SSPP_STAAU
ID SSPP_STAAU Reviewed; 388 AA.
AC P81297; Q70UR0;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2005, sequence version 2.
DT 03-AUG-2022, entry version 108.
DE RecName: Full=Staphopain A;
DE EC=3.4.22.48 {ECO:0000269|PubMed:3422637};
DE AltName: Full=Staphylococcal cysteine proteinase A;
DE AltName: Full=Staphylopain A;
DE Flags: Precursor;
GN Name=sspP; Synonyms=scpA;
OS Staphylococcus aureus.
OC Bacteria; Firmicutes; Bacilli; Bacillales; Staphylococcaceae;
OC Staphylococcus.
OX NCBI_TaxID=1280;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=ATCC 27733 / V8;
RX PubMed=15576326; DOI=10.1515/bc.2004.137;
RA Golonka E., Filipek R., Sabat A., Sinczak A., Potempa J.;
RT "Genetic characterization of staphopain genes in Staphylococcus aureus.";
RL Biol. Chem. 385:1059-1067(2004).
RN [2]
RP PROTEIN SEQUENCE OF 215-388.
RC STRAIN=ATCC 27733 / V8;
RA Kiess M., Hofmann B., Weissflog S., Schomburg D.;
RL Submitted (APR-1998) to UniProtKB.
RN [3]
RP FUNCTION, ACTIVITY REGULATION, AND BIOPHYSICOCHEMICAL PROPERTIES.
RC STRAIN=ATCC 27733 / V8;
RX PubMed=3422637; DOI=10.1016/s0021-9258(18)69118-5;
RA Potempa J., Dubin A., Korzus G., Travis J.;
RT "Degradation of elastin by a cysteine proteinase from Staphylococcus
RT aureus.";
RL J. Biol. Chem. 263:2664-2667(1988).
RN [4]
RP INTERACTION WITH STAPHOSTATIN A.
RC STRAIN=ATCC 27733 / V8;
RX PubMed=14621990; DOI=10.1021/bi035310j;
RA Dubin G., Krajewski M., Popowicz G., Stec-Niemczyk J., Bochtler M.,
RA Potempa J., Dubin A., Holak T.A.;
RT "A novel class of cysteine protease inhibitors: solution structure of
RT staphostatin A from Staphylococcus aureus.";
RL Biochemistry 42:13449-13456(2003).
RN [5]
RP INTERACTION WITH STAPHOSTATIN A.
RC STRAIN=ATCC 27733 / V8;
RX PubMed=12890028; DOI=10.1046/j.1365-2958.2003.03613.x;
RA Rzychon M., Sabat A., Kosowska K., Potempa J., Dubin A.;
RT "Staphostatins: an expanding new group of proteinase inhibitors with a
RT unique specificity for the regulation of staphopains, Staphylococcus spp.
RT cysteine proteinases.";
RL Mol. Microbiol. 49:1051-1066(2003).
RN [6]
RP FUNCTION.
RC STRAIN=V8-BC10;
RX PubMed=15897280; DOI=10.1084/jem.20042041;
RA Imamura T., Tanase S., Szmyd G., Kozik A., Travis J., Potempa J.;
RT "Induction of vascular leakage through release of bradykinin and a novel
RT kinin by cysteine proteinases from Staphylococcus aureus.";
RL J. Exp. Med. 201:1669-1676(2005).
RN [7]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=22850671; DOI=10.1038/emboj.2012.212;
RA Laarman A.J., Mijnheer G., Mootz J.M., van Rooijen W.J., Ruyken M.,
RA Malone C.L., Heezius E.C., Ward R., Milligan G., van Strijp J.A.,
RA de Haas C.J., Horswill A.R., van Kessel K.P., Rooijakkers S.H.;
RT "Staphylococcus aureus Staphopain A inhibits CXCR2-dependent neutrophil
RT activation and chemotaxis.";
RL EMBO J. 31:3607-3619(2012).
RN [8]
RP FUNCTION.
RC STRAIN=LAC;
RX PubMed=23235402; DOI=10.1159/000345417;
RA Kantyka T., Pyrc K., Gruca M., Smagur J., Plaza K., Guzik K., Zeglen S.,
RA Ochman M., Potempa J.;
RT "Staphylococcus aureus proteases degrade lung surfactant protein A
RT potentially impairing innate immunity of the lung.";
RL J. Innate Immun. 5:251-260(2013).
RN [9]
RP X-RAY CRYSTALLOGRAPHY (1.75 ANGSTROMS) OF 215-388 IN COMPLEX WITH E-64.
RC STRAIN=ATCC 27733 / V8;
RA Hofmann B., Schomburg D., Hecht H.-J.;
RT "Crystal structure of a thiol proteinase from Staphylococcus aureus V-8 in
RT the E-64 inhibitor complex.";
RL Acta Crystallogr. A 49:102-102(1993).
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 (PubMed:3422637,
CC PubMed:23235402). Proteolytic cleavage of surfactant protein A impairs
CC bacterial phagocytosis by neutrophils while CXCR2 degradation blocks
CC neutrophil activation and chemotaxis (PubMed:3422637, PubMed:23235402).
CC Additionally, promotes vascular leakage by activating the plasma
CC kallikerin/kinin system, resulting in hypotension (PubMed:15897280).
CC {ECO:0000269|PubMed:15897280, ECO:0000269|PubMed:23235402,
CC ECO:0000269|PubMed:3422637}.
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 Also inactivated by heavy metal ions such as Hg(2+) or Ag(+),
CC iodoacetamide, E-64 and human plasma. {ECO:0000269|PubMed:3422637}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.5 mM for CBZ-Phe-Leu-Glu-pNA {ECO:0000269|PubMed:3422637};
CC pH dependence:
CC Optimum pH is 6.5 for elastin hydrolysis.
CC {ECO:0000269|PubMed:3422637};
CC -!- SUBUNIT: In the cytoplasm, prematurely activated/folded ScpA forms a
CC stable non-covalent complex with ScpB. {ECO:0000269|Ref.9}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:22850671}.
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.
CC -!- PTM: Cleavage leads to the activation of ScpA probably by an auto-
CC catalytic manner.
CC -!- MISCELLANEOUS: The catalytic maturation of ScpA appears to reside
CC outside the cascade of activation started by the metalloprotease
CC aureolysin (aur).
CC -!- SIMILARITY: Belongs to the peptidase C47 family. {ECO:0000305}.
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DR EMBL; AJ538362; CAD61962.1; -; Genomic_DNA.
DR PDB; 1CV8; X-ray; 1.75 A; A=215-388.
DR PDBsum; 1CV8; -.
DR AlphaFoldDB; P81297; -.
DR SMR; P81297; -.
DR MEROPS; C47.001; -.
DR BRENDA; 3.4.22.48; 3352.
DR EvolutionaryTrace; P81297; -.
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 3D-structure; Direct protein sequencing; Hydrolase; Protease; Secreted;
KW Signal; Thiol protease; Virulence; Zymogen.
FT SIGNAL 1..25
FT /evidence="ECO:0000255"
FT PROPEP 26..214
FT /evidence="ECO:0000269|Ref.2"
FT /id="PRO_0000026545"
FT CHAIN 215..388
FT /note="Staphopain A"
FT /id="PRO_0000026546"
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 CONFLICT 288
FT /note="E -> G (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
FT STRAND 217..222
FT /evidence="ECO:0007829|PDB:1CV8"
FT STRAND 234..236
FT /evidence="ECO:0007829|PDB:1CV8"
FT HELIX 238..251
FT /evidence="ECO:0007829|PDB:1CV8"
FT HELIX 258..265
FT /evidence="ECO:0007829|PDB:1CV8"
FT HELIX 271..276
FT /evidence="ECO:0007829|PDB:1CV8"
FT HELIX 281..290
FT /evidence="ECO:0007829|PDB:1CV8"
FT STRAND 296..300
FT /evidence="ECO:0007829|PDB:1CV8"
FT HELIX 304..312
FT /evidence="ECO:0007829|PDB:1CV8"
FT STRAND 317..325
FT /evidence="ECO:0007829|PDB:1CV8"
FT STRAND 333..344
FT /evidence="ECO:0007829|PDB:1CV8"
FT STRAND 349..354
FT /evidence="ECO:0007829|PDB:1CV8"
FT STRAND 362..365
FT /evidence="ECO:0007829|PDB:1CV8"
FT STRAND 370..372
FT /evidence="ECO:0007829|PDB:1CV8"
FT STRAND 378..386
FT /evidence="ECO:0007829|PDB:1CV8"
SQ SEQUENCE 388 AA; 44120 MW; 6E29DE8D0D7DFC42 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 PREMIYFEQT QGRSPQLLNR
MTTYNEVDNL TKNNKGIAIL GSRVESRNGM HAGHAMAVVG NAKLNNGQEV IIIWNPWDNG
FMTQDAKNNV IPVSNGDHYQ WYSSIYGY
