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Escherichia coli K-12 substr. MG1655 Polypeptide: IscR DNA-binding transcriptional dual regulator



Gene: iscR Accession Numbers: G7326 (EcoCyc), b2531, ECK2528

Synonyms: yfhP

Regulation Summary Diagram: ?

Component of: IscR-2Fe-2S DNA binding transcriptional repressor

Summary:
The transcription factor IscR, for "Iron-sulfur cluster Regulator," is negatively autoregulated, and it contains an iron-sulfur cluster that could act as a sensor of iron-sulfur cluster assembly [Schwartz01, Giel06]. This protein regulates the expression of the operons that encode components of a secondary pathway of iron-sulfur cluster assembly, iron-sulfur proteins, anaerobic respiration enzymes, and biofilm formation [Tokumoto01, Schwartz01, Giel06, Lee08b, Yeo06, Wu09].

IscR is a member of the Rrf2 family [Nesbit09] and carries a predicted N-terminal helix-turn-helix DNA-binding motif and three conserved cysteines in its C terminus. IscR is a dimer in solution [Nesbit09], and it contains the [2Fe-2S]1+ cluster when purified under anaerobic conditions [Schwartz01]. This [2Fe-2S]1+ cluster has an unusual (Cys)3(His)1 ligand scheme and is essential for cluster ligation [Fleischhacker12]. Some proteins, such as SufB, IscU, EprA, and IscA, are involved in the assembly and transfer of the [2Fe-2S]cluster to IscR [Vinella13]

Two types of DNA-binding sites have been described for IscR: type 1 and type 2. Both sites resemble 25-bp imperfect palindromes but differ in their sequence [Giel06, Nesbit09]. IscR requires the iron-sulfur cluster for its activity when bound to type 1 sites. The binding of the [2Fe-2S]1+ cluster allows IscR to induce a conformational change, mainly around the residue Glu43, that modifies its DNA-binding affinity. This modification enables IscR to bind to type 1 DNA-binding sites [Rajagopalan13].

PiscR contains two type 1 sites [Giel06]. Therefore, under conditions when Fe-S cluster assembly becomes rate limiting, levels of [2Fe-2S]-containing IscR may decrease due to a lower rate of its synthesis, thus relieving repression of the iscRSUA operon for the biogenesis of the iron-sulfur cluster [Schwartz01, Frazzon01, Giel13]. In contrast, for the regulation of promoters containing type 2 sites, such as PsufA, the [2Fe-2S] cluster of IscR is dispensable [Yeo06, Lee08b].

IscR binds cooperatively to DNA, and four protomers bind to one palindromic site [Nesbit09].

Gene Citations: [Takahashi99]

Locations: cytosol

Map Position: [2,659,665 <- 2,660,153] (57.32 centisomes)
Length: 489 bp / 162 aa

Molecular Weight of Polypeptide: 17.337 kD (from nucleotide sequence)

Unification Links: ASAP:ABE-0008326 , DIP:DIP-47974N , EchoBASE:EB3178 , EcoGene:EG13397 , EcoliWiki:b2531 , ModBase:P0AGK8 , OU-Microarray:b2531 , PortEco:iscR , PR:PRO_000023032 , Pride:P0AGK8 , Protein Model Portal:P0AGK8 , RefSeq:NP_417026 , RegulonDB:G7326 , SMR:P0AGK8 , String:511145.b2531 , UniProt:P0AGK8

Relationship Links: InterPro:IN-FAMILY:IPR000944 , InterPro:IN-FAMILY:IPR010242 , InterPro:IN-FAMILY:IPR011991 , PDB:Structure:4HF0 , PDB:Structure:4HF1 , PDB:Structure:4HF2 , Pfam:IN-FAMILY:PF02082 , Prosite:IN-FAMILY:PS01332 , Prosite:IN-FAMILY:PS51197

In Paralogous Gene Group: 577 (2 members)

Gene-Reaction Schematic: ?

Genetic Regulation Schematic: ?

GO Terms:

Biological Process: GO:0006355 - regulation of transcription, DNA-templated Inferred from experiment Inferred by computational analysis [UniProtGOA11a, GOA06, GOA01, Giel06, Schwartz01]
GO:0006351 - transcription, DNA-templated Inferred by computational analysis [UniProtGOA11a]
GO:0006950 - response to stress Inferred by computational analysis [UniProtGOA11a]
Molecular Function: GO:0003700 - sequence-specific DNA binding transcription factor activity Inferred from experiment Inferred by computational analysis [GOA06, GOA01, Schwartz01, Giel06]
GO:0003677 - DNA binding Inferred by computational analysis [UniProtGOA11a]
GO:0003690 - double-stranded DNA binding Inferred by computational analysis [GOA06, GOA01]
GO:0005506 - iron ion binding Inferred by computational analysis [GOA06]
GO:0046872 - metal ion binding Inferred by computational analysis [UniProtGOA11a]
GO:0051536 - iron-sulfur cluster binding Inferred by computational analysis [UniProtGOA11a]
GO:0051537 - 2 iron, 2 sulfur cluster binding Inferred by computational analysis [UniProtGOA11a]
Cellular Component: GO:0005829 - cytosol Inferred from experiment Inferred by computational analysis [DiazMejia09, Ishihama08]

MultiFun Terms: information transfer RNA related Transcription related
regulation genetic unit regulated operon
regulation type of regulation transcriptional level activator
regulation type of regulation transcriptional level repressor

DNA binding site length: 25 base-pairs

Symmetry: Inverted Repeat

Consensus DNA Binding Sequence: ATAcccGAcTAAAtTAcTCgGgTAT

Regulated Transcription Units (8 total): ?

Notes:

Essentiality data for iscR 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]

Subunit of: IscR-2Fe-2S DNA binding transcriptional repressor

Subunit composition of IscR-2Fe-2S DNA binding transcriptional repressor = [IscR][[2Fe-2S] iron-sulfur cluster]
         IscR DNA-binding transcriptional dual regulator = IscR (extended summary available)

Citations: [Giel13]

Sequence Length: 162 AAs

MultiFun Terms: information transfer RNA related Transcription related
regulation genetic unit regulated operon
regulation type of regulation transcriptional level activator
regulation type of regulation transcriptional level repressor

Credits:
Created 25-Jan-2013 by Gama-Castro S , UNAM

Symmetry: Inverted Repeat

Regulated Transcription Units (1 total): ?

Notes:


Sequence Features

Feature Class Location Citations Comment
Conserved-Region 2 -> 131
[UniProt09]
UniProt: HTH rrf2-type;
DNA-Binding-Region 28 -> 51
[UniProt10a]
UniProt: H-T-H motif; Non-Experimental Qualifier: by similarity;
Mutagenesis-Variant 92
[Otsuka10, Yeo06, UniProt13]
Alternate sequence: C → A; UniProt: No effect on activation of the suf operon, no effect on repression of rnlA.
Metal-Binding-Site 92
[UniProt10a]
UniProt: Iron-sulfur (2Fe-2S); Non-Experimental Qualifier: potential;
Mutagenesis-Variant 98
[Otsuka10, Yeo06, UniProt13]
Alternate sequence: C → A; UniProt: No effect on activation of the suf operon, no effect on repression of rnlA.
Metal-Binding-Site 98
[UniProt10a]
UniProt: Iron-sulfur (2Fe-2S); Non-Experimental Qualifier: potential;
Mutagenesis-Variant 104
[Otsuka10, Yeo06, UniProt13]
Alternate sequence: C → A; UniProt: No effect on activation of the suf operon, no effect on repression of rnlA.
Metal-Binding-Site 104
[UniProt10a]
UniProt: Iron-sulfur (2Fe-2S); Non-Experimental Qualifier: potential;


Gene Local Context (not to scale): ?

Transcription Unit:

Notes:

History:
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 ].
Markus Krummenacker on Tue Oct 14, 1997:
Gene object created from Blattner lab Genbank (v. M52) entry.


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

Fleischhacker12: Fleischhacker AS, Stubna A, Hsueh KL, Guo Y, Teter SJ, Rose JC, Brunold TC, Markley JL, Munck E, Kiley PJ (2012). "Characterization of the [2Fe-2S] Cluster of Escherichia coli Transcription Factor IscR." Biochemistry 51(22);4453-62. PMID: 22583201

Frazzon01: Frazzon J, Dean DR (2001). "Feedback regulation of iron-sulfur cluster biosynthesis." Proc Natl Acad Sci U S A 98(26);14751-3. PMID: 11752417

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

Giel06: Giel JL, Rodionov D, Liu M, Blattner FR, Kiley PJ (2006). "IscR-dependent gene expression links iron-sulphur cluster assembly to the control of O-regulated genes in Escherichia coli." Mol Microbiol 60(4);1058-75. PMID: 16677314

Giel13: Giel JL, Nesbit AD, Mettert EL, Fleischhacker AS, Wanta BT, Kiley PJ (2013). "Regulation of iron-sulphur cluster homeostasis through transcriptional control of the Isc pathway by [2Fe-2S]-IscR in Escherichia coli." Mol Microbiol 87(3);478-92. PMID: 23075318

GOA01: 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."

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

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

Lee08b: Lee KC, Yeo WS, Roe JH (2008). "Oxidant-responsive induction of the suf operon, encoding a Fe-S assembly system, through Fur and IscR in Escherichia coli." J Bacteriol 190(24);8244-7. PMID: 18849427

Nesbit09: Nesbit AD, Giel JL, Rose JC, Kiley PJ (2009). "Sequence-specific binding to a subset of IscR-regulated promoters does not require IscR Fe-S cluster ligation." J Mol Biol 387(1);28-41. PMID: 19361432

Otsuka10: Otsuka Y, Miki K, Koga M, Katayama N, Morimoto W, Takahashi Y, Yonesaki T (2010). "IscR regulates RNase LS activity by repressing rnlA transcription." Genetics 185(3);823-30. PMID: 20421606

Rajagopalan13: Rajagopalan S, Teter SJ, Zwart PH, Brennan RG, Phillips KJ, Kiley PJ (2013). "Studies of IscR reveal a unique mechanism for metal-dependent regulation of DNA binding specificity." Nat Struct Mol Biol 20(6);740-7. PMID: 23644595

Schwartz01: Schwartz CJ, Giel JL, Patschkowski T, Luther C, Ruzicka FJ, Beinert H, Kiley PJ (2001). "IscR, an Fe-S cluster-containing transcription factor, represses expression of Escherichia coli genes encoding Fe-S cluster assembly proteins." Proc Natl Acad Sci U S A 2001;98(26);14895-900. PMID: 11742080

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

Takahashi99: Takahashi Y, Nakamura M (1999). "Functional assignment of the ORF2-iscS-iscU-iscA-hscB-hscA-fdx-ORF3 gene cluster involved in the assembly of Fe-S clusters in Escherichia coli." J Biochem (Tokyo) 1999;126(5);917-26. PMID: 10544286

Tokumoto01: Tokumoto U, Takahashi Y (2001). "Genetic analysis of the isc operon in Escherichia coli involved in the biogenesis of cellular iron-sulfur proteins." J Biochem (Tokyo) 130(1);63-71. PMID: 11432781

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

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

UniProt13: UniProt Consortium (2013). "UniProt version 2013-08 released on 2013-08-01 00:00:00." Database.

UniProtGOA11a: UniProt-GOA (2011). "Gene Ontology annotation based on manual assignment of UniProtKB keywords in UniProtKB/Swiss-Prot entries."

Vinella13: Vinella D, Loiseau L, de Choudens SO, Fontecave M, Barras F (2013). "In vivo [Fe-S] cluster acquisition by IscR and NsrR, two stress regulators in Escherichia coli." Mol Microbiol 87(3);493-508. PMID: 23320508

Wu09: Wu Y, Outten FW (2009). "IscR controls iron-dependent biofilm formation in Escherichia coli by regulating type I fimbria expression." J Bacteriol 191(4);1248-57. PMID: 19074392

Yeo06: Yeo WS, Lee JH, Lee KC, Roe JH (2006). "IscR acts as an activator in response to oxidative stress for the suf operon encoding Fe-S assembly proteins." Mol Microbiol 61(1);206-18. PMID: 16824106

Other References Related to Gene Regulation

Desnoyers09: Desnoyers G, Morissette A, Prevost K, Masse E (2009). "Small RNA-induced differential degradation of the polycistronic mRNA iscRSUA." EMBO J 28(11);1551-61. PMID: 19407815

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

Prevost11: Prevost K, Desnoyers G, Jacques JF, Lavoie F, Masse E (2011). "Small RNA-induced mRNA degradation achieved through both translation block and activated cleavage." Genes Dev 25(4);385-96. PMID: 21289064

Wright13: Wright PR, Richter AS, Papenfort K, Mann M, Vogel J, Hess WR, Backofen R, Georg J (2013). "Comparative genomics boosts target prediction for bacterial small RNAs." Proc Natl Acad Sci U S A 110(37);E3487-96. PMID: 23980183

Zheng01: Zheng M, Wang X, Templeton LJ, Smulski DR, LaRossa RA, Storz G (2001). "DNA microarray-mediated transcriptional profiling of the Escherichia coli response to hydrogen peroxide." J Bacteriol 183(15);4562-70. PMID: 11443091


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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 18.5 on Fri Dec 19, 2014, biocyc14.