SPEB_STRPY
ID SPEB_STRPY Reviewed; 398 AA.
AC P0C0J0; P00788; P26296; P68883; Q54960; Q54961; Q54962; Q54963; Q54964;
AC Q54965; Q54966; Q54967; Q54968; Q57024; Q57082; Q57202; Q57211; Q57212;
AC Q9S680;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 13-SEP-2005, sequence version 1.
DT 03-AUG-2022, entry version 87.
DE RecName: Full=Streptopain;
DE EC=3.4.22.10;
DE AltName: Full=Exotoxin type B;
DE AltName: Full=SPE B;
DE AltName: Full=Streptococcal cysteine proteinase;
DE AltName: Full=Streptococcus peptidase A;
DE Short=SPP;
DE Flags: Precursor;
GN Name=speB;
OS Streptococcus pyogenes.
OC Bacteria; Firmicutes; Bacilli; Lactobacillales; Streptococcaceae;
OC Streptococcus.
OX NCBI_TaxID=1314;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND PROTEIN SEQUENCE OF 28-32 AND
RP 146-162.
RC STRAIN=86-858, and NY-5;
RX PubMed=2198264; DOI=10.1128/jb.172.8.4536-4542.1990;
RA Hauser A.R., Schlievert P.M.;
RT "Nucleotide sequence of the streptococcal pyrogenic exotoxin type B gene
RT and relationship between the toxin and the streptococcal proteinase
RT precursor.";
RL J. Bacteriol. 172:4536-4542(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND CHARACTERIZATION.
RC STRAIN=1226 / Serotype M44, 1233 / Serotype M17, 1289 / Serotype M5,
RC 1294 / Serotype M19, 1590, 162 / Serotype M22, 165 / Serotype M,
RC 168 / Serotype M66, 1719 / Serotype T8, 1832 / Serotype M76,
RC 1838 / Serotype M27, 1841 / Serotype M41, 1842 / Serotype M43,
RC 1864 / Serotype M56, 1870, 1871, 1872, 1882 / Serotype M59, 1893,
RC 1896 / Serotype M10, 1898 / Serotype M15, 1901 / Serotype M23,
RC 1911 / Serotype M75, 1914A, 1990 / Serotype M, 1991 / Serotype M,
RC 2017 / Serotype M, 2018 / Serotype M, 262 / Serotype M, 282 / Serotype M12,
RC 289 / Serotype T28, 302 / Serotype M73, 317 / Serotype M,
RC 321 / Serotype M4, 327 / Serotype M2, 366 / Serotype M30,
RC 427 / Serotype M31, 429 / Serotype M8, 650 / Serotype M11,
RC 659 / Serotype M13, 660 / Serotype M14, 684 / Serotype M24,
RC 686 / Serotype M25, 719 / Serotype M49, 758 / Serotype M75,
RC 796 / Serotype M9, 800 / Serotype M9, and 807 / Serotype M33;
RX PubMed=7516997; DOI=10.1006/mpat.1993.1083;
RA Kapur V., Topouzis S., Majesky M.W., Li L.L., Hamrick M.R., Hamill R.J.,
RA Patti J.M., Musser J.M.;
RT "A conserved Streptococcus pyogenes extracellular cysteine protease cleaves
RT human fibronectin and degrades vitronectin.";
RL Microb. Pathog. 15:327-346(1993).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=Sv / Serotype M23;
RA Hong K.;
RT "A novel cloning method used arbitrarily primed PCR.";
RL Submitted (JUL-1999) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP PRELIMINARY PROTEIN SEQUENCE OF 28-86 AND 121-398.
RA Yonaha K., Elliott S.D., Liu T.-Y.;
RT "Primary structure of zymogen of streptococcal proteinase.";
RL J. Protein Chem. 1:317-334(1982).
RN [5]
RP PRELIMINARY PROTEIN SEQUENCE OF 146-398.
RX PubMed=1270417; DOI=10.1016/s0021-9258(17)33640-2;
RA Tai J.Y., Kortt A.A., Liu T.-Y., Elliott S.D.;
RT "Primary structure of streptococcal proteinase. III. Isolation of cyanogen
RT bromide peptides: complete covalent structure of the polypeptide chain.";
RL J. Biol. Chem. 251:1955-1959(1976).
RN [6]
RP METHYLTHIOLATION AT CYS-192.
RX PubMed=6381494; DOI=10.1016/s0021-9258(18)90619-8;
RA Lo S.S., Fraser B.A., Liu T.-Y.;
RT "The mixed disulfide in the zymogen of streptococcal proteinase.
RT Characterization and implication for its biosynthesis.";
RL J. Biol. Chem. 259:11041-11045(1984).
RN [7]
RP FUNCTION.
RC STRAIN=NZ131 / Serotype M49,T14;
RX PubMed=9864206; DOI=10.1128/iai.67.1.126-130.1999;
RA Kuo C.-F., Wu J.-J., Tsai P.-J., Kao F.-J., Lei H.-Y., Lin M.T., Lin Y.-S.;
RT "Streptococcal pyrogenic exotoxin B induces apoptosis and reduces
RT phagocytic activity in U937 cells.";
RL Infect. Immun. 67:126-130(1999).
RN [8]
RP X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) OF 28-398.
RX PubMed=10681429; DOI=10.1073/pnas.040549997;
RA Kagawa T.F., Cooney J.C., Baker H.M., McSweeney S., Liu M., Gubba S.,
RA Musser J.M., Baker E.N.;
RT "Crystal structure of the zymogen form of the group A Streptococcus
RT virulence factor SpeB: an integrin-binding cysteine protease.";
RL Proc. Natl. Acad. Sci. U.S.A. 97:2235-2240(2000).
RN [9]
RP X-RAY CRYSTALLOGRAPHY (1.55 ANGSTROMS) OF 146-398 IN COMPLEX WITH THE
RP SYNTHETIC INHIBITOR E64, ACTIVE SITE, AND SUBUNIT.
RX PubMed=19712682; DOI=10.1016/j.jmb.2009.08.046;
RA Olsen J.G., Dagil R., Niclasen L.M., Sorensen O.E., Kragelund B.B.;
RT "Structure of the mature Streptococcal cysteine protease exotoxin mSpeB in
RT its active dimeric form.";
RL J. Mol. Biol. 393:693-703(2009).
CC -!- FUNCTION: Important streptococcal virulence factor which cleaves human
CC fibronectin and degrades vitronectin. Also cleaves human IL1B precursor
CC to form biologically active IL1B. Can induce apoptosis in human
CC monocytes and epithelial cells in vitro, and reduces phagocytic
CC activity in monocytic cells. Thus, may play a role in bacterial
CC colonization, invasion, and inhibition of wound healing.
CC {ECO:0000269|PubMed:9864206}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Preferential cleavage with hydrophobic residues at P2, P1 and
CC P1'.; EC=3.4.22.10;
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:19712682}.
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- SIMILARITY: Belongs to the peptidase C10 family. {ECO:0000305}.
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DR EMBL; M86905; AAA26978.1; -; Genomic_DNA.
DR EMBL; L26126; AAA26992.1; -; Genomic_DNA.
DR EMBL; L26127; AAA26993.1; -; Genomic_DNA.
DR EMBL; L26128; AAA26994.1; -; Genomic_DNA.
DR EMBL; L26129; AAA26995.1; -; Genomic_DNA.
DR EMBL; L26130; AAA26996.1; -; Genomic_DNA.
DR EMBL; L26131; AAA26997.1; -; Genomic_DNA.
DR EMBL; L26132; AAA26998.1; -; Genomic_DNA.
DR EMBL; L26133; AAA26999.1; -; Genomic_DNA.
DR EMBL; L26135; AAA27001.1; -; Genomic_DNA.
DR EMBL; L26136; AAA27002.1; -; Genomic_DNA.
DR EMBL; L26137; AAA27003.1; -; Genomic_DNA.
DR EMBL; L26138; AAA27004.1; -; Genomic_DNA.
DR EMBL; L26139; AAA27005.1; -; Genomic_DNA.
DR EMBL; L26140; AAA27006.1; -; Genomic_DNA.
DR EMBL; L26141; AAA27007.1; -; Genomic_DNA.
DR EMBL; L26142; AAA27008.1; -; Genomic_DNA.
DR EMBL; L26143; AAA27009.1; -; Genomic_DNA.
DR EMBL; L26144; AAA27010.1; -; Genomic_DNA.
DR EMBL; L26145; AAA27011.1; -; Genomic_DNA.
DR EMBL; L26147; AAA27013.1; -; Genomic_DNA.
DR EMBL; L26148; AAA27014.1; -; Genomic_DNA.
DR EMBL; L26149; AAA27015.1; -; Genomic_DNA.
DR EMBL; L26150; AAA27016.1; -; Genomic_DNA.
DR EMBL; L26151; AAA26980.1; -; Genomic_DNA.
DR EMBL; L26152; AAA26981.1; -; Genomic_DNA.
DR EMBL; L26153; AAA26982.1; -; Genomic_DNA.
DR EMBL; L26154; AAA26983.1; -; Genomic_DNA.
DR EMBL; L26155; AAA26984.1; -; Genomic_DNA.
DR EMBL; L26156; AAA26985.1; -; Genomic_DNA.
DR EMBL; L26157; AAA26986.1; -; Genomic_DNA.
DR EMBL; L26159; AAA26988.1; -; Genomic_DNA.
DR EMBL; L26160; AAA26989.1; -; Genomic_DNA.
DR EMBL; L26161; AAA26990.1; -; Genomic_DNA.
DR EMBL; L26162; AAA26991.1; -; Genomic_DNA.
DR EMBL; AB030578; BAB16027.1; -; Genomic_DNA.
DR PIR; A37768; A37768.
DR RefSeq; WP_002982421.1; NZ_UHHE01000001.1.
DR RefSeq; WP_002991253.1; NZ_WXZH01000036.1.
DR RefSeq; WP_009881074.1; NZ_WVHC01000003.1.
DR RefSeq; WP_011285235.1; NZ_WUCG01000003.1.
DR RefSeq; WP_014407896.1; NZ_WXZK01000022.1.
DR RefSeq; WP_021733538.1; NZ_QFXT01000046.1.
DR RefSeq; WP_023611203.1; NZ_WVFH01000004.1.
DR RefSeq; WP_031488619.1; NZ_WVFK01000003.1.
DR RefSeq; WP_038433740.1; NZ_LS483353.1.
DR RefSeq; WP_076639504.1; NZ_WXZI01000010.1.
DR PDB; 1DKI; X-ray; 1.60 A; A/B/C/D=28-398.
DR PDB; 1PVJ; X-ray; 3.00 A; A/B/C/D=31-398.
DR PDB; 2UZJ; X-ray; 1.55 A; A/B=146-398.
DR PDB; 6UKD; X-ray; 1.59 A; A=28-398.
DR PDB; 6UQD; X-ray; 2.02 A; A/B=28-398.
DR PDBsum; 1DKI; -.
DR PDBsum; 1PVJ; -.
DR PDBsum; 2UZJ; -.
DR PDBsum; 6UKD; -.
DR PDBsum; 6UQD; -.
DR AlphaFoldDB; P0C0J0; -.
DR BMRB; P0C0J0; -.
DR SMR; P0C0J0; -.
DR BindingDB; P0C0J0; -.
DR ChEMBL; CHEMBL2034806; -.
DR DrugBank; DB02766; N-[(2R)-4-diazonio-3-oxoniumylidene-1-phenylbutan-2-yl]-1-phenylmethoxymethanimidate.
DR eggNOG; ENOG5031HIX; Bacteria.
DR OMA; WESQIDK; -.
DR BRENDA; 3.4.22.10; 5935.
DR SABIO-RK; P0C0J0; -.
DR EvolutionaryTrace; P0C0J0; -.
DR PHI-base; PHI:5437; -.
DR PHI-base; PHI:7040; -.
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:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR Gene3D; 3.90.70.50; -; 1.
DR InterPro; IPR038765; Papain-like_cys_pep_sf.
DR InterPro; IPR000200; Peptidase_C10.
DR InterPro; IPR025896; Spi_Prtas-inh.
DR InterPro; IPR044934; Streptopain_sf.
DR Pfam; PF13734; Inhibitor_I69; 1.
DR Pfam; PF01640; Peptidase_C10; 1.
DR PRINTS; PR00797; STREPTOPAIN.
DR SUPFAM; SSF54001; SSF54001; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Direct protein sequencing; Hydrolase; Methylation; Protease;
KW Secreted; Signal; Thiol protease; Toxin; Virulence; Zymogen.
FT SIGNAL 1..27
FT /evidence="ECO:0000269|PubMed:2198264"
FT PROPEP 28..145
FT /evidence="ECO:0000269|PubMed:2198264"
FT /id="PRO_0000028503"
FT CHAIN 146..398
FT /note="Streptopain"
FT /id="PRO_0000028504"
FT ACT_SITE 192
FT /note="Nucleophile"
FT /evidence="ECO:0000269|PubMed:19712682"
FT ACT_SITE 340
FT /note="Proton acceptor"
FT /evidence="ECO:0000269|PubMed:19712682"
FT MOD_RES 192
FT /note="Cysteine methyl disulfide; in zymogen form"
FT /evidence="ECO:0000269|PubMed:6381494"
FT VARIANT 17
FT /note="G -> S (in strain: MGAS 1896)"
FT VARIANT 80
FT /note="V -> I (in strain: MGAS 168)"
FT VARIANT 111
FT /note="A -> V (in strain: MGAS 165, 168, 429, 659, 660,
FT 796, 800, 1719, 1838, 1882, 2017 and 2018)"
FT VARIANT 137
FT /note="T -> I (in strain: MGAS 650)"
FT VARIANT 154
FT /note="D -> N (in strain: MGAS 684)"
FT VARIANT 211
FT /note="L -> V (in strain: MGAS 366, 427, 758, 1294, 1911,
FT 1914A and 1991)"
FT VARIANT 305
FT /note="I -> V (in strain: MGAS 1901 and Sv)"
FT VARIANT 308
FT /note="S -> G (in strain: MGAS 429, 659, 807, 1226, 1719,
FT 1832, 1842, 1871, 1872, 2017 and 2018)"
FT VARIANT 317
FT /note="A -> S (in strain: MGAS 165, 168, 289, 302, 1233 and
FT 1898)"
FT VARIANT 384
FT /note="G -> D (in strain: MGAS 1871)"
FT VARIANT 394
FT /note="V -> I (in strain: MGAS 366 and 1294)"
FT CONFLICT 84..85
FT /note="ST -> AS (in Ref. 4; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 169
FT /note="L -> I (in Ref. 4; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 187..191
FT /note="HAATG -> AATGH (in Ref. 4; AA sequence and 5; AA
FT sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 208
FT /note="N -> D (in Ref. 4; AA sequence and 5; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 213
FT /note="D -> N (in Ref. 4; AA sequence and 5; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 222..223
FT /note="NP -> PD (in Ref. 4; AA sequence and 5; AA
FT sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 226
FT /note="N -> D (in Ref. 4; AA sequence and 5; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 241
FT /note="N -> D (in Ref. 4; AA sequence and 5; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 253..257
FT /note="ESNVQ -> QSQNV (in Ref. 4; AA sequence and 5; AA
FT sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 306
FT /note="N -> D (in Ref. 4; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 332
FT /note="Q -> E (in Ref. 4; AA sequence and 5; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 346..348
FT /note="GAD -> DGA (in Ref. 4; AA sequence and 5; AA
FT sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 356
FT /note="N -> D (in Ref. 4; AA sequence and 5; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 390
FT /note="Q -> E (in Ref. 4; AA sequence and 5; AA sequence)"
FT /evidence="ECO:0000305"
FT HELIX 35..38
FT /evidence="ECO:0007829|PDB:1DKI"
FT HELIX 40..47
FT /evidence="ECO:0007829|PDB:1DKI"
FT STRAND 64..66
FT /evidence="ECO:0007829|PDB:1PVJ"
FT TURN 71..73
FT /evidence="ECO:0007829|PDB:1PVJ"
FT STRAND 75..82
FT /evidence="ECO:0007829|PDB:1DKI"
FT STRAND 84..86
FT /evidence="ECO:0007829|PDB:1DKI"
FT STRAND 88..93
FT /evidence="ECO:0007829|PDB:1DKI"
FT STRAND 99..107
FT /evidence="ECO:0007829|PDB:1DKI"
FT HELIX 115..130
FT /evidence="ECO:0007829|PDB:1DKI"
FT HELIX 131..133
FT /evidence="ECO:0007829|PDB:1DKI"
FT HELIX 152..155
FT /evidence="ECO:0007829|PDB:2UZJ"
FT TURN 164..169
FT /evidence="ECO:0007829|PDB:2UZJ"
FT HELIX 192..204
FT /evidence="ECO:0007829|PDB:2UZJ"
FT STRAND 214..217
FT /evidence="ECO:0007829|PDB:2UZJ"
FT STRAND 230..233
FT /evidence="ECO:0007829|PDB:2UZJ"
FT HELIX 235..237
FT /evidence="ECO:0007829|PDB:2UZJ"
FT TURN 242..244
FT /evidence="ECO:0007829|PDB:2UZJ"
FT HELIX 255..271
FT /evidence="ECO:0007829|PDB:2UZJ"
FT STRAND 277..279
FT /evidence="ECO:0007829|PDB:2UZJ"
FT HELIX 285..294
FT /evidence="ECO:0007829|PDB:2UZJ"
FT STRAND 303..306
FT /evidence="ECO:0007829|PDB:2UZJ"
FT HELIX 307..309
FT /evidence="ECO:0007829|PDB:2UZJ"
FT HELIX 312..324
FT /evidence="ECO:0007829|PDB:2UZJ"
FT STRAND 329..335
FT /evidence="ECO:0007829|PDB:2UZJ"
FT STRAND 338..351
FT /evidence="ECO:0007829|PDB:2UZJ"
FT STRAND 353..356
FT /evidence="ECO:0007829|PDB:2UZJ"
FT TURN 360..363
FT /evidence="ECO:0007829|PDB:2UZJ"
FT STRAND 365..368
FT /evidence="ECO:0007829|PDB:2UZJ"
FT HELIX 375..377
FT /evidence="ECO:0007829|PDB:2UZJ"
FT STRAND 379..381
FT /evidence="ECO:0007829|PDB:6UKD"
FT STRAND 388..394
FT /evidence="ECO:0007829|PDB:2UZJ"
SQ SEQUENCE 398 AA; 43174 MW; 16FF180D720AEE0F CRC64;
MNKKKLGIRL LSLLALGGFV LANPVFADQN FARNEKEAKD SAITFIQKSA AIKAGARSAE
DIKLDKVNLG GELSGSNMYV YNISTGGFVI VSGDKRSPEI LGYSTSGSFD ANGKENIASF
MESYVEQIKE NKKLDTTYAG TAEIKQPVVK SLLDSKGIHY NQGNPYNLLT PVIEKVKPGE
QSFVGQHAAT GCVATATAQI MKYHNYPNKG LKDYTYTLSS NNPYFNHPKN LFAAISTRQY
NWNNILPTYS GRESNVQKMA ISELMADVGI SVDMDYGPSS GSAGSSRVQR ALKENFGYNQ
SVHQINRSDF SKQDWEAQID KELSQNQPVY YQGVGKVGGH AFVIDGADGR NFYHVNWGWG
GVSDGFFRLD ALNPSALGTG GGAGGFNGYQ SAVVGIKP
