ID   TACY_STRPN              Reviewed;         471 AA.
AC   P0C2J9; P11990;
DT   06-MAR-2007, integrated into UniProtKB/Swiss-Prot.
DT   06-MAR-2007, sequence version 1.
DT   03-AUG-2022, entry version 88.
DE   RecName: Full=Pneumolysin;
DE            Short=PLY;
DE   AltName: Full=Thiol-activated cytolysin;
GN   Name=ply; OrderedLocusNames=SP_1923;
OS   Streptococcus pneumoniae serotype 4 (strain ATCC BAA-334 / TIGR4).
OC   Bacteria; Firmicutes; Bacilli; Lactobacillales; Streptococcaceae;
OC   Streptococcus.
OX   NCBI_TaxID=170187;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC BAA-334 / TIGR4;
RX   PubMed=11463916; DOI=10.1126/science.1061217;
RA   Tettelin H., Nelson K.E., Paulsen I.T., Eisen J.A., Read T.D.,
RA   Peterson S.N., Heidelberg J.F., DeBoy R.T., Haft D.H., Dodson R.J.,
RA   Durkin A.S., Gwinn M.L., Kolonay J.F., Nelson W.C., Peterson J.D.,
RA   Umayam L.A., White O., Salzberg S.L., Lewis M.R., Radune D.,
RA   Holtzapple E.K., Khouri H.M., Wolf A.M., Utterback T.R., Hansen C.L.,
RA   McDonald L.A., Feldblyum T.V., Angiuoli S.V., Dickinson T., Hickey E.K.,
RA   Holt I.E., Loftus B.J., Yang F., Smith H.O., Venter J.C., Dougherty B.A.,
RA   Morrison D.A., Hollingshead S.K., Fraser C.M.;
RT   "Complete genome sequence of a virulent isolate of Streptococcus
RT   pneumoniae.";
RL   Science 293:498-506(2001).
RN   [2]
RP   FUNCTION, SUBCELLULAR LOCATION, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF
RP   THR-63.
RC   STRAIN=ATCC BAA-334 / TIGR4;
RX   PubMed=28456649; DOI=10.1016/j.micinf.2017.04.003;
RA   Bandara M., Skehel J.M., Kadioglu A., Collinson I., Nobbs A.H.,
RA   Blocker A.J., Jenkinson H.F.;
RT   "The accessory Sec system (SecY2A2) in Streptococcus pneumoniae is involved
RT   in export of pneumolysin toxin, adhesion and biofilm formation.";
RL   Microbes Infect. 19:402-412(2017).
CC   -!- FUNCTION: A cholesterol-dependent toxin that causes cytolysis by
CC       forming pores in cholesterol containing host membranes (Probable).
CC       After binding to target membranes, the protein undergoes a major
CC       conformation change, leading to its insertion in the host membrane and
CC       formation of an oligomeric pore complex. Cholesterol is required for
CC       binding to host membranes, membrane insertion and pore formation;
CC       cholesterol binding is mediated by a Thr-Leu pair in the C-terminus.
CC       Can be reversibly inactivated by oxidation.
CC       {ECO:0000250|UniProtKB:P0C2E9, ECO:0000305|PubMed:28456649}.
CC   -!- SUBUNIT: Homooligomeric pore complex of 35 to 50 subunits; when
CC       inserted in the host membrane. {ECO:0000250|UniProtKB:Q04IN8}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:28456649}. Secreted,
CC       cell wall {ECO:0000269|PubMed:28456649}. Host cell membrane
CC       {ECO:0000250}; Multi-pass membrane protein
CC       {ECO:0000250|UniProtKB:Q04IN8}. Note=Secreted as soluble protein by the
CC       accessory Sec system (PubMed:28456649). It then inserts into the host
CC       cell membrane and forms pores formed by transmembrane beta-strands (By
CC       similarity). {ECO:0000250|UniProtKB:Q04IN8,
CC       ECO:0000269|PubMed:28456649}.
CC   -!- PTM: Has a slightly altered apparent molecular weight in a secA2
CC       deletion mutant, but no post-translational modifications have been
CC       found. {ECO:0000269|PubMed:28456649}.
CC   -!- DISRUPTION PHENOTYPE: No change in biofilm formation, about 35%
CC       decreased adherence to human lung pneumocytes. Complete loss of host
CC       cell hemolytic activity. {ECO:0000269|PubMed:28456649}.
CC   -!- SIMILARITY: Belongs to the cholesterol-dependent cytolysin family.
CC       {ECO:0000305}.
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DR   EMBL; AE005672; AAK75991.1; -; Genomic_DNA.
DR   PIR; A28568; A28568.
DR   PIR; A99089; A99089.
DR   RefSeq; WP_001284361.1; NZ_AKVY01000001.1.
DR   AlphaFoldDB; P0C2J9; -.
DR   SMR; P0C2J9; -.
DR   STRING; 170187.SP_1923; -.
DR   ChEMBL; CHEMBL5117; -.
DR   TCDB; 1.C.12.1.5; the thiol-activated cholesterol-dependent cytolysin (cdc) family.
DR   EnsemblBacteria; AAK75991; AAK75991; SP_1923.
DR   KEGG; spn:SP_1923; -.
DR   eggNOG; ENOG502Z7ST; Bacteria.
DR   OMA; NDRTYPG; -.
DR   BioCyc; SPNE170187:G1FZB-1978-MON; -.
DR   PRO; PR:P0C2J9; -.
DR   Proteomes; UP000000585; Chromosome.
DR   GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR   GO; GO:0020002; C:host cell plasma membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR   GO; GO:0015485; F:cholesterol binding; IEA:InterPro.
DR   GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR   GO; GO:0044179; P:hemolysis in another organism; IEA:UniProtKB-KW.
DR   Gene3D; 2.60.40.1430; -; 1.
DR   Gene3D; 3.90.840.10; -; 1.
DR   InterPro; IPR035390; Thiol_cytolys_C.
DR   InterPro; IPR038700; Thiol_cytolys_C_sf.
DR   InterPro; IPR001869; Thiol_cytolysin.
DR   InterPro; IPR036363; Thiol_cytolysin_ab_sf.
DR   InterPro; IPR036359; Thiol_cytolysin_sf.
DR   Pfam; PF17440; Thiol_cytolys_C; 1.
DR   Pfam; PF01289; Thiol_cytolysin; 1.
DR   PRINTS; PR01400; TACYTOLYSIN.
DR   SUPFAM; SSF56978; SSF56978; 1.
DR   PROSITE; PS00481; THIOL_CYTOLYSINS; 1.
PE   1: Evidence at protein level;
KW   Cell wall; Cytolysis; Hemolysis; Host cell membrane; Host membrane;
KW   Lipid-binding; Membrane; Secreted; Toxin; Transmembrane;
KW   Transmembrane beta strand; Virulence.
FT   INIT_MET        1
FT                   /note="Removed"
FT                   /evidence="ECO:0000250|UniProtKB:Q04IN8"
FT   CHAIN           2..471
FT                   /note="Pneumolysin"
FT                   /id="PRO_0000204251"
FT   TRANSMEM        158..171
FT                   /note="Beta stranded"
FT                   /evidence="ECO:0000250|UniProtKB:Q04IN8"
FT   TRANSMEM        178..187
FT                   /note="Beta stranded"
FT                   /evidence="ECO:0000250|UniProtKB:Q04IN8"
FT   TRANSMEM        256..265
FT                   /note="Beta stranded"
FT                   /evidence="ECO:0000250|UniProtKB:Q04IN8"
FT   TRANSMEM        273..285
FT                   /note="Beta stranded"
FT                   /evidence="ECO:0000250|UniProtKB:Q04IN8"
FT   MOTIF           427..437
FT                   /note="Conserved undecapeptide"
FT                   /evidence="ECO:0000305"
FT   MOTIF           459..460
FT                   /note="Cholesterol binding"
FT                   /evidence="ECO:0000250|UniProtKB:P0C2E9"
FT   MUTAGEN         63
FT                   /note="T->A: 70% reduction in host cell hemolytic activity,
FT                   no change in apparent molecular weight."
FT                   /evidence="ECO:0000269|PubMed:28456649"
SQ   SEQUENCE   471 AA;  52898 MW;  986A146548E0F738 CRC64;
     MANKAVNDFI LAMNYDKKKL LTHQGESIEN RFIKEGNQLP DEFVVIERKK RSLSTNTSDI
     SVTATNDSRL YPGALLVVDE TLLENNPTLL AVDRAPMTYS IDLPGLASSD SFLQVEDPSN
     SSVRGAVNDL LAKWHQDYGQ VNNVPARMQY EKITAHSMEQ LKVKFGSDFE KTGNSLDIDF
     NSVHSGEKQI QIVNFKQIYY TVSVDAVKNP GDVFQDTVTV EDLKQRGISA ERPLVYISSV
     AYGRQVYLKL ETTSKSDEVE AAFEALIKGV KVAPQTEWKQ ILDNTEVKAV ILGGDPSSGA
     RVVTGKVDMV EDLIQEGSRF TADHPGLPIS YTTSFLRDNV VATFQNSTDY VETKVTAYRN
     GDLLLDHSGA YVAQYYITWN ELSYDHQGKE VLTPKAWDRN GQDLTAHFTT SIPLKGNVRN
     LSVKIRECTG LAWEWWRTVY EKTDLPLVRK RTISIWGTTL YPQVEDKVEN D