ID   SSPP_STAAC              Reviewed;         388 AA.
AC   Q5HEL3;
DT   05-JUL-2005, integrated into UniProtKB/Swiss-Prot.
DT   15-FEB-2005, sequence version 1.
DT   03-AUG-2022, entry version 92.
DE   RecName: Full=Staphopain A;
DE            EC=3.4.22.48;
DE   AltName: Full=Staphylococcal cysteine proteinase A;
DE   AltName: Full=Staphylopain A;
DE   Flags: Precursor;
GN   Name=sspP; Synonyms=scpA, sspB2; OrderedLocusNames=SACOL1970;
OS   Staphylococcus aureus (strain COL).
OC   Bacteria; Firmicutes; Bacilli; Bacillales; Staphylococcaceae;
OC   Staphylococcus.
OX   NCBI_TaxID=93062;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=COL;
RX   PubMed=15774886; DOI=10.1128/jb.187.7.2426-2438.2005;
RA   Gill S.R., Fouts D.E., Archer G.L., Mongodin E.F., DeBoy R.T., Ravel J.,
RA   Paulsen I.T., Kolonay J.F., Brinkac L.M., Beanan M.J., Dodson R.J.,
RA   Daugherty S.C., Madupu R., Angiuoli S.V., Durkin A.S., Haft D.H.,
RA   Vamathevan J.J., Khouri H., Utterback T.R., Lee C., Dimitrov G., Jiang L.,
RA   Qin H., Weidman J., Tran K., Kang K.H., Hance I.R., Nelson K.E.,
RA   Fraser C.M.;
RT   "Insights on evolution of virulence and resistance from the complete genome
RT   analysis of an early methicillin-resistant Staphylococcus aureus strain and
RT   a biofilm-producing methicillin-resistant Staphylococcus epidermidis
RT   strain.";
RL   J. Bacteriol. 187:2426-2438(2005).
CC   -!- FUNCTION: Cysteine protease that plays an important role in the
CC       inhibition of host innate immune response. Cleaves host elastins found
CC       in connective tissues, pulmonary surfactant protein A in the lungs, and
CC       the chemokine receptor CXCR2 on leukocytes. Proteolytic cleavage of
CC       surfactant protein A impairs bacterial phagocytosis by neutrophils
CC       while CXCR2 degradation blocks neutrophil activation and chemotaxis.
CC       Additionally, promotes vascular leakage by activating the plasma
CC       kallikerin/kinin system, resulting in hypotension.
CC       {ECO:0000250|UniProtKB:P81297}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=Broad endopeptidase action on proteins including elastin, but
CC         rather limited hydrolysis of small-molecule substrates. Assays are
CC         conveniently made with hemoglobin, casein or Z-Phe-Arg-NHMec as
CC         substrate.; EC=3.4.22.48;
CC   -!- ACTIVITY REGULATION: Prematurely activated/folded staphopain A is
CC       inhibited by staphostatin A (ScpB), which is probably required to
CC       protect staphylococcal cytoplasmic proteins from degradation by ScpA.
CC       {ECO:0000250}.
CC   -!- SUBUNIT: In the cytoplasm, prematurely activated/folded ScpA forms a
CC       stable non-covalent complex with ScpB. {ECO:0000250}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:P81297}.
CC   -!- PTM: Cleavage leads to the activation of ScpA probably by an auto-
CC       catalytic manner. {ECO:0000250}.
CC   -!- MISCELLANEOUS: The catalytic maturation of ScpA appears to reside
CC       outside the cascade of activation started by the metalloprotease
CC       aureolysin (aur). {ECO:0000250}.
CC   -!- SIMILARITY: Belongs to the peptidase C47 family. {ECO:0000305}.
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DR   EMBL; CP000046; AAW36940.1; -; Genomic_DNA.
DR   RefSeq; WP_000827749.1; NC_002951.2.
DR   AlphaFoldDB; Q5HEL3; -.
DR   SMR; Q5HEL3; -.
DR   MEROPS; C47.001; -.
DR   EnsemblBacteria; AAW36940; AAW36940; SACOL1970.
DR   KEGG; sac:SACOL1970; -.
DR   HOGENOM; CLU_069043_0_0_9; -.
DR   OMA; NKLENFR; -.
DR   PRO; PR:Q5HEL3; -.
DR   Proteomes; UP000000530; 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   3: Inferred from homology;
KW   Hydrolase; Protease; Secreted; Signal; Thiol protease; Virulence; Zymogen.
FT   SIGNAL          1..25
FT                   /evidence="ECO:0000255"
FT   PROPEP          26..214
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000026547"
FT   CHAIN           215..388
FT                   /note="Staphopain A"
FT                   /id="PRO_0000026548"
FT   ACT_SITE        238
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10089"
FT   ACT_SITE        334
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10089"
FT   ACT_SITE        355
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10089"
FT   SITE            214..215
FT                   /note="Cleavage"
FT                   /evidence="ECO:0000250"
SQ   SEQUENCE   388 AA;  44252 MW;  472A423341101F0D CRC64;
     MKRNFPKLIA LSLIFSLSVT PIANAESNSN IKAKDKKHVQ VNVEDKSVPT DVRNLAQKDY
     LSYVTSLDKI YNKEKASYTL GEPFKIYKFN KKSDGNYYFP VLNTEGNIDY IVTISPKITK
     YSSSSSKYTI NVSPFLSKVL NQYKDQQITI LTNSKGYYVV TQNHKAKLVL KTPRLEDKKL
     KKTESIPTGN NVTQLKQKAS VTMPTSQFKS NNYTYNEQYI NKLENFKIRE TQGNNGWCAG
     YTMSELLNAT YNTNKYHAEA VMRFLHPNLQ GQRFQFTGLT PREMIYFGQT QGRSPQLLNR
     MTTYNEVDNL TKNNKGIAVL GSRVESRNGM HAGHAMAVVG NAKLDNGQEV IIIWNSWDNG
     FMTQDAKNNV IPVSNGDHYR WYSSIYGY