P18014 · IPA7_SHIFL

  • Protein
    E3 ubiquitin-protein ligase ipaH7.8
  • Gene
    ipaH7.8
  • Status
    UniProtKB reviewed (Swiss-Prot)
  • Amino acids
  • Protein existence
    Evidence at protein level
  • Annotation score
    5/5

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).

Catalytic activity

  • S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + N6-ubiquitinyl-[acceptor protein]-L-lysine.
    EC:2.3.2.27 (UniProtKB | ENZYME | Rhea)

Pathway

Protein modification; protein ubiquitination.

Features

Showing features for active site.

TypeIDPosition(s)Description
Active site357Glycyl thioester intermediate

GO annotations

AspectTerm
Cellular Componentextracellular region
Cellular Componenthost cell cytoplasm
Molecular Functionubiquitin protein ligase activity
Biological Processeffector-mediated activation of programmed cell death in host
Biological Processprotein ubiquitination
Biological Processsymbiont-mediated suppression of host programmed cell death
Biological Processubiquitin-dependent protein catabolic process

Keywords

Enzyme and pathway databases

Names & Taxonomy

Protein names

  • Recommended name
    E3 ubiquitin-protein ligase ipaH7.8
  • EC number
  • Alternative names
    • Invasion plasmid antigen 7.8

Gene names

    • Name
      ipaH7.8
    • ORF names
      pWR501_0084, SFLP133
    • Ordered locus names
      CP0078

Encoded on

  • Plasmid pWR100
  • Plasmid pWR501
  • Plasmid pCP301
  • Plasmid pSF5

Organism names

  • Taxonomic identifier
  • Strains
    • M90T / Serotype 5a
    • Serotype 5
    • 301 / Serotype 2a
  • Taxonomic lineage
    Bacteria > Pseudomonadota > Gammaproteobacteria > Enterobacterales > Enterobacteriaceae > Shigella

Accessions

  • Primary accession
    P18014
  • Secondary accessions
    • Q7BCM7
    • Q7BEH5
    • Q99Q94

Proteomes

Subcellular Location

Secreted
Host cytoplasm
Note: Secreted via Mxi-Spa type III secretion system (T3SS), and delivered into the host cytoplasm.

Keywords

Phenotypes & Variants

Features

Showing features for mutagenesis.

TypeIDPosition(s)Description
Mutagenesis105-106Abolished ability to ubiquitinate GSDMB.
Mutagenesis125Abolished ability to ubiquitinate GSDMB.
Mutagenesis143Abolished ability to ubiquitinate GSDMB.
Mutagenesis146Does not affect ability to interact with host GSDMB.
Mutagenesis161Abolished ability to ubiquitinate GSDMB; when associated with G-181.
Mutagenesis161-166Abolished ability to ubiquitinate GSDMB.
Mutagenesis165-166Abolished ability to ubiquitinate GSDMB.
Mutagenesis181Abolished ability to ubiquitinate GSDMB; when associated with G-161.
Mutagenesis186Abolished ability to ubiquitinate GSDMB.
Mutagenesis205-207Abolished ability to ubiquitinate GSDMB.
Mutagenesis205-210Abolished ability to ubiquitinate GSDMB.
Mutagenesis209Abolished ability to ubiquitinate GSDMB.
Mutagenesis228Abolished ability to ubiquitinate GSDMB.
Mutagenesis228-230Abolished ability to ubiquitinate GSDMB.
Mutagenesis228-232Abolished ability to ubiquitinate GSDMB.
Mutagenesis357Abolished ubiquitin ligase activity and ability to ubiquitinate host Nlrp1b, GSDMB and GSDMD.

PTM/Processing

Features

Showing features for chain.

TypeIDPosition(s)Description
ChainPRO_00000842181-565E3 ubiquitin-protein ligase ipaH7.8

Post-translational modification

Ubiquitinated in the presence of host E1 ubiquitin-activating enzyme, E2 ubiquitin-conjugating enzyme and ubiquitin.

Keywords

Proteomic databases

Family & Domains

Features

Showing features for region, repeat, domain.

TypeIDPosition(s)Description
Region1-22Disordered
Region1-262Interaction with target proteins
Repeat58-79LRR 1
Repeat80-97LRR 2
Repeat98-119LRR 3
Repeat120-137LRR 4
Repeat138-157LRR 5
Repeat158-179LRR 6
Repeat180-199LRR 7
Repeat202-223LRR 8
Repeat225-248LRR 9
Region263-270Linker
Region271-565E3 ubiquitin-protein ligase catalytic domain
Domain281-491NEL

Domain

The LRR (leucine-rich repeat) domain forms a slightly curved solenoid and may mediate interaction with target proteins.

Sequence similarities

Keywords

Phylogenomic databases

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Length
    565
  • Mass (Da)
    64,532
  • Last updated
    2007-07-24 v2
  • Checksum
    9294E03F99189520
MFSVNNTHSSVSCSPSINSNSTSNEHYLRILTEWEKNSSPGEERGIAFNRLSQCFQNQEAVLNLSDLNLTSLPELPKHISALIVENNKLTSLPKLPAFLKELNADNNRLSVIPELPESLTTLSVRSNQLENLPVLPNHLTSLFVENNRLYNLPALPEKLKFLHVYYNRLTTLPDLPDKLEILCAQRNNLVTFPQFSDRNNIRQKEYYFHFNQITTLPESFSQLDSSYRINISGNPLSTRVLQSLQRLTSSPDYHGPQIYFSMSDGQQNTLHRPLADAVTAWFPENKQSDVSQIWHAFEHEEHANTFSAFLDRLSDTVSARNTSGFREQVAAWLEKLSASAELRQQSFAVAADATESCEDRVALTWNNLRKTLLVHQASEGLFDNDTGALLSLGREMFRLEILEDIARDKVRTLHFVDEIEVYLAFQTMLAEKLQLSTAVKEMRFYGVSGVTANDLRTAEAMVRSREENEFTDWFSLWGPWHAVLKRTEADRWAQAEEQKYEMLENEYSQRVADRLKASGLSGDADAEREAGAQVMRETEQQIYRQLTDEVLALRLSENGSRLHHS

Sequence caution

The sequence AAA26526.1 differs from that shown. Reason: Frameshift

Features

Showing features for sequence conflict.

TypeIDPosition(s)Description
Sequence conflict527in Ref. 5; AAA26526

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
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

Genome annotation databases

Similar Proteins

Disclaimer

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