Streptopain
Details
- Name
- Streptopain
- Kind
- protein
- Synonyms
- 3.4.22.10
- Exotoxin type B
- SPE B
- SPP
- Streptococcal cysteine proteinase
- Streptococcus peptidase A
- Gene Name
- speB
- UniProtKB Entry
- P0C0J0Swiss-Prot
- Organism
- Streptococcus pyogenes
- NCBI Taxonomy ID
- 1314
- Amino acid sequence
>lcl|BSEQ0011460|Streptopain MNKKKLGIRLLSLLALGGFVLANPVFADQNFARNEKEAKDSAITFIQKSAAIKAGARSAE DIKLDKVNLGGELSGSNMYVYNISTGGFVIVSGDKRSPEILGYSTSGSFDANGKENIASF MESYVEQIKENKKLDTTYAGTAEIKQPVVKSLLDSKGIHYNQGNPYNLLTPVIEKVKPGE QSFVGQHAATGCVATATAQIMKYHNYPNKGLKDYTYTLSSNNPYFNHPKNLFAAISTRQY NWNNILPTYSGRESNVQKMAISELMADVGISVDMDYGPSSGSAGSSRVQRALKENFGYNQ SVHQINRSDFSKQDWEAQIDKELSQNQPVYYQGVGKVGGHAFVIDGADGRNFYHVNWGWG GVSDGFFRLDALNPSALGTGGGAGGFNGYQSAVVGIKP
- Number of residues
- 398
- Molecular Weight
- 43174.095
- Theoretical pI
- 9.11
- GO Classification
- Functionscysteine-type peptidase activityProcessespathogenesis / proteolysis in other organismComponentsextracellular region
- General Function
- Cysteine protease that acts as a key streptococcal virulence factor by cleaving host proteins involved in immune response (PubMed:10429198, PubMed:11553627, PubMed:1987034, PubMed:22645124, PubMed:8675287, PubMed:9169486, PubMed:9864206). 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 (PubMed:7689226). 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).
- Specific Function
- cysteine-type endopeptidase activity
- Pfam Domain Function
- Signal Regions
- 1-27
- Transmembrane Regions
- Not Available
- Cellular Location
- Secreted
- Gene sequence
>lcl|BSEQ0004001|1197 bp ATGAATAAAAAGAAATTAGGTATCAGATTATTAAGTCTTTTAGCATTAGGTGGATTTGTT CTTGCTAACCCAGTATTTGCCGATCAAAACTTTGCTCGTAACGAAAAAGAAGCAAAAGAT AGCGCTATCACATTTATCCAAAAATCAGCAGCTATCAAAGCAGGTGCACGAAGCGCAGAA GATATTAAGCTTGACAAAGTTAACTTAGGTGGAGAACTTTCTGGCTCTAATATGTATGTT TACAATATTTCTACTGGAGGATTTGTTATCGTTTCAGGAGATAAACGTTCTCCAGAAATT CTAGGATACTCTACCAGCGGATCATTTGACGCTAACGGTAAAGAAAACATTGCTTCCTTC ATGGAAAGTTATGTCGAACAAATCAAAGAAAACAAAAAATTAGACACTACTTATGCTGGT ACCGCTGAGATTAAACAACCAGTTGTTAAATCTCTCCTTGATTCAAAAGGCATTCATTAC AACCAAGGTAACCCTTACAACCTATTGACACCTGTTATTGAAAAAGTAAAACCAGGTGAA CAATCTTTTGTAGGTCAACATGCAGCTACAGGATGTGTTGCTACTGCAACTGCTCAAATT ATGAAATATCATAATTACCCTAACAAAGGGTTGAAAGACTACACTTACACACTAAGCTCA AATAACCCATATTTCAACCATCCTAAGAACTTGTTTGCAGCTATCTCTACTAGACAATAC AACTGGAACAACATCCTACCTACTTATAGCGGAAGAGAATCTAACGTTCAAAAAATGGCG ATTTCAGAATTGATGGCTGATGTTGGTATTTCAGTAGACATGGATTATGGTCCATCTAGT GGTTCTGCAGGTAGCTCTCGTGTTCAAAGAGCCTTGAAAGAAAACTTTGGCTACAACCAA TCTGTTCACCAAATTAACCGTAGCGACTTTAGCAAACAAGATTGGGAAGCACAAATTGAC AAAGAATTATCTCAAAACCAACCAGTATACTACCAAGGTGTCGGTAAAGTAGGCGGACAT GCCTTTGTTATCGATGGTGCTGACGGACGTAACTTCTACCATGTTAACTGGGGTTGGGGT GGAGTCTCTGACGGCTTCTTCCGTCTTGACGCACTAAACCCTTCAGCTCTTGGTACTGGT GGCGGCGCAGGCGGCTTCAACGGTTACCAAAGTGCTGTTGTAGGCATCAAACCTTAG
- Chromosome Location
- Not Available
- Locus
- Not Available
- External Identifiers
Resource Link UniProtKB ID P0C0J0 UniProtKB Entry Name SPEB_STRPY GenBank Protein ID 153819 GenBank Gene ID M86905 PDB ID(s) 1DKI, 1PVJ, 2UZJ - General References
- Hauser AR, Schlievert PM: Nucleotide sequence of the streptococcal pyrogenic exotoxin type B gene and relationship between the toxin and the streptococcal proteinase precursor. J Bacteriol. 1990 Aug;172(8):4536-42. [Article]
- Kapur V, Topouzis S, Majesky MW, Li LL, Hamrick MR, Hamill RJ, Patti JM, Musser JM: A conserved Streptococcus pyogenes extracellular cysteine protease cleaves human fibronectin and degrades vitronectin. Microb Pathog. 1993 Nov;15(5):327-46. [Article]
- Tai JY, Kortt AA, Liu TY, Elliott SD: Primary structure of streptococcal proteinase. III. Isolation of cyanogen bromide peptides: complete covalent structure of the polypeptide chain. J Biol Chem. 1976 Apr 10;251(7):1955-9. [Article]
- Lo SS, Fraser BA, Liu TY: The mixed disulfide in the zymogen of streptococcal proteinase. Characterization and implication for its biosynthesis. J Biol Chem. 1984 Sep 10;259(17):11041-5. [Article]
- Kuo CF, Wu JJ, Tsai PJ, Kao FJ, Lei HY, Lin MT, Lin YS: Streptococcal pyrogenic exotoxin B induces apoptosis and reduces phagocytic activity in U937 cells. Infect Immun. 1999 Jan;67(1):126-30. [Article]
- Kagawa TF, Cooney JC, Baker HM, McSweeney S, Liu M, Gubba S, Musser JM, Baker EN: Crystal structure of the zymogen form of the group A Streptococcus virulence factor SpeB: an integrin-binding cysteine protease. Proc Natl Acad Sci U S A. 2000 Feb 29;97(5):2235-40. [Article]
- Olsen JG, Dagil R, Niclasen LM, Sorensen OE, Kragelund BB: Structure of the mature Streptococcal cysteine protease exotoxin mSpeB in its active dimeric form. J Mol Biol. 2009 Oct 30;393(3):693-703. doi: 10.1016/j.jmb.2009.08.046. Epub 2009 Aug 25. [Article]
Associated Data
- Drug Relations
Drug Drug group Pharmacological action? Type Actions Details (3R)-3-{[(Benzyloxy)carbonyl]amino}-2-oxo-4-phenylbutane-1-diazonium experimental unknown target Details