Escherichia coli K-12 substr. MG1655 Enzyme: ferritin iron-storage complex

Gene: ftnA Accession Numbers: EG10921 (EcoCyc), b1905, ECK1904

Synonyms: ftn, gen-165, rsgA

Regulation Summary Diagram: ?

Regulation summary diagram for ftnA

Subunit composition of ferritin iron-storage complex = [FtnA]24
         ferritin iron storage protein = FtnA

ftnA encodes the iron-storage protein ferritin, which is similar to human ferritin H [Izuhara91, Hudson93]. Ferritin forms a multi-subunit, hollow spherical shell of 24 individual ferritin polypeptides that can sequester more than 2000 iron atoms in the center [Hudson93]. Ferritin and bacterioferritin are distantly related [Andrews91, Andrews92].

The crystal structure of ferritin has been determined, identifying three iron-binding sites per subunit [Hempstead94, Stillman01, Stillman03]. Two of these sites form a dinuclear iron center where oxidation of Fe(II) occurs, allowing iron to be stored as ferric phosphate [Treffry98, BouAbdallah05]. The third site appears to modulate Fe2+ binding to the dinuclear iron center [BouAbdallah05]. No protons are released upon initial binding of Fe2+. Subsequent oxidation of Fe2+ leads to production of H2O2, which is itself utilized for oxidation of Fe2+ bound at other ferroxidase centers [BouAbdallah14].

In vitro, FtnA was shown to sequester iron released from damaged [2Fe-2S] clusters of IscU. Iron sequestered by FtnA can be transferred to IscA, but not IscU [Bitoun08].

Overexpression of ftnA rescues the oxygen sensitivity of a Δfur ΔrecA mutant, presumably by preventing toxic iron accumulation [Touati95]. An ftnA mutant shows impaired growth in iron-deficient media [AbdulTehrani99].

Expression of ftnA is higher in stationary phase than log phase cells and is dependent on iron and Fur [Nandal10]. Although ftnA expression was thought to be regulated by RyhB [Masse02], microarray experiments indicated that it is not dependent on RyhB [Masse05]. It was later shown that ftnA expression is directly regulated by Fur, which reverses silencing by H-NS [Nandal10].

Review: [Andrews03]

Citations: [Sevcenco11, Bauminger00, Treffry98a]

Locations: cytosol

Map Position: [1,986,740 -> 1,987,237] (42.82 centisomes, 154°)
Length: 498 bp / 165 aa

Molecular Weight of Polypeptide: 19.424 kD (from nucleotide sequence), 19.4 kD (experimental) [Hudson93 ]

Molecular Weight of Multimer: 500.0 kD (experimental) [Hudson93]

Unification Links: ASAP:ABE-0006342 , CGSC:32521 , DIP:DIP-36198N , EchoBASE:EB0914 , EcoGene:EG10921 , EcoliWiki:b1905 , ModBase:P0A998 , OU-Microarray:b1905 , PortEco:ftnA , PR:PRO_000022712 , Pride:P0A998 , Protein Model Portal:P0A998 , RefSeq:NP_416418 , RegulonDB:EG10921 , SMR:P0A998 , String:511145.b1905 , UniProt:P0A998

Relationship Links: InterPro:IN-FAMILY:IPR001519 , InterPro:IN-FAMILY:IPR008331 , InterPro:IN-FAMILY:IPR009040 , InterPro:IN-FAMILY:IPR009078 , InterPro:IN-FAMILY:IPR012347 , Panther:IN-FAMILY:PTHR11431 , PDB:Structure:1EUM , Pfam:IN-FAMILY:PF00210 , Prosite:IN-FAMILY:PS50905

In Paralogous Gene Group: 359 (2 members)

Gene-Reaction Schematic: ?

Gene-Reaction Schematic

Genetic Regulation Schematic: ?

Genetic regulation schematic for ftnA

GO Terms:

Biological Process: GO:0006880 - intracellular sequestering of iron ion Inferred from experiment [AbdulTehrani99]
GO:0006974 - cellular response to DNA damage stimulus Inferred from experiment [Khil02]
GO:0006979 - response to oxidative stress Inferred from experiment [Bitoun08]
GO:0006826 - iron ion transport Inferred by computational analysis [GOA01a]
GO:0006879 - cellular iron ion homeostasis Inferred by computational analysis [UniProtGOA11a, GOA01a]
GO:0055114 - oxidation-reduction process Inferred by computational analysis [UniProtGOA11a]
Molecular Function: GO:0004322 - ferroxidase activity Inferred from experiment [Treffry98]
GO:0008199 - ferric iron binding Inferred from experiment Inferred by computational analysis [GOA01a, Hudson93]
GO:0042802 - identical protein binding Inferred from experiment [Hudson93]
GO:0016491 - oxidoreductase activity Inferred by computational analysis [UniProtGOA11a]
GO:0046872 - metal ion binding Inferred by computational analysis [UniProtGOA11a]
Cellular Component: GO:0005829 - cytosol Inferred from experiment Inferred by computational analysis [DiazMejia09, Ishihama08, Lasserre06]
GO:0005737 - cytoplasm Inferred by computational analysis [UniProtGOA11, UniProtGOA11a]

MultiFun Terms: cell processes adaptations Fe aquisition

Essentiality data for ftnA 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]

Created 21-Jun-2006 by Johnson A , TIGR
Last-Curated ? 23-Dec-2009 by Keseler I , SRI International

Enzymatic reaction of: non-heme bacterial ferritin (ferritin iron-storage complex)

EC Number:

4 Fe2+ + oxygen + 6 H2O <=> 4 [FeO(OH)] monomer + 8 H+

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the direction in which it was curated.

The reaction is physiologically favored in the direction shown.

Thermodynamic parameters of Fe2+ binding to the binding sites within FtnA have been determined [BouAbdallah05].

Inhibitors (Unknown Mechanism): Zn2+ [Treffry98a]

Sequence Features

Protein sequence of ferritin iron storage protein with features indicated

Feature Class Location Citations Comment
Conserved-Region 1 -> 145
UniProt: Ferritin-like diiron;
Metal-Binding-Site 17
UniProt: Iron 1.
Mutagenesis-Variant 17
[BouAbdallah14, UniProt14a]
UniProt: Initially 100-fold slower Fe(2+) oxidation rate.
Mutagenesis-Variant 24
[BouAbdallah14, UniProt14a]
UniProt: Initially reduces Fe(2+)/O(2) stoichiometry from 3.1 to 2.2.
Metal-Binding-Site 49
UniProt: Iron 3.
Mutagenesis-Variant 49
[BouAbdallah14, UniProt14a]
UniProt: Initially reduces Fe(2+)/O(2) stoichiometry from ~3 to ~2.
Metal-Binding-Site 50
UniProt: Iron 1.
Metal-Binding-Site 53
UniProt: Iron 1.
Mutagenesis-Variant 53
[BouAbdallah14, UniProt14a]
UniProt: Initially 6000-fold slower Fe(2+) oxidation rate.
Metal-Binding-Site 94
UniProt: Iron 2.
Mutagenesis-Variant 94
[BouAbdallah14, UniProt14a]
UniProt: Initially 200-fold slower Fe(2+) oxidation rate.
Metal-Binding-Site 126
UniProt: Iron 3.
Mutagenesis-Variant 126
[BouAbdallah14, UniProt14a]
UniProt: Initially reduces Fe(2+)/O(2) stoichiometry from ~3 to ~2.
Metal-Binding-Site 127
UniProt: Iron 2.
Metal-Binding-Site 130
UniProt: Iron 2.
Mutagenesis-Variant 130
[BouAbdallah14, UniProt14a]
UniProt: Initially reduces Fe(2+)/O(2) stoichiometry from ~3 to ~2.

Gene Local Context (not to scale): ?

Gene local context diagram

Transcription Unit:

Transcription-unit diagram


10/20/97 Gene b1905 from Blattner lab Genbank (v. M52) entry merged into EcoCyc gene EG10921; confirmed by SwissProt match.


AbdulTehrani99: Abdul-Tehrani H, Hudson AJ, Chang YS, Timms AR, Hawkins C, Williams JM, Harrison PM, Guest JR, Andrews SC (1999). "Ferritin mutants of Escherichia coli are iron deficient and growth impaired, and fur mutants are iron deficient." J Bacteriol 181(5);1415-28. PMID: 10049371

Andrews03: Andrews SC, Robinson AK, Rodriguez-Quinones F (2003). "Bacterial iron homeostasis." FEMS Microbiol Rev 27(2-3);215-37. PMID: 12829269

Andrews91: Andrews SC, Smith JM, Yewdall SJ, Guest JR, Harrison PM (1991). "Bacterioferritins and ferritins are distantly related in evolution. Conservation of ferroxidase-centre residues." FEBS Lett 293(1-2);164-8. PMID: 1959654

Andrews92: Andrews SC, Arosio P, Bottke W, Briat JF, von Darl M, Harrison PM, Laulhere JP, Levi S, Lobreaux S, Yewdall SJ (1992). "Structure, function, and evolution of ferritins." J Inorg Biochem 47(3-4);161-74. PMID: 1431878

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

Bauminger00: Bauminger ER, Treffry A, Quail MA, Zhao Z, Nowik I, Harrison PM (2000). "Metal binding at the active centre of the ferritin of Escherichia coli (EcFtnA). A Mossbauer spectroscopic study." Inorg Chim Acta 297, 171-180.

Bauminger99: Bauminger ER, Treffry A, Quail MA, Zhao Z, Nowik I, Harrison PM (1999). "Stages in iron storage in the ferritin of Escherichia coli (EcFtnA): analysis of Mossbauer spectra reveals a new intermediate." Biochemistry 38(24);7791-802. PMID: 10387019

Bitoun08: Bitoun JP, Wu G, Ding H (2008). "Escherichia coli FtnA acts as an iron buffer for re-assembly of iron-sulfur clusters in response to hydrogen peroxide stress." Biometals 21(6);693-703. PMID: 18618270

BouAbdallah05: Bou-Abdallah F, Woodhall MR, Velazquez-Campoy A, Andrews SC, Chasteen ND (2005). "Thermodynamic analysis of ferrous ion binding to Escherichia coli ferritin EcFtnA." Biochemistry 44(42);13837-46. PMID: 16229472

BouAbdallah14: Bou-Abdallah F, Yang H, Awomolo A, Cooper B, Woodhall MR, Andrews SC, Chasteen ND (2014). "Functionality of the three-site ferroxidase center of Escherichia coli bacterial ferritin (EcFtnA)." Biochemistry 53(3);483-95. PMID: 24380371

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

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

Hempstead94: Hempstead PD, Hudson AJ, Artymiuk PJ, Andrews SC, Banfield MJ, Guest JR, Harrison PM (1994). "Direct observation of the iron binding sites in a ferritin." FEBS Lett 350(2-3);258-62. PMID: 8070575

Hudson93: Hudson AJ, Andrews SC, Hawkins C, Williams JM, Izuhara M, Meldrum FC, Mann S, Harrison PM, Guest JR (1993). "Overproduction, purification and characterization of the Escherichia coli ferritin." Eur J Biochem 218(3);985-95. PMID: 8281950

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

Izuhara91: Izuhara M, Takamune K, Takata R (1991). "Cloning and sequencing of an Escherichia coli K12 gene which encodes a polypeptide having similarity to the human ferritin H subunit." Mol Gen Genet 225(3);510-3. PMID: 2017145

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

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

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

Masse02: Masse E, Gottesman S (2002). "A small RNA regulates the expression of genes involved in iron metabolism in Escherichia coli." Proc Natl Acad Sci U S A 99(7);4620-5. PMID: 11917098

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

Nandal10: Nandal A, Huggins CC, Woodhall MR, McHugh J, Rodriguez-Quinones F, Quail MA, Guest JR, Andrews SC (2010). "Induction of the ferritin gene (ftnA) of Escherichia coli by Fe(2+)-Fur is mediated by reversal of H-NS silencing and is RyhB independent." Mol Microbiol 75(3):637-57. PMID: 20015147

Sevcenco11: Sevcenco AM, Pinkse MW, Wolterbeek HT, Verhaert PD, Hagen WR, Hagedoorn PL (2011). "Exploring the microbial metalloproteome using MIRAGE." Metallomics 3(12);1324-30. PMID: 22094925

Stillman01: Stillman TJ, Hempstead PD, Artymiuk PJ, Andrews SC, Hudson AJ, Treffry A, Guest JR, Harrison PM (2001). "The high-resolution X-ray crystallographic structure of the ferritin (EcFtnA) of Escherichia coli; comparison with human H ferritin (HuHF) and the structures of the Fe(3+) and Zn(2+) derivatives." J Mol Biol 307(2);587-603. PMID: 11254384

Stillman03: Stillman TJ, Connolly PP, Latimer CL, Morland AF, Quail MA, Andrews SC, Treffry A, Guest JR, Artymiuk PJ, Harrison PM (2003). "Insights into the effects on metal binding of the systematic substitution of five key glutamate ligands in the ferritin of Escherichia coli." J Biol Chem 278(28);26275-86. PMID: 12730190

Touati95: Touati D, Jacques M, Tardat B, Bouchard L, Despied S (1995). "Lethal oxidative damage and mutagenesis are generated by iron in delta fur mutants of Escherichia coli: protective role of superoxide dismutase." J Bacteriol 177(9);2305-14. PMID: 7730258

Treffry98: Treffry A, Zhao Z, Quail MA, Guest JR, Harrison PM (1998). "How the presence of three iron binding sites affects the iron storage function of the ferritin (EcFtnA) of Escherichia coli." FEBS Lett 432(3);213-8. PMID: 9720927

Treffry98a: Treffry A, Zhao Z, Quail MA, Guest JR, Harrison PM (1998). "The use of zinc(II) to probe iron binding and oxidation by the ferritin (EcFtnA) of Escherichia coli." J. Biol. Inorg. Chem. 3, 682-688.

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

UniProt14a: UniProt Consortium (2014). "UniProt version 2014-08 released on 2014-08-01 00:00:00." Database.

UniProt15: UniProt Consortium (2015). "UniProt version 2015-01 released on 2015-01-16 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."

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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 19.0 on Tue Oct 13, 2015, biocyc13.