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Escherichia coli K-12 substr. MG1655 Polypeptide: ATP-dependent zinc metalloprotease FtsH



Gene: ftsH Accession Numbers: EG11506 (EcoCyc), b3178, ECK3167

Synonyms: std, hflB, mrsC, tolZ

Regulation Summary Diagram: ?

Component of: HflB, integral membrane ATP-dependent zinc metallopeptidase (extended summary available)

Summary:
FtsH is a membrane-bound, ATP-dependent metalloprotease which has been shown to be involved in the degradation of some aberrant membrane and cytoplasmic proteins [Akiyama00, Akiyama96, Akiyama98, Akiyama96, Kihara95]. FtsH-mediated proteolysis has been shown to be directly related to the proton motive force (pmf) across the membrane [Akiyama03]. Topology mapping indicates that FtsH has two transmembrane segments near the N-terminus and a large cytoplasmic domain which comprises two subdomains: an ATPase domain and a zinc metalloprotease motif-containing protease domain [Tomoyasu93].

Deletion mutation studies have shown that FtsH may also play a role in the proper assembly of proteins into and through the inner membrane by assuring effective stop-transfer of some transmembrane proteins [Akiyama94]. Protein purification and cross-linking studies indicate that FtsH is physically and functionally connected to YidC and that this complex may be involved in quality control of inner membrane proteins (IMPs) during biogenesis [vanBloois08].

Review: [Akiyama09]

Gene Citations: [Tomoyasu93a, Herman95]

Locations: inner membrane

Map Position: [3,323,023 <- 3,324,957] (71.62 centisomes)
Length: 1935 bp / 644 aa

Molecular Weight of Polypeptide: 70.708 kD (from nucleotide sequence)

Unification Links: ASAP:ABE-0010444 , CGSC:735 , DIP:DIP-35828N , EchoBASE:EB1469 , EcoGene:EG11506 , EcoliWiki:b3178 , Mint:MINT-1226643 , ModBase:P0AAI3 , OU-Microarray:b3178 , PortEco:ftsH , PR:PRO_000022717 , Pride:P0AAI3 , Protein Model Portal:P0AAI3 , RefSeq:NP_417645 , RegulonDB:EG11506 , SMR:P0AAI3 , String:511145.b3178 , Swiss-Model:P0AAI3 , UniProt:P0AAI3

Relationship Links: InterPro:IN-FAMILY:IPR000642 , InterPro:IN-FAMILY:IPR003593 , InterPro:IN-FAMILY:IPR003959 , InterPro:IN-FAMILY:IPR003960 , InterPro:IN-FAMILY:IPR005936 , InterPro:IN-FAMILY:IPR011546 , InterPro:IN-FAMILY:IPR027417 , PDB:Structure:1LV7 , Pfam:IN-FAMILY:PF00004 , Pfam:IN-FAMILY:PF01434 , Pfam:IN-FAMILY:PF06480 , Prosite:IN-FAMILY:PS00674 , Smart:IN-FAMILY:SM00382

In Paralogous Gene Group: 134 (5 members)

Gene-Reaction Schematic: ?

GO Terms:

Biological Process: GO:0006200 - ATP catabolic process Inferred by computational analysis Inferred from experiment [Tomoyasu95, GOA06]
GO:0006508 - proteolysis Inferred from experiment Inferred by computational analysis [UniProtGOA11a, GOA01a, Tomoyasu95]
GO:0030163 - protein catabolic process Inferred by computational analysis [GOA06]
Molecular Function: GO:0008270 - zinc ion binding Inferred from experiment Inferred by computational analysis [GOA06, GOA01a, Tomoyasu95]
GO:0016887 - ATPase activity Inferred from experiment Inferred by computational analysis [GOA06, Tomoyasu95]
GO:0030145 - manganese ion binding Inferred from experiment [Tomoyasu95]
GO:0043273 - CTPase activity Inferred from experiment [Tomoyasu95]
GO:0000166 - nucleotide binding Inferred by computational analysis [UniProtGOA11a]
GO:0004222 - metalloendopeptidase activity Inferred by computational analysis [GOA01a]
GO:0005524 - ATP binding Inferred by computational analysis [UniProtGOA11a, GOA06, GOA01a]
GO:0008233 - peptidase activity Inferred by computational analysis [UniProtGOA11a, GOA06]
GO:0008237 - metallopeptidase activity Inferred by computational analysis [UniProtGOA11a]
GO:0016787 - hydrolase activity Inferred by computational analysis [UniProtGOA11a]
GO:0046872 - metal ion binding Inferred by computational analysis [UniProtGOA11a]
Cellular Component: GO:0016021 - integral component of membrane Inferred from experiment Inferred by computational analysis [UniProtGOA11a, GOA01a, Tomoyasu93]
GO:0005886 - plasma membrane Inferred by computational analysis [UniProtGOA11, UniProtGOA11a, Tomoyasu93]
GO:0016020 - membrane Inferred by computational analysis [UniProtGOA11a, GOA01a]

MultiFun Terms: cell processes cell division
cell structure membrane
extrachromosomal plasmid related
information transfer protein related turnover, degradation
information transfer RNA related Transcription related
metabolism degradation of macromolecules proteins/peptides/glycopeptides

Essentiality data for ftsH 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 No 37 Aerobic 7   No [Baba06, Comment 2]

Subunit of: HflB, integral membrane ATP-dependent zinc metallopeptidase

Subunit composition of HflB, integral membrane ATP-dependent zinc metallopeptidase = [(HflK)(HflC)]6[FtsH]6
         HflK-HflC complex; regulator of FtsH protease = (HflK)(HflC) (extended summary available)
                 regulator of FtsH protease = HflK (summary available)
                 regulator of FtsH protease = HflC (summary available)
         ATP-dependent zinc metalloprotease FtsH = FtsH (extended summary available)

Summary:
FtsH is a zinc-dependent metalloendoprotease required for survival [Jayasekera00]. Cells lacking functional FtsH fail to septate, instead forming multinucleate filaments [Santos75]. FtsH degrades a number of cellular proteins, including the membrane protein YccA and orphaned complex components such as SecY in the absence of SecE and unaccompanied ATPase F0 [Kihara98, Kihara95, Akiyama96a]. FtsH degrades SecY and to a lesser extent SecE in LamB-LacZ fusion strains with a 'jammed' Sec translocator [vanStelten09]. FtsH degrades the heat shock promoter protein sigma32 [Herman95]. FtsH also controls the abundance of a number of phage proteins, modulating levels of lambda cIII, cleaving cII into peptides of 13-20 residues and degrading Xis, which is required for excision of lambda phage from the chromosome [Herman97, Shotland00, Leffers98]. In addition to the roles described above, FtsH can also break down proteins tagged with the SsrA degradation peptide [Herman98, Herman03].

FtsH is a multiprotein complex comprising a hexamer of FtsH monomers and a hexamer of HflKC pairs [Karata01, Saikawa, Bruckner03]. Though the FtsH monomer can bind both ATP and denatured protein, only the hexamer is capable of proteolysis, and the FtsH membrane domain is required for oligomerization and degradation of membrane protein substrates, even with solubilized membrane proteins [Akiyama95, Makino99, Akiyama01, Akiyama00]. The periplasmic portion of the FtsH monomer is required for degradation of cII, as well as for effective interaction between FtsH and HflKC [Akiyama98]. As with many AAA proteases, FtsH has a proteolytic component, the FtsH monomer and a regulatory component, HflKC, which modulates its protease activity [Dougan02, Kihara96, Kihara97].

The crystal structure of the ATPase module has been solved and is similar to other AAA domains [Krzywda02, Krzywda02a]. Three leucines in a coiled-coil motif at the carboxy-terminus of the FtsH subunit are required for proteolytic and substrate binding activities though they are not needed for ATPase function [Shotland00a]. Phenylalanine-228 and glycine-230, predicted to be in the central pore of the FtsH hexamer, are required for ATPase function and proteolysis of casein, though mutants lacking Phenylalanine-228 were still able to degrade sigma32 [YamadaInagawa03]. FtsH has a zinc-binding motif and requires zinc for its proteolytic function [Tomoyasu95]. Glutamate-479 is one of the residues coordinating this zinc cofactor [Saikawa02].

FtsH function is ATP dependent, with ATP binding to two sites in the carboxy-terminal ATPase module of FtsH and inducing a conformational change [Akiyama94a, Akiyama96, Akiyama98a]. Mutations in the SRH (Second Region of Homology) portion of the FtsH subunit disrupt the protein's ATPase and protease activities, but still allow this conformational change, suggesting that binding of ATP alone is insufficient for activation of the protease [Karata99]. FtsH takes two minutes to degrade sigma32 and uses 140 ATP molecules to do so [Okuno04].

FtsH degradation of cII in vitro does not require any chaperones and proceeds ten times faster than degradation of sigma32 [Shotland97]. FtsH cleaves cII into peptides of 13-20 peptides without much cut-site specificity [Shotland00]. The carboxy-terminal end of cII is required for FtsH degradation, and can also prompt degradation of other proteins if if is appended to them. Degradation of cII is inhibited by cIII and requires HflD [Kobiler02, Kihara01].

FtsH is able to dislocate membrane proteins from the membrane and is able to degrade from both the amino- and carboxy-terminal ends of its substrates [Kihara99, Okuno04]. Degradation of YccA depends on its amino-terminal tail being twenty residues long or longer, though there is no sequence specificity involved and adding twenty-residue tails to SecE and Y sensitized them to FtsH-mediated degradation [Chiba00]. Proteolysis from the amino-terminus requires only ten residues [Chiba02]. FtsH proteolyzes Arc repressor when it is tagged with the SsrA degradation tag, breaking the protein down from the tagged end. Generally, FtsH is most effective at degrading thermodynamically unstable proteins [Herman03].

FtsH-mediated degradation of sigma32 has been shown to either require or not require its carboxy-terminus and to depend on proper sequence in the middle of the protein [Blaszczak99, Tomoyasu01, Bertani01]. Sigma32 is broken down into ten peptide products less than 3 kDa in size [Bruckner03].

FtsH degradation in membrane vesicles requires only FtsH, substrate and ATP [Akiyama03]. In vivo, degradation slows when the proton-motive force is diminished and is stimulated by enhancement of the proton-motive force [Akiyama02].

FtsH cleaves the carboxy-terminus of the FtsH subunit in an ATP-dependent manner. The cut, between methionine-640 and serine-641, removes five residues from the end of the protein and appears not to affect protein function [Akiyama99].

FtsH is required for mRNA synthesis and appears to modulate mRNA lifespan as well [Granger98]. Both functions depend on the ATPase activity of FtsH [Wang98f].

Loss of FtsH or its ATPase activity results in "stop-transfer defects," or mislocalization of protein segments that are normally anchored in the membranes or transported out of the cell [Akiyama94]. This may relate to the role of FtsH in maintenance of proper membrane structures and LPS production, possibly based on degradation of UDP-3-O-(R-3-hydroxymyristoyl)-N-acetylglucosamine deacetylase (LpxC/EnvA) [Ogura99]. Similarly, the effect of FtsH on membranes may explain the requirement for FtsH in proper plasmid partitioning [Inagawa01]. FtsH is required for sensitivity to colicin [Holland76, Matsuzawa84, Qu96].

Lack of FtsH function leads to reduced sigma54 activity and can be suppressed by overexpressing chaperones such as GroEL/GroES and HtpG or by overexpressing PBP-3 [Carmona99, Shirai96, Ferreira87].

Citations: [Ito05]

Locations: inner membrane

GO Terms:

Cellular Component: GO:0005886 - plasma membrane [Tomoyasu93]


Enzymatic reaction of: ATP-dependent zinc metalloendoprotease (HflB, integral membrane ATP-dependent zinc metallopeptidase)

EC Number: 3.4.24.-

a protein + H2O <=> a peptide + a peptide

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.

Cofactors or Prosthetic Groups: Zn2+ [Tomoyasu95]


Sequence Features

Feature Class Location Citations Comment
Transmembrane-Region 5 -> 25
[UniProt10]
UniProt: Helical;; Non-Experimental Qualifier: probable;
Transmembrane-Region 99 -> 119
[UniProt10]
UniProt: Helical;; Non-Experimental Qualifier: probable;
Acetylation-Modification 179
[Yu08]
 
Nucleotide-Phosphate-Binding-Region 192 -> 199
[UniProt10a]
UniProt: ATP; Non-Experimental Qualifier: potential;
Mutagenesis-Variant 201
[Karata99, UniProt11a]
Alternate sequence: L → N; UniProt: No in vivo protease activity, no in vitro ATPase activity.
Mutagenesis-Variant 225
[YamadaInagawa03, UniProt11a]
Alternate sequence: F → Y; UniProt: Complements ftsH1 at 42 degrees Celsius, restores protease activity in vivo.
Alternate sequence: F → W; UniProt: Complements ftsH1 at 42 degrees Celsius, restores protease activity in vivo.
Alternate sequence: F → V; UniProt: Complements ftsH1 at 42 degrees Celsius, restores protease activity in vivo.
Alternate sequence: F → M; UniProt: Complements ftsH1 at 42 degrees Celsius, restores protease activity in vivo.
Alternate sequence: F → L; UniProt: Complements ftsH1 at 42 degrees Celsius, restores protease activity in vivo.
Alternate sequence: F → I; UniProt: Complements ftsH1 at 42 degrees Celsius, restores protease activity in vivo.
Alternate sequence: F → H; UniProt: Partially complements ftsH1 at 42 degrees Celsius, some protease activity in vivo.
Alternate sequence: F → C; UniProt: Partially complements ftsH1 at 42 degrees Celsius, some protease activity in vivo.
Alternate sequence: F → T; UniProt: Does not complement ftsH1 at 42 degrees Celsius, no protease activity in vivo.
Alternate sequence: F → S; UniProt: Does not complement ftsH1 at 42 degrees Celsius, no protease activity in vivo.
Alternate sequence: F → R; UniProt: Does not complement ftsH1 at 42 degrees Celsius, no protease activity in vivo.
Alternate sequence: F → Q; UniProt: Does not complement ftsH1 at 42 degrees Celsius, no protease activity in vivo.
Alternate sequence: F → N; UniProt: Does not complement ftsH1 at 42 degrees Celsius, no protease activity in vivo.
Alternate sequence: F → G; UniProt: Does not complement ftsH1 at 42 degrees Celsius, no protease activity in vivo.
Alternate sequence: F → E; UniProt: Does not complement ftsH1 at 42 degrees Celsius, no protease activity in vivo.
Alternate sequence: F → D; UniProt: Does not complement ftsH1 at 42 degrees Celsius, no protease activity in vivo.
Alternate sequence: F → A; UniProt: Does not complement ftsH1 at 42 degrees Celsius, no protease activity in vivo.
Amino-Acid-Site 225
[UniProt10]
UniProt: Substrate binding; Sequence Annotation Type: site; Non-Experimental Qualifier: probable;
Mutagenesis-Variant 227
[YamadaInagawa03, UniProt11a]
Alternate sequence: G → A; UniProt: Does not complement ftsH1 at 42 degrees Celsius, no protease activity in vivo.
Mutagenesis-Variant 297
[Karata99, UniProt11a]
Alternate sequence: T → A; UniProt: Low protease activity in vivo, low ATPase activity in vitro, complements ftsH1 at 42 degrees Celsius.
Mutagenesis-Variant 298
[Karata99, UniProt11a]
Alternate sequence: N → A; UniProt: No in vivo protease activity.
Mutagenesis-Variant 304
[Karata99, UniProt11a]
Alternate sequence: D → E; UniProt: Low protease activity in vivo, low ATPase activity in vitro, complements ftsH1 at 42 degrees Celsius.
Alternate sequence: D → N; UniProt: No in vivo protease activity, no in vitro ATPase activity; probably still binds ATP.
Alternate sequence: D → A; UniProt: No in vivo protease activity, no in vitro ATPase activity; probably still binds ATP.
Mutagenesis-Variant 307
[Karata99, UniProt11a]
Alternate sequence: L → A; UniProt: Low protease activity in vivo.
Mutagenesis-Variant 309
[Karata99, UniProt11a]
Alternate sequence: R → K; UniProt: No in vivo protease activity, no ATPase activity in vitro; probably still binds ATP.
Alternate sequence: R → L; UniProt: No in vivo protease activity, no ATPase activity in vitro; probably still binds ATP.
Alternate sequence: R → A; UniProt: No in vivo protease activity, no ATPase activity in vitro; probably still binds ATP.
Mutagenesis-Variant 312
[Karata99, UniProt11a]
Alternate sequence: R → K; UniProt: No in vivo protease activity, no ATPase activity in vitro; probably still binds ATP.
Alternate sequence: R → L; UniProt: No in vivo protease activity, no ATPase activity in vitro; probably still binds ATP.
Alternate sequence: R → A; UniProt: No in vivo protease activity, no ATPase activity in vitro; probably still binds ATP.
Mutagenesis-Variant 414
[Saikawa02, UniProt11a]
Alternate sequence: H → Y; UniProt: Loss of protease function.
Alternate sequence: HEAGH → KEAGK; UniProt: Loss of protease function.
Metal-Binding-Site 414
[UniProt10a]
UniProt: Zinc; catalytic; Non-Experimental Qualifier: by similarity;
Mutagenesis-Variant 415
[Karata99, UniProt11a]
Alternate sequence: E → Q; UniProt: Loss of protease activity in vivo.
Active-Site 415
[UniProt10a]
UniProt: Non-Experimental Qualifier: by similarity;
Mutagenesis-Variant 418
[Saikawa02, Karata99, UniProt11a]
Alternate sequence: H → Y; UniProt: In tolZ21; loss of protease function in vivo, retains about 25% ATPase activity, temperature sensitive.
Metal-Binding-Site 418
[UniProt10a]
UniProt: Zinc; catalytic; Non-Experimental Qualifier: by similarity;
Mutagenesis-Variant 463
[Tomoyasu93a, UniProt11a]
Alternate sequence: E → K; UniProt: In ftsH1; a temperature-sensitive mutant which increases the frequency of lysogenization of phage lambda; when associated with A-587.
Mutagenesis-Variant 476
[Saikawa02, UniProt11a]
Alternate sequence: E → Q; UniProt: Little effect on protease function.
Alternate sequence: E → V; UniProt: Severe loss of protease function that is restored by excess Zn.
Alternate sequence: E → K; UniProt: Severe loss of protease function that is restored by excess Zn.
Alternate sequence: E → D; UniProt: Severe loss of protease function that is restored by excess Zn.
Metal-Binding-Site 492
[UniProt10]
UniProt: Zinc; catalytic; Non-Experimental Qualifier: by similarity;
Mutagenesis-Variant 536
[Tomoyasu93a, UniProt11a]
Alternate sequence: H → R; UniProt: In hflB29; increases the frequency of lysogenization of phage lambda.
Mutagenesis-Variant 582
[Saikawa02, UniProt11a]
Alternate sequence: E → V; UniProt: Decreased protease function.
Alternate sequence: E → Q; UniProt: No effect on protease function.
Alternate sequence: E → K; UniProt: No effect on protease function.
Alternate sequence: E → D; UniProt: No effect on protease function.


Gene Local Context (not to scale): ?

Transcription Units:

Notes:

History:
3/19/1998 (pkarp) Merged genes G528/b3178 and EG11506/hflB
10/20/97 Gene b3178 from Blattner lab Genbank (v. M52) entry merged into EcoCyc gene EG11506; confirmed by SwissProt match.


References

Akiyama00: Akiyama Y, Ito K (2000). "Roles of multimerization and membrane association in the proteolytic functions of FtsH (HflB)." EMBO J 19(15);3888-95. PMID: 10921871

Akiyama01: Akiyama Y, Ito K (2001). "Roles of homooligomerization and membrane association in ATPase and proteolytic activities of FtsH in vitro." Biochemistry 40(25);7687-93. PMID: 11412122

Akiyama02: Akiyama Y (2002). "Proton-motive force stimulates the proteolytic activity of FtsH, a membrane-bound ATP-dependent protease in Escherichia coli." Proc Natl Acad Sci U S A 99(12);8066-71. PMID: 12034886

Akiyama03: Akiyama Y, Ito K (2003). "Reconstitution of membrane proteolysis by FtsH." J Biol Chem 278(20);18146-53. PMID: 12642574

Akiyama09: Akiyama Y (2009). "Quality control of cytoplasmic membrane proteins in Escherichia coli." J Biochem 146(4);449-54. PMID: 19454621

Akiyama94: Akiyama Y, Ogura T, Ito K (1994). "Involvement of FtsH in protein assembly into and through the membrane. I. Mutations that reduce retention efficiency of a cytoplasmic reporter." J Biol Chem 269(7);5218-24. PMID: 8106504

Akiyama94a: Akiyama Y, Shirai Y, Ito K (1994). "Involvement of FtsH in protein assembly into and through the membrane. II. Dominant mutations affecting FtsH functions." J Biol Chem 269(7);5225-9. PMID: 8106505

Akiyama95: Akiyama Y, Yoshihisa T, Ito K (1995). "FtsH, a membrane-bound ATPase, forms a complex in the cytoplasmic membrane of Escherichia coli." J Biol Chem 270(40);23485-90. PMID: 7559511

Akiyama96: Akiyama Y, Kihara A, Tokuda H, Ito K (1996). "FtsH (HflB) is an ATP-dependent protease selectively acting on SecY and some other membrane proteins." J Biol Chem 271(49);31196-201. PMID: 8940120

Akiyama96a: Akiyama Y, Kihara A, Ito K (1996). "Subunit a of proton ATPase F0 sector is a substrate of the FtsH protease in Escherichia coli." FEBS Lett 399(1-2);26-8. PMID: 8980112

Akiyama98: Akiyama Y, Kihara A, Mori H, Ogura T, Ito K (1998). "Roles of the periplasmic domain of Escherichia coli FtsH (HflB) in protein interactions and activity modulation." J Biol Chem 273(35);22326-33. PMID: 9712851

Akiyama98a: Akiyama Y, Ehrmann M, Kihara A, Ito K (1998). "Polypeptide binding of Escherichia coli FtsH (HflB)." Mol Microbiol 28(4);803-12. PMID: 9643547

Akiyama99: Akiyama Y (1999). "Self-processing of FtsH and its implication for the cleavage specificity of this protease." Biochemistry 38(36);11693-9. PMID: 10512625

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

Bertani01: Bertani D, Oppenheim AB, Narberhaus F (2001). "An internal region of the RpoH heat shock transcription factor is critical for rapid degradation by the FtsH protease." FEBS Lett 493(1);17-20. PMID: 11277997

Blaszczak99: Blaszczak A, Georgopoulos C, Liberek K (1999). "On the mechanism of FtsH-dependent degradation of the sigma 32 transcriptional regulator of Escherichia coli and the role of the Dnak chaperone machine." Mol Microbiol 31(1);157-66. PMID: 9987118

Bruckner03: Bruckner RC, Gunyuzlu PL, Stein RL (2003). "Coupled kinetics of ATP and peptide hydrolysis by Escherichia coli FtsH protease." Biochemistry 42(36);10843-52. PMID: 12962509

Carmona99: Carmona M, de Lorenzo V (1999). "Involvement of the FtsH (HflB) protease in the activity of sigma 54 promoters." Mol Microbiol 31(1);261-70. PMID: 9987127

Chiba00: Chiba S, Akiyama Y, Mori H, Matsuo E, Ito K (2000). "Length recognition at the N-terminal tail for the initiation of FtsH-mediated proteolysis." EMBO Rep 1(1);47-52. PMID: 11256624

Chiba02: Chiba S, Akiyama Y, Ito K (2002). "Membrane protein degradation by FtsH can be initiated from either end." J Bacteriol 184(17);4775-82. PMID: 12169602

Dougan02: Dougan DA, Mogk A, Zeth K, Turgay K, Bukau B (2002). "AAA+ proteins and substrate recognition, it all depends on their partner in crime." FEBS Lett 529(1);6-10. PMID: 12354604

Ferreira87: Ferreira LC, Keck W, Betzner A, Schwarz U (1987). "In vivo cell division gene product interactions in Escherichia coli K-12." J Bacteriol 169(12);5776-81. PMID: 3316193

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."

GOA06: GOA, SIB (2006). "Electronic Gene Ontology annotations created by transferring manual GO annotations between orthologous microbial proteins."

Granger98: Granger LL, O'Hara EB, Wang RF, Meffen FV, Armstrong K, Yancey SD, Babitzke P, Kushner SR (1998). "The Escherichia coli mrsC gene is required for cell growth and mRNA decay." J Bacteriol 180(7);1920-8. PMID: 9537393

Herman03: Herman C, Prakash S, Lu CZ, Matouschek A, Gross CA (2003). "Lack of a robust unfoldase activity confers a unique level of substrate specificity to the universal AAA protease FtsH." Mol Cell 11(3);659-69. PMID: 12667449

Herman95: Herman C, Thevenet D, D'Ari R, Bouloc P (1995). "Degradation of sigma 32, the heat shock regulator in Escherichia coli, is governed by HflB." Proc Natl Acad Sci U S A 1995;92(8);3516-20. PMID: 7724592

Herman97: Herman C, Thevenet D, D'Ari R, Bouloc P (1997). "The HflB protease of Escherichia coli degrades its inhibitor lambda cIII." J Bacteriol 179(2);358-63. PMID: 8990286

Herman98: Herman C, Thevenet D, Bouloc P, Walker GC, D'Ari R (1998). "Degradation of carboxy-terminal-tagged cytoplasmic proteins by the Escherichia coli protease HflB (FtsH)." Genes Dev 12(9);1348-55. PMID: 9573051

Holland76: Holland IB, Darby V (1976). "Genetical and physiological studies on a thermosensitive mutant of Escherichia coli defective in cell division." J Gen Microbiol 92(1);156-66. PMID: 1107480

Inagawa01: Inagawa T, Kato J, Niki H, Karata K, Ogura T (2001). "Defective plasmid partition in ftsH mutants of Escherichia coli." Mol Genet Genomics 265(5);755-62. PMID: 11523792

Ito05: Ito K, Akiyama Y (2005). "Cellular functions, mechanism of action, and regulation of FtsH protease." Annu Rev Microbiol 59;211-31. PMID: 15910274

Jayasekera00: Jayasekera MM, Foltin SK, Olson ER, Holler TP (2000). "Escherichia coli requires the protease activity of FtsH for growth." Arch Biochem Biophys 380(1);103-7. PMID: 10900138

Karata01: Karata K, Verma CS, Wilkinson AJ, Ogura T (2001). "Probing the mechanism of ATP hydrolysis and substrate translocation in the AAA protease FtsH by modelling and mutagenesis." Mol Microbiol 39(4);890-903. PMID: 11251810

Karata99: Karata K, Inagawa T, Wilkinson AJ, Tatsuta T, Ogura T (1999). "Dissecting the role of a conserved motif (the second region of homology) in the AAA family of ATPases. Site-directed mutagenesis of the ATP-dependent protease FtsH." J Biol Chem 274(37);26225-32. PMID: 10473576

Kihara01: Kihara A, Akiyama Y, Ito K (2001). "Revisiting the lysogenization control of bacteriophage lambda. Identification and characterization of a new host component, HflD." J Biol Chem 276(17);13695-700. PMID: 11278968

Kihara95: Kihara A, Akiyama Y, Ito K (1995). "FtsH is required for proteolytic elimination of uncomplexed forms of SecY, an essential protein translocase subunit." Proc Natl Acad Sci U S A 92(10);4532-6. PMID: 7753838

Kihara96: Kihara A, Akiyama Y, Ito K (1996). "A protease complex in the Escherichia coli plasma membrane: HflKC (HflA) forms a complex with FtsH (HflB), regulating its proteolytic activity against SecY." EMBO J 15(22);6122-31. PMID: 8947034

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vanStelten09: van Stelten J, Silva F, Belin D, Silhavy TJ (2009). "Effects of antibiotics and a proto-oncogene homolog on destruction of protein translocator SecY." Science 325(5941);753-6. PMID: 19661432

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Other References Related to Gene Regulation

Nonaka06: Nonaka G, Blankschien M, Herman C, Gross CA, Rhodius VA (2006). "Regulon and promoter analysis of the E. coli heat-shock factor, sigma32, reveals a multifaceted cellular response to heat stress." Genes Dev 20(13);1776-89. PMID: 16818608

Partridge09: Partridge JD, Bodenmiller DM, Humphrys MS, Spiro S (2009). "NsrR targets in the Escherichia coli genome: new insights into DNA sequence requirements for binding and a role for NsrR in the regulation of motility." Mol Microbiol 73(4);680-94. PMID: 19656291

Wade06: Wade JT, Roa DC, Grainger DC, Hurd D, Busby SJ, Struhl K, Nudler E (2006). "Extensive functional overlap between sigma factors in Escherichia coli." Nat Struct Mol Biol 13(9);806-14. PMID: 16892065


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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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