ID   SSPB_STAA8              Reviewed;         393 AA.
AC   Q2FZL3; Q70UQ8; Q70UQ9; Q9EYW7;
DT   22-AUG-2006, integrated into UniProtKB/Swiss-Prot.
DT   21-MAR-2006, sequence version 1.
DT   03-AUG-2022, entry version 87.
DE   RecName: Full=Staphopain B;
DE            EC=3.4.22.-;
DE   AltName: Full=Staphylococcal cysteine proteinase B;
DE   AltName: Full=Staphylopain B;
DE   Flags: Precursor;
GN   Name=sspB; OrderedLocusNames=SAOUHSC_00987;
OS   Staphylococcus aureus (strain NCTC 8325 / PS 47).
OC   Bacteria; Firmicutes; Bacilli; Bacillales; Staphylococcaceae;
OC   Staphylococcus.
OX   NCBI_TaxID=93061;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], PROTEIN SEQUENCE OF 37-47, AND CLEAVAGE
RP   BY SSPA.
RX   PubMed=11119502; DOI=10.1128/iai.69.1.159-169.2001;
RA   Rice K., Peralta R., Bast D., de Azavedo J., McGavin M.J.;
RT   "Description of Staphylococcus serine protease (ssp) operon in
RT   Staphylococcus aureus and nonpolar inactivation of sspA-encoded serine
RT   protease.";
RL   Infect. Immun. 69:159-169(2001).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=NCTC 8325 / PS 47;
RA   Gillaspy A.F., Worrell V., Orvis J., Roe B.A., Dyer D.W., Iandolo J.J.;
RT   "The Staphylococcus aureus NCTC 8325 genome.";
RL   (In) Fischetti V., Novick R., Ferretti J., Portnoy D., Rood J. (eds.);
RL   Gram positive pathogens, 2nd edition, pp.381-412, ASM Press, Washington
RL   D.C. (2006).
RN   [3]
RP   PROTEIN SEQUENCE OF 211-229, FUNCTION, ACTIVITY REGULATION, CATALYTIC
RP   ACTIVITY, AND CLEAVAGE BY SSPA.
RX   PubMed=12207024; DOI=10.1074/jbc.m207162200;
RA   Massimi I., Park E., Rice K., Mueller-Esterl W., Sauder D., McGavin M.J.;
RT   "Identification of a novel maturation mechanism and restricted substrate
RT   specificity for the sspB cysteine protease of Staphylococcus aureus.";
RL   J. Biol. Chem. 277:41770-41777(2002).
RN   [4]
RP   REGULATION.
RX   PubMed=10517329; DOI=10.1007/s004380051090;
RA   Lindsay J.A., Foster S.J.;
RT   "Interactive regulatory pathways control virulence determinant production
RT   and stability in response to environmental conditions in Staphylococcus
RT   aureus.";
RL   Mol. Gen. Genet. 262:323-331(1999).
RN   [5]
RP   INDUCTION.
RX   PubMed=14702415; DOI=10.1099/mic.0.26634-0;
RA   Shaw L., Golonka E., Potempa J., Foster S.J.;
RT   "The role and regulation of the extracellular proteases of Staphylococcus
RT   aureus.";
RL   Microbiology 150:217-228(2004).
RN   [6]
RP   INHIBITION BY STAPHOSTATIN B.
RX   PubMed=15716447; DOI=10.1128/jb.187.5.1751-1762.2005;
RA   Shaw L.N., Golonka E., Szmyd G., Foster S.J., Travis J., Potempa J.;
RT   "Cytoplasmic control of premature activation of a secreted protease
RT   zymogen: deletion of staphostatin B (sspC) in Staphylococcus aureus 8325-4
RT   yields a profound pleiotropic phenotype.";
RL   J. Bacteriol. 187:1751-1762(2005).
CC   -!- FUNCTION: Cysteine protease that plays an important role in the
CC       inhibition of host innate immune response. Degrades host elastin,
CC       fibrogen, fibronectin and kininogen. Blocks phagocytosis of opsonised
CC       S. aureus by neutrophils and monocytes by inducing their death in a
CC       proteolytic activity-dependent manner. Decreases surface expression of
CC       the 'don't eat me' signal CD31 on neutrophils. Cleaves host galectin-
CC       3/LGALS3, thereby inhibiting the neutrophil-activating ability of the
CC       lectin. {ECO:0000250|UniProtKB:P0C1S6}.
CC   -!- ACTIVITY REGULATION: Prematurely activated/folded staphopain B is
CC       inhibited by staphostatin B (SspC), which is probably required to
CC       protect staphylococcal cytoplasmic proteins from degradation by SspB.
CC       Also inactivated by E-64 and stimulated by EDTA.
CC       {ECO:0000269|PubMed:12207024}.
CC   -!- SUBUNIT: In the cytoplasm, prematurely activated/folded SspB forms a
CC       stable non-covalent complex with SspC. {ECO:0000250}.
CC   -!- SUBCELLULAR LOCATION: Secreted.
CC   -!- INDUCTION: Expression occurs in a growth phase-dependent manner with
CC       optimal expression at post-exponential phase. Environmental conditions
CC       such as degree of aeration and salt concentration are also important in
CC       control of transcription and processing of SspB. Up-regulated by agr
CC       (accessory gene regulator) and repressed by SarA (staphylococcal
CC       accessory regulator) and sigmaB factor. {ECO:0000269|PubMed:14702415}.
CC   -!- PTM: Proteolytically cleaved by staphylococcal serine protease (SspA).
CC       {ECO:0000269|PubMed:11119502, ECO:0000269|PubMed:12207024}.
CC   -!- MISCELLANEOUS: The cascade of activation of extracellular proteases
CC       proceeds from the metalloprotease aureolysin (aur), through SspA to
CC       SspB.
CC   -!- SIMILARITY: Belongs to the peptidase C47 family. {ECO:0000305}.
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DR   EMBL; AF309515; AAG45844.1; -; Genomic_DNA.
DR   EMBL; CP000253; ABD30112.1; -; Genomic_DNA.
DR   RefSeq; WP_001088780.1; NZ_LS483365.1.
DR   RefSeq; YP_499540.1; NC_007795.1.
DR   AlphaFoldDB; Q2FZL3; -.
DR   SMR; Q2FZL3; -.
DR   STRING; 1280.SAXN108_1045; -.
DR   MEROPS; C47.002; -.
DR   EnsemblBacteria; ABD30112; ABD30112; SAOUHSC_00987.
DR   GeneID; 3920388; -.
DR   KEGG; sao:SAOUHSC_00987; -.
DR   PATRIC; fig|93061.5.peg.907; -.
DR   eggNOG; ENOG502ZWEC; Bacteria.
DR   HOGENOM; CLU_069043_0_0_9; -.
DR   OMA; SCKTRVF; -.
DR   BRENDA; 3.4.22.48; 3352.
DR   PRO; PR:Q2FZL3; -.
DR   Proteomes; UP000008816; Chromosome.
DR   GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR   GO; GO:0008234; F:cysteine-type peptidase activity; IEA:UniProtKB-KW.
DR   GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR   Gene3D; 3.10.500.10; -; 1.
DR   InterPro; IPR046350; Cystatin_sf.
DR   InterPro; IPR038765; Papain-like_cys_pep_sf.
DR   InterPro; IPR025660; Pept_his_AS.
DR   InterPro; IPR008750; Peptidase_C47.
DR   InterPro; IPR028076; Staphopain_pro.
DR   InterPro; IPR037155; Staphopain_pro_sf.
DR   Pfam; PF05543; Peptidase_C47; 1.
DR   Pfam; PF14731; Staphopain_pro; 1.
DR   SUPFAM; SSF54001; SSF54001; 1.
DR   SUPFAM; SSF54403; SSF54403; 1.
DR   PROSITE; PS00639; THIOL_PROTEASE_HIS; 1.
PE   1: Evidence at protein level;
KW   Direct protein sequencing; Hydrolase; Protease; Reference proteome;
KW   Secreted; Signal; Thiol protease; Virulence; Zymogen.
FT   SIGNAL          1..36
FT                   /evidence="ECO:0000269|PubMed:11119502"
FT   PROPEP          37..219
FT                   /id="PRO_0000247969"
FT   CHAIN           220..393
FT                   /note="Staphopain B"
FT                   /id="PRO_0000247970"
FT   ACT_SITE        243
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10089"
FT   ACT_SITE        340
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10089"
FT   ACT_SITE        360
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10089"
FT   SITE            219..220
FT                   /note="Cleavage; by SspA"
SQ   SEQUENCE   393 AA;  44519 MW;  3949DA046DC3819B CRC64;
     MNSSCKSRVF NIISIIMVSM LILSLGAFAN NNKAKADSHS KQLEINVKSD KVPQKVKDLA
     QQQFAGYAKA LDKQSNAKTG KYELGEAFKI YKFNGEEDNS YYYPVIKDGK IVYTLTLSPK
     NKDDLNKSKE DMNYSVKISN FIAKDLDQIK DKNSNITVLT DEKGFYFEED GKVRLVKATP
     LPGNVKEKES AKTVSAKLKQ ELKNTVTPTK VEENEAIQED QVQYENTLKN FKIREQQFDN
     SWCAGFSMAA LLNATKNTDT YNAHDIMRTL YPEVSEQDLP NCATFPNQMI EYGKSQGRDI
     HYQEGVPSYE QVDQLTKDNV GIMILAQSVS QNPNDPHLGH ALAVVGNAKI NDQEKLIYWN
     PWDTELSIQD ADSSLLHLSF NRDYNWYGSM IGY