FTSH_ECOLI
ID FTSH_ECOLI Reviewed; 644 AA.
AC P0AAI3; P28691; Q2M934;
DT 11-OCT-2005, integrated into UniProtKB/Swiss-Prot.
DT 11-OCT-2005, sequence version 1.
DT 03-AUG-2022, entry version 137.
DE RecName: Full=ATP-dependent zinc metalloprotease FtsH {ECO:0000255|HAMAP-Rule:MF_01458};
DE EC=3.4.24.- {ECO:0000255|HAMAP-Rule:MF_01458};
DE AltName: Full=Cell division protease FtsH;
GN Name=ftsH {ECO:0000255|HAMAP-Rule:MF_01458};
GN Synonyms=hflB, mrsC, std, tolZ; OrderedLocusNames=b3178, JW3145;
OS Escherichia coli (strain K12).
OC Bacteria; Proteobacteria; Gammaproteobacteria; Enterobacterales;
OC Enterobacteriaceae; Escherichia.
OX NCBI_TaxID=83333;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND MUTAGENESIS OF GLU-463 AND HIS-536.
RC STRAIN=K12 / W3110 / ATCC 27325 / DSM 5911;
RX PubMed=8444796; DOI=10.1128/jb.175.5.1344-1351.1993;
RA Tomoyasu T., Yuki T., Morimura S., Mori H., Yamanaka K., Niki H.,
RA Hiraga S., Ogura T.;
RT "The Escherichia coli FtsH protein is a prokaryotic member of a protein
RT family of putative ATPases involved in membrane functions, cell cycle
RT control, and gene expression.";
RL J. Bacteriol. 175:1344-1351(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=K12;
RA Wang R., Kushner S.R.;
RT "Identification and physical analysis of new genes in the argG region (69
RT min) of Escherichia coli chromosome.";
RL Submitted (SEP-1993) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=K12 / MG1655 / ATCC 47076;
RX PubMed=9278503; DOI=10.1126/science.277.5331.1453;
RA Blattner F.R., Plunkett G. III, Bloch C.A., Perna N.T., Burland V.,
RA Riley M., Collado-Vides J., Glasner J.D., Rode C.K., Mayhew G.F.,
RA Gregor J., Davis N.W., Kirkpatrick H.A., Goeden M.A., Rose D.J., Mau B.,
RA Shao Y.;
RT "The complete genome sequence of Escherichia coli K-12.";
RL Science 277:1453-1462(1997).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=K12 / W3110 / ATCC 27325 / DSM 5911;
RX PubMed=16738553; DOI=10.1038/msb4100049;
RA Hayashi K., Morooka N., Yamamoto Y., Fujita K., Isono K., Choi S.,
RA Ohtsubo E., Baba T., Wanner B.L., Mori H., Horiuchi T.;
RT "Highly accurate genome sequences of Escherichia coli K-12 strains MG1655
RT and W3110.";
RL Mol. Syst. Biol. 2:E1-E5(2006).
RN [5]
RP SUBCELLULAR LOCATION, AND TOPOLOGY.
RC STRAIN=K12 / W3110 / ATCC 27325 / DSM 5911;
RX PubMed=8444797; DOI=10.1128/jb.175.5.1352-1357.1993;
RA Tomoyasu T., Yamanaka K., Murata K., Suzaki T., Bouloc P., Kato A.,
RA Niki H., Hiraga S., Ogura T.;
RT "Topology and subcellular localization of FtsH protein in Escherichia
RT coli.";
RL J. Bacteriol. 175:1352-1357(1993).
RN [6]
RP DISCUSSION OF SEQUENCE.
RX PubMed=1925026; DOI=10.1016/0923-2508(91)90041-8;
RA Ogura T., Tomoyasu T., Yuki T., Morimura S., Begg K.J., Donachie W.D.,
RA Mori H., Niki H., Hiraga S.;
RT "Structure and function of the ftsH gene in Escherichia coli.";
RL Res. Microbiol. 142:279-282(1991).
RN [7]
RP IDENTIFICATION OF HFLB AS FTSH.
RX PubMed=8248182; DOI=10.1073/pnas.90.22.10861;
RA Herman C., Ogura T., Tomoyasu T., Hiraga S., Akiyama Y., Ito K., Thomas R.,
RA D'Ari R., Bouloc P.;
RT "Cell growth and lambda phage development controlled by the same essential
RT Escherichia coli gene, ftsH/hflB.";
RL Proc. Natl. Acad. Sci. U.S.A. 90:10861-10865(1993).
RN [8]
RP CHARACTERIZATION.
RX PubMed=8106505; DOI=10.1016/s0021-9258(17)37678-0;
RA Akiyama Y., Shirai Y., Ito K.;
RT "Involvement of FtsH in protein assembly into and through the membrane. II.
RT Dominant mutations affecting FtsH functions.";
RL J. Biol. Chem. 269:5225-5229(1994).
RN [9]
RP FUNCTION, AND SIGMA-32 AS SUBSTRATE.
RX PubMed=7781608; DOI=10.1002/j.1460-2075.1995.tb07253.x;
RA Tomoyasu T., Gamer J., Bukau B., Kanemori M., Mori H., Rutman A.J.,
RA Oppenheim A.B., Yura T., Yamanaka K., Niki H., Hiraga S., Ogura T.;
RT "Escherichia coli FtsH is a membrane-bound, ATP-dependent protease which
RT degrades the heat-shock transcription factor sigma 32.";
RL EMBO J. 14:2551-2560(1995).
RN [10]
RP FUNCTION, AND SECY AS SUBSTRATE.
RX PubMed=7753838; DOI=10.1073/pnas.92.10.4532;
RA Kihara A., Akiyama Y., Ito K.;
RT "FtsH is required for proteolytic elimination of uncomplexed forms of SecY,
RT an essential protein translocase subunit.";
RL Proc. Natl. Acad. Sci. U.S.A. 92:4532-4536(1995).
RN [11]
RP INTERACTION WITH HFLC AND HFLK, AND SUBCELLULAR LOCATION.
RC STRAIN=K12 / CSH26 / AD16;
RX PubMed=8947034; DOI=10.1002/j.1460-2075.1996.tb01000.x;
RA Kihara A., Akiyama Y., Ito K.;
RT "A protease complex in the Escherichia coli plasma membrane: HflKC (HflA)
RT forms a complex with FtsH (HflB), regulating its proteolytic activity
RT against SecY.";
RL EMBO J. 15:6122-6131(1996).
RN [12]
RP ACTIVITY REGULATION (MICROBIAL INFECTION), AND INTERACTION WITH HFLKC.
RC STRAIN=K12 / CSH26 / AD16;
RX PubMed=9159109; DOI=10.1073/pnas.94.11.5544;
RA Kihara A., Akiyama Y., Ito K.;
RT "Host regulation of lysogenic decision in bacteriophage lambda:
RT transmembrane modulation of FtsH (HflB), the cII degrading protease, by
RT HflKC (HflA).";
RL Proc. Natl. Acad. Sci. U.S.A. 94:5544-5549(1997).
RN [13]
RP CHARACTERIZATION.
RX PubMed=9573051; DOI=10.1101/gad.12.9.1348;
RA Herman C., Thevenet D., Bouloc P., Walker G.C., D'Ari R.;
RT "Degradation of carboxy-terminal-tagged cytoplasmic proteins by the
RT Escherichia coli protease HflB (FtsH).";
RL Genes Dev. 12:1348-1355(1998).
RN [14]
RP MEMBRANE SUBSTRATES, AND INTERACTION WITH YCCA.
RC STRAIN=K12 / CSH26 / AD16;
RX PubMed=9636708; DOI=10.1006/jmbi.1998.1781;
RA Kihara A., Akiyama Y., Ito K.;
RT "Different pathways for protein degradation by the FtsH/HflKC membrane-
RT embedded protease complex: an implication from the interference by a mutant
RT form of a new substrate protein, YccA.";
RL J. Mol. Biol. 279:175-188(1998).
RN [15]
RP MECHANISM OF MEMBRANE SUBSTRATE RECOGNITION.
RC STRAIN=K12 / CSH26 / AD16;
RX PubMed=10357810; DOI=10.1093/emboj/18.11.2970;
RA Kihara A., Akiyama Y., Ito K.;
RT "Dislocation of membrane proteins in FtsH-mediated proteolysis.";
RL EMBO J. 18:2970-2981(1999).
RN [16]
RP MUTAGENESIS OF LEU-201; THR-297; ASN-298; ASP-304; LEU-307; ARG-309;
RP ARG-312; GLU-415 AND HIS-418.
RX PubMed=10473576; DOI=10.1074/jbc.274.37.26225;
RA Karata K., Inagawa T., Wilkinson A.J., Tatsuta T., Ogura T.;
RT "Dissecting the role of a conserved motif (the second region of homology)
RT in the AAA family of ATPases. Site-directed mutagenesis of the ATP-
RT dependent protease FtsH.";
RL J. Biol. Chem. 274:26225-26232(1999).
RN [17]
RP LPXC AS SUBSTRATE, FUNCTION IN REGULATING LIPOPOLYSACCHARIDE SYNTHESIS, AND
RP DISRUPTION PHENOTYPE.
RC STRAIN=K12 / W3110, and W2252;
RX PubMed=10048027; DOI=10.1046/j.1365-2958.1999.01221.x;
RA Ogura T., Inoue K., Tatsuta T., Suzaki T., Karata K., Young K., Su L.H.,
RA Fierke C.A., Jackman J.E., Raetz C.R., Coleman J., Tomoyasu T.,
RA Matsuzawa H.;
RT "Balanced biosynthesis of major membrane components through regulated
RT degradation of the committed enzyme of lipid A biosynthesis by the AAA
RT protease FtsH (HflB) in Escherichia coli.";
RL Mol. Microbiol. 31:833-844(1999).
RN [18]
RP RECOGNITION OF MEMBRANE SUBSTRATE FROM N-TERMINUS.
RX PubMed=11256624; DOI=10.1093/embo-reports/kvd005;
RA Chiba S., Akiyama Y., Mori H., Matsuo E., Ito K.;
RT "Length recognition at the N-terminal tail for the initiation of FtsH-
RT mediated proteolysis.";
RL EMBO Rep. 1:47-52(2000).
RN [19]
RP ZINC-BINDING, AND MUTAGENESIS OF HIS-414; HIS-418; GLU-476 AND GLU-582.
RC STRAIN=K12;
RX PubMed=11827531; DOI=10.1021/bi015748o;
RA Saikawa N., Ito K., Akiyama Y.;
RT "Identification of glutamic acid 479 as the gluzincin coordinator of zinc
RT in FtsH (HflB).";
RL Biochemistry 41:1861-1868(2002).
RN [20]
RP RECOGNITION OF MEMBRANE SUBSTRATE FROM C-TERMINUS.
RC STRAIN=K12 / JM103;
RX PubMed=12169602; DOI=10.1128/jb.184.17.4775-4782.2002;
RA Chiba S., Akiyama Y., Ito K.;
RT "Membrane protein degradation by FtsH can be initiated from either end.";
RL J. Bacteriol. 184:4775-4782(2002).
RN [21]
RP REQUIREMENT FOR ATP, AND MUTAGENESIS OF PHE-225 AND GLY-227.
RX PubMed=14514680; DOI=10.1074/jbc.m308327200;
RA Yamada-Inagawa T., Okuno T., Karata K., Yamanaka K., Ogura T.;
RT "Conserved pore residues in the AAA protease FtsH are important for
RT proteolysis and its coupling to ATP hydrolysis.";
RL J. Biol. Chem. 278:50182-50187(2003).
RN [22]
RP TOPOLOGY [LARGE SCALE ANALYSIS], AND SUBCELLULAR LOCATION.
RC STRAIN=K12 / MG1655 / ATCC 47076;
RX PubMed=15919996; DOI=10.1126/science.1109730;
RA Daley D.O., Rapp M., Granseth E., Melen K., Drew D., von Heijne G.;
RT "Global topology analysis of the Escherichia coli inner membrane
RT proteome.";
RL Science 308:1321-1323(2005).
RN [23]
RP POSSIBLE INTERACTION WITH QMCA.
RC STRAIN=K12;
RX PubMed=16573693; DOI=10.1111/j.1365-2958.2006.05104.x;
RA Chiba S., Ito K., Akiyama Y.;
RT "The Escherichia coli plasma membrane contains two PHB (prohibitin
RT homology) domain protein complexes of opposite orientations.";
RL Mol. Microbiol. 60:448-457(2006).
RN [24]
RP INTERACTION WITH YIDC (OXAA).
RX PubMed=18387365; DOI=10.1016/j.febslet.2008.02.082;
RA van Bloois E., Dekker H.L., Froderberg L., Houben E.N., Urbanus M.L.,
RA de Koster C.G., de Gier J.W., Luirink J.;
RT "Detection of cross-links between FtsH, YidC, HflK/C suggests a linked role
RT for these proteins in quality control upon insertion of bacterial inner
RT membrane proteins.";
RL FEBS Lett. 582:1419-1424(2008).
RN [25]
RP KDO TRANSFERASE (KDTA) AS SUBSTRATE, AND FUNCTION IN REGULATING
RP LIPOPOLYSACCHARIDE BIOSYNTHESIS.
RC STRAIN=K12 / MG1655 / ATCC 47076;
RX PubMed=18776015; DOI=10.1128/jb.00871-08;
RA Katz C., Ron E.Z.;
RT "Dual role of FtsH in regulating lipopolysaccharide biosynthesis in
RT Escherichia coli.";
RL J. Bacteriol. 190:7117-7122(2008).
RN [26]
RP RECEPTOR FOR CDI TOXIN ENTRY INTO TARGET CELL CYTOPLASM (MICROBIAL
RP INFECTION), AND DISRUPTION PHENOTYPE.
RC STRAIN=K12 / MC4100 / ATCC 35695 / DSM 6574;
RX PubMed=26305955; DOI=10.1073/pnas.1512124112;
RA Willett J.L., Gucinski G.C., Fatherree J.P., Low D.A., Hayes C.S.;
RT "Contact-dependent growth inhibition toxins exploit multiple independent
RT cell-entry pathways.";
RL Proc. Natl. Acad. Sci. U.S.A. 112:11341-11346(2015).
RN [27]
RP PRELIMINARY CRYSTALLIZATION.
RX PubMed=12037319; DOI=10.1107/s0907444902006972;
RA Krzywda S., Brzozowski A.M., Karata K., Ogura T., Wilkinson A.J.;
RT "Crystallization of the AAA domain of the ATP-dependent protease FtsH of
RT Escherichia coli.";
RL Acta Crystallogr. D 582:1066-1067(2002).
RN [28]
RP X-RAY CRYSTALLOGRAPHY (1.5 ANGSTROMS) OF 141-395.
RX PubMed=12176385; DOI=10.1016/s0969-2126(02)00806-7;
RA Krzywda S., Brzozowski A.M., Verma C., Karata K., Ogura T., Wilkinson A.J.;
RT "The crystal structure of the AAA domain of the ATP-dependent protease FtsH
RT of Escherichia coli at 1.5 A resolution.";
RL Structure 10:1073-1083(2002).
RN [29]
RP REVIEW.
RX PubMed=19454621; DOI=10.1093/jb/mvp071;
RA Akiyama Y.;
RT "Quality control of cytoplasmic membrane proteins in Escherichia coli.";
RL J. Biochem. 146:449-454(2009).
RN [30]
RP REVIEW.
RX PubMed=19744556; DOI=10.1016/j.resmic.2009.08.011;
RA Narberhaus F., Obrist M., Fuhrer F., Langklotz S.;
RT "Degradation of cytoplasmic substrates by FtsH, a membrane-anchored
RT protease with many talents.";
RL Res. Microbiol. 160:652-659(2009).
CC -!- FUNCTION: Acts as a processive, ATP-dependent zinc metallopeptidase for
CC both cytoplasmic and membrane proteins. Plays a role in the quality
CC control of integral membrane proteins. Degrades a few membrane proteins
CC that have not been assembled into complexes such as SecY, F(0) ATPase
CC subunit a and YccA, and also cytoplasmic proteins sigma-32, LpxC, KdtA
CC and phage lambda cII protein among others. Degrades membrane proteins
CC in a processive manner starting at either the N- or C-terminus;
CC recognition requires a cytoplasmic tail of about 20 residues with no
CC apparent sequence requirements. It presumably dislocates membrane-
CC spanning and periplasmic segments of the protein into the cytoplasm to
CC degrade them, this probably requires ATP. Degrades C-terminal-tagged
CC cytoplasmic proteins which are tagged with an 11-amino-acid nonpolar
CC destabilizing tail via a mechanism involving the 10SA (SsrA) stable
CC RNA.
CC -!- FUNCTION: As FtsH regulates the levels of both LpxC and KdtA it is
CC required for synthesis of both the protein and lipid components of
CC lipopolysaccharide (LPS). {ECO:0000269|PubMed:18776015}.
CC -!- FUNCTION: (Microbial infection) Probably transports the toxic C-
CC terminal region of CdiA from E.coli strain 536, E.cloacae strain ATCC
CC 13047 and of Y.pestis strain A across the inner membrane to the
CC cytoplasm, where CdiA has a toxic effect. Toxin transport is strain-
CC specific, mutations in this gene do not confer resistance to several
CC other tested CdiA toxins. {ECO:0000269|PubMed:26305955}.
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Note=Binds 1 zinc ion per subunit.;
CC -!- ACTIVITY REGULATION: (Microbial infection) Activity against phage
CC lambda cII protein is inhibited by EDTA but not by PMSF. In vitro pre-
CC incubation of FtsH with HflKC abolishes its activity against phage
CC lambda cII protein at the cytoplasmic side of the membrane.
CC {ECO:0000269|PubMed:9159109}.
CC -!- SUBUNIT: The E.coli AAA domain has been modeled as a homohexamer, in
CC Thermus thermophilus the same domain crystallizes as a homohexamer.
CC Forms a complex with HflKC (formerly called HflA); complex formation is
CC stimulated by ATP. Interacts with YccA, and probably weakly with QmcA.
CC Can be cross-linked to YidC (OxaA) and to a nascent polypeptide chain
CC for an integral membrane protein. {ECO:0000269|PubMed:18387365,
CC ECO:0000269|PubMed:8947034, ECO:0000269|PubMed:9159109,
CC ECO:0000269|PubMed:9636708}.
CC -!- INTERACTION:
CC P0AAI3; P0ABC3: hflC; NbExp=9; IntAct=EBI-548381, EBI-551642;
CC P0AAI3; P0ABC7: hflK; NbExp=7; IntAct=EBI-548381, EBI-558599;
CC P0AAI3; P0AGB3: rpoH; NbExp=4; IntAct=EBI-548381, EBI-555342;
CC P0AAI3; P03042: cII; Xeno; NbExp=5; IntAct=EBI-548381, EBI-4478343;
CC -!- SUBCELLULAR LOCATION: Cell inner membrane {ECO:0000255|HAMAP-
CC Rule:MF_01458, ECO:0000269|PubMed:15919996, ECO:0000269|PubMed:8444797,
CC ECO:0000269|PubMed:8947034}; Multi-pass membrane protein
CC {ECO:0000255|HAMAP-Rule:MF_01458, ECO:0000269|PubMed:15919996,
CC ECO:0000269|PubMed:8444797, ECO:0000269|PubMed:8947034}.
CC -!- DISRUPTION PHENOTYPE: Lethality, due to increased levels of LpxC, which
CC increases the level of LPS in the cell and results in formation of
CC abnormal membrane structures in the periplasm. Lethality is suppressed
CC under conditions in which LPS synthesis is reduced (PubMed:10048027).
CC Disruption confers resistance to cellular contact-dependent growth
CC inhibition (CDI) CdiA of E.coli strain 536, E.cloacae strain ATCC 13047
CC and of Y.pestis strain A, but not to CdiA from E.coli strain 93 toxin
CC (PubMed:26305955). {ECO:0000269|PubMed:10048027,
CC ECO:0000269|PubMed:26305955}.
CC -!- MISCELLANEOUS: The ftsH gene was discovered independently through 3
CC different phenotypes and received 3 different names: ftsH, for
CC filamentous temperature-sensitive; tolZ, for colicin tolerance, and
CC hlfB, because mutants show a high frequency of lysogenization when
CC infected with phage lambda. {ECO:0000305|PubMed:19744556}.
CC -!- MISCELLANEOUS: Requires ATP for protease catalytic activity, probably
CC due to tight coupling of the 2 activities; ADP or non-hydrolyzable
CC analogs cannot substitute, except when unfolded, non-physiological
CC substrates are tested.
CC -!- SIMILARITY: In the central section; belongs to the AAA ATPase family.
CC {ECO:0000255|HAMAP-Rule:MF_01458}.
CC -!- SIMILARITY: In the C-terminal section; belongs to the peptidase M41
CC family. {ECO:0000255|HAMAP-Rule:MF_01458}.
CC -!- CAUTION: Glu-476 was identified as the third Zn ligand
CC (PubMed:11827531), however in other crystal structures (Aquifex
CC aeolicus and Thermotoga maritima) the conserved equivalent residue does
CC not bind Zn. Instead it makes a hydrogen bond with the side chain of
CC the first catalytic Zn-binding residue and indirectly stabilizes the
CC Zn. {ECO:0000305|PubMed:11827531}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA97508.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; M83138; AAA23813.1; -; Genomic_DNA.
DR EMBL; U01376; AAA97508.1; ALT_INIT; Genomic_DNA.
DR EMBL; U18997; AAA57979.1; -; Genomic_DNA.
DR EMBL; U00096; AAC76210.1; -; Genomic_DNA.
DR EMBL; AP009048; BAE77222.1; -; Genomic_DNA.
DR PIR; S35109; S35109.
DR RefSeq; NP_417645.1; NC_000913.3.
DR RefSeq; WP_001107467.1; NZ_STEB01000012.1.
DR PDB; 1LV7; X-ray; 1.50 A; A=141-395.
DR PDB; 4V0B; X-ray; 2.55 A; A/B/C=25-96.
DR PDBsum; 1LV7; -.
DR PDBsum; 4V0B; -.
DR AlphaFoldDB; P0AAI3; -.
DR SMR; P0AAI3; -.
DR BioGRID; 4262980; 385.
DR ComplexPortal; CPX-5046; FtsH-HflKC complex.
DR DIP; DIP-35828N; -.
DR IntAct; P0AAI3; 30.
DR MINT; P0AAI3; -.
DR STRING; 511145.b3178; -.
DR MEROPS; M41.001; -.
DR TCDB; 3.A.29.1.5; the mitochondrial inner membrane i-aaa protease complex (mimp) familly.
DR jPOST; P0AAI3; -.
DR PaxDb; P0AAI3; -.
DR PRIDE; P0AAI3; -.
DR EnsemblBacteria; AAC76210; AAC76210; b3178.
DR EnsemblBacteria; BAE77222; BAE77222; BAE77222.
DR GeneID; 66672920; -.
DR GeneID; 947690; -.
DR KEGG; ecj:JW3145; -.
DR KEGG; eco:b3178; -.
DR PATRIC; fig|511145.12.peg.3271; -.
DR EchoBASE; EB1469; -.
DR eggNOG; COG0465; Bacteria.
DR HOGENOM; CLU_000688_16_2_6; -.
DR InParanoid; P0AAI3; -.
DR OMA; QYGMTER; -.
DR PhylomeDB; P0AAI3; -.
DR BioCyc; EcoCyc:EG11506-MON; -.
DR BioCyc; MetaCyc:EG11506-MON; -.
DR BRENDA; 3.4.24.B17; 2026.
DR BRENDA; 3.4.24.B20; 2026.
DR SABIO-RK; P0AAI3; -.
DR EvolutionaryTrace; P0AAI3; -.
DR PRO; PR:P0AAI3; -.
DR Proteomes; UP000000318; Chromosome.
DR Proteomes; UP000000625; Chromosome.
DR GO; GO:0005887; C:integral component of plasma membrane; ISM:EcoCyc.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0098797; C:plasma membrane protein complex; IPI:ComplexPortal.
DR GO; GO:0005524; F:ATP binding; ISM:EcoCyc.
DR GO; GO:0016887; F:ATP hydrolysis activity; IEA:UniProtKB-UniRule.
DR GO; GO:0004176; F:ATP-dependent peptidase activity; IDA:EcoCyc.
DR GO; GO:0004222; F:metalloendopeptidase activity; IDA:EcoCyc.
DR GO; GO:0008270; F:zinc ion binding; IDA:EcoCyc.
DR GO; GO:0010466; P:negative regulation of peptidase activity; IDA:ComplexPortal.
DR GO; GO:0030163; P:protein catabolic process; IBA:GO_Central.
DR GO; GO:0006508; P:proteolysis; IDA:EcoCyc.
DR Gene3D; 1.20.58.760; -; 1.
DR Gene3D; 3.40.50.300; -; 1.
DR HAMAP; MF_01458; FtsH; 1.
DR InterPro; IPR003593; AAA+_ATPase.
DR InterPro; IPR041569; AAA_lid_3.
DR InterPro; IPR003959; ATPase_AAA_core.
DR InterPro; IPR003960; ATPase_AAA_CS.
DR InterPro; IPR005936; FtsH.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR011546; Pept_M41_FtsH_extracell.
DR InterPro; IPR000642; Peptidase_M41.
DR InterPro; IPR037219; Peptidase_M41-like.
DR Pfam; PF00004; AAA; 1.
DR Pfam; PF17862; AAA_lid_3; 1.
DR Pfam; PF06480; FtsH_ext; 1.
DR Pfam; PF01434; Peptidase_M41; 1.
DR SMART; SM00382; AAA; 1.
DR SUPFAM; SSF140990; SSF140990; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR TIGRFAMs; TIGR01241; FtsH_fam; 1.
DR PROSITE; PS00674; AAA; 1.
PE 1: Evidence at protein level;
KW 3D-structure; ATP-binding; Cell inner membrane; Cell membrane; Hydrolase;
KW Membrane; Metal-binding; Metalloprotease; Nucleotide-binding; Protease;
KW Reference proteome; Transmembrane; Transmembrane helix; Zinc.
FT CHAIN 1..644
FT /note="ATP-dependent zinc metalloprotease FtsH"
FT /id="PRO_0000084631"
FT TOPO_DOM 1..4
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305|PubMed:8444797"
FT TRANSMEM 5..25
FT /note="Helical"
FT /evidence="ECO:0000305"
FT TOPO_DOM 26..98
FT /note="Periplasmic"
FT /evidence="ECO:0000305|PubMed:8444797"
FT TRANSMEM 99..119
FT /note="Helical"
FT /evidence="ECO:0000305"
FT TOPO_DOM 120..644
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:15919996,
FT ECO:0000305|PubMed:8444797"
FT REGION 598..644
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 415
FT /evidence="ECO:0000305"
FT BINDING 192..199
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01458"
FT BINDING 414
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000305"
FT BINDING 418
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000305"
FT BINDING 492
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01458"
FT SITE 225
FT /note="Substrate binding"
FT /evidence="ECO:0000305"
FT MUTAGEN 201
FT /note="L->N: No in vivo protease activity, no in vitro
FT ATPase activity."
FT /evidence="ECO:0000269|PubMed:10473576"
FT MUTAGEN 225
FT /note="F->A,D,E,G,N,Q,R,S,T: Does not complement ftsH1 at
FT 42 degrees Celsius, no protease activity in vivo."
FT /evidence="ECO:0000269|PubMed:14514680"
FT MUTAGEN 225
FT /note="F->C,H: Partially complements ftsH1 at 42 degrees
FT Celsius, some protease activity in vivo."
FT /evidence="ECO:0000269|PubMed:14514680"
FT MUTAGEN 225
FT /note="F->I,L,M,V,W,Y: Complements ftsH1 at 42 degrees
FT Celsius, restores protease activity in vivo."
FT /evidence="ECO:0000269|PubMed:14514680"
FT MUTAGEN 227
FT /note="G->A: Does not complement ftsH1 at 42 degrees
FT Celsius, no protease activity in vivo."
FT /evidence="ECO:0000269|PubMed:14514680"
FT MUTAGEN 297
FT /note="T->A: Low protease activity in vivo, low ATPase
FT activity in vitro, complements ftsH1 at 42 degrees
FT Celsius."
FT /evidence="ECO:0000269|PubMed:10473576"
FT MUTAGEN 298
FT /note="N->A: No in vivo protease activity."
FT /evidence="ECO:0000269|PubMed:10473576"
FT MUTAGEN 304
FT /note="D->A,N: No in vivo protease activity, no in vitro
FT ATPase activity; probably still binds ATP."
FT /evidence="ECO:0000269|PubMed:10473576"
FT MUTAGEN 304
FT /note="D->E: Low protease activity in vivo, low ATPase
FT activity in vitro, complements ftsH1 at 42 degrees
FT Celsius."
FT /evidence="ECO:0000269|PubMed:10473576"
FT MUTAGEN 307
FT /note="L->A: Low protease activity in vivo."
FT /evidence="ECO:0000269|PubMed:10473576"
FT MUTAGEN 309
FT /note="R->A,L,K: No in vivo protease activity, no ATPase
FT activity in vitro; probably still binds ATP."
FT /evidence="ECO:0000269|PubMed:10473576"
FT MUTAGEN 312
FT /note="R->A,L,K: No in vivo protease activity, no ATPase
FT activity in vitro; probably still binds ATP."
FT /evidence="ECO:0000269|PubMed:10473576"
FT MUTAGEN 414..418
FT /note="HEAGH->KEAGK: Loss of protease function."
FT MUTAGEN 414
FT /note="H->Y: Loss of protease function."
FT /evidence="ECO:0000269|PubMed:11827531"
FT MUTAGEN 415
FT /note="E->Q: Loss of protease activity in vivo."
FT /evidence="ECO:0000269|PubMed:10473576"
FT MUTAGEN 418
FT /note="H->Y: In tolZ21; loss of protease function in vivo,
FT retains about 25% ATPase activity, temperature sensitive."
FT /evidence="ECO:0000269|PubMed:10473576,
FT ECO:0000269|PubMed:11827531"
FT MUTAGEN 463
FT /note="E->K: In ftsH1; a temperature-sensitive mutant which
FT increases the frequency of lysogenization of phage lambda;
FT when associated with A-587."
FT /evidence="ECO:0000269|PubMed:8444796"
FT MUTAGEN 476
FT /note="E->D,K,V: Severe loss of protease function that is
FT restored by excess Zn."
FT /evidence="ECO:0000269|PubMed:11827531"
FT MUTAGEN 476
FT /note="E->Q: Little effect on protease function."
FT /evidence="ECO:0000269|PubMed:11827531"
FT MUTAGEN 536
FT /note="H->R: In hflB29; increases the frequency of
FT lysogenization of phage lambda."
FT /evidence="ECO:0000269|PubMed:8444796"
FT MUTAGEN 582
FT /note="E->D,K,Q: No effect on protease function."
FT /evidence="ECO:0000269|PubMed:11827531"
FT MUTAGEN 582
FT /note="E->V: Decreased protease function."
FT /evidence="ECO:0000269|PubMed:11827531"
FT HELIX 34..42
FT /evidence="ECO:0007829|PDB:4V0B"
FT STRAND 46..52
FT /evidence="ECO:0007829|PDB:4V0B"
FT STRAND 55..60
FT /evidence="ECO:0007829|PDB:4V0B"
FT STRAND 65..69
FT /evidence="ECO:0007829|PDB:4V0B"
FT HELIX 77..83
FT /evidence="ECO:0007829|PDB:4V0B"
FT STRAND 87..90
FT /evidence="ECO:0007829|PDB:4V0B"
FT STRAND 142..144
FT /evidence="ECO:0007829|PDB:1LV7"
FT HELIX 151..153
FT /evidence="ECO:0007829|PDB:1LV7"
FT HELIX 158..163
FT /evidence="ECO:0007829|PDB:1LV7"
FT HELIX 165..172
FT /evidence="ECO:0007829|PDB:1LV7"
FT HELIX 174..176
FT /evidence="ECO:0007829|PDB:1LV7"
FT STRAND 187..191
FT /evidence="ECO:0007829|PDB:1LV7"
FT HELIX 198..209
FT /evidence="ECO:0007829|PDB:1LV7"
FT STRAND 213..216
FT /evidence="ECO:0007829|PDB:1LV7"
FT HELIX 230..241
FT /evidence="ECO:0007829|PDB:1LV7"
FT STRAND 245..250
FT /evidence="ECO:0007829|PDB:1LV7"
FT HELIX 253..256
FT /evidence="ECO:0007829|PDB:1LV7"
FT HELIX 270..283
FT /evidence="ECO:0007829|PDB:1LV7"
FT STRAND 287..289
FT /evidence="ECO:0007829|PDB:1LV7"
FT STRAND 291..298
FT /evidence="ECO:0007829|PDB:1LV7"
FT TURN 300..302
FT /evidence="ECO:0007829|PDB:1LV7"
FT HELIX 305..308
FT /evidence="ECO:0007829|PDB:1LV7"
FT STRAND 315..318
FT /evidence="ECO:0007829|PDB:1LV7"
FT HELIX 324..335
FT /evidence="ECO:0007829|PDB:1LV7"
FT HELIX 346..351
FT /evidence="ECO:0007829|PDB:1LV7"
FT HELIX 358..374
FT /evidence="ECO:0007829|PDB:1LV7"
FT STRAND 378..380
FT /evidence="ECO:0007829|PDB:1LV7"
FT HELIX 382..392
FT /evidence="ECO:0007829|PDB:1LV7"
SQ SEQUENCE 644 AA; 70708 MW; E24A753D8F486CA1 CRC64;
MAKNLILWLV IAVVLMSVFQ SFGPSESNGR KVDYSTFLQE VNNDQVREAR INGREINVTK
KDSNRYTTYI PVQDPKLLDN LLTKNVKVVG EPPEEPSLLA SIFISWFPML LLIGVWIFFM
RQMQGGGGKG AMSFGKSKAR MLTEDQIKTT FADVAGCDEA KEEVAELVEY LREPSRFQKL
GGKIPKGVLM VGPPGTGKTL LAKAIAGEAK VPFFTISGSD FVEMFVGVGA SRVRDMFEQA
KKAAPCIIFI DEIDAVGRQR GAGLGGGHDE REQTLNQMLV EMDGFEGNEG IIVIAATNRP
DVLDPALLRP GRFDRQVVVG LPDVRGREQI LKVHMRRVPL APDIDAAIIA RGTPGFSGAD
LANLVNEAAL FAARGNKRVV SMVEFEKAKD KIMMGAERRS MVMTEAQKES TAYHEAGHAI
IGRLVPEHDP VHKVTIIPRG RALGVTFFLP EGDAISASRQ KLESQISTLY GGRLAEEIIY
GPEHVSTGAS NDIKVATNLA RNMVTQWGFS EKLGPLLYAE EEGEVFLGRS VAKAKHMSDE
TARIIDQEVK ALIERNYNRA RQLLTDNMDI LHAMKDALMK YETIDAPQID DLMARRDVRP
PAGWEEPGAS NNSGDNGSPK APRPVDEPRT PNPGNTMSEQ LGDK
