of unknown function." J Bacteriol 187(3);1135-60. PMID: 15659690

Khil02: Khil PP, Camerini-Otero RD (2002). "Over 1000 genes are involved in the DNA damage response of Escherichia coli." Mol Microbiol 44(1);89-105. PMID: 11967071

Letoffe09: Letoffe S, Heuck G, Delepelaire P, Lange N, Wandersman C (2009). "Bacteria capture iron from heme by keeping tetrapyrrol skeleton intact." Proc Natl Acad Sci U S A 106(28):11719-24. PMID: 19564607

Masse05: Masse E, Vanderpool CK, Gottesman S (2005). "Effect of RyhB small RNA on global iron use in Escherichia coli." J Bacteriol 187(20);6962-71. PMID: 16199566

Maurer05a: Maurer LM, Yohannes E, Bondurant SS, Radmacher M, Slonczewski JL (2005). "pH regulates genes for flagellar motility, catabolism, and oxidative stress in Escherichia coli K-12." J Bacteriol 187(1);304-19. PMID: 15601715

McConville79b: McConville ML, Charles HP (1979). "Mutants of Escherichia coli K12 permeable to haemin." J Gen Microbiol 113(1);165-8. PMID: 387910

Pruss03: Pruss BM, Campbell JW, Van Dyk TK, Zhu C, Kogan Y, Matsumura P (2003). "FlhD/FlhC is a regulator of anaerobic respiration and the Entner-Doudoroff pathway through induction of the methyl-accepting chemotaxis protein Aer." J Bacteriol 185(2);534-43. PMID: 12511500

Ren04: Ren D, Bedzyk LA, Ye RW, Thomas SM, Wood TK (2004). "Stationary-phase quorum-sensing signals affect autoinducer-2 and gene expression in Escherichia coli." Appl Environ Microbiol 70(4);2038-43. PMID: 15066794

Sasarman68: Sasarman A, Surdeanu M, Szegli G, Horodniceanu T, Greceanu V, Dumitrescu A (1968). "Hemin-deficient mutants of Escherichia coli K-12." J Bacteriol 96(2);570-2. PMID: 4877132

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

Stancik02: Stancik LM, Stancik DM, Schmidt B, Barnhart DM, Yoncheva YN, Slonczewski JL (2002). "pH-dependent expression of periplasmic proteins and amino acid catabolism in Escherichia coli." J Bacteriol 184(15);4246-58. PMID: 12107143

Sturm06: Sturm A, Schierhorn A, Lindenstrauss U, Lilie H, Bruser T (2006). "YcdB from Escherichia coli reveals a novel class of Tat-dependently translocated hemoproteins." J Biol Chem 281(20);13972-8. PMID: 16551627

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."

Wang05: Wang L, Li J, March JC, Valdes JJ, Bentley WE (2005). "luxS-dependent gene regulation in Escherichia coli K-12 revealed by genomic expression profiling." J Bacteriol 187(24);8350-60. PMID: 16321939

Weber02: Weber A, Jung K (2002). "Profiling early osmostress-dependent gene expression in Escherichia coli using DNA macroarrays." J Bacteriol 184(19);5502-7. PMID: 12218039

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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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