Protein: Streptopain (EC 3.4.22.10) (Exotoxin type B) (Group A streptococcal cysteine protease) (Streptococcal cysteine proteinase) (SPE B) (Streptococcus peptidase A) (SPP) (P0C0J1)
Organism: Streptococcus pyogenes serotype M1
Function: Cysteine protease that acts as a key streptococcal virulence factor by cleaving host proteins involved in immune response. 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. Cleaves host gasdermin-A (GSDMA) in epithelial cells, promoting GSDMA activation and formation of gasdermin pores, triggering pyroptosis. Pyroptosis triggers the elimination of the infected skin cell, depriving the pathogen of its protective niche, while inducing an inflammatory response. This ultimately prevents bacterial penetration of the epithelial barrier and a subsequent systemic dissemination of the pathogen. Also mediates cleavage of the cytokine precursor interleukin-1 beta (IL1B) to its mature form, resulting in inflammation and septic shock. 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. Inhibits host autophagy be catalyzing cleavage and inactivation of key autophagy factors, such as CALCOCO2, NBR1 and SQSTM1. 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. 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. Catalyzes maturation and release of the peptide hormone bradykinin from the precursor Kininogen-1 (KNG1) to produce hypotension during septic shock. 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. Additionally, has been involved in degradation of fibronectin and vitronectin, two host extracellular matrix proteins involved in tissue integrity. Also able to catalyze cleavage and degradation of streptococcal proteins, such as C5a peptidase, EndoS or SmeZ. Degradation of streptococcal proteins is however strictly regulated to preserve integrity of other virulence factors.
Subcellular location: Secreted {ECO:0000269|PubMed:7516997}. Host extracellular space {ECO:0000269|PubMed:18160402, ECO:0000269|PubMed:7516997}. Host cytoplasm {ECO:0000269|PubMed:35545676}.
Interaction partners:
Sequence:
MNKKKLGVRLLSLLALGGFVLANPVFADQNFARNEKEAKDSAITFIQKSAAIKAGARSAEDIKLDKVNLGGELSGSNMYVYNISTGGFVIVSGDKRSPEILGYSTSGSFDANGKENIASFMESYVEQIKENKKLDTTYAGTAEIKQPVVKSLLDSKGIHYNQGNPYNLLTPVIEKVKPGEQSFVGQHAATGCVATATAQIMKYHNYPNKGLKDYTYTLSSNNPYFNHPKNLFAAISTRQYNWNNILPTYSGRESNVQKMAISELMADVGISVDMDYGPSSGSAGSSRVQRALKENFGYNQSVHQINRGDFSKQDWEAQIDKELSQNQPVYYQGVGKVGGHAFVIDGADGRNFYHVNWGWGGVSDGFFRLDALNPSALGTGGGAGGFNGYQSAVVGIKP