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
Functions
cysteine-type peptidase activity
Processes
pathogenesis / proteolysis in other organism
Components
extracellular 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
ResourceLink
UniProtKB IDP0C0J0
UniProtKB Entry NameSPEB_STRPY
GenBank Protein ID153819
GenBank Gene IDM86905
PDB ID(s)1DKI, 1PVJ, 2UZJ
General References
  1. 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]
  2. 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]
  3. 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]
  4. 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]
  5. 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]
  6. 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]
  7. 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
DrugDrug groupPharmacological action?TypeActionsDetails
(3R)-3-{[(Benzyloxy)carbonyl]amino}-2-oxo-4-phenylbutane-1-diazoniumexperimentalunknowntargetDetails