P0AAI3 · FTSH_ECOLI
- ProteinATP-dependent zinc metalloprotease FtsH
- GeneftsH
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids644 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
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).
(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.
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.
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.
Cofactor
Note: Binds 1 zinc ion per subunit.
Activity regulation
(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.
Features
Showing features for binding site, site, active site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 192-199 | ATP (UniProtKB | ChEBI) | ||||
Sequence: GPPGTGKT | ||||||
Site | 225 | Substrate binding | ||||
Sequence: F | ||||||
Binding site | 414 | Zn2+ (UniProtKB | ChEBI); catalytic | ||||
Sequence: H | ||||||
Active site | 415 | |||||
Sequence: E | ||||||
Binding site | 418 | Zn2+ (UniProtKB | ChEBI); catalytic | ||||
Sequence: H | ||||||
Binding site | 492 | Zn2+ (UniProtKB | ChEBI); catalytic | ||||
Sequence: D |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | membrane protein complex | |
Cellular Component | plasma membrane | |
Cellular Component | plasma membrane protein complex | |
Molecular Function | ATP binding | |
Molecular Function | ATP hydrolysis activity | |
Molecular Function | ATP-dependent peptidase activity | |
Molecular Function | metalloendopeptidase activity | |
Molecular Function | zinc ion binding | |
Biological Process | protein catabolic process | |
Biological Process | proteolysis |
Keywords
- Molecular function
- Ligand
Enzyme and pathway databases
Protein family/group databases
Names & Taxonomy
Protein names
- Recommended nameATP-dependent zinc metalloprotease FtsH
- EC number
- Alternative names
Gene names
Organism names
- Organism
- Strains
- Taxonomic lineageBacteria > Pseudomonadota > Gammaproteobacteria > Enterobacterales > Enterobacteriaceae > Escherichia
Accessions
- Primary accessionP0AAI3
- Secondary accessions
Proteomes
Subcellular Location
UniProt Annotation
GO Annotation
Cell inner membrane ; Multi-pass membrane protein
Features
Showing features for topological domain, transmembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Topological domain | 1-4 | Cytoplasmic | ||||
Sequence: MAKN | ||||||
Transmembrane | 5-25 | Helical | ||||
Sequence: LILWLVIAVVLMSVFQSFGPS | ||||||
Topological domain | 26-98 | Periplasmic | ||||
Sequence: ESNGRKVDYSTFLQEVNNDQVREARINGREINVTKKDSNRYTTYIPVQDPKLLDNLLTKNVKVVGEPPEEPSL | ||||||
Transmembrane | 99-119 | Helical | ||||
Sequence: LASIFISWFPMLLLIGVWIFF | ||||||
Topological domain | 120-644 | Cytoplasmic | ||||
Sequence: MRQMQGGGGKGAMSFGKSKARMLTEDQIKTTFADVAGCDEAKEEVAELVEYLREPSRFQKLGGKIPKGVLMVGPPGTGKTLLAKAIAGEAKVPFFTISGSDFVEMFVGVGASRVRDMFEQAKKAAPCIIFIDEIDAVGRQRGAGLGGGHDEREQTLNQMLVEMDGFEGNEGIIVIAATNRPDVLDPALLRPGRFDRQVVVGLPDVRGREQILKVHMRRVPLAPDIDAAIIARGTPGFSGADLANLVNEAALFAARGNKRVVSMVEFEKAKDKIMMGAERRSMVMTEAQKESTAYHEAGHAIIGRLVPEHDPVHKVTIIPRGRALGVTFFLPEGDAISASRQKLESQISTLYGGRLAEEIIYGPEHVSTGASNDIKVATNLARNMVTQWGFSEKLGPLLYAEEEGEVFLGRSVAKAKHMSDETARIIDQEVKALIERNYNRARQLLTDNMDILHAMKDALMKYETIDAPQIDDLMARRDVRPPAGWEEPGASNNSGDNGSPKAPRPVDEPRTPNPGNTMSEQLGDK |
Keywords
- Cellular component
Phenotypes & Variants
Disruption phenotype
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 (PubMed:10048027).
Disruption confers resistance to cellular contact-dependent growth inhibition (CDI) CdiA of E.coli strain 536, E.cloacae strain ATCC 13047 and of Y.pestis strain A, but not to CdiA from E.coli strain 93 toxin (PubMed:26305955).
Disruption confers resistance to cellular contact-dependent growth inhibition (CDI) CdiA of E.coli strain 536, E.cloacae strain ATCC 13047 and of Y.pestis strain A, but not to CdiA from E.coli strain 93 toxin (PubMed:26305955).
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 201 | No in vivo protease activity, no in vitro ATPase activity. | ||||
Sequence: L → N | ||||||
Mutagenesis | 225 | Does not complement ftsH1 at 42 degrees Celsius, no protease activity in vivo. | ||||
Sequence: F → A, D, E, G, N, Q, R, S, or T | ||||||
Mutagenesis | 225 | Partially complements ftsH1 at 42 degrees Celsius, some protease activity in vivo. | ||||
Sequence: F → C or H | ||||||
Mutagenesis | 225 | Complements ftsH1 at 42 degrees Celsius, restores protease activity in vivo. | ||||
Sequence: F → I, L, M, V, W, or Y | ||||||
Mutagenesis | 227 | Does not complement ftsH1 at 42 degrees Celsius, no protease activity in vivo. | ||||
Sequence: G → A | ||||||
Mutagenesis | 297 | Low protease activity in vivo, low ATPase activity in vitro, complements ftsH1 at 42 degrees Celsius. | ||||
Sequence: T → A | ||||||
Mutagenesis | 298 | No in vivo protease activity. | ||||
Sequence: N → A | ||||||
Mutagenesis | 304 | No in vivo protease activity, no in vitro ATPase activity; probably still binds ATP. | ||||
Sequence: D → A or N | ||||||
Mutagenesis | 304 | Low protease activity in vivo, low ATPase activity in vitro, complements ftsH1 at 42 degrees Celsius. | ||||
Sequence: D → E | ||||||
Mutagenesis | 307 | Low protease activity in vivo. | ||||
Sequence: L → A | ||||||
Mutagenesis | 309 | No in vivo protease activity, no ATPase activity in vitro; probably still binds ATP. | ||||
Sequence: R → A, L, or K | ||||||
Mutagenesis | 312 | No in vivo protease activity, no ATPase activity in vitro; probably still binds ATP. | ||||
Sequence: R → A, L, or K | ||||||
Mutagenesis | 414 | Loss of protease function. | ||||
Sequence: H → Y | ||||||
Mutagenesis | 414-418 | Loss of protease function. | ||||
Sequence: HEAGH → KEAGK | ||||||
Mutagenesis | 415 | Loss of protease activity in vivo. | ||||
Sequence: E → Q | ||||||
Mutagenesis | 418 | In tolZ21; loss of protease function in vivo, retains about 25% ATPase activity, temperature sensitive. | ||||
Sequence: H → Y | ||||||
Mutagenesis | 463 | In ftsH1; a temperature-sensitive mutant which increases the frequency of lysogenization of phage lambda; when associated with A-587. | ||||
Sequence: E → K | ||||||
Mutagenesis | 476 | Severe loss of protease function that is restored by excess Zn. | ||||
Sequence: E → D, K, or V | ||||||
Mutagenesis | 476 | Little effect on protease function. | ||||
Sequence: E → Q | ||||||
Mutagenesis | 536 | In hflB29; increases the frequency of lysogenization of phage lambda. | ||||
Sequence: H → R | ||||||
Mutagenesis | 582 | No effect on protease function. | ||||
Sequence: E → D, K, or Q | ||||||
Mutagenesis | 582 | Decreased protease function. | ||||
Sequence: E → V |
PTM/Processing
Features
Showing features for chain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000084631 | 1-644 | ATP-dependent zinc metalloprotease FtsH | |||
Sequence: MAKNLILWLVIAVVLMSVFQSFGPSESNGRKVDYSTFLQEVNNDQVREARINGREINVTKKDSNRYTTYIPVQDPKLLDNLLTKNVKVVGEPPEEPSLLASIFISWFPMLLLIGVWIFFMRQMQGGGGKGAMSFGKSKARMLTEDQIKTTFADVAGCDEAKEEVAELVEYLREPSRFQKLGGKIPKGVLMVGPPGTGKTLLAKAIAGEAKVPFFTISGSDFVEMFVGVGASRVRDMFEQAKKAAPCIIFIDEIDAVGRQRGAGLGGGHDEREQTLNQMLVEMDGFEGNEGIIVIAATNRPDVLDPALLRPGRFDRQVVVGLPDVRGREQILKVHMRRVPLAPDIDAAIIARGTPGFSGADLANLVNEAALFAARGNKRVVSMVEFEKAKDKIMMGAERRSMVMTEAQKESTAYHEAGHAIIGRLVPEHDPVHKVTIIPRGRALGVTFFLPEGDAISASRQKLESQISTLYGGRLAEEIIYGPEHVSTGASNDIKVATNLARNMVTQWGFSEKLGPLLYAEEEGEVFLGRSVAKAKHMSDETARIIDQEVKALIERNYNRARQLLTDNMDILHAMKDALMKYETIDAPQIDDLMARRDVRPPAGWEEPGASNNSGDNGSPKAPRPVDEPRTPNPGNTMSEQLGDK |
Proteomic databases
Interaction
Subunit
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.
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
XENO | P0AAI3 | cII P03042 | 5 | EBI-548381, EBI-4478343 | |
BINARY | P0AAI3 | hflC P0ABC3 | 9 | EBI-548381, EBI-551642 | |
BINARY | P0AAI3 | hflK P0ABC7 | 7 | EBI-548381, EBI-558599 | |
BINARY | P0AAI3 | rpoH P0AGB3 | 4 | EBI-548381, EBI-555342 |
Protein-protein interaction databases
Structure
Family & Domains
Features
Showing features for region.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 598-644 | Disordered | ||||
Sequence: VRPPAGWEEPGASNNSGDNGSPKAPRPVDEPRTPNPGNTMSEQLGDK |
Sequence similarities
In the central section; belongs to the AAA ATPase family.
In the C-terminal section; belongs to the peptidase M41 family.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length644
- Mass (Da)70,708
- Last updated2005-10-11 v1
- ChecksumE24A753D8F486CA1
Sequence caution
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
M83138 EMBL· GenBank· DDBJ | AAA23813.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
U01376 EMBL· GenBank· DDBJ | AAA97508.1 EMBL· GenBank· DDBJ | Genomic DNA | Different initiation | |
U18997 EMBL· GenBank· DDBJ | AAA57979.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
U00096 EMBL· GenBank· DDBJ | AAC76210.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AP009048 EMBL· GenBank· DDBJ | BAE77222.1 EMBL· GenBank· DDBJ | Genomic DNA |