UniProtKB - P0AAI3 (FTSH_ECOLI)
ATP-dependent zinc metalloprotease FtsH
ftsH
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).
1 Publication(Microbial infection) Probably transports the toxic C-terminal region of CdiA from E.coli strain 536, E.cloacae strain ATCC 13047 and of Y.pestis strain A across the inner membrane to the cytoplasm, where CdiA has a toxic effect. Toxin transport is strain-specific, mutations in this gene do not confer resistance to several other tested CdiA toxins.
1 PublicationMiscellaneous
Caution
Cofactori
Activity regulationi
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sitei | 225 | Substrate bindingCurated | 1 | |
Metal bindingi | 414 | Zinc; catalyticCurated | 1 | |
Active sitei | 415 | Curated | 1 | |
Metal bindingi | 418 | Zinc; catalyticCurated | 1 | |
Metal bindingi | 492 | Zinc; catalyticUniRule annotation | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Nucleotide bindingi | 192 – 199 | ATPUniRule annotation | 8 |
GO - Molecular functioni
- ATP binding Source: EcoCyc
- ATP-dependent peptidase activity Source: EcoCyc
- ATP hydrolysis activity Source: UniProtKB-UniRule
- metalloendopeptidase activity Source: EcoCyc
- zinc ion binding Source: EcoCyc
GO - Biological processi
- negative regulation of peptidase activity Source: ComplexPortal
- protein catabolic process Source: GO_Central
- proteolysis Source: EcoCyc
Keywordsi
Molecular function | Hydrolase, Metalloprotease, Protease |
Ligand | ATP-binding, Metal-binding, Nucleotide-binding, Zinc |
Enzyme and pathway databases
BioCyci | EcoCyc:EG11506-MONOMER |
BRENDAi | 3.4.24.B17, 2026 3.4.24.B20, 2026 |
SABIO-RKi | P0AAI3 |
Protein family/group databases
MEROPSi | M41.001 |
TCDBi | 3.A.29.1.5, the mitochondrial inner membrane i-aaa protease complex (mimp) familly |
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 |
Organismi | Escherichia coli (strain K12) |
Taxonomic identifieri | 83333 [NCBI] |
Taxonomic lineagei | Bacteria › Proteobacteria › Gammaproteobacteria › Enterobacterales › Enterobacteriaceae › Escherichia › |
Proteomesi |
|
Subcellular locationi
Plasma membrane
- Cell inner membrane UniRule annotation3 Publications; Multi-pass membrane protein UniRule annotation3 Publications
Plasma Membrane
- integral component of plasma membrane Source: EcoCyc
- plasma membrane Source: GO_Central
- plasma membrane protein complex Source: ComplexPortal
Other locations
- membrane protein complex Source: EcoCyc
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Topological domaini | 1 – 4 | Cytoplasmic1 Publication | 4 | |
Transmembranei | 5 – 25 | HelicalCuratedAdd BLAST | 21 | |
Topological domaini | 26 – 98 | Periplasmic1 PublicationAdd BLAST | 73 | |
Transmembranei | 99 – 119 | HelicalCuratedAdd BLAST | 21 | |
Topological domaini | 120 – 644 | Cytoplasmic1 Publication1 PublicationAdd BLAST | 525 |
Keywords - Cellular componenti
Cell inner membrane, Cell membrane, MembranePathology & Biotechi
Disruption phenotypei
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 201 | L → N: No in vivo protease activity, no in vitro ATPase activity. 1 Publication | 1 | |
Mutagenesisi | 225 | F → A, D, E, G, N, Q, R, S or T: Does not complement ftsH1 at 42 degrees Celsius, no protease activity in vivo. 1 Publication | 1 | |
Mutagenesisi | 225 | F → C or H: Partially complements ftsH1 at 42 degrees Celsius, some protease activity in vivo. 1 Publication | 1 | |
Mutagenesisi | 225 | F → I, L, M, V, W or Y: Complements ftsH1 at 42 degrees Celsius, restores protease activity in vivo. 1 Publication | 1 | |
Mutagenesisi | 227 | G → A: Does not complement ftsH1 at 42 degrees Celsius, no protease activity in vivo. 1 Publication | 1 | |
Mutagenesisi | 297 | T → A: Low protease activity in vivo, low ATPase activity in vitro, complements ftsH1 at 42 degrees Celsius. 1 Publication | 1 | |
Mutagenesisi | 298 | N → A: No in vivo protease activity. 1 Publication | 1 | |
Mutagenesisi | 304 | D → A or N: No in vivo protease activity, no in vitro ATPase activity; probably still binds ATP. 1 Publication | 1 | |
Mutagenesisi | 304 | D → E: Low protease activity in vivo, low ATPase activity in vitro, complements ftsH1 at 42 degrees Celsius. 1 Publication | 1 | |
Mutagenesisi | 307 | L → A: Low protease activity in vivo. 1 Publication | 1 | |
Mutagenesisi | 309 | R → A, L or K: No in vivo protease activity, no ATPase activity in vitro; probably still binds ATP. 1 Publication | 1 | |
Mutagenesisi | 312 | R → A, L or K: No in vivo protease activity, no ATPase activity in vitro; probably still binds ATP. 1 Publication | 1 | |
Mutagenesisi | 414 – 418 | HEAGH → KEAGK: Loss of protease function. | 5 | |
Mutagenesisi | 414 | H → Y: Loss of protease function. 1 Publication | 1 | |
Mutagenesisi | 415 | E → Q: Loss of protease activity in vivo. 1 Publication | 1 | |
Mutagenesisi | 418 | H → Y in tolZ21; loss of protease function in vivo, retains about 25% ATPase activity, temperature sensitive. 2 Publications | 1 | |
Mutagenesisi | 463 | E → K in ftsH1; a temperature-sensitive mutant which increases the frequency of lysogenization of phage lambda; when associated with A-587. 1 Publication | 1 | |
Mutagenesisi | 476 | E → D, K or V: Severe loss of protease function that is restored by excess Zn. 1 Publication | 1 | |
Mutagenesisi | 476 | E → Q: Little effect on protease function. 1 Publication | 1 | |
Mutagenesisi | 536 | H → R in hflB29; increases the frequency of lysogenization of phage lambda. 1 Publication | 1 | |
Mutagenesisi | 582 | E → D, K or Q: No effect on protease function. 1 Publication | 1 | |
Mutagenesisi | 582 | E → V: Decreased protease function. 1 Publication | 1 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000084631 | 1 – 644 | ATP-dependent zinc metalloprotease FtsHAdd BLAST | 644 |
Proteomic databases
jPOSTi | P0AAI3 |
PaxDbi | P0AAI3 |
PRIDEi | P0AAI3 |
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 PublicationsBinary interactionsi
P0AAI3
With | #Exp. | IntAct |
---|---|---|
hflC [P0ABC3] | 9 | EBI-548381,EBI-551642 |
hflK [P0ABC7] | 7 | EBI-548381,EBI-558599 |
rpoH [P0AGB3] | 4 | EBI-548381,EBI-555342 |
cII [P03042] from Escherichia phage lambda. | 5 | EBI-548381,EBI-4478343 |
Protein-protein interaction databases
BioGRIDi | 4262980, 385 interactors |
ComplexPortali | CPX-5046, FtsH-HflKC complex |
DIPi | DIP-35828N |
IntActi | P0AAI3, 30 interactors |
MINTi | P0AAI3 |
STRINGi | 511145.b3178 |
Structurei
Secondary structure
3D structure databases
SMRi | P0AAI3 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | P0AAI3 |
Family & Domainsi
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 598 – 644 | DisorderedSequence analysisAdd BLAST | 47 |
Sequence similaritiesi
Keywords - Domaini
Transmembrane, Transmembrane helixPhylogenomic databases
eggNOGi | COG0465, Bacteria |
HOGENOMi | CLU_000688_16_2_6 |
InParanoidi | P0AAI3 |
PhylomeDBi | P0AAI3 |
Family and domain databases
Gene3Di | 1.20.58.760, 1 hit 3.40.50.300, 1 hit |
HAMAPi | MF_01458, FtsH, 1 hit |
InterProi | View protein in InterPro IPR003593, AAA+_ATPase IPR041569, AAA_lid_3 IPR003959, ATPase_AAA_core IPR003960, ATPase_AAA_CS IPR005936, FtsH IPR027417, P-loop_NTPase IPR011546, Pept_M41_FtsH_extracell IPR000642, Peptidase_M41 IPR037219, Peptidase_M41-like |
Pfami | View protein in Pfam PF00004, AAA, 1 hit PF17862, AAA_lid_3, 1 hit PF06480, FtsH_ext, 1 hit PF01434, Peptidase_M41, 1 hit |
SMARTi | View protein in SMART SM00382, AAA, 1 hit |
SUPFAMi | SSF140990, SSF140990, 1 hit SSF52540, SSF52540, 1 hit |
TIGRFAMsi | TIGR01241, FtsH_fam, 1 hit |
PROSITEi | View protein in PROSITE PS00674, AAA, 1 hit |
i Sequence
Sequence statusi: Complete.
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
Sequence cautioni
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 |
PIRi | S35109 |
RefSeqi | NP_417645.1, NC_000913.3 WP_001107467.1, NZ_STEB01000012.1 |
Genome annotation databases
EnsemblBacteriai | AAC76210; AAC76210; b3178 BAE77222; BAE77222; BAE77222 |
GeneIDi | 66672920 947690 |
KEGGi | ecj:JW3145 eco:b3178 |
PATRICi | fig|511145.12.peg.3271 |
Similar proteinsi
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 |
PIRi | S35109 |
RefSeqi | NP_417645.1, NC_000913.3 WP_001107467.1, NZ_STEB01000012.1 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
1LV7 | X-ray | 1.50 | A | 141-395 | [»] | |
4V0B | X-ray | 2.55 | A/B/C | 25-96 | [»] | |
SMRi | P0AAI3 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 4262980, 385 interactors |
ComplexPortali | CPX-5046, FtsH-HflKC complex |
DIPi | DIP-35828N |
IntActi | P0AAI3, 30 interactors |
MINTi | P0AAI3 |
STRINGi | 511145.b3178 |
Protein family/group databases
MEROPSi | M41.001 |
TCDBi | 3.A.29.1.5, the mitochondrial inner membrane i-aaa protease complex (mimp) familly |
Proteomic databases
jPOSTi | P0AAI3 |
PaxDbi | P0AAI3 |
PRIDEi | P0AAI3 |
Genome annotation databases
EnsemblBacteriai | AAC76210; AAC76210; b3178 BAE77222; BAE77222; BAE77222 |
GeneIDi | 66672920 947690 |
KEGGi | ecj:JW3145 eco:b3178 |
PATRICi | fig|511145.12.peg.3271 |
Organism-specific databases
EchoBASEi | EB1469 |
Phylogenomic databases
eggNOGi | COG0465, Bacteria |
HOGENOMi | CLU_000688_16_2_6 |
InParanoidi | P0AAI3 |
PhylomeDBi | P0AAI3 |
Enzyme and pathway databases
BioCyci | EcoCyc:EG11506-MONOMER |
BRENDAi | 3.4.24.B17, 2026 3.4.24.B20, 2026 |
SABIO-RKi | P0AAI3 |
Miscellaneous databases
EvolutionaryTracei | P0AAI3 |
PROi | PR:P0AAI3 |
Family and domain databases
Gene3Di | 1.20.58.760, 1 hit 3.40.50.300, 1 hit |
HAMAPi | MF_01458, FtsH, 1 hit |
InterProi | View protein in InterPro IPR003593, AAA+_ATPase IPR041569, AAA_lid_3 IPR003959, ATPase_AAA_core IPR003960, ATPase_AAA_CS IPR005936, FtsH IPR027417, P-loop_NTPase IPR011546, Pept_M41_FtsH_extracell IPR000642, Peptidase_M41 IPR037219, Peptidase_M41-like |
Pfami | View protein in Pfam PF00004, AAA, 1 hit PF17862, AAA_lid_3, 1 hit PF06480, FtsH_ext, 1 hit PF01434, Peptidase_M41, 1 hit |
SMARTi | View protein in SMART SM00382, AAA, 1 hit |
SUPFAMi | SSF140990, SSF140990, 1 hit SSF52540, SSF52540, 1 hit |
TIGRFAMsi | TIGR01241, FtsH_fam, 1 hit |
PROSITEi | View protein in PROSITE PS00674, AAA, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | FTSH_ECOLI | |
Accessioni | P0AAI3Primary (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: | February 23, 2022 | |
This is version 135 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Prokaryotic Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
3D-structure, Reference proteomeDocuments
- Peptidase families
Classification of peptidase families and list of entries - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families