SSPP_STAA8
ID SSPP_STAA8 Reviewed; 388 AA.
AC Q2G2R8;
DT 25-JUL-2006, integrated into UniProtKB/Swiss-Prot.
DT 21-MAR-2006, sequence version 1.
DT 03-AUG-2022, entry version 87.
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; OrderedLocusNames=SAOUHSC_02127;
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 [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 [2]
RP PROTEIN SEQUENCE OF 215-222, AND 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).
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 -!- INDUCTION: Expression occurs in a growth phase-dependent manner with
CC optimal expression at post-exponential phase. 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: 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; CP000253; ABD31176.1; -; Genomic_DNA.
DR RefSeq; WP_000827748.1; NZ_LS483365.1.
DR RefSeq; YP_500618.1; NC_007795.1.
DR AlphaFoldDB; Q2G2R8; -.
DR SMR; Q2G2R8; -.
DR STRING; 1280.SAXN108_2009; -.
DR MEROPS; C47.001; -.
DR EnsemblBacteria; ABD31176; ABD31176; SAOUHSC_02127.
DR GeneID; 3921198; -.
DR KEGG; sao:SAOUHSC_02127; -.
DR PATRIC; fig|93061.5.peg.1930; -.
DR eggNOG; ENOG502ZWEC; Bacteria.
DR HOGENOM; CLU_069043_0_0_9; -.
DR OMA; NKLENFR; -.
DR BRENDA; 3.4.22.48; 3352.
DR PRO; PR:Q2G2R8; -.
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..25
FT /evidence="ECO:0000255"
FT PROPEP 26..214
FT /evidence="ECO:0000250"
FT /id="PRO_0000247954"
FT CHAIN 215..388
FT /note="Staphopain A"
FT /id="PRO_0000247955"
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; 44262 MW; 45D76DE341101F0D 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 IIIWNPWDNG
FMTQDAKNNV IPVSNGDHYR WYSSIYGY
