ID   ZMPB_STRPN              Reviewed;        1906 AA.
AC   Q9L7Q2; Q7D4C2;
DT   01-FEB-2005, integrated into UniProtKB/Swiss-Prot.
DT   01-FEB-2005, sequence version 2.
DT   03-AUG-2022, entry version 111.
DE   RecName: Full=Zinc metalloprotease ZmpB;
DE            EC=3.4.24.-;
DE   Flags: Precursor;
GN   Name=zmpB; OrderedLocusNames=SP_0664;
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 [GENOMIC DNA], AND CELL SURFACE LOCALIZATION.
RC   STRAIN=Serotype 4;
RX   PubMed=10792723; DOI=10.1046/j.1365-2958.2000.01854.x;
RA   Novak R., Charpentier E., Braun J.S., Park E., Murti S., Tuomanen E.,
RA   Masure R.;
RT   "Extracellular targeting of choline-binding proteins in Streptococcus
RT   pneumoniae by a zinc metalloprotease.";
RL   Mol. Microbiol. 36:366-376(2000).
RN   [2]
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   [3]
RP   DISCUSSION OF FUNCTION.
RX   PubMed=11260480; DOI=10.1046/j.1365-2958.2001.02359.x;
RA   Berge M., Garcia P., Iannelli F., Prere M.F., Granadel C., Polissi A.,
RA   Claverys J.-P.;
RT   "The puzzle of zmpB and extensive chain formation, autolysis defect and
RT   non-translocation of choline-binding proteins in Streptococcus
RT   pneumoniae.";
RL   Mol. Microbiol. 39:1651-1660(2001).
RN   [4]
RP   ROLE IN VIRULENCE.
RC   STRAIN=ATCC BAA-334 / TIGR4;
RX   PubMed=12841855; DOI=10.1186/1471-2180-3-14;
RA   Chiavolini D., Memmi G., Maggi T., Iannelli F., Pozzi G., Oggioni M.R.;
RT   "The three extra-cellular zinc metalloproteinases of Streptococcus
RT   pneumoniae have a different impact on virulence in mice.";
RL   BMC Microbiol. 3:14-14(2003).
RN   [5]
RP   ROLE IN INFLAMMATION.
RC   STRAIN=Serotype 2;
RX   PubMed=12933834; DOI=10.1128/iai.71.9.4925-4935.2003;
RA   Blue C.E., Paterson G.K., Kerr A.R., Berge M., Claverys J.-P.,
RA   Mitchell T.J.;
RT   "ZmpB, a novel virulence factor of Streptococcus pneumoniae that induces
RT   tumor necrosis factor alpha production in the respiratory tract.";
RL   Infect. Immun. 71:4925-4935(2003).
CC   -!- FUNCTION: Is a virulence factor capable of inducing inflammation in the
CC       lower respiratory tract, by increasing tumor necrosis factor alpha
CC       (TNF-alpha) concentration in the lungs. Also appears to have other
CC       functions important in virulence in models of pneumonia and septicemia.
CC       {ECO:0000269|PubMed:12841855, ECO:0000269|PubMed:12933834}.
CC   -!- COFACTOR:
CC       Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000250};
CC       Note=Binds 1 zinc ion per subunit. {ECO:0000250};
CC   -!- SUBCELLULAR LOCATION: Secreted, cell wall. Membrane; Multi-pass
CC       membrane protein. Secreted, cell wall; Peptidoglycan-anchor.
CC   -!- PTM: The Gram-positive cell-wall anchor motif LPXTG is located in the
CC       N-terminal part, in contrast to such motifs in other known
CC       streptococcal and staphylococcal proteins. The protease could be
CC       cleaved by the sortase and anchored in the membrane via the two
CC       potential N-terminal transmembrane domains, whereas the propeptide
CC       located prior to the LPXTG motif would remain attached to the cell wall
CC       peptidoglycan by an amide bond.
CC   -!- SIMILARITY: Belongs to the peptidase M26 family. {ECO:0000305}.
CC   -!- CAUTION: Was originally (PubMed:10792723) thought to control
CC       translocation of choline-binding proteins to the cell surface but
CC       PubMed:11260480 failed to confirm this observation. The conflicting
CC       observations could be explained by the fact that the mutant strain used
CC       in PubMed:10792723 lacked capsule. {ECO:0000305|PubMed:10792723}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=AAF31454.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC       Sequence=AAK74809.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR   EMBL; AF221126; AAF31454.1; ALT_INIT; Genomic_DNA.
DR   EMBL; AE005672; AAK74809.1; ALT_INIT; Genomic_DNA.
DR   PIR; H95076; H95076.
DR   RefSeq; WP_000472995.1; NZ_AKVY01000001.1.
DR   AlphaFoldDB; Q9L7Q2; -.
DR   SMR; Q9L7Q2; -.
DR   STRING; 170187.SP_0664; -.
DR   MEROPS; M26.002; -.
DR   EnsemblBacteria; AAK74809; AAK74809; SP_0664.
DR   KEGG; spn:SP_0664; -.
DR   eggNOG; COG3064; Bacteria.
DR   OMA; TQEVGHE; -.
DR   PhylomeDB; Q9L7Q2; -.
DR   BioCyc; SPNE170187:G1FZB-687-MON; -.
DR   Proteomes; UP000000585; Chromosome.
DR   GO; GO:0009986; C:cell surface; IDA:CACAO.
DR   GO; GO:0005576; C:extracellular region; IEA:UniProtKB-KW.
DR   GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR   GO; GO:0004222; F:metalloendopeptidase activity; IEA:InterPro.
DR   GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR   GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR   InterPro; IPR019931; LPXTG_anchor.
DR   InterPro; IPR011505; Peptidase_M26_C_dom.
DR   InterPro; IPR008006; Peptidase_M26_N_dom.
DR   Pfam; PF00746; Gram_pos_anchor; 1.
DR   Pfam; PF07580; Peptidase_M26_C; 1.
DR   Pfam; PF05342; Peptidase_M26_N; 1.
DR   PROSITE; PS50847; GRAM_POS_ANCHORING; 1.
PE   3: Inferred from homology;
KW   Cell wall; Hydrolase; Membrane; Metal-binding; Metalloprotease;
KW   Peptidoglycan-anchor; Protease; Repeat; Secreted; Signal; Transmembrane;
KW   Transmembrane helix; Virulence; Zinc.
FT   SIGNAL          1..33
FT                   /evidence="ECO:0000255"
FT   PROPEP          34..76
FT                   /evidence="ECO:0000255"
FT                   /id="PRO_0000026841"
FT   CHAIN           77..1906
FT                   /note="Zinc metalloprotease ZmpB"
FT                   /id="PRO_0000026842"
FT   TRANSMEM        77..98
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        105..127
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        128..1906
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   REPEAT          277..291
FT                   /note="1-1"
FT   REPEAT          293..315
FT                   /note="2-1"
FT   REPEAT          361..375
FT                   /note="1-2"
FT   REPEAT          380..402
FT                   /note="2-2"
FT   REGION          178..436
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          277..375
FT                   /note="2 X 15 AA repeats of K-V-E-Q-A-G-E-P-V-A-P-R-E-D-E"
FT   REGION          293..375
FT                   /note="2 X 23 AA approximate repeats"
FT   MOTIF           73..77
FT                   /note="LPXTG sorting signal"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00477"
FT   COMPBIAS        178..193
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        194..339
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        351..370
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        386..421
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        422..436
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   ACT_SITE        1563
FT                   /evidence="ECO:0000250"
FT   BINDING         1562
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /evidence="ECO:0000250"
FT   BINDING         1566
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /evidence="ECO:0000250"
FT   BINDING         1586
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /evidence="ECO:0000250"
FT   MOD_RES         76
FT                   /note="Pentaglycyl murein peptidoglycan amidated threonine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00477"
SQ   SEQUENCE   1906 AA;  213535 MW;  2A03CB9311E06928 CRC64;
     MFKKDRFSIR KIKGVVGSVF LGSLLMAPSV VDAATYHYVN KEIISQEAKD LIQTGKPDRN
     EVVYGLVYQK DQLPQTGTEA SVLTAFGLLT VGSLLLIYKR KKIASVFLVG AMGLVVLPSA
     GAVDPVATLA LASREGVVEM EGYRYVGYLS GDILKTLGLD TVLEETSAKP GEVTVVEVET
     PQSITNQEQA RTENQVVETE EAPKEEAPKT EESPKEEPKS EVKPTDDTLP KVEEGKEDSA
     EPAPVEEVGG EVESKPEEKV AVKPESQPSD KPAEESKVEQ AGEPVAPRED EKAPVEPEKQ
     PEAPEEEKAV EETPKQEEST PDTKAEETVE PKEETVNQSI EQPKVETPAV EKQTEPTEEP
     KVEQAGEPVA PREDEQAPTA PVEPEKQPEV PEEEKAVEET PKPEDKIKGI GTKEPVDKSE
     LNNQIDKASS VSPTDYSTAS YNALGPVLET AKGVYASEPV KQPEVNSETN KLKTAIDALN
     VDKTELNNTI ADAKTKVKEH YSDRSWQNLQ TEVTKAEKVA ANTDAKQSEV NEAVEKLTAT
     IEKLVELSEK PILTLTSTDK KILEREAVAK YTLENQNKTK IKSITAELKK GEEVINTVVL
     TDDKVTTETI SAAFKNLEYY KEYTLSTTMI YDRGNGEETE TLENQNIQLD LKKVELKNIK
     RTDLIKYENG KETNESLITT IPDDKSNYYL KITSNNQKTT LLAVKNIEET TVNGTPVYKV
     TAIADNLVSR TADNKFEEEY VHYIEKPKVH EDNVYYNFKE LVEAIQNDPS KEYRLGQSMS
     ARNVVPNGKS YITKEFTGKL LSSEGKQFAI TELEHPLFNV ITNATINNVN FENVEIERSG
     QDNIASLANT MKGSSVITNV KITGTLSGRN NVAGFVNNMN DGTRIENVAF FGKLHSTSGN
     GSHTGGIAGT NYRGIVRKAY VDATITGNKT RASLLVPKVD YGLTLDHLIG TKALLTESVV
     KGKIDVSNPV EVGAIASKTW PVGTVSNSVS YAKIIRGEEL FGSNDVDDSD YASAHIKDLY
     AVEGYSSGNR SFRKSKTFTK LTKEQADAKV TTFNITADKL ESDLSPLAKL NEEKAYSSIQ
     DYNAEYNQAY KNLEKLIPFY NKDYIVYQGN KLNKEHHLNT KEVLSVTAMN NNEFITNLDE
     ANKIIVHYAD GTKDYFNLSS SSEGLSNVKE YTITDLGIKY TPNIVQKDNT TLVNDIKSIL
     ESVELQSQTM YQHLNRLGDY RVNAIKDLYL EESFTDVKEN LTNLITKLVQ NEEHQLNDSP
     AARQMIRDKV EKNKAALLLG LTYLNRYYGV KFGDVNIKEL MLFKPDFYGE KVSVLDRLIE
     IGSKENNIKG SRTFDAFGQV LAKYTKSGNL DAFLNYNRQL FTNIDNMNDW FIDATEDHVY
     IAERASEVEE IKNSKHRAFD NLKRSHLRNT ILPLLNIDKA HLYLISNYNA IAFGSAERLG
     KKSLEDIKDI VNKAADGYRN YYDFWYRLAS DNVKQRLLRD AVIPIWEGYN APGGWVEKYG
     RYNTDKVYTP LREFFGPMDK YYNYNGTGAY AAIYPNSDDI RTDVKYVHLE MVGEYGISVY
     THETTHVNDR AIYLGGFGHR EGTDAEAYAQ GMLQTPVTGS GFDEFGSLGI NMVFKRKNDG
     NQWYITDPKT LKTREDINRY MKGYNDTLTL LDEIEAESVI SQQNKDLNSA WFKKIDREYR
     DNNKLNQWDK IRNLSQEEKN ELNIQSVNDL VDQQLMTNRN PGNGIYKPEA ISYNDQSPYV
     GVRMMTGIYG GNTSKGAPGA VSFKHNAFRL WGYYGYENGF LGYASNKYKQ QSKTDGESVL
     SDEYIIKKIS NNTFNTIEEF KKAYFKEVKD KATKGLTTFE VNGSSVSSYD DLLTLFKEAV
     KKDAETLKQE ANGNKTVSMN NTVKLKEAVY KKLLQQTNSF KTSIFK