P0DD38 · SPEB_STRP3

Function

function

Cysteine protease that acts as a key streptococcal virulence factor by cleaving host proteins involved in immune response (PubMed:7516997).
Triggers inflammation by mediating cleavage of host proteins, which can both promote host pathogenesis by triggering sterile inflammation and/or restrict streptococcal infection, depending on host immune statue and infection site (By similarity).
Cleaves host gasdermin-A (GSDMA) in epithelial cells, promoting GSDMA activation and formation of gasdermin pores, triggering pyroptosis (By similarity).
Pyroptosis triggers the elimination of the infected skin cell, depriving the pathogen of its protective niche, while inducing an inflammatory response (By similarity).
This ultimately prevents bacterial penetration of the epithelial barrier and a subsequent systemic dissemination of the pathogen (By similarity).
Also mediates cleavage of the cytokine precursor interleukin-1 beta (IL1B) to its mature form, resulting in inflammation and septic shock (By similarity).
SpeB-mediated maturation of IL1B plays a dual role depending on infection site: while IL1B inflammatory response prevents bacterial growth during invasive skin infections, it promotes streptococcal infection of the nasopharynx by disrupting colonization resistance mediated by the microbiota (By similarity).
Inhibits host autophagy be catalyzing cleavage and inactivation of key autophagy factors, such as CALCOCO2, NBR1 and SQSTM1 (By similarity).
Cleaves and inhibits a number of complement factors, such as C2, C3-beta chain of C3, C4, C5 or SERPING1, thereby promoting evasion of host immunity (By similarity).
May also impair adaptive immunity by catalyzing cleavage and degradation of host immunoglobulins to promote immune system evasion; the relevance of this activity is however unsure in vivo (By similarity).
Catalyzes maturation and release of the peptide hormone bradykinin from the precursor Kininogen-1 (KNG1) to produce hypotension during septic shock (By similarity).
Also involved in bacterial translocation across the host epithelial barrier by mediating cleavage and degradation of host epithelial junction proteins, such as CDH1 and OCLN (By similarity).
Additionally, has been involved in degradation of fibronectin and vitronectin, two host extracellular matrix proteins involved in tissue integrity (PubMed:7516997).
Also able to catalyze cleavage and degradation of streptococcal proteins, such as C5a peptidase, EndoS or SmeZ (By similarity).
Degradation of streptococcal proteins is however strictly regulated to preserve integrity of other virulence factors (By similarity).

Catalytic activity

  • Preferential cleavage with hydrophobic residues at P2, P1 and P1'.
    EC:3.4.22.10 (UniProtKB | ENZYME | Rhea)

Activity regulation

Synthesized as an inactive zymogen to protect the intracellular components of the bacteria from proteolytic activity during protein production (By similarity).
Once secreted into the extracellular milieu, cleaved into the active protease: maturation can be mediated in cis by autocatalytic cleavage, or in trans by mature SpeB or host proteases. Protease activity is strongly inhibited by zinc and copper, which prevent its maturation into an active protease: inhibition by metal ions may be required to prevent proteolysis of streptococcal proteins (By similarity).

Features

Showing features for active site, binding site.

TypeIDPosition(s)Description
Active site192Nucleophile
Binding site282a protein (UniProtKB | ChEBI)
Binding site339a protein (UniProtKB | ChEBI)
Active site340Proton acceptor

GO annotations

AspectTerm
Cellular Componentextracellular region
Cellular Componenthost cell cytosol
Cellular Componenthost extracellular space
Molecular Functioncysteine-type endopeptidase activity
Molecular Functiontoxin activity
Biological Processevasion of host immune response
Biological Processproteolysis
Biological Processsymbiont-induced defense-related programmed cell death
Biological Processsymbiont-mediated suppression of host autophagy

Keywords

Enzyme and pathway databases

Protein family/group databases

Names & Taxonomy

Protein names

  • Recommended name
    Streptopain
  • EC number
  • Alternative names
    • Exotoxin type B
    • SPE B
    • Streptococcal cysteine proteinase
    • Streptococcus peptidase A (SPP)

Gene names

    • Name
      speB
    • Ordered locus names
      SpyM3_1742

Organism names

Accessions

  • Primary accession
    P0DD38
  • Secondary accessions
    • P00788
    • P26296
    • P68884
    • Q54960
    • Q54961

Proteomes

Subcellular Location

Phenotypes & Variants

Disruption phenotype

Cells lacking SpeB display a strongly decreased virulence.

PTM/Processing

Features

Showing features for signal, propeptide, chain, modified residue.

TypeIDPosition(s)Description
Signal1-27
PropeptidePRO_000002850528-145
ChainPRO_0000028506146-398Streptopain
Modified residue192Cysteine methyl disulfide; in zymogen form

Post-translational modification

The mature protease is derived from the precursor sequence by cleavage, either in cis via an autocatalytic mechanism, or in trans by mature SpeB or host proteases (trypsin, plasmin or subtilisin). Maturation can involve a number of protein cleavage intermediates. Mature SpeB probably plays the most important role in protein maturation in physiological conditions.
Methylthiolation at Cys-192 of the inactive zymogen form is probably involved in the mechanism of secretion of the proteinase into the culture fluid.

Keywords

Interaction

Subunit

Monomer.

Family & Domains

Features

Showing features for region.

TypeIDPosition(s)Description
Region368-390C-terminal active site loop

Domain

The C-terminal active site loop is required for the recognition and recruitment of substrates and release of hydrolyzed products.

Sequence similarities

Belongs to the peptidase C10 family.

Keywords

Phylogenomic databases

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Sequence processing
    The displayed sequence is further processed into a mature form.
  • Length
    398
  • Mass (Da)
    43,174
  • Last updated
    2011-07-27 v1
  • Checksum
    16FF180D720AEE0F
MNKKKLGIRLLSLLALGGFVLANPVFADQNFARNEKEAKDSAITFIQKSAAIKAGARSAEDIKLDKVNLGGELSGSNMYVYNISTGGFVIVSGDKRSPEILGYSTSGSFDANGKENIASFMESYVEQIKENKKLDTTYAGTAEIKQPVVKSLLDSKGIHYNQGNPYNLLTPVIEKVKPGEQSFVGQHAATGCVATATAQIMKYHNYPNKGLKDYTYTLSSNNPYFNHPKNLFAAISTRQYNWNNILPTYSGRESNVQKMAISELMADVGISVDMDYGPSSGSAGSSRVQRALKENFGYNQSVHQINRSDFSKQDWEAQIDKELSQNQPVYYQGVGKVGGHAFVIDGADGRNFYHVNWGWGGVSDGFFRLDALNPSALGTGGGAGGFNGYQSAVVGIKP

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
L26146
EMBL· GenBank· DDBJ
AAA27012.1
EMBL· GenBank· DDBJ
Genomic DNA
AE014074
EMBL· GenBank· DDBJ
AAM80349.1
EMBL· GenBank· DDBJ
Genomic DNA

Genome annotation databases

Similar Proteins

Disclaimer

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