P18014 · IPA7_SHIFL
- ProteinE3 ubiquitin-protein ligase ipaH7.8
- GeneipaH7.8
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids565 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
E3 ubiquitin ligase effector protein that interferes with host's innate immunity (PubMed:30872533, PubMed:34022140, PubMed:34492225, PubMed:36599845, PubMed:36991122, PubMed:36991125).
Functions to alter host cell physiology and promote bacterial survival in host tissues (PubMed:30872533, PubMed:34022140, PubMed:34492225).
Catalyzes ubiquitination of human gasdermins GSDMB and GSDMD, promoting their degradation by the proteasome, thereby preventing cell death (PubMed:34022140, PubMed:34492225, PubMed:36599845, PubMed:36991122, PubMed:36991125).
In contrast, activates host cell pyroptosis in mouse cells: catalyzes ubiquitination of mouse Nlrp1b allele 1 protein, releasing the cleaved C-terminal part of Nlrp1b, which polymerizes and forms the Nlrp1b inflammasome followed by host cell pyroptosis (PubMed:30872533).
Does not catalyze ubiquitination of mouse GSDMD (PubMed:36599845, PubMed:36991122, PubMed:36991125).
Functions to alter host cell physiology and promote bacterial survival in host tissues (PubMed:30872533, PubMed:34022140, PubMed:34492225).
Catalyzes ubiquitination of human gasdermins GSDMB and GSDMD, promoting their degradation by the proteasome, thereby preventing cell death (PubMed:34022140, PubMed:34492225, PubMed:36599845, PubMed:36991122, PubMed:36991125).
In contrast, activates host cell pyroptosis in mouse cells: catalyzes ubiquitination of mouse Nlrp1b allele 1 protein, releasing the cleaved C-terminal part of Nlrp1b, which polymerizes and forms the Nlrp1b inflammasome followed by host cell pyroptosis (PubMed:30872533).
Does not catalyze ubiquitination of mouse GSDMD (PubMed:36599845, PubMed:36991122, PubMed:36991125).
Catalytic activity
Pathway
Protein modification; protein ubiquitination.
Features
Showing features for active site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Active site | 357 | Glycyl thioester intermediate | ||||
Sequence: C |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | extracellular region | |
Cellular Component | host cell cytoplasm | |
Molecular Function | ubiquitin protein ligase activity | |
Biological Process | effector-mediated activation of programmed cell death in host | |
Biological Process | protein ubiquitination | |
Biological Process | symbiont-mediated suppression of host programmed cell death | |
Biological Process | ubiquitin-dependent protein catabolic process |
Keywords
- Molecular function
- Biological process
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameE3 ubiquitin-protein ligase ipaH7.8
- EC number
- Alternative names
Gene names
Encoded on
- Plasmid pWR100
- Plasmid pWR501
- Plasmid pCP301
- Plasmid pSF5
Organism names
- Organism
- Strains
- Taxonomic lineageBacteria > Pseudomonadota > Gammaproteobacteria > Enterobacterales > Enterobacteriaceae > Shigella
Accessions
- Primary accessionP18014
- Secondary accessions
Proteomes
Subcellular Location
UniProt Annotation
GO Annotation
Note: Secreted via Mxi-Spa type III secretion system (T3SS), and delivered into the host cytoplasm.
Keywords
- Cellular component
Phenotypes & Variants
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 105-106 | Abolished ability to ubiquitinate GSDMB. | ||||
Sequence: DN → AA | ||||||
Mutagenesis | 125 | Abolished ability to ubiquitinate GSDMB. | ||||
Sequence: R → A | ||||||
Mutagenesis | 143 | Abolished ability to ubiquitinate GSDMB. | ||||
Sequence: F → S | ||||||
Mutagenesis | 146 | Does not affect ability to interact with host GSDMB. | ||||
Sequence: N → A | ||||||
Mutagenesis | 161 | Abolished ability to ubiquitinate GSDMB; when associated with G-181. | ||||
Sequence: F → G | ||||||
Mutagenesis | 161-166 | Abolished ability to ubiquitinate GSDMB. | ||||
Sequence: FLHVYY → ALHVAA | ||||||
Mutagenesis | 165-166 | Abolished ability to ubiquitinate GSDMB. | ||||
Sequence: YY → AA or EE | ||||||
Mutagenesis | 181 | Abolished ability to ubiquitinate GSDMB; when associated with G-161. | ||||
Sequence: I → G | ||||||
Mutagenesis | 186 | Abolished ability to ubiquitinate GSDMB. | ||||
Sequence: R → E | ||||||
Mutagenesis | 205-207 | Abolished ability to ubiquitinate GSDMB. | ||||
Sequence: EYY → AYA | ||||||
Mutagenesis | 205-210 | Abolished ability to ubiquitinate GSDMB. | ||||
Sequence: EYYFHF → AYAFAA | ||||||
Mutagenesis | 209 | Abolished ability to ubiquitinate GSDMB. | ||||
Sequence: H → G | ||||||
Mutagenesis | 228 | Abolished ability to ubiquitinate GSDMB. | ||||
Sequence: R → D | ||||||
Mutagenesis | 228-230 | Abolished ability to ubiquitinate GSDMB. | ||||
Sequence: RIN → DID | ||||||
Mutagenesis | 228-232 | Abolished ability to ubiquitinate GSDMB. | ||||
Sequence: RINIS → AIAIA | ||||||
Mutagenesis | 357 | Abolished ubiquitin ligase activity and ability to ubiquitinate host Nlrp1b, GSDMB and GSDMD. | ||||
Sequence: C → A |
PTM/Processing
Features
Showing features for chain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000084218 | 1-565 | E3 ubiquitin-protein ligase ipaH7.8 | |||
Sequence: MFSVNNTHSSVSCSPSINSNSTSNEHYLRILTEWEKNSSPGEERGIAFNRLSQCFQNQEAVLNLSDLNLTSLPELPKHISALIVENNKLTSLPKLPAFLKELNADNNRLSVIPELPESLTTLSVRSNQLENLPVLPNHLTSLFVENNRLYNLPALPEKLKFLHVYYNRLTTLPDLPDKLEILCAQRNNLVTFPQFSDRNNIRQKEYYFHFNQITTLPESFSQLDSSYRINISGNPLSTRVLQSLQRLTSSPDYHGPQIYFSMSDGQQNTLHRPLADAVTAWFPENKQSDVSQIWHAFEHEEHANTFSAFLDRLSDTVSARNTSGFREQVAAWLEKLSASAELRQQSFAVAADATESCEDRVALTWNNLRKTLLVHQASEGLFDNDTGALLSLGREMFRLEILEDIARDKVRTLHFVDEIEVYLAFQTMLAEKLQLSTAVKEMRFYGVSGVTANDLRTAEAMVRSREENEFTDWFSLWGPWHAVLKRTEADRWAQAEEQKYEMLENEYSQRVADRLKASGLSGDADAEREAGAQVMRETEQQIYRQLTDEVLALRLSENGSRLHHS |
Post-translational modification
Ubiquitinated in the presence of host E1 ubiquitin-activating enzyme, E2 ubiquitin-conjugating enzyme and ubiquitin.
Keywords
- PTM
Proteomic databases
Structure
Family & Domains
Features
Showing features for region, repeat, domain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 1-22 | Disordered | ||||
Sequence: MFSVNNTHSSVSCSPSINSNST | ||||||
Region | 1-262 | Interaction with target proteins | ||||
Sequence: MFSVNNTHSSVSCSPSINSNSTSNEHYLRILTEWEKNSSPGEERGIAFNRLSQCFQNQEAVLNLSDLNLTSLPELPKHISALIVENNKLTSLPKLPAFLKELNADNNRLSVIPELPESLTTLSVRSNQLENLPVLPNHLTSLFVENNRLYNLPALPEKLKFLHVYYNRLTTLPDLPDKLEILCAQRNNLVTFPQFSDRNNIRQKEYYFHFNQITTLPESFSQLDSSYRINISGNPLSTRVLQSLQRLTSSPDYHGPQIYFSM | ||||||
Repeat | 58-79 | LRR 1 | ||||
Sequence: QEAVLNLSDLNLTSLPELPKHI | ||||||
Repeat | 80-97 | LRR 2 | ||||
Sequence: SALIVENNKLTSLPKLPA | ||||||
Repeat | 98-119 | LRR 3 | ||||
Sequence: FLKELNADNNRLSVIPELPESL | ||||||
Repeat | 120-137 | LRR 4 | ||||
Sequence: TTLSVRSNQLENLPVLPN | ||||||
Repeat | 138-157 | LRR 5 | ||||
Sequence: HLTSLFVENNRLYNLPALPE | ||||||
Repeat | 158-179 | LRR 6 | ||||
Sequence: KLKFLHVYYNRLTTLPDLPDKL | ||||||
Repeat | 180-199 | LRR 7 | ||||
Sequence: EILCAQRNNLVTFPQFSDRN | ||||||
Repeat | 202-223 | LRR 8 | ||||
Sequence: RQKEYYFHFNQITTLPESFSQL | ||||||
Repeat | 225-248 | LRR 9 | ||||
Sequence: SSYRINISGNPLSTRVLQSLQRLT | ||||||
Region | 263-270 | Linker | ||||
Sequence: SDGQQNTL | ||||||
Region | 271-565 | E3 ubiquitin-protein ligase catalytic domain | ||||
Sequence: HRPLADAVTAWFPENKQSDVSQIWHAFEHEEHANTFSAFLDRLSDTVSARNTSGFREQVAAWLEKLSASAELRQQSFAVAADATESCEDRVALTWNNLRKTLLVHQASEGLFDNDTGALLSLGREMFRLEILEDIARDKVRTLHFVDEIEVYLAFQTMLAEKLQLSTAVKEMRFYGVSGVTANDLRTAEAMVRSREENEFTDWFSLWGPWHAVLKRTEADRWAQAEEQKYEMLENEYSQRVADRLKASGLSGDADAEREAGAQVMRETEQQIYRQLTDEVLALRLSENGSRLHHS | ||||||
Domain | 281-491 | NEL | ||||
Sequence: WFPENKQSDVSQIWHAFEHEEHANTFSAFLDRLSDTVSARNTSGFREQVAAWLEKLSASAELRQQSFAVAADATESCEDRVALTWNNLRKTLLVHQASEGLFDNDTGALLSLGREMFRLEILEDIARDKVRTLHFVDEIEVYLAFQTMLAEKLQLSTAVKEMRFYGVSGVTANDLRTAEAMVRSREENEFTDWFSLWGPWHAVLKRTEADR |
Domain
The LRR (leucine-rich repeat) domain forms a slightly curved solenoid and may mediate interaction with target proteins.
Sequence similarities
Belongs to the LRR-containing bacterial E3 ligase family.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length565
- Mass (Da)64,532
- Last updated2007-07-24 v2
- Checksum9294E03F99189520
Sequence caution
Features
Showing features for sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 527 | in Ref. 5; AAA26526 | ||||
Sequence: E → Q |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AF386526 EMBL· GenBank· DDBJ | AAL72346.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AF348706 EMBL· GenBank· DDBJ | AAK18394.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AY879342 EMBL· GenBank· DDBJ | AAW64892.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AL391753 EMBL· GenBank· DDBJ | CAC05787.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
M32063 EMBL· GenBank· DDBJ | AAA26526.1 EMBL· GenBank· DDBJ | Genomic DNA | Frameshift |