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Escherichia coli K-12 substr. MG1655 Polypeptide: regulator of FtsH protease

Gene: hflK Accession Numbers: EG10436 (EcoCyc), b4174, ECK4170

Synonyms: hslY, hflA

Regulation Summary Diagram: ?

Regulation summary diagram for hflK

Component of:
HflK-HflC complex; regulator of FtsH protease (extended summary available)
HflB, integral membrane ATP-dependent zinc metallopeptidase (extended summary available)

HflK is an inner membrane protein which forms part of the HflCK complex that interacts with and regulates, the ATP-dependent protease FtsH [Banuett87, Kihara96]. HflK expressed as a single subunit is unstable in vivo [Kihara98]. HflK has been purified as a single subunit after overexpression of both hflK and hflC in an E. coli strain lacking the chromosomal hflCK genes. The purified subunit can inhibit FtsH mediated proteolysis of the bacteriophage lambda cII protein in vitro [Bandyopadhyay10].

Gene Citations: [Nonaka06, Kitagawa96, Tsui94a, Tsui94, Tsui96a]

Locations: cytosol, periplasmic space, inner membrane

Map Position: [4,400,061 -> 4,401,320] (94.84 centisomes, 341°)
Length: 1260 bp / 419 aa

Molecular Weight of Polypeptide: 45.545 kD (from nucleotide sequence), 46 kD (experimental) [Banuett87 ]

Unification Links: ASAP:ABE-0013663 , CGSC:639 , DIP:DIP-47481N , EchoBASE:EB0431 , EcoGene:EG10436 , EcoliWiki:b4174 , Mint:MINT-1271770 , OU-Microarray:b4174 , PortEco:hflK , PR:PRO_000022884 , Pride:P0ABC7 , Protein Model Portal:P0ABC7 , RefSeq:NP_418595 , RegulonDB:EG10436 , SMR:P0ABC7 , String:511145.b4174 , UniProt:P0ABC7

Relationship Links: InterPro:IN-FAMILY:IPR001107 , InterPro:IN-FAMILY:IPR001972 , InterPro:IN-FAMILY:IPR010201 , InterPro:IN-FAMILY:IPR020980 , Panther:IN-FAMILY:PTHR10264 , Panther:IN-FAMILY:PTHR10264:SF51 , Pfam:IN-FAMILY:PF01145 , Pfam:IN-FAMILY:PF12221 , Prints:IN-FAMILY:PR00721 , Smart:IN-FAMILY:SM00244

In Paralogous Gene Group: 142 (3 members)

Gene-Reaction Schematic: ?

Gene-Reaction Schematic

Genetic Regulation Schematic: ?

Genetic regulation schematic for hflK

GO Terms:

Biological Process: GO:0009408 - response to heat Inferred from experiment [Chuang93]
GO:0048553 - negative regulation of metalloenzyme activity Inferred from experiment [Kihara96]
Molecular Function: GO:0005515 - protein binding Inferred from experiment [Kihara96]
Cellular Component: GO:0005829 - cytosol Inferred from experiment [Ishihama08]
GO:0071575 - integral component of external side of plasma membrane Inferred from experiment [Zorick91, Kihara98]
GO:0005886 - plasma membrane Inferred by computational analysis [UniProtGOA11, UniProtGOA11a, Zorick91]
GO:0016020 - membrane Inferred by computational analysis [UniProtGOA11a, GOA01a]
GO:0016021 - integral component of membrane Inferred by computational analysis [UniProtGOA11a, GOA01a]
GO:0030288 - outer membrane-bounded periplasmic space [Kihara98]

MultiFun Terms: extrachromosomal prophage genes and phage related functions
metabolism degradation of macromolecules proteins/peptides/glycopeptides
regulation type of regulation posttranscriptional proteases, cleavage of compounds

Essentiality data for hflK 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]

Last-Curated ? 15-Jun-2011 by Mackie A , Macquarie University

Subunit of: HflK-HflC complex; regulator of FtsH protease

Synonyms: HflA

Subunit composition of HflK-HflC complex; regulator of FtsH protease = [HflK][HflC]
         regulator of FtsH protease = HflK (summary available)
         regulator of FtsH protease = HflC (summary available)

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

The HflK-HflC (HflKC) complex interacts with the ATP-dependent protease FtsH, regulating the latter's degradation of different substrate proteins such as SecY [Kihara96] and the lambda cII protein [Kihara97, Cheng88]. HflKC may act as an FtsH specificity factor [Kihara97].

HflK and HflC are inner membrane proteins, each containing a single N-terminal transmembrane domain and a large C-terminal domain which is exposed to the periplasm [Zorick91, Noble93a, Kihara98]. HflC and HflK interact [Banuett87], and uncomplexed subunits are unstable [Banuett87, Kihara98]. The HflK-HflC (HflKC) complex interacts with FtsH [Kihara96].

Historically, the hflKC genes were described as part of the hflA class of E. coli mutations which cause high frequency of bacteriophage lambda lysogenization through stabilisation of the cII protein [Banuett87, Hoyt82, Banuett86]. A third gene hflX, is also part of the "hflA" locus - however it does not play a role in the lambda lysogenization process [Dutta09] and does not interact with HflK or HflC [Dutta09]. The purified products of the "hflA" locus exhibited protease activity against the lambda cII protein resulting in the suggestion that HflKC was a cII protease [Cheng88] however mutation of the HflC protease domain did not affect lambda lysogenization which indicated that a protease activity was not responsible [Kihara97].

An hflC mutant exhibits decreased abundance of HflK, and an hflK mutant exhibits decreased abundance of HflC, compared to wild type [Banuett87]. An hflKC gain of function mutation causes reduced proteolysis of SecY, which is suppressed by FtsH overproduction [Kihara96]. An hflKC null mutation causes increased proteolysis of SecY [Kihara96]. An hflKC null mutation also causes increases abundance of lambda cII protein, as does HflKC overproduction [Kihara97].

hflK and hflC form part of a 'superoperon' which shows complex transcriptional patterns [Banuett87, Tsui94, Tsui94a, Tsui96a].

Hfl: "high frequency of lysogeny"

Review: [Schumann99]

Locations: inner membrane

GO Terms:

Biological Process: GO:0048553 - negative regulation of metalloenzyme activity Inferred from experiment [Kihara96]
Molecular Function: GO:0005515 - protein binding Inferred from experiment [Kihara96]
Cellular Component: GO:0005887 - integral component of plasma membrane Inferred from experiment [Zorick91]

Last-Curated ? 14-Jun-2011 by Mackie A , Macquarie University

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)

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 [Kihara98a, Kihara95, Akiyama96]. 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 [Akiyama94, Akiyama96a, 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 [Wang98b].

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 [Akiyama94a]. 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

Protein sequence of regulator of FtsH protease with features indicated

Feature Class Location Citations Comment
Transmembrane-Region 80 -> 100
UniProt: Helical;; Non-Experimental Qualifier: potential;
Mutagenesis-Variant 145
[Kihara96, UniProt11a]
UniProt: In hflK13; stabilizes overproduced SecY but not overproduced cII protein.

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

Transcription-unit diagram

Transcription-unit diagram

Transcription-unit diagram

Transcription-unit diagram


10/20/97 Gene b4174 from Blattner lab Genbank (v. M52) entry merged into EcoCyc gene EG10436; confirmed by SwissProt match.


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

Akiyama94: 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

Akiyama94a: 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

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, 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

Akiyama96a: 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

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

Bandyopadhyay10: Bandyopadhyay K, Parua PK, Datta AB, Parrack P (2010). "Escherichia coli HflK and HflC can individually inhibit the HflB (FtsH)-mediated proteolysis of lambdaCII in vitro." Arch Biochem Biophys 501(2);239-43. PMID: 20599668

Banuett86: Banuett F, Hoyt MA, McFarlane L, Echols H, Herskowitz I (1986). "hflB, a new Escherichia coli locus regulating lysogeny and the level of bacteriophage lambda cII protein." J Mol Biol 187(2);213-24. PMID: 2939254

Banuett87: Banuett F, Herskowitz I (1987). "Identification of polypeptides encoded by an Escherichia coli locus (hflA) that governs the lysis-lysogeny decision of bacteriophage lambda." J Bacteriol 169(9);4076-85. PMID: 3040675

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

Cheng88: Cheng HH, Muhlrad PJ, Hoyt MA, Echols H (1988). "Cleavage of the cII protein of phage lambda by purified HflA protease: control of the switch between lysis and lysogeny." Proc Natl Acad Sci U S A 85(21);7882-6. PMID: 2973057

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

Chuang93: Chuang SE, Blattner FR (1993). "Characterization of twenty-six new heat shock genes of Escherichia coli." J Bacteriol 175(16);5242-52. PMID: 8349564

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

Dutta09: Dutta D, Bandyopadhyay K, Datta AB, Sardesai AA, Parrack P (2009). "Properties of HflX, an enigmatic protein from Escherichia coli." J Bacteriol 191(7):2307-14. PMID: 19181811

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."

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

Hoyt82: Hoyt MA, Knight DM, Das A, Miller HI, Echols H (1982). "Control of phage lambda development by stability and synthesis of cII protein: role of the viral cIII and host hflA, himA and himD genes." Cell 31(3 Pt 2);565-73. PMID: 6218885

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

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

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

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

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

Kihara97: Kihara A, Akiyama Y, Ito K (1997). "Host regulation of lysogenic decision in bacteriophage lambda: transmembrane modulation of FtsH (HflB), the cII degrading protease, by HflKC (HflA)." Proc Natl Acad Sci U S A 94(11);5544-9. PMID: 9159109

Kihara98: Kihara A, Ito K (1998). "Translocation, folding, and stability of the HflKC complex with signal anchor topogenic sequences." J Biol Chem 273(45);29770-5. PMID: 9792691

Kihara98a: Kihara A, Akiyama Y, Ito K (1998). "Different pathways for protein degradation by the FtsH/HflKC membrane-embedded protease complex: an implication from the interference by a mutant form of a new substrate protein, YccA." J Mol Biol 279(1);175-88. PMID: 9636708

Kihara99: Kihara A, Akiyama Y, Ito K (1999). "Dislocation of membrane proteins in FtsH-mediated proteolysis." EMBO J 18(11);2970-81. PMID: 10357810

Kitagawa96: Kitagawa R, Mitsuki H, Okazaki T, Ogawa T (1996). "A novel DnaA protein-binding site at 94.7 min on the Escherichia coli chromosome." Mol Microbiol 1996;19(5);1137-47. PMID: 8830270

Kobiler02: Kobiler O, Koby S, Teff D, Court D, Oppenheim AB (2002). "The phage lambda CII transcriptional activator carries a C-terminal domain signaling for rapid proteolysis." Proc Natl Acad Sci U S A 99(23);14964-9. PMID: 12397182

Krzywda02: Krzywda S, Brzozowski AM, Verma C, Karata K, Ogura T, Wilkinson AJ (2002). "The crystal structure of the AAA domain of the ATP-dependent protease FtsH of Escherichia coli at 1.5 A resolution." Structure (Camb) 10(8);1073-83. PMID: 12176385

Krzywda02a: Krzywda S, Brzozowski AM, Karata K, Ogura T, Wilkinson AJ (2002). "Crystallization of the AAA domain of the ATP-dependent protease FtsH of Escherichia coli." Acta Crystallogr D Biol Crystallogr 58(Pt 6 Pt 2);1066-7. PMID: 12037319

Leffers98: Leffers GG, Gottesman S (1998). "Lambda Xis degradation in vivo by Lon and FtsH." J Bacteriol 180(6);1573-7. PMID: 9515930

Makino99: Makino S, Makino T, Abe K, Hashimoto J, Tatsuta T, Kitagawa M, Mori H, Ogura T, Fujii T, Fushinobu S, Wakagi T, Matsuzawa H, Makinoa T (1999). "Second transmembrane segment of FtsH plays a role in its proteolytic activity and homo-oligomerization." FEBS Lett 460(3);554-8. PMID: 10556534

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Other References Related to Gene Regulation

Lin11: Lin HH, Hsu CC, Yang CD, Ju YW, Chen YP, Tseng CP (2011). "Negative Effect of Glucose on ompA mRNA Stability: a Potential Role of Cyclic AMP in the Repression of hfq in Escherichia coli." J Bacteriol 193(20);5833-40. PMID: 21840983

Maciag11: Maciag A, Peano C, Pietrelli A, Egli T, De Bellis G, Landini P (2011). "In vitro transcription profiling of the {sigma}S subunit of bacterial RNA polymerase: re-definition of the {sigma}S regulon and identification of {sigma}S-specific promoter sequence elements." Nucleic Acids Res 39(13);5338-55. PMID: 21398637

Mangat08: Mangat CS, Brown ED (2008). "Known bioactive small molecules probe the function of a widely conserved but enigmatic bacterial ATPase, YjeE." Chem Biol 15(12);1287-95. PMID: 19101473

Zaslaver06: Zaslaver A, Bren A, Ronen M, Itzkovitz S, Kikoin I, Shavit S, Liebermeister W, Surette MG, Alon U (2006). "A comprehensive library of fluorescent transcriptional reporters for Escherichia coli." Nat Methods 3(8);623-8. PMID: 16862137

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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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