ID   SSPP_STAAR              Reviewed;         388 AA.
AC   Q6GFE8;
DT   05-JUL-2005, integrated into UniProtKB/Swiss-Prot.
DT   19-JUL-2004, sequence version 1.
DT   03-AUG-2022, entry version 90.
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; OrderedLocusNames=SAR2001;
OS   Staphylococcus aureus (strain MRSA252).
OC   Bacteria; Firmicutes; Bacilli; Bacillales; Staphylococcaceae;
OC   Staphylococcus.
OX   NCBI_TaxID=282458;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=MRSA252;
RX   PubMed=15213324; DOI=10.1073/pnas.0402521101;
RA   Holden M.T.G., Feil E.J., Lindsay J.A., Peacock S.J., Day N.P.J.,
RA   Enright M.C., Foster T.J., Moore C.E., Hurst L., Atkin R., Barron A.,
RA   Bason N., Bentley S.D., Chillingworth C., Chillingworth T., Churcher C.,
RA   Clark L., Corton C., Cronin A., Doggett J., Dowd L., Feltwell T., Hance Z.,
RA   Harris B., Hauser H., Holroyd S., Jagels K., James K.D., Lennard N.,
RA   Line A., Mayes R., Moule S., Mungall K., Ormond D., Quail M.A.,
RA   Rabbinowitsch E., Rutherford K.M., Sanders M., Sharp S., Simmonds M.,
RA   Stevens K., Whitehead S., Barrell B.G., Spratt B.G., Parkhill J.;
RT   "Complete genomes of two clinical Staphylococcus aureus strains: evidence
RT   for the rapid evolution of virulence and drug resistance.";
RL   Proc. Natl. Acad. Sci. U.S.A. 101:9786-9791(2004).
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; BX571856; CAG40986.1; -; Genomic_DNA.
DR   RefSeq; WP_000827736.1; NC_002952.2.
DR   AlphaFoldDB; Q6GFE8; -.
DR   SMR; Q6GFE8; -.
DR   MEROPS; C47.001; -.
DR   KEGG; sar:SAR2001; -.
DR   HOGENOM; CLU_069043_0_0_9; -.
DR   OMA; NKLENFR; -.
DR   OrthoDB; 743974at2; -.
DR   PRO; PR:Q6GFE8; -.
DR   Proteomes; UP000000596; 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_0000026553"
FT   CHAIN           215..388
FT                   /note="Staphopain A"
FT                   /id="PRO_0000026554"
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;  44048 MW;  44017EA70E289F14 CRC64;
     MKRNFPKLIA LSLIFSLSIT PIANAESNSN IKAKDKRHVQ VNVEDKSVPT DVRNLAQKDY
     LSYVTSLDKI YNKEKASYTL GEPFKIYKFN KKSDGNYYFP VLNTEGNIDY IVTISPKVTK
     DSSSSSKYTI NVSSFLSKAL NEYKDQQITI LTNSKGYYVV TQNHKAKLVL KTPRLEDKKA
     KKTESIPTGN NVTQLKQKAS VTMPTSQFKS NNYTYNEQYV NKLENFKIRE TQGNNGWCAG
     YTMSALLNAT YNTNKYHAEA VMRFLHPNLQ GQQFQFTGLT PREMIYFGQT QGRSPQLLNR
     MTTYNEVDNL TKNNKGIAIL GSRVESRNGM HAGHAMAVVG NAKLNNGQEV IIIWNPWDNG
     FMTQDAKNNV IPVSNGDHYQ WYSSIYGY