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Protein

ATP-dependent zinc metalloprotease FtsH

Gene

ftsH

Organism
Escherichia coli (strain K12)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Acts as a processive, ATP-dependent zinc metallopeptidase for both cytoplasmic and membrane proteins. Plays a role in the quality control of integral membrane proteins. Degrades a few membrane proteins that have not been assembled into complexes such as SecY, F0 ATPase subunit a and YccA, and also cytoplasmic proteins sigma-32, LpxC, KdtA and phage lambda cII protein among others. Degrades membrane proteins in a processive manner starting at either the N- or C-terminus; recognition requires a cytoplasmic tail of about 20 residues with no apparent sequence requirements. It presumably dislocates membrane-spanning and periplasmic segments of the protein into the cytoplasm to degrade them, this probably requires ATP. Degrades C-terminal-tagged cytoplasmic proteins which are tagged with an 11-amino-acid nonpolar destabilizing tail via a mechanism involving the 10SA (SsrA) stable RNA.
As FtsH regulates the levels of both LpxC and KdtA it is required for synthesis of both the protein and lipid components of lipopolysaccharide (LPS).

Cofactori

Zn2+Note: Binds 1 zinc ion per subunit.

Enzyme regulationi

(Microbial infection) Activity against phage lambda cII protein is inhibited by EDTA but not by PMSF. In vitro pre-incubation of FtsH with HflKC abolishes its activity against phage lambda cII protein at the cytoplasmic side of the membrane.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei225Substrate bindingCurated1
Metal bindingi414Zinc; catalyticCurated1
Active sitei415Curated1
Metal bindingi418Zinc; catalyticCurated1
Metal bindingi492Zinc; catalyticUniRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi192 – 199ATPUniRule annotation8

GO - Molecular functioni

  • ATPase activity Source: EcoliWiki
  • ATP binding Source: UniProtKB-HAMAP
  • ATP-dependent peptidase activity Source: GO_Central
  • CTPase activity Source: EcoliWiki
  • manganese ion binding Source: EcoliWiki
  • metalloendopeptidase activity Source: InterPro
  • metallopeptidase activity Source: GO_Central
  • zinc ion binding Source: EcoliWiki

GO - Biological processi

  • protein catabolic process Source: GO_Central
  • proteolysis Source: EcoliWiki
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Metalloprotease, Protease

Keywords - Ligandi

ATP-binding, Metal-binding, Nucleotide-binding, Zinc

Enzyme and pathway databases

BioCyciEcoCyc:EG11506-MONOMER.
ECOL316407:JW3145-MONOMER.
MetaCyc:EG11506-MONOMER.
BRENDAi3.4.24.B17. 2026.
3.4.24.B20. 2026.
SABIO-RKP0AAI3.

Protein family/group databases

MEROPSiM41.001.

Names & Taxonomyi

Protein namesi
Recommended name:
ATP-dependent zinc metalloprotease FtsHUniRule annotation (EC:3.4.24.-UniRule annotation)
Alternative name(s):
Cell division protease FtsH
Gene namesi
Name:ftsHUniRule annotation
Synonyms:hflB, mrsC, std, tolZ
Ordered Locus Names:b3178, JW3145
OrganismiEscherichia coli (strain K12)
Taxonomic identifieri83333 [NCBI]
Taxonomic lineageiBacteriaProteobacteriaGammaproteobacteriaEnterobacteralesEnterobacteriaceaeEscherichia
Proteomesi
  • UP000000318 Componenti: Chromosome
  • UP000000625 Componenti: Chromosome

Organism-specific databases

EcoGeneiEG11506. ftsH.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 4Cytoplasmic1 Publication4
Transmembranei5 – 25HelicalCuratedAdd BLAST21
Topological domaini26 – 98Periplasmic1 PublicationAdd BLAST73
Transmembranei99 – 119HelicalCuratedAdd BLAST21
Topological domaini120 – 644Cytoplasmic1 PublicationAdd BLAST525

GO - Cellular componenti

  • integral component of membrane Source: EcoliWiki
  • plasma membrane Source: GO_Central
Complete GO annotation...

Keywords - Cellular componenti

Cell inner membrane, Cell membrane, Membrane

Pathology & Biotechi

Disruption phenotypei

Lethality, due to increased levels of LpxC, which increases the level of LPS in the cell and results in formation of abnormal membrane structures in the periplasm. Lethality is suppressed under conditions in which LPS synthesis is reduced.1 Publication

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi201L → N: No in vivo protease activity, no in vitro ATPase activity. 1 Publication1
Mutagenesisi225F → A, D, E, G, N, Q, R, S or T: Does not complement ftsH1 at 42 degrees Celsius, no protease activity in vivo. 1 Publication1
Mutagenesisi225F → C or H: Partially complements ftsH1 at 42 degrees Celsius, some protease activity in vivo. 1 Publication1
Mutagenesisi225F → I, L, M, V, W or Y: Complements ftsH1 at 42 degrees Celsius, restores protease activity in vivo. 1 Publication1
Mutagenesisi227G → A: Does not complement ftsH1 at 42 degrees Celsius, no protease activity in vivo. 1 Publication1
Mutagenesisi297T → A: Low protease activity in vivo, low ATPase activity in vitro, complements ftsH1 at 42 degrees Celsius. 1 Publication1
Mutagenesisi298N → A: No in vivo protease activity. 1 Publication1
Mutagenesisi304D → A or N: No in vivo protease activity, no in vitro ATPase activity; probably still binds ATP. 1 Publication1
Mutagenesisi304D → E: Low protease activity in vivo, low ATPase activity in vitro, complements ftsH1 at 42 degrees Celsius. 1 Publication1
Mutagenesisi307L → A: Low protease activity in vivo. 1 Publication1
Mutagenesisi309R → A, L or K: No in vivo protease activity, no ATPase activity in vitro; probably still binds ATP. 1 Publication1
Mutagenesisi312R → A, L or K: No in vivo protease activity, no ATPase activity in vitro; probably still binds ATP. 1 Publication1
Mutagenesisi414 – 418HEAGH → KEAGK: Loss of protease function. 5
Mutagenesisi414H → Y: Loss of protease function. 1 Publication1
Mutagenesisi415E → Q: Loss of protease activity in vivo. 1 Publication1
Mutagenesisi418H → Y in tolZ21; loss of protease function in vivo, retains about 25% ATPase activity, temperature sensitive. 2 Publications1
Mutagenesisi463E → K in ftsH1; a temperature-sensitive mutant which increases the frequency of lysogenization of phage lambda; when associated with A-587. 1 Publication1
Mutagenesisi476E → D, K or V: Severe loss of protease function that is restored by excess Zn. 1 Publication1
Mutagenesisi476E → Q: Little effect on protease function. 1 Publication1
Mutagenesisi536H → R in hflB29; increases the frequency of lysogenization of phage lambda. 1 Publication1
Mutagenesisi582E → D, K or Q: No effect on protease function. 1 Publication1
Mutagenesisi582E → V: Decreased protease function. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000846311 – 644ATP-dependent zinc metalloprotease FtsHAdd BLAST644

Proteomic databases

EPDiP0AAI3.
PaxDbiP0AAI3.
PRIDEiP0AAI3.

Interactioni

Subunit structurei

The E.coli AAA domain has been modeled as a homohexamer, in Thermus thermophilus the same domain crystallizes as a homohexamer. Forms a complex with HflKC (formerly called HflA); complex formation is stimulated by ATP. Interacts with YccA, and probably weakly with QmcA. Can be cross-linked to YidC (OxaA) and to a nascent polypeptide chain for an integral membrane protein.4 Publications

Protein-protein interaction databases

BioGridi4262980. 336 interactors.
DIPiDIP-35828N.
IntActiP0AAI3. 28 interactors.
MINTiMINT-1226643.
STRINGi511145.b3178.

Structurei

Secondary structure

1644
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi34 – 42Combined sources9
Beta strandi46 – 52Combined sources7
Beta strandi55 – 60Combined sources6
Beta strandi65 – 69Combined sources5
Helixi77 – 83Combined sources7
Beta strandi87 – 90Combined sources4
Beta strandi142 – 144Combined sources3
Helixi151 – 153Combined sources3
Helixi158 – 163Combined sources6
Helixi165 – 172Combined sources8
Helixi174 – 176Combined sources3
Beta strandi187 – 191Combined sources5
Helixi198 – 209Combined sources12
Beta strandi213 – 216Combined sources4
Helixi230 – 241Combined sources12
Beta strandi245 – 250Combined sources6
Helixi253 – 256Combined sources4
Helixi270 – 283Combined sources14
Beta strandi287 – 289Combined sources3
Beta strandi291 – 298Combined sources8
Turni300 – 302Combined sources3
Helixi305 – 308Combined sources4
Beta strandi315 – 318Combined sources4
Helixi324 – 335Combined sources12
Helixi346 – 351Combined sources6
Helixi358 – 374Combined sources17
Beta strandi378 – 380Combined sources3
Helixi382 – 392Combined sources11

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1LV7X-ray1.50A141-395[»]
4V0BX-ray2.55A/B/C25-96[»]
ProteinModelPortaliP0AAI3.
SMRiP0AAI3.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP0AAI3.

Family & Domainsi

Sequence similaritiesi

In the central section; belongs to the AAA ATPase family.UniRule annotation
In the C-terminal section; belongs to the peptidase M41 family.UniRule annotation

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG4105C3H. Bacteria.
COG0465. LUCA.
HOGENOMiHOG000217276.
InParanoidiP0AAI3.
KOiK03798.
OMAiNMDILHS.
PhylomeDBiP0AAI3.

Family and domain databases

Gene3Di3.40.50.300. 1 hit.
HAMAPiMF_01458. FtsH. 1 hit.
InterProiIPR003593. AAA+_ATPase.
IPR003959. ATPase_AAA_core.
IPR003960. ATPase_AAA_CS.
IPR005936. FtsH.
IPR027417. P-loop_NTPase.
IPR011546. Pept_M41_FtsH_extracell.
IPR000642. Peptidase_M41.
[Graphical view]
PfamiPF00004. AAA. 1 hit.
PF06480. FtsH_ext. 1 hit.
PF01434. Peptidase_M41. 1 hit.
[Graphical view]
SMARTiSM00382. AAA. 1 hit.
[Graphical view]
SUPFAMiSSF52540. SSF52540. 1 hit.
TIGRFAMsiTIGR01241. FtsH_fam. 1 hit.
PROSITEiPS00674. AAA. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

P0AAI3-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAKNLILWLV IAVVLMSVFQ SFGPSESNGR KVDYSTFLQE VNNDQVREAR
60 70 80 90 100
INGREINVTK KDSNRYTTYI PVQDPKLLDN LLTKNVKVVG EPPEEPSLLA
110 120 130 140 150
SIFISWFPML LLIGVWIFFM RQMQGGGGKG AMSFGKSKAR MLTEDQIKTT
160 170 180 190 200
FADVAGCDEA KEEVAELVEY LREPSRFQKL GGKIPKGVLM VGPPGTGKTL
210 220 230 240 250
LAKAIAGEAK VPFFTISGSD FVEMFVGVGA SRVRDMFEQA KKAAPCIIFI
260 270 280 290 300
DEIDAVGRQR GAGLGGGHDE REQTLNQMLV EMDGFEGNEG IIVIAATNRP
310 320 330 340 350
DVLDPALLRP GRFDRQVVVG LPDVRGREQI LKVHMRRVPL APDIDAAIIA
360 370 380 390 400
RGTPGFSGAD LANLVNEAAL FAARGNKRVV SMVEFEKAKD KIMMGAERRS
410 420 430 440 450
MVMTEAQKES TAYHEAGHAI IGRLVPEHDP VHKVTIIPRG RALGVTFFLP
460 470 480 490 500
EGDAISASRQ KLESQISTLY GGRLAEEIIY GPEHVSTGAS NDIKVATNLA
510 520 530 540 550
RNMVTQWGFS EKLGPLLYAE EEGEVFLGRS VAKAKHMSDE TARIIDQEVK
560 570 580 590 600
ALIERNYNRA RQLLTDNMDI LHAMKDALMK YETIDAPQID DLMARRDVRP
610 620 630 640
PAGWEEPGAS NNSGDNGSPK APRPVDEPRT PNPGNTMSEQ LGDK
Length:644
Mass (Da):70,708
Last modified:October 11, 2005 - v1
Checksum:iE24A753D8F486CA1
GO

Sequence cautioni

The sequence AAA97508 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M83138 Genomic DNA. Translation: AAA23813.1.
U01376 Genomic DNA. Translation: AAA97508.1. Different initiation.
U18997 Genomic DNA. Translation: AAA57979.1.
U00096 Genomic DNA. Translation: AAC76210.1.
AP009048 Genomic DNA. Translation: BAE77222.1.
PIRiS35109.
RefSeqiNP_417645.1. NC_000913.3.
WP_001107467.1. NZ_LN832404.1.

Genome annotation databases

EnsemblBacteriaiAAC76210; AAC76210; b3178.
BAE77222; BAE77222; BAE77222.
GeneIDi947690.
KEGGiecj:JW3145.
eco:b3178.
PATRICi32121774. VBIEscCol129921_3271.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M83138 Genomic DNA. Translation: AAA23813.1.
U01376 Genomic DNA. Translation: AAA97508.1. Different initiation.
U18997 Genomic DNA. Translation: AAA57979.1.
U00096 Genomic DNA. Translation: AAC76210.1.
AP009048 Genomic DNA. Translation: BAE77222.1.
PIRiS35109.
RefSeqiNP_417645.1. NC_000913.3.
WP_001107467.1. NZ_LN832404.1.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1LV7X-ray1.50A141-395[»]
4V0BX-ray2.55A/B/C25-96[»]
ProteinModelPortaliP0AAI3.
SMRiP0AAI3.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi4262980. 336 interactors.
DIPiDIP-35828N.
IntActiP0AAI3. 28 interactors.
MINTiMINT-1226643.
STRINGi511145.b3178.

Protein family/group databases

MEROPSiM41.001.

Proteomic databases

EPDiP0AAI3.
PaxDbiP0AAI3.
PRIDEiP0AAI3.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsemblBacteriaiAAC76210; AAC76210; b3178.
BAE77222; BAE77222; BAE77222.
GeneIDi947690.
KEGGiecj:JW3145.
eco:b3178.
PATRICi32121774. VBIEscCol129921_3271.

Organism-specific databases

EchoBASEiEB1469.
EcoGeneiEG11506. ftsH.

Phylogenomic databases

eggNOGiENOG4105C3H. Bacteria.
COG0465. LUCA.
HOGENOMiHOG000217276.
InParanoidiP0AAI3.
KOiK03798.
OMAiNMDILHS.
PhylomeDBiP0AAI3.

Enzyme and pathway databases

BioCyciEcoCyc:EG11506-MONOMER.
ECOL316407:JW3145-MONOMER.
MetaCyc:EG11506-MONOMER.
BRENDAi3.4.24.B17. 2026.
3.4.24.B20. 2026.
SABIO-RKP0AAI3.

Miscellaneous databases

EvolutionaryTraceiP0AAI3.
PROiP0AAI3.

Family and domain databases

Gene3Di3.40.50.300. 1 hit.
HAMAPiMF_01458. FtsH. 1 hit.
InterProiIPR003593. AAA+_ATPase.
IPR003959. ATPase_AAA_core.
IPR003960. ATPase_AAA_CS.
IPR005936. FtsH.
IPR027417. P-loop_NTPase.
IPR011546. Pept_M41_FtsH_extracell.
IPR000642. Peptidase_M41.
[Graphical view]
PfamiPF00004. AAA. 1 hit.
PF06480. FtsH_ext. 1 hit.
PF01434. Peptidase_M41. 1 hit.
[Graphical view]
SMARTiSM00382. AAA. 1 hit.
[Graphical view]
SUPFAMiSSF52540. SSF52540. 1 hit.
TIGRFAMsiTIGR01241. FtsH_fam. 1 hit.
PROSITEiPS00674. AAA. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiFTSH_ECOLI
AccessioniPrimary (citable) accession number: P0AAI3
Secondary accession number(s): P28691, Q2M934
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 11, 2005
Last sequence update: October 11, 2005
Last modified: November 2, 2016
This is version 102 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programProkaryotic Protein Annotation Program

Miscellaneousi

Miscellaneous

The ftsH gene was discovered independently through 3 different phenotypes and received 3 different names: ftsH, for filamentous temperature-sensitive; tolZ, for colicin tolerance, and hlfB, because mutants show a high frequency of lysogenization when infected with phage lambda.1 Publication
Requires ATP for protease catalytic activity, probably due to tight coupling of the 2 activities; ADP or non-hydrolyzable analogs cannot substitute, except when unfolded, non-physiological substrates are tested.

Caution

Glu-476 was identified as the third Zn ligand (PubMed:11827531), however in other crystal structures (Aquifex aeolicus and Thermotoga maritima) the conserved equivalent residue does not bind Zn. Instead it makes a hydrogen bond with the side chain of the first catalytic Zn-binding residue and indirectly stabilizes the Zn.1 Publication

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Escherichia coli
    Escherichia coli (strain K12): entries and cross-references to EcoGene
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. Peptidase families
    Classification of peptidase families and list of entries
  4. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.