ID SSPA_STAA8 Reviewed; 336 AA. AC Q2FZL2; P04188; DT 05-SEP-2006, integrated into UniProtKB/Swiss-Prot. DT 21-MAR-2006, sequence version 1. DT 02-DEC-2020, entry version 86. DE RecName: Full=Glutamyl endopeptidase; DE EC=3.4.21.19; DE AltName: Full=Endoproteinase Glu-C; DE AltName: Full=Staphylococcal serine proteinase; DE AltName: Full=V8 protease; DE AltName: Full=V8 proteinase; DE Flags: Precursor; GN Name=sspA; OrderedLocusNames=SAOUHSC_00988; 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], AND FUNCTION. 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 69-76, FUNCTION, 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). 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 FUNCTION. RX PubMed=11447146; DOI=10.1128/iai.69.8.4742-4748.2001; RA Karlsson A., Saravia-Otten P., Tegmark K., Morfeldt E., Arvidson S.; RT "Decreased amounts of cell wall-associated protein A and fibronectin- RT binding proteins in Staphylococcus aureus sarA mutants due to up-regulation RT of extracellular proteases."; RL Infect. Immun. 69:4742-4748(2001). RN [6] RP INDUCTION. RX PubMed=12117932; DOI=10.1128/iai.70.8.4239-4246.2002; RA Karlsson A., Arvidson S.; RT "Variation in extracellular protease production among clinical isolates of RT Staphylococcus aureus due to different levels of expression of the protease RT repressor sarA."; RL Infect. Immun. 70:4239-4246(2002). RN [7] RP FUNCTION. 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). CC -!- FUNCTION: Preferentially cleaves peptide bonds on the carboxyl-terminal CC side of aspartate and glutamate. Along with other extracellular CC proteases it is involved in colonization and infection of human CC tissues. Required for proteolytic maturation of thiol protease SspB and CC inactivation of SspC, an inhibitor of SspB. It is the most important CC protease for degradation of fibronectin-binding protein (FnBP) and CC surface protein A, which are involved in adherence to host cells. May CC also protect bacteria against host defense mechanism by cleaving the CC immunoglobulin classes IgG, IgA and IgM. May be involved in the CC stability of secreted lipases. {ECO:0000269|PubMed:11119502, CC ECO:0000269|PubMed:11447146, ECO:0000269|PubMed:12207024, CC ECO:0000269|PubMed:14702415}. CC -!- CATALYTIC ACTIVITY: CC Reaction=Preferential cleavage: Glu-|-Xaa, Asp-|-Xaa.; EC=3.4.21.19; CC Evidence={ECO:0000255|PROSITE-ProRule:PRU10083}; CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250}. 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 SspA. Up-regulated by Agr CC (accessory gene regulator) and repressed by sigmaB factor and SarA. CC {ECO:0000269|PubMed:12117932, ECO:0000269|PubMed:14702415}. CC -!- PTM: Proteolytically cleaved by aureolysin (aur). This cleavage leads CC to the activation of SspA. 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 S1B family. {ECO:0000305}. CC -!- WEB RESOURCE: Name=Worthington enzyme manual; CC URL="http://www.worthington-biochem.com/STAP/"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF309515; AAG45843.1; -; Genomic_DNA. DR EMBL; CP000253; ABD30113.1; -; Genomic_DNA. DR RefSeq; WP_000676548.1; NZ_LS483365.1. DR RefSeq; YP_499541.1; NC_007795.1. DR SMR; Q2FZL2; -. DR STRING; 1280.SAXN108_1046; -. DR EnsemblBacteria; ABD30113; ABD30113; SAOUHSC_00988. DR GeneID; 3920389; -. DR GeneID; 45574285; -. DR KEGG; sao:SAOUHSC_00988; -. DR PATRIC; fig|93061.5.peg.908; -. DR eggNOG; COG3591; Bacteria. DR HOGENOM; CLU_073589_1_0_9; -. DR OMA; NFANDDQ; -. DR PRO; PR:Q2FZL2; -. DR Proteomes; UP000008816; Chromosome. DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell. DR GO; GO:0004252; F:serine-type endopeptidase activity; IEA:InterPro. DR GO; GO:0009405; P:pathogenesis; IEA:UniProtKB-KW. DR Gene3D; 2.40.10.10; -; 2. DR InterPro; IPR009003; Peptidase_S1_PA. DR InterPro; IPR043504; Peptidase_S1_PA_chymotrypsin. DR InterPro; IPR008256; Peptidase_S1B. DR InterPro; IPR008353; Peptidase_S1B_tx. DR InterPro; IPR028301; V8_his_AS. DR InterPro; IPR000126; V8_ser_AS. DR PRINTS; PR01774; EXFOLTOXIN. DR PRINTS; PR00839; V8PROTEASE. DR SUPFAM; SSF50494; SSF50494; 1. DR PROSITE; PS00672; V8_HIS; 1. DR PROSITE; PS00673; V8_SER; 1. PE 1: Evidence at protein level; KW Direct protein sequencing; Hydrolase; Protease; Reference proteome; Repeat; KW Secreted; Serine protease; Signal; Virulence; Zymogen. FT SIGNAL 1..29 FT /evidence="ECO:0000255" FT PROPEP 30..68 FT /evidence="ECO:0000269|PubMed:14702415" FT /id="PRO_0000249327" FT CHAIN 69..336 FT /note="Glutamyl endopeptidase" FT /id="PRO_0000249328" FT REPEAT 289..291 FT /note="1" FT REPEAT 292..294 FT /note="2" FT REPEAT 295..297 FT /note="3" FT REPEAT 298..300 FT /note="4" FT REPEAT 301..303 FT /note="5" FT REPEAT 304..306 FT /note="6" FT REPEAT 310..312 FT /note="7" FT REPEAT 313..315 FT /note="8" FT REPEAT 316..318 FT /note="9" FT REPEAT 319..321 FT /note="10" FT REPEAT 322..324 FT /note="11" FT REGION 289..324 FT /note="11 X 3 AA repeats of P-[DN]-N" FT ACT_SITE 119 FT /note="Charge relay system" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10083" FT ACT_SITE 161 FT /note="Charge relay system" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10083" FT ACT_SITE 237 FT /note="Charge relay system" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10083" FT SITE 68..69 FT /note="Cleavage; by aureolysin" SQ SEQUENCE 336 AA; 36326 MW; 8B138D0C7996AA3E CRC64; MKGKFLKVSS LFVATLTTAT LVSSPAANAL SSKAMDNHPQ QTQSSKQQTP KIQKGGNLKP LEQREHANVI LPNNDRHQIT DTTNGHYAPV TYIQVEAPTG TFIASGVVVG KDTLLTNKHV VDATHGDPHA LKAFPSAINQ DNYPNGGFTA EQITKYSGEG DLAIVKFSPN EQNKHIGEVV KPATMSNNAE TQVNQNITVT GYPGDKPVAT MWESKGKITY LKGEAMQYDL STTGGNSGSP VFNEKNEVIG IHWGGVPNEF NGAVFINENV RNFLKQNIED IHFANDDQPN NPDNPDNPNN PDNPNNPDEP NNPDNPNNPD NPDNGDNNNS DNPDAA //