TCDB_CLODI
ID TCDB_CLODI Reviewed; 2366 AA.
AC P18177; M4NW36;
DT 01-NOV-1990, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 136.
DE RecName: Full=Toxin B {ECO:0000303|PubMed:2374729, ECO:0000303|PubMed:3384474};
DE EC=3.4.22.- {ECO:0000269|PubMed:17334356, ECO:0000269|PubMed:27571750};
DE Contains:
DE RecName: Full=Glucosyltransferase TcdB {ECO:0000305};
DE EC=2.4.1.- {ECO:0000269|PubMed:16157585, ECO:0000269|PubMed:17901056, ECO:0000269|PubMed:24905543, ECO:0000269|PubMed:24919149, ECO:0000269|PubMed:7777059};
GN Name=tcdB {ECO:0000303|PubMed:24958798};
GN Synonyms=toxB {ECO:0000303|PubMed:2374729, ECO:0000303|PubMed:3384474};
OS Clostridioides difficile (Peptoclostridium difficile).
OC Bacteria; Firmicutes; Clostridia; Eubacteriales; Peptostreptococcaceae;
OC Clostridioides.
OX NCBI_TaxID=1496;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=ATCC 4325 / VPI 10463;
RX PubMed=2374729; DOI=10.1093/nar/18.13.4004;
RA Barroso L.A., Wang S.Z., Phelps C.J., Johnson J.L., Wilkins T.D.;
RT "Nucleotide sequence of Clostridium difficile toxin B gene.";
RL Nucleic Acids Res. 18:4004-4004(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=ATCC 4325 / VPI 10463 {ECO:0000312|EMBL:AGG91608.1},
RC ZR20 {ECO:0000312|EMBL:AGG91601.1}, ZR30 {ECO:0000312|EMBL:AGG91640.1},
RC ZR4 {ECO:0000312|EMBL:AGG91584.1}, and ZR74 {ECO:0000312|EMBL:AGG91605.1};
RX PubMed=24958798; DOI=10.1128/jcm.03487-13;
RA Du P., Cao B., Wang J., Li W., Jia H., Zhang W., Lu J., Li Z., Yu H.,
RA Chen C., Cheng Y.;
RT "Sequence variation in tcdA and tcdB of Clostridium difficile: ST37 with
RT truncated tcdA is a potential epidemic strain in China.";
RL J. Clin. Microbiol. 52:3264-3270(2014).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=ATCC 4325 / VPI 10463;
RA von Eichel-Streiber C.;
RL Submitted (JAN-1997) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP PROTEIN SEQUENCE OF 2-18.
RX PubMed=3384474; DOI=10.1128/iai.56.7.1708-1714.1988;
RA Meador J. III, Tweten R.K.;
RT "Purification and characterization of toxin B from Clostridium difficile.";
RL Infect. Immun. 56:1708-1714(1988).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1271-2366.
RC STRAIN=ATCC 4325 / VPI 10463;
RX PubMed=1603068; DOI=10.1007/bf00587587;
RA von Eichel-Streiber C., Laufenberg-Feldmann R., Sartingen S., Schulze J.,
RA Sauerborn M.;
RT "Comparative sequence analysis of the Clostridium difficile toxins A and
RT B.";
RL Mol. Gen. Genet. 233:260-268(1992).
RN [6]
RP PROTEIN SEQUENCE OF 2-11 AND 544-558, PROTEOLYTIC CLEAVAGE, AND SUBCELLULAR
RP LOCATION (GLUCOSYLTRANSFERASE TCDB).
RC STRAIN=ATCC 4325 / VPI 10463;
RX PubMed=15632438; DOI=10.1099/mic.0.27474-0;
RA Rupnik M., Pabst S., Rupnik M., von Eichel-Streiber C., Urlaub H.,
RA Soeling H.D.;
RT "Characterization of the cleavage site and function of resulting cleavage
RT fragments after limited proteolysis of Clostridium difficile toxin B (TcdB)
RT by host cells.";
RL Microbiology 151:199-208(2005).
RN [7]
RP FUNCTION (GLUCOSYLTRANSFERASE TCDB).
RC STRAIN=ATCC 4325 / VPI 10463;
RX PubMed=8144660; DOI=10.1016/s0021-9258(17)34116-9;
RA Just I., Fritz G., Aktories K., Giry M., Popoff M.R., Boquet P.,
RA Hegenbarth S., von Eichel-Streiber C.;
RT "Clostridium difficile toxin B acts on the GTP-binding protein Rho.";
RL J. Biol. Chem. 269:10706-10712(1994).
RN [8]
RP FUNCTION (GLUCOSYLTRANSFERASE TCDB), AND CATALYTIC ACTIVITY
RP (GLUCOSYLTRANSFERASE TCDB).
RC STRAIN=ATCC 4325 / VPI 10463;
RX PubMed=7777059; DOI=10.1038/375500a0;
RA Just I., Selzer J., Wilm M., von Eichel-Streiber C., Mann M., Aktories K.;
RT "Glucosylation of Rho proteins by Clostridium difficile toxin B.";
RL Nature 375:500-503(1995).
RN [9]
RP SUBCELLULAR LOCATION (TOXIN B).
RC STRAIN=ATCC 4325 / VPI 10463;
RX PubMed=10768933; DOI=10.1128/iai.68.5.2470-2474.2000;
RA Qa'Dan M., Spyres L.M., Ballard J.D.;
RT "pH-induced conformational changes in Clostridium difficile toxin B.";
RL Infect. Immun. 68:2470-2474(2000).
RN [10]
RP FUNCTION (TOXIN B), AND SUBCELLULAR LOCATION (TOXIN B).
RC STRAIN=ATCC 4325 / VPI 10463;
RX PubMed=11152463; DOI=10.1074/jbc.m009445200;
RA Barth H., Pfeifer G., Hofmann F., Maier E., Benz R., Aktories K.;
RT "Low pH-induced formation of ion channels by clostridium difficile toxin B
RT in target cells.";
RL J. Biol. Chem. 276:10670-10676(2001).
RN [11]
RP FUNCTION (TOXIN B), SUBCELLULAR LOCATION (GLUCOSYLTRANSFERASE TCDB AND
RP TOXIN B), BIOPHYSICOCHEMICAL PROPERTIES, AND PROTEOLYTIC CLEAVAGE.
RC STRAIN=ATCC 4325 / VPI 10463;
RX PubMed=12941936; DOI=10.1074/jbc.m307540200;
RA Pfeifer G., Schirmer J., Leemhuis J., Busch C., Meyer D.K., Aktories K.,
RA Barth H.;
RT "Cellular uptake of Clostridium difficile toxin B. Translocation of the N-
RT terminal catalytic domain into the cytosol of eukaryotic cells.";
RL J. Biol. Chem. 278:44535-44541(2003).
RN [12]
RP FUNCTION (GLUCOSYLTRANSFERASE TCDB), CATALYTIC ACTIVITY
RP (GLUCOSYLTRANSFERASE TCDB), BIOPHYSICOCHEMICAL PROPERTIES
RP (GLUCOSYLTRANSFERASE TCDB), AND MUTAGENESIS OF 383-ILE--GLN-385.
RC STRAIN=ATCC 4325 / VPI 10463;
RX PubMed=16157585; DOI=10.1074/jbc.m506836200;
RA Jank T., Reinert D.J., Giesemann T., Schulz G.E., Aktories K.;
RT "Change of the donor substrate specificity of Clostridium difficile toxin B
RT by site-directed mutagenesis.";
RL J. Biol. Chem. 280:37833-37838(2005).
RN [13]
RP FUNCTION (GLUCOSYLTRANSFERASE TCDB), CATALYTIC ACTIVITY
RP (GLUCOSYLTRANSFERASE TCDB), BIOPHYSICOCHEMICAL PROPERTIES
RP (GLUCOSYLTRANSFERASE TCDB), AND MUTAGENESIS OF ASP-270; ARG-273; TYR-284;
RP ASN-384; ARG-455; ASP-461; LYS-463; GLU-472 AND TRP-520.
RC STRAIN=ATCC 4325 / VPI 10463;
RX PubMed=17901056; DOI=10.1074/jbc.m703138200;
RA Jank T., Giesemann T., Aktories K.;
RT "Clostridium difficile glucosyltransferase toxin B-essential amino acids
RT for substrate binding.";
RL J. Biol. Chem. 282:35222-35231(2007).
RN [14]
RP FUNCTION (TOXIN B), ACTIVITY REGULATION (TOXIN B), SUBCELLULAR LOCATION
RP (TOXIN B), AND PROTEOLYTIC CLEAVAGE (TOXIN B).
RC STRAIN=ATCC 4325 / VPI 10463;
RX PubMed=17334356; DOI=10.1038/nature05622;
RA Reineke J., Tenzer S., Rupnik M., Koschinski A., Hasselmayer O.,
RA Schrattenholz A., Schild H., von Eichel-Streiber C.;
RT "Autocatalytic cleavage of Clostridium difficile toxin B.";
RL Nature 446:415-419(2007).
RN [15]
RP FUNCTION.
RC STRAIN=630 / Type X;
RX PubMed=19252482; DOI=10.1038/nature07822;
RA Lyras D., O'Connor J.R., Howarth P.M., Sambol S.P., Carter G.P.,
RA Phumoonna T., Poon R., Adams V., Vedantam G., Johnson S., Gerding D.N.,
RA Rood J.I.;
RT "Toxin B is essential for virulence of Clostridium difficile.";
RL Nature 458:1176-1179(2009).
RN [16]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RC STRAIN=630 / Type X;
RX PubMed=20844489; DOI=10.1038/nature09397;
RA Kuehne S.A., Cartman S.T., Heap J.T., Kelly M.L., Cockayne A., Minton N.P.;
RT "The role of toxin A and toxin B in Clostridium difficile infection.";
RL Nature 467:711-713(2010).
RN [17]
RP SUBCELLULAR LOCATION (TOXIN B).
RX PubMed=20498856; DOI=10.1371/journal.pone.0010673;
RA Papatheodorou P., Zamboglou C., Genisyuerek S., Guttenberg G., Aktories K.;
RT "Clostridial glucosylating toxins enter cells via clathrin-mediated
RT endocytosis.";
RL PLoS ONE 5:e10673-e10673(2010).
RN [18]
RP SUBCELLULAR LOCATION (TOXIN B).
RC STRAIN=630 / Type X;
RX PubMed=22685398; DOI=10.1371/journal.ppat.1002727;
RA Govind R., Dupuy B.;
RT "Secretion of Clostridium difficile toxins A and B requires the holin-like
RT protein TcdE.";
RL PLoS Pathog. 8:e1002727-e1002727(2012).
RN [19]
RP FUNCTION (GLUCOSYLTRANSFERASE TCDB), AND CATALYTIC ACTIVITY
RP (GLUCOSYLTRANSFERASE TCDB).
RC STRAIN=ATCC 4325 / VPI 10463;
RX PubMed=24905543; DOI=10.1111/cmi.12321;
RA Genth H., Pauillac S., Schelle I., Bouvet P., Bouchier C.,
RA Varela-Chavez C., Just I., Popoff M.R.;
RT "Haemorrhagic toxin and lethal toxin from Clostridium sordellii strain
RT vpi9048: molecular characterization and comparative analysis of substrate
RT specificity of the large clostridial glucosylating toxins.";
RL Cell. Microbiol. 16:1706-1721(2014).
RN [20]
RP FUNCTION, CATALYTIC ACTIVITY (GLUCOSYLTRANSFERASE TCDB), AND MUTAGENESIS OF
RP TRP-102 AND ASP-288.
RX PubMed=24919149; DOI=10.1038/nature13449;
RA Xu H., Yang J., Gao W., Li L., Li P., Zhang L., Gong Y.N., Peng X.,
RA Xi J.J., Chen S., Wang F., Shao F.;
RT "Innate immune sensing of bacterial modifications of Rho GTPases by the
RT Pyrin inflammasome.";
RL Nature 513:237-241(2014).
RN [21]
RP FUNCTION (TOXIN B), AND MUTAGENESIS OF ASP-270; ILE-1035; ASP-1037;
RP GLY-1038; LEU-1041; PRO-1095; GLY-1098; ILE-1099; LEU-1106 AND VAL-1107.
RC STRAIN=ATCC 4325 / VPI 10463;
RX PubMed=24567384; DOI=10.1073/pnas.1400680111;
RA Zhang Z., Park M., Tam J., Auger A., Beilhartz G.L., Lacy D.B.,
RA Melnyk R.A.;
RT "Translocation domain mutations affecting cellular toxicity identify the
RT Clostridium difficile toxin B pore.";
RL Proc. Natl. Acad. Sci. U.S.A. 111:3721-3726(2014).
RN [22]
RP INTERACTION WITH HOST CSPG4.
RX PubMed=25547119; DOI=10.1038/cr.2014.169;
RA Yuan P., Zhang H., Cai C., Zhu S., Zhou Y., Yang X., He R., Li C., Guo S.,
RA Li S., Huang T., Perez-Cordon G., Feng H., Wei W.;
RT "Chondroitin sulfate proteoglycan 4 functions as the cellular receptor for
RT Clostridium difficile toxin B.";
RL Cell Res. 25:157-168(2015).
RN [23]
RP DOMAIN.
RX PubMed=25882477; DOI=10.1111/cmi.12449;
RA Varela Chavez C., Hoos S., Haustant G.M., Chenal A., England P.,
RA Blondel A., Pauillac S., Lacy D.B., Popoff M.R.;
RT "The catalytic domains of Clostridium sordellii lethal toxin and related
RT large clostridial glucosylating toxins specifically recognize the
RT negatively charged phospholipids phosphatidylserine and phosphatidic
RT acid.";
RL Cell. Microbiol. 17:1477-1493(2015).
RN [24]
RP INTERACTION WITH HOST NECTIN3.
RX PubMed=26038560; DOI=10.1073/pnas.1500791112;
RA LaFrance M.E., Farrow M.A., Chandrasekaran R., Sheng J., Rubin D.H.,
RA Lacy D.B.;
RT "Identification of an epithelial cell receptor responsible for Clostridium
RT difficile TcdB-induced cytotoxicity.";
RL Proc. Natl. Acad. Sci. U.S.A. 112:7073-7078(2015).
RN [25]
RP FUNCTION (TOXIN B), AND INTERACTION WITH HOST CSPG4; FZD1; FZD2 AND FZD7.
RX PubMed=27680706; DOI=10.1038/nature19799;
RA Tao L., Zhang J., Meraner P., Tovaglieri A., Wu X., Gerhard R., Zhang X.,
RA Stallcup W.B., Miao J., He X., Hurdle J.G., Breault D.T., Brass A.L.,
RA Dong M.;
RT "Frizzled proteins are colonic epithelial receptors for C. difficile toxin
RT B.";
RL Nature 538:350-355(2016).
RN [26]
RP FUNCTION (TOXIN B), COFACTOR, ACTIVE SITES, AND MUTAGENESIS OF HIS-653;
RP CYS-698 AND HIS-757.
RC STRAIN=ATCC 4325 / VPI 10463;
RX PubMed=27571750; DOI=10.1038/nmicrobiol.2015.2;
RA Chumbler N.M., Rutherford S.A., Zhang Z., Farrow M.A., Lisher J.P.,
RA Farquhar E., Giedroc D.P., Spiller B.W., Melnyk R.A., Lacy D.B.;
RT "Crystal structure of Clostridium difficile toxin A.";
RL Nat. Microbiol. 1:15002-15002(2016).
RN [27]
RP COFACTOR (GLUCOSYLTRANSFERASE TCDB).
RC STRAIN=ATCC 4325 / VPI 10463;
RX PubMed=27089365; DOI=10.3390/toxins8040109;
RA Genth H., Schelle I., Just I.;
RT "Metal ion activation of clostridium sordellii lethal toxin and Clostridium
RT difficile toxin B.";
RL Toxins 8:109-109(2016).
RN [28]
RP REVIEW.
RX PubMed=29146177; DOI=10.1016/j.toxicon.2017.11.003;
RA Popoff M.R.;
RT "Clostridium difficile and Clostridium sordellii toxins, proinflammatory
RT versus anti-inflammatory response.";
RL Toxicon 149:54-64(2018).
RN [29] {ECO:0007744|PDB:2BVL, ECO:0007744|PDB:2BVM}
RP X-RAY CRYSTALLOGRAPHY (2.20 ANGSTROMS) OF 1-543 IN COMPLEX WITH
RP UDP-ALPHA-D-GLUCOSE AND MANGANESE, AND COFACTOR.
RC STRAIN=ATCC 4325 / VPI 10463;
RX PubMed=16054646; DOI=10.1016/j.jmb.2005.06.071;
RA Reinert D.J., Jank T., Aktories K., Schulz G.E.;
RT "Structural basis for the function of Clostridium difficile toxin B.";
RL J. Mol. Biol. 351:973-981(2005).
RN [30] {ECO:0007744|PDB:4NP4}
RP X-RAY CRYSTALLOGRAPHY (2.89 ANGSTROMS) OF 1834-2099 IN COMPLEX WITH
RP BEZLOTOXUMAB, AND ACTIVITY REGULATION (TOXIN B).
RC STRAIN=ATCC 4325 / VPI 10463;
RX PubMed=24821719; DOI=10.1074/jbc.m114.560748;
RA Orth P., Xiao L., Hernandez L.D., Reichert P., Sheth P.R., Beaumont M.,
RA Yang X., Murgolo N., Ermakov G., DiNunzio E., Racine F., Karczewski J.,
RA Secore S., Ingram R.N., Mayhood T., Strickland C., Therien A.G.;
RT "Mechanism of action and epitopes of Clostridium difficile toxin B-
RT neutralizing antibody bezlotoxumab revealed by X-ray crystallography.";
RL J. Biol. Chem. 289:18008-18021(2014).
RN [31] {ECO:0007744|PDB:4NC2}
RP X-RAY CRYSTALLOGRAPHY (2.50 ANGSTROMS) OF 2248-2366.
RC STRAIN=ATCC 4325 / VPI 10463;
RX PubMed=24311789; DOI=10.1074/jbc.m113.505917;
RA Murase T., Eugenio L., Schorr M., Hussack G., Tanha J., Kitova E.N.,
RA Klassen J.S., Ng K.K.;
RT "Structural basis for antibody recognition in the receptor-binding domains
RT of toxins A and B from Clostridium difficile.";
RL J. Biol. Chem. 289:2331-2343(2014).
RN [32] {ECO:0007744|PDB:5UQM, ECO:0007744|PDB:5UQN, ECO:0007744|PDB:5UQT}
RP X-RAY CRYSTALLOGRAPHY (2.03 ANGSTROMS) OF 1-543 IN COMPLEX WITH
RP UDP-ALPHA-D-GLUCOSE AND MANGANESE.
RC STRAIN=ATCC 4325 / VPI 10463;
RX PubMed=28433497; DOI=10.1016/j.jsb.2017.04.006;
RA Alvin J.W., Lacy D.B.;
RT "Clostridium difficile toxin glucosyltransferase domains in complex with a
RT non-hydrolyzable UDP-glucose analogue.";
RL J. Struct. Biol. 198:203-209(2017).
RN [33] {ECO:0007744|PDB:6AR6}
RP STRUCTURE BY ELECTRON MICROSCOPY (9.00 ANGSTROMS) OF 4-2099, AND
RP INTERACTION WITH HOST FZD2 AND CSPG4.
RC STRAIN=ATCC 4325 / VPI 10463;
RX PubMed=31233493; DOI=10.1371/journal.pbio.3000311;
RA Simeon R., Jiang M., Chamoun-Emanuelli A.M., Yu H., Zhang Y., Meng R.,
RA Peng Z., Jakana J., Zhang J., Feng H., Chen Z.;
RT "Selection and characterization of ultrahigh potency designed ankyrin
RT repeat protein inhibitors of C. difficile toxin B.";
RL PLoS Biol. 17:e3000311-e3000311(2019).
RN [34] {ECO:0007744|PDB:6C0B}
RP X-RAY CRYSTALLOGRAPHY (2.50 ANGSTROMS) OF 1285-1804 IN COMPLEX WITH HOST
RP FZD2, FUNCTION, INTERACTION WITH HOST FZD2, AND MUTAGENESIS OF
RP 1433-LEU--MET-1437; MET-1437; LEU-1493; ASP-1501; 1509-TYR--ASN-1511;
RP TYR-1509; PHE-1597 AND GLN-1599.
RX PubMed=29748286; DOI=10.1126/science.aar1999;
RA Chen P., Tao L., Wang T., Zhang J., He A., Lam K.H., Liu Z., He X.,
RA Perry K., Dong M., Jin R.;
RT "Structural basis for recognition of frizzled proteins by Clostridium
RT difficile toxin B.";
RL Science 360:664-669(2018).
RN [35] {ECO:0007744|PDB:6OQ5, ECO:0007744|PDB:6OQ6, ECO:0007744|PDB:6OQ7, ECO:0007744|PDB:6OQ8}
RP X-RAY CRYSTALLOGRAPHY (2.20 ANGSTROMS) IN COMPLEX WITH UDP-ALPHA-D-GLUCOSE;
RP MAGNESIUM AND ZINC, COFACTOR, AND DOMAIN.
RC STRAIN=M68;
RX PubMed=31308519; DOI=10.1038/s41594-019-0268-0;
RA Chen P., Lam K.H., Liu Z., Mindlin F.A., Chen B., Gutierrez C.B., Huang L.,
RA Zhang Y., Hamza T., Feng H., Matsui T., Bowen M.E., Perry K., Jin R.;
RT "Structure of the full-length Clostridium difficile toxin B.";
RL Nat. Struct. Mol. Biol. 26:712-719(2019).
CC -!- FUNCTION: [Toxin B]: Precursor of a cytotoxin that targets and disrupts
CC the colonic epithelium, inducing the host inflammatory and innate
CC immune responses and resulting in diarrhea and pseudomembranous colitis
CC (PubMed:20844489, PubMed:24919149). TcdB constitutes the main toxin
CC that mediates the pathology of C.difficile infection, an opportunistic
CC pathogen that colonizes the colon when the normal gut microbiome is
CC disrupted (PubMed:19252482, PubMed:20844489). Compared to TcdA, TcdB is
CC more virulent and more important for inducing the host inflammatory and
CC innate immune responses (PubMed:19252482, PubMed:24919149). This form
CC constitutes the precursor of the toxin: it enters into host cells and
CC mediates autoprocessing to release the active toxin
CC (Glucosyltransferase TcdB) into the host cytosol (PubMed:10768933,
CC PubMed:11152463, PubMed:12941936, PubMed:17334356, PubMed:20498856).
CC Targets colonic epithelia by binding to the frizzled receptors FZD1,
CC FZD2 and FZD7, and enters host cells via clathrin-mediated endocytosis
CC (PubMed:27680706). Frizzled receptors constitute the major host
CC receptors in the colonic epithelium, but other receptors, such as CSPG4
CC or NECTIN3/PVRL3, have been identified (PubMed:25547119,
CC PubMed:26038560, PubMed:27680706). Binding to carbohydrates and
CC sulfated glycosaminoglycans on host cell surface also contribute to
CC entry into cells (By similarity). Once entered into host cells,
CC acidification in the endosome promotes the membrane insertion of the
CC translocation region and formation of a pore, leading to translocation
CC of the GT44 and peptidase C80 domains across the endosomal membrane
CC (PubMed:11152463, PubMed:12941936, PubMed:24567384). This activates the
CC peptidase C80 domain and autocatalytic processing, releasing the N-
CC terminal part (Glucosyltransferase TcdB), which constitutes the active
CC part of the toxin, in the cytosol (PubMed:17334356, PubMed:27571750).
CC {ECO:0000250|UniProtKB:P16154, ECO:0000269|PubMed:10768933,
CC ECO:0000269|PubMed:11152463, ECO:0000269|PubMed:12941936,
CC ECO:0000269|PubMed:17334356, ECO:0000269|PubMed:19252482,
CC ECO:0000269|PubMed:20498856, ECO:0000269|PubMed:20844489,
CC ECO:0000269|PubMed:24567384, ECO:0000269|PubMed:24919149,
CC ECO:0000269|PubMed:25547119, ECO:0000269|PubMed:26038560,
CC ECO:0000269|PubMed:27571750, ECO:0000269|PubMed:27680706}.
CC -!- FUNCTION: [Glucosyltransferase TcdB]: Active form of the toxin, which
CC is released into the host cytosol following autoprocessing and
CC inactivates small GTPases (PubMed:8144660, PubMed:7777059,
CC PubMed:16157585, PubMed:17901056, PubMed:24905543, PubMed:24919149).
CC Acts by mediating monoglucosylation of small GTPases of the Rho family
CC (Rac1, RhoA, RhoB, RhoC, RhoG and Cdc42) in host cells at the conserved
CC threonine residue located in the switch I region ('Thr-37/35'), using
CC UDP-alpha-D-glucose as the sugar donor (PubMed:7777059,
CC PubMed:16157585, PubMed:17901056, PubMed:24905543, PubMed:24919149).
CC Monoglucosylation of host small GTPases completely prevents the
CC recognition of the downstream effector, blocking the GTPases in their
CC inactive form, leading to actin cytoskeleton disruption and cell death,
CC resulting in the loss of colonic epithelial barrier function
CC (PubMed:7777059, PubMed:24919149). {ECO:0000269|PubMed:16157585,
CC ECO:0000269|PubMed:17901056, ECO:0000269|PubMed:24905543,
CC ECO:0000269|PubMed:24919149, ECO:0000269|PubMed:7777059,
CC ECO:0000269|PubMed:8144660}.
CC -!- CATALYTIC ACTIVITY: [Glucosyltransferase TcdB]:
CC Reaction=L-threonyl-[protein] + UDP-alpha-D-glucose = 3-O-(alpha-D-
CC glucosyl)-L-threonyl-[protein] + H(+) + UDP; Xref=Rhea:RHEA:64684,
CC Rhea:RHEA-COMP:11060, Rhea:RHEA-COMP:16656, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30013, ChEBI:CHEBI:58223, ChEBI:CHEBI:58885,
CC ChEBI:CHEBI:156085; Evidence={ECO:0000269|PubMed:16157585,
CC ECO:0000269|PubMed:17901056, ECO:0000269|PubMed:24905543,
CC ECO:0000269|PubMed:24919149, ECO:0000269|PubMed:7777059};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:64685;
CC Evidence={ECO:0000269|PubMed:16157585, ECO:0000269|PubMed:17901056,
CC ECO:0000269|PubMed:24905543, ECO:0000269|PubMed:24919149,
CC ECO:0000269|PubMed:7777059};
CC -!- COFACTOR: [Toxin B]:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000269|PubMed:27571750, ECO:0000269|PubMed:31308519};
CC Note=Binds 1 Zn(2+) ion per subunit (PubMed:27571750, PubMed:31308519).
CC Zn(2+) is required for autocatalytic cleavage (PubMed:27571750).
CC {ECO:0000269|PubMed:27571750, ECO:0000269|PubMed:31308519};
CC -!- COFACTOR: [Glucosyltransferase TcdB]:
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000269|PubMed:16054646, ECO:0000269|PubMed:27089365,
CC ECO:0000269|PubMed:28433497, ECO:0000305|PubMed:31308519};
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:27089365};
CC Note=Has higher activity with Mn(2+), but most likely uses Mg(2+) in
CC host cells (PubMed:16054646, PubMed:28433497). Mn(2+) or Mg(2+) are
CC required for glucosyltransferase activity (PubMed:27089365).
CC {ECO:0000269|PubMed:16054646, ECO:0000269|PubMed:27089365,
CC ECO:0000269|PubMed:28433497};
CC -!- ACTIVITY REGULATION: [Toxin B]: Protease activity is activated upon
CC binding to 1D-myo-inositol hexakisphosphate (InsP6), which induces
CC conformational reorganization (PubMed:17334356). Inhibited by
CC bezlotoxumab, also named Zinplava, a monoclonal antibody approved by
CC the Food and Drug Administration (FDA), which specifically targets TcdB
CC (PubMed:24821719). {ECO:0000269|PubMed:17334356,
CC ECO:0000269|PubMed:24821719}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES: [Glucosyltransferase TcdB]:
CC Kinetic parameters:
CC KM=6 uM for UDP-alpha-D-glucose {ECO:0000269|PubMed:16157585};
CC KM=4.3 uM for UDP-alpha-D-glucose {ECO:0000269|PubMed:17901056};
CC KM=960 uM for UDP-N-acetyl-alpha-D-glucosamine
CC {ECO:0000269|PubMed:16157585};
CC Note=kcat is 2120 h(-1) with UDP-alpha-D-glucose as substrate
CC (PubMed:16157585). kcat is 11 h(-1) with UDP-N-acetyl-alpha-D-
CC glucosamine as substrate (PubMed:16157585).
CC {ECO:0000269|PubMed:16157585};
CC -!- SUBUNIT: [Toxin B]: Interacts with host FZD1 (PubMed:27680706).
CC Interacts with host FZD2; interaction promotes toxin entry into host
CC cell and occupies the binding site for Wnt-adducted palmitoleate in
CC FZD2, leading to prevent Wnt-binding and downstream Wnt signaling
CC (PubMed:27680706, PubMed:31233493, PubMed:29748286). Interacts with
CC host FZD7 (PubMed:27680706). Interacts with host CSPG4
CC (PubMed:25547119, PubMed:31233493). Interacts with host NECTIN3/PVRL3
CC (PubMed:26038560). {ECO:0000269|PubMed:25547119,
CC ECO:0000269|PubMed:26038560, ECO:0000269|PubMed:27680706,
CC ECO:0000269|PubMed:29748286, ECO:0000269|PubMed:31233493}.
CC -!- SUBCELLULAR LOCATION: [Toxin B]: Secreted
CC {ECO:0000269|PubMed:22685398}. Host endosome membrane
CC {ECO:0000269|PubMed:11152463, ECO:0000305|PubMed:12941936}.
CC Note=Secreted from C.difficile cell into the extracellular environment
CC via help of holin-like protein TcdE/UtxA (PubMed:22685398). Binds to
CC the cell surface receptors via the receptor-binding region and enters
CC the cells via clathrin-mediated endocytosis (PubMed:20498856).
CC Acidification in the endosome triggers conformational changes that
CC promote the membrane insertion of the translocation region, allowing
CC formation of a pore, leading to translocation of the GT44 and peptidase
CC C80 domains across the endosomal membrane (PubMed:10768933,
CC PubMed:11152463, PubMed:12941936). 1D-myo-inositol hexakisphosphate-
CC binding (InsP6) activates the peptidase C80 domain and autoprocessing,
CC generating the Glucosyltransferase TcdB form, which is released in the
CC host cytosol (PubMed:17334356). {ECO:0000269|PubMed:10768933,
CC ECO:0000269|PubMed:11152463, ECO:0000269|PubMed:12941936,
CC ECO:0000269|PubMed:17334356, ECO:0000269|PubMed:20498856,
CC ECO:0000269|PubMed:22685398}.
CC -!- SUBCELLULAR LOCATION: [Glucosyltransferase TcdB]: Host cytoplasm, host
CC cytosol {ECO:0000269|PubMed:12941936, ECO:0000269|PubMed:15632438}.
CC Host cell membrane {ECO:0000250|UniProtKB:Q46342}; Peripheral membrane
CC protein {ECO:0000250|UniProtKB:Q46342}; Cytoplasmic side
CC {ECO:0000250|UniProtKB:Q46342}. Note=Binding to phospholipids, such as
CC phosphatidylserine and phosphatidic acid promotes localization to the
CC inner face of the cell membrane close to its membrane anchored
CC substrates (small GTPases). {ECO:0000250|UniProtKB:Q46342}.
CC -!- DOMAIN: [Toxin B]: Consists of 4 functional domains: (1) the N-terminal
CC GT44 domain (glucosyltransferase, also named GTD), which mediates
CC glucosylation of host small GTPases, (2) an autoprocessing region that
CC catalyzes autoprocessing to release the N-terminal GT44 domain in the
CC host cytosol, (3) the translocation region that forms a pore to promote
CC translocation of the GT44 and peptidase C80 domains across the
CC endosomal membrane and (4) the receptor-binding (CROPS) region that
CC mediates binding to host cells and contribute to entry into cells.
CC {ECO:0000269|PubMed:31308519, ECO:0000303|PubMed:29146177}.
CC -!- DOMAIN: [Toxin B]: The receptor-binding (CROPS) region is dynamic and
CC can have open and closed conformations depending of the pH: has an open
CC conformation at endosomal pH and a closed conformation at neutral pH.
CC {ECO:0000269|PubMed:31308519}.
CC -!- DOMAIN: [Toxin B]: The cell wall-binding repeats bind carbohydrates,
CC probably contributing to entry into cells.
CC {ECO:0000250|UniProtKB:P16154}.
CC -!- DOMAIN: [Glucosyltransferase TcdB]: The four-helical bundle region
CC mediates binding to phospholipids, such as phosphatidylserine and
CC phosphatidic acid (PubMed:25882477). This promotes localization to the
CC inner face of the cell membrane close to small GTPases (By similarity).
CC {ECO:0000250|UniProtKB:Q46342, ECO:0000269|PubMed:25882477}.
CC -!- PTM: [Toxin B]: Undergoes autocatalytic cleavage to release the N-
CC terminal part (Glucosyltransferase TcdB), which constitutes the active
CC part of the toxin, in the host cytosol (PubMed:12941936,
CC PubMed:17334356, PubMed:27571750). 1D-myo-inositol hexakisphosphate-
CC binding (InsP6) activates the peptidase C80 domain and promotes
CC autoprocessing (PubMed:17334356). {ECO:0000269|PubMed:12941936,
CC ECO:0000269|PubMed:17334356, ECO:0000269|PubMed:27571750}.
CC -!- DISRUPTION PHENOTYPE: Cells lacking tcdB display virulence and
CC cytotoxicity, because of the presence of TcdA (PubMed:20844489). Cells
CC lacking both tcdA and tcdB display a strongly reduced virulence
CC (PubMed:20844489). {ECO:0000269|PubMed:20844489}.
CC -!- SIMILARITY: Belongs to the clostridial glucosylating toxin (LCGT)
CC family. {ECO:0000305}.
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DR EMBL; X53138; CAA37298.1; -; Genomic_DNA.
DR EMBL; KC292194; AGG91640.1; -; Genomic_DNA.
DR EMBL; KC292155; AGG91601.1; -; Genomic_DNA.
DR EMBL; KC292159; AGG91605.1; -; Genomic_DNA.
DR EMBL; KC292162; AGG91608.1; -; Genomic_DNA.
DR EMBL; KC292138; AGG91584.1; -; Genomic_DNA.
DR EMBL; X92982; CAA63562.1; -; Genomic_DNA.
DR EMBL; X60984; CAA43299.1; -; Genomic_DNA.
DR PIR; A27636; A27636.
DR PIR; S10317; S10317.
DR RefSeq; WP_009902069.1; NZ_SRKJ01000018.1.
DR PDB; 2BVL; X-ray; 2.20 A; A=2-541.
DR PDB; 2BVM; X-ray; 2.55 A; A=2-542.
DR PDB; 4NC2; X-ray; 2.50 A; A=2248-2366.
DR PDB; 4NP4; X-ray; 2.89 A; A=1834-2099.
DR PDB; 5UQM; X-ray; 2.03 A; A=1-543.
DR PDB; 5UQN; X-ray; 2.06 A; A=1-543.
DR PDB; 5UQT; X-ray; 2.75 A; A/B=1-543.
DR PDB; 6AR6; EM; 9.00 A; A=4-2099.
DR PDB; 6C0B; X-ray; 2.50 A; A=1285-1804.
DR PDB; 6OQ5; X-ray; 3.87 A; A=1-2366.
DR PDB; 6OQ6; X-ray; 2.97 A; A=1071-1432.
DR PDB; 6OQ7; X-ray; 2.39 A; A=1-543.
DR PDB; 6OQ8; X-ray; 2.20 A; A/B=1-542.
DR PDB; 7LOU; X-ray; 1.82 A; A/B=2-543.
DR PDB; 7LOV; X-ray; 2.50 A; A/B=2-545.
DR PDB; 7ML7; EM; 3.17 A; A=1-1967.
DR PDB; 7N8X; EM; 3.40 A; A=374-1876.
DR PDB; 7N95; EM; 4.10 A; A=1-2366.
DR PDB; 7N97; EM; 5.10 A; A=2-2366.
DR PDB; 7N9Q; EM; 4.60 A; A=2-2366.
DR PDB; 7N9R; EM; 5.90 A; A=1-2366.
DR PDB; 7N9S; EM; 5.10 A; A=2-2366.
DR PDB; 7N9Y; EM; 4.80 A; A=2-2366.
DR PDB; 7S0Y; X-ray; 2.79 A; A=1-540.
DR PDBsum; 2BVL; -.
DR PDBsum; 2BVM; -.
DR PDBsum; 4NC2; -.
DR PDBsum; 4NP4; -.
DR PDBsum; 5UQM; -.
DR PDBsum; 5UQN; -.
DR PDBsum; 5UQT; -.
DR PDBsum; 6AR6; -.
DR PDBsum; 6C0B; -.
DR PDBsum; 6OQ5; -.
DR PDBsum; 6OQ6; -.
DR PDBsum; 6OQ7; -.
DR PDBsum; 6OQ8; -.
DR PDBsum; 7LOU; -.
DR PDBsum; 7LOV; -.
DR PDBsum; 7ML7; -.
DR PDBsum; 7N8X; -.
DR PDBsum; 7N95; -.
DR PDBsum; 7N97; -.
DR PDBsum; 7N9Q; -.
DR PDBsum; 7N9R; -.
DR PDBsum; 7N9S; -.
DR PDBsum; 7N9Y; -.
DR PDBsum; 7S0Y; -.
DR AlphaFoldDB; P18177; -.
DR SMR; P18177; -.
DR IntAct; P18177; 5.
DR MINT; P18177; -.
DR BindingDB; P18177; -.
DR ChEMBL; CHEMBL3580505; -.
DR DrugBank; DB13140; Bezlotoxumab.
DR DrugCentral; P18177; -.
DR CAZy; GT44; Glycosyltransferase Family 44.
DR MEROPS; C80.003; -.
DR TCDB; 1.C.57.1.1; the clostridial cytotoxin (cct) family.
DR ABCD; P18177; 5 sequenced antibodies.
DR BRENDA; 2.4.1.B62; 1473.
DR BRENDA; 3.1.4.B4; 1473.
DR EvolutionaryTrace; P18177; -.
DR PHI-base; PHI:2619; -.
DR PHI-base; PHI:4964; -.
DR PHI-base; PHI:5010; -.
DR PHI-base; PHI:6499; -.
DR PHI-base; PHI:7473; -.
DR PHI-base; PHI:9029; -.
DR GO; GO:0005576; C:extracellular region; IDA:UniProtKB.
DR GO; GO:0044164; C:host cell cytosol; IDA:UniProtKB.
DR GO; GO:0044174; C:host cell endosome; IDA:UniProtKB.
DR GO; GO:0044175; C:host cell endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0020002; C:host cell plasma membrane; IMP:AgBase.
DR GO; GO:0016020; C:membrane; IEA:UniProtKB-KW.
DR GO; GO:0008234; F:cysteine-type peptidase activity; IEA:UniProtKB-KW.
DR GO; GO:0046527; F:glucosyltransferase activity; IDA:UniProtKB.
DR GO; GO:0046789; F:host cell surface receptor binding; IPI:UniProtKB.
DR GO; GO:0000822; F:inositol hexakisphosphate binding; IDA:UniProtKB.
DR GO; GO:0008289; F:lipid binding; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0008233; F:peptidase activity; IDA:UniProtKB.
DR GO; GO:0090729; F:toxin activity; IDA:UniProtKB.
DR GO; GO:0035251; F:UDP-glucosyltransferase activity; IDA:UniProtKB.
DR GO; GO:0044083; P:modulation by symbiont of host Rho protein signal transduction; IDA:UniProtKB.
DR GO; GO:0034260; P:negative regulation of GTPase activity; IDA:UniProtKB.
DR GO; GO:0030178; P:negative regulation of Wnt signaling pathway; IDA:UniProtKB.
DR GO; GO:0030836; P:positive regulation of actin filament depolymerization; IDA:UniProtKB.
DR GO; GO:0016540; P:protein autoprocessing; IDA:UniProtKB.
DR GO; GO:0018243; P:protein O-linked glycosylation via threonine; IDA:UniProtKB.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR Gene3D; 3.40.50.11050; -; 1.
DR InterPro; IPR018337; Cell_wall/Cho-bd_repeat.
DR InterPro; IPR020974; CPD_dom.
DR InterPro; IPR038383; CPD_dom_sf.
DR InterPro; IPR020972; Dermonecrotic/RTX_toxin_MLD.
DR InterPro; IPR029044; Nucleotide-diphossugar_trans.
DR InterPro; IPR024770; TcdA/TcdB_cat.
DR InterPro; IPR024772; TcdA/TcdB_N.
DR InterPro; IPR024769; TcdA/TcdB_pore_forming.
DR Pfam; PF01473; Choline_bind_1; 2.
DR Pfam; PF19127; Choline_bind_3; 1.
DR Pfam; PF11647; MLD; 1.
DR Pfam; PF11713; Peptidase_C80; 1.
DR Pfam; PF12919; TcdA_TcdB; 1.
DR Pfam; PF12920; TcdA_TcdB_pore; 1.
DR Pfam; PF12918; TcdB_N; 1.
DR SUPFAM; SSF53448; SSF53448; 1.
DR PROSITE; PS51771; CGT_MARTX_CPD; 1.
DR PROSITE; PS51170; CW; 18.
PE 1: Evidence at protein level;
KW 3D-structure; Autocatalytic cleavage; Direct protein sequencing;
KW Enterotoxin; Glycosyltransferase; Host cell membrane; Host cytoplasm;
KW Host endosome; Host membrane; Hydrolase; Lipid-binding; Magnesium;
KW Manganese; Membrane; Metal-binding; Protease; Repeat; Secreted;
KW Thiol protease; Toxin; Transferase; Virulence; Zinc.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:15632438,
FT ECO:0000269|PubMed:3384474"
FT CHAIN 2..2366
FT /note="Toxin B"
FT /id="PRO_0000072636"
FT CHAIN 2..543
FT /note="Glucosyltransferase TcdB"
FT /evidence="ECO:0000305|PubMed:15632438"
FT /id="PRO_0000451194"
FT DOMAIN 96..468
FT /note="GT44"
FT /evidence="ECO:0000255"
FT DOMAIN 567..774
FT /note="Peptidase C80"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01107"
FT REPEAT 1832..1851
FT /note="Cell wall-binding 1"
FT REPEAT 1853..1872
FT /note="Cell wall-binding 2"
FT REPEAT 1875..1894
FT /note="Cell wall-binding 3"
FT REPEAT 1925..1944
FT /note="Cell wall-binding 4"
FT REPEAT 1966..1985
FT /note="Cell wall-binding 5"
FT REPEAT 1986..2005
FT /note="Cell wall-binding 6"
FT REPEAT 2006..2025
FT /note="Cell wall-binding 7"
FT REPEAT 2056..2075
FT /note="Cell wall-binding 8"
FT REPEAT 2076..2096
FT /note="Cell wall-binding 9"
FT REPEAT 2098..2117
FT /note="Cell wall-binding 10"
FT REPEAT 2118..2137
FT /note="Cell wall-binding 11"
FT REPEAT 2138..2157
FT /note="Cell wall-binding 12"
FT REPEAT 2208..2230
FT /note="Cell wall-binding 13"
FT REPEAT 2232..2251
FT /note="Cell wall-binding 14"
FT REPEAT 2252..2271
FT /note="Cell wall-binding 15"
FT REPEAT 2272..2291
FT /note="Cell wall-binding 16"
FT REPEAT 2322..2341
FT /note="Cell wall-binding 17"
FT REPEAT 2342..2361
FT /note="Cell wall-binding 18"
FT REGION 2..91
FT /note="Four-helical bundle"
FT /evidence="ECO:0000305|PubMed:25882477"
FT REGION 96..468
FT /note="Glucosyltransferase region"
FT /evidence="ECO:0000303|PubMed:29146177"
FT REGION 544..799
FT /note="Autoprocessing region"
FT /evidence="ECO:0000303|PubMed:29146177"
FT REGION 800..1500
FT /note="Translocation region"
FT /evidence="ECO:0000303|PubMed:29146177"
FT REGION 1433..1438
FT /note="Interaction with host frizzled receptors FZD1, FZD2
FT and FZD7"
FT /evidence="ECO:0000269|PubMed:29748286"
FT REGION 1486..1511
FT /note="Interaction with host frizzled receptors FZD1, FZD2
FT and FZD7"
FT /evidence="ECO:0000269|PubMed:29748286"
FT REGION 1597..1599
FT /note="Interaction with host frizzled receptors FZD1, FZD2
FT and FZD7"
FT /evidence="ECO:0000269|PubMed:29748286"
FT REGION 1834..2366
FT /note="Receptor-binding (CROPS) region"
FT /evidence="ECO:0000303|PubMed:29146177"
FT ACT_SITE 653
FT /note="For protease activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01107,
FT ECO:0000269|PubMed:27571750"
FT ACT_SITE 698
FT /note="Nucleophile; for protease activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01107,
FT ECO:0000269|PubMed:27571750"
FT BINDING 101..103
FT /ligand="UDP-alpha-D-glucose"
FT /ligand_id="ChEBI:CHEBI:58885"
FT /evidence="ECO:0000269|PubMed:16054646,
FT ECO:0000269|PubMed:28433497, ECO:0000269|PubMed:31308519,
FT ECO:0007744|PDB:2BVL, ECO:0007744|PDB:2BVM,
FT ECO:0007744|PDB:5UQM, ECO:0007744|PDB:5UQN,
FT ECO:0007744|PDB:6OQ7"
FT BINDING 139
FT /ligand="UDP-alpha-D-glucose"
FT /ligand_id="ChEBI:CHEBI:58885"
FT /evidence="ECO:0000269|PubMed:16054646,
FT ECO:0000269|PubMed:28433497, ECO:0007744|PDB:2BVL,
FT ECO:0007744|PDB:2BVM, ECO:0007744|PDB:5UQM,
FT ECO:0007744|PDB:5UQN"
FT BINDING 269..273
FT /ligand="UDP-alpha-D-glucose"
FT /ligand_id="ChEBI:CHEBI:58885"
FT /evidence="ECO:0000269|PubMed:16054646,
FT ECO:0000269|PubMed:28433497, ECO:0000269|PubMed:31308519,
FT ECO:0007744|PDB:2BVL, ECO:0007744|PDB:2BVM,
FT ECO:0007744|PDB:5UQM, ECO:0007744|PDB:5UQN,
FT ECO:0007744|PDB:6OQ7"
FT BINDING 286..288
FT /ligand="UDP-alpha-D-glucose"
FT /ligand_id="ChEBI:CHEBI:58885"
FT /evidence="ECO:0000269|PubMed:16054646,
FT ECO:0000269|PubMed:28433497, ECO:0000269|PubMed:31308519,
FT ECO:0007744|PDB:2BVL, ECO:0007744|PDB:2BVM,
FT ECO:0007744|PDB:5UQM, ECO:0007744|PDB:5UQN,
FT ECO:0007744|PDB:6OQ7"
FT BINDING 286
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000305|PubMed:31308519,
FT ECO:0007744|PDB:6OQ5"
FT BINDING 288
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000305|PubMed:31308519,
FT ECO:0007744|PDB:6OQ5"
FT BINDING 288
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /evidence="ECO:0000269|PubMed:16054646,
FT ECO:0000269|PubMed:28433497, ECO:0000305|PubMed:31308519,
FT ECO:0007744|PDB:2BVL, ECO:0007744|PDB:5UQM,
FT ECO:0007744|PDB:5UQN, ECO:0007744|PDB:5UQT,
FT ECO:0007744|PDB:6OQ7"
FT BINDING 515
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000305|PubMed:31308519,
FT ECO:0007744|PDB:6OQ5"
FT BINDING 515
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /evidence="ECO:0000269|PubMed:16054646,
FT ECO:0000269|PubMed:28433497, ECO:0000305|PubMed:31308519,
FT ECO:0007744|PDB:2BVL, ECO:0007744|PDB:5UQM,
FT ECO:0007744|PDB:5UQN, ECO:0007744|PDB:5UQT,
FT ECO:0007744|PDB:6OQ7"
FT BINDING 518..520
FT /ligand="UDP-alpha-D-glucose"
FT /ligand_id="ChEBI:CHEBI:58885"
FT /evidence="ECO:0000269|PubMed:16054646,
FT ECO:0000269|PubMed:28433497, ECO:0000269|PubMed:31308519,
FT ECO:0007744|PDB:2BVL, ECO:0007744|PDB:2BVM,
FT ECO:0007744|PDB:5UQM, ECO:0007744|PDB:5UQN,
FT ECO:0007744|PDB:6OQ7"
FT BINDING 545
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:P16154"
FT BINDING 546
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:31308519,
FT ECO:0007744|PDB:6OQ5"
FT BINDING 577
FT /ligand="1D-myo-inositol hexakisphosphate"
FT /ligand_id="ChEBI:CHEBI:58130"
FT /evidence="ECO:0000250|UniProtKB:P16154"
FT BINDING 600
FT /ligand="1D-myo-inositol hexakisphosphate"
FT /ligand_id="ChEBI:CHEBI:58130"
FT /evidence="ECO:0000250|UniProtKB:P16154"
FT BINDING 647
FT /ligand="1D-myo-inositol hexakisphosphate"
FT /ligand_id="ChEBI:CHEBI:58130"
FT /evidence="ECO:0000250|UniProtKB:P16154"
FT BINDING 653
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:31308519,
FT ECO:0007744|PDB:6OQ5"
FT BINDING 757
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:31308519,
FT ECO:0000305|PubMed:27571750, ECO:0007744|PDB:6OQ5"
FT BINDING 764
FT /ligand="1D-myo-inositol hexakisphosphate"
FT /ligand_id="ChEBI:CHEBI:58130"
FT /evidence="ECO:0000250|UniProtKB:P16154"
FT BINDING 775
FT /ligand="1D-myo-inositol hexakisphosphate"
FT /ligand_id="ChEBI:CHEBI:58130"
FT /evidence="ECO:0000250|UniProtKB:P16154"
FT BINDING 792
FT /ligand="1D-myo-inositol hexakisphosphate"
FT /ligand_id="ChEBI:CHEBI:58130"
FT /evidence="ECO:0000250|UniProtKB:P16154"
FT SITE 543..544
FT /note="Cleavage; by autolysis"
FT /evidence="ECO:0000269|PubMed:15632438"
FT MUTAGEN 102
FT /note="W->A: Abolished glucosyltransferase activity and
FT ability to induce the host inflammatory and innate immune
FT responses; when associated with N-288."
FT /evidence="ECO:0000269|PubMed:24919149"
FT MUTAGEN 270
FT /note="D->A: Does not affect ability to form a pore in the
FT membrane of host endosomes at low pH to translocate the
FT GT44 and peptidase C80 domains across the endosomal
FT membrane. Strongly reduced glucosyltransferase activity."
FT /evidence="ECO:0000269|PubMed:17901056,
FT ECO:0000269|PubMed:24567384"
FT MUTAGEN 273
FT /note="R->A: Strongly reduced glucosyltransferase
FT activity."
FT /evidence="ECO:0000269|PubMed:17901056"
FT MUTAGEN 284
FT /note="Y->A: Strongly reduced glucosyltransferase
FT activity."
FT /evidence="ECO:0000269|PubMed:17901056"
FT MUTAGEN 288
FT /note="D->N: Abolished glucosyltransferase activity and
FT ability to induce the host inflammatory and innate immune
FT responses; when associated with A-102."
FT /evidence="ECO:0000269|PubMed:24919149"
FT MUTAGEN 383..385
FT /note="INQ->SNN: Changes substrate preference and promotes
FT N-acetylglucosaminyltransferase activity instead of
FT glucosyltransferase activity."
FT /evidence="ECO:0000269|PubMed:16157585"
FT MUTAGEN 384
FT /note="N->A: Strongly reduced glucosyltransferase
FT activity."
FT /evidence="ECO:0000269|PubMed:17901056"
FT MUTAGEN 455
FT /note="R->E: Impaired ability to recognize RhoA substrate."
FT /evidence="ECO:0000269|PubMed:17901056"
FT MUTAGEN 461
FT /note="D->R: Impaired ability to recognize RhoA substrate."
FT /evidence="ECO:0000269|PubMed:17901056"
FT MUTAGEN 463
FT /note="K->E: Impaired ability to recognize RhoA substrate."
FT /evidence="ECO:0000269|PubMed:17901056"
FT MUTAGEN 472
FT /note="E->R: Impaired ability to recognize RhoA substrate."
FT /evidence="ECO:0000269|PubMed:17901056"
FT MUTAGEN 520
FT /note="W->A: Strongly reduced glucosyltransferase
FT activity."
FT /evidence="ECO:0000269|PubMed:17901056"
FT MUTAGEN 653
FT /note="H->A: Abolished protease activity and
FT autoprocessing."
FT /evidence="ECO:0000269|PubMed:27571750"
FT MUTAGEN 698
FT /note="C->A: Abolished protease activity and
FT autoprocessing."
FT /evidence="ECO:0000269|PubMed:27571750"
FT MUTAGEN 757
FT /note="H->A: Abolished autoprocessing."
FT /evidence="ECO:0000269|PubMed:27571750"
FT MUTAGEN 1035
FT /note="I->C,K: Reduced ability to form a pore in the
FT membrane of host endosomes to translocate the GT44 and
FT peptidase C80 domains across the endosomal membrane."
FT /evidence="ECO:0000269|PubMed:24567384"
FT MUTAGEN 1037
FT /note="D->K: Slightly reduced ability to form a pore in the
FT membrane of host endosomes to translocate the GT44 and
FT peptidase C80 domains across the endosomal membrane."
FT /evidence="ECO:0000269|PubMed:24567384"
FT MUTAGEN 1038
FT /note="G->K: Slightly reduced ability to form a pore in the
FT membrane of host endosomes to translocate the GT44 and
FT peptidase C80 domains across the endosomal membrane."
FT /evidence="ECO:0000269|PubMed:24567384"
FT MUTAGEN 1041
FT /note="L->K: Reduced ability to form a pore in the membrane
FT of host endosomes to translocate the GT44 and peptidase C80
FT domains across the endosomal membrane."
FT /evidence="ECO:0000269|PubMed:24567384"
FT MUTAGEN 1095
FT /note="P->K: Reduced ability to form a pore in the membrane
FT of host endosomes to translocate the GT44 and peptidase C80
FT domains across the endosomal membrane."
FT /evidence="ECO:0000269|PubMed:24567384"
FT MUTAGEN 1098
FT /note="G->K: Reduced ability to form a pore in the membrane
FT of host endosomes to translocate the GT44 and peptidase C80
FT domains across the endosomal membrane."
FT /evidence="ECO:0000269|PubMed:24567384"
FT MUTAGEN 1099
FT /note="I->K: Reduced ability to form a pore in the membrane
FT of host endosomes to translocate the GT44 and peptidase C80
FT domains across the endosomal membrane."
FT /evidence="ECO:0000269|PubMed:24567384"
FT MUTAGEN 1106
FT /note="L->C: Reduced ability to form a pore in the membrane
FT of host endosomes to translocate the GT44 and peptidase C80
FT domains across the endosomal membrane."
FT /evidence="ECO:0000269|PubMed:24567384"
FT MUTAGEN 1106
FT /note="L->K: Strongly reduced ability to form a pore in the
FT membrane of host endosomes to translocate the GT44 and
FT peptidase C80 domains across the endosomal membrane."
FT /evidence="ECO:0000269|PubMed:24567384"
FT MUTAGEN 1107
FT /note="V->K: Reduced ability to form a pore in the membrane
FT of host endosomes to translocate the GT44 and peptidase C80
FT domains across the endosomal membrane."
FT /evidence="ECO:0000269|PubMed:24567384"
FT MUTAGEN 1433..1437
FT /note="LKILM->DKILD: Abolished interaction with host FZD2;
FT when associated with A-1493."
FT /evidence="ECO:0000269|PubMed:29748286"
FT MUTAGEN 1437
FT /note="M->D: Abolished interaction with host FZD2; when
FT associated with A-1493."
FT /evidence="ECO:0000269|PubMed:29748286"
FT MUTAGEN 1493
FT /note="L->A: Abolished interaction with host FZD2; when
FT associated with D-1437 or 1433-D--D-1437."
FT /evidence="ECO:0000269|PubMed:29748286"
FT MUTAGEN 1501
FT /note="D->A: Strongly reduced interaction with host FZD2."
FT /evidence="ECO:0000269|PubMed:29748286"
FT MUTAGEN 1509..1511
FT /note="YSN->ASA: Strongly reduced interaction with host
FT FZD2."
FT /evidence="ECO:0000269|PubMed:29748286"
FT MUTAGEN 1509
FT /note="Y->A: Strongly reduced interaction with host FZD2;
FT when associated with A-1599."
FT /evidence="ECO:0000269|PubMed:29748286"
FT MUTAGEN 1597
FT /note="F->D: Abolished interaction with host FZD2."
FT /evidence="ECO:0000269|PubMed:29748286"
FT MUTAGEN 1597
FT /note="F->G,D: Abolished interaction with host FZD2."
FT /evidence="ECO:0000269|PubMed:29748286"
FT MUTAGEN 1599
FT /note="Q->A: Strongly reduced interaction with host FZD2;
FT when associated with A-1509."
FT /evidence="ECO:0000269|PubMed:29748286"
FT HELIX 6..12
FT /evidence="ECO:0007829|PDB:7LOU"
FT STRAND 16..18
FT /evidence="ECO:0007829|PDB:5UQN"
FT HELIX 22..34
FT /evidence="ECO:0007829|PDB:7LOU"
FT HELIX 42..62
FT /evidence="ECO:0007829|PDB:7LOU"
FT TURN 63..65
FT /evidence="ECO:0007829|PDB:2BVM"
FT STRAND 66..68
FT /evidence="ECO:0007829|PDB:7ML7"
FT HELIX 69..89
FT /evidence="ECO:0007829|PDB:7LOU"
FT STRAND 96..101
FT /evidence="ECO:0007829|PDB:7LOU"
FT HELIX 109..121
FT /evidence="ECO:0007829|PDB:7LOU"
FT STRAND 125..131
FT /evidence="ECO:0007829|PDB:7LOU"
FT HELIX 138..156
FT /evidence="ECO:0007829|PDB:7LOU"
FT HELIX 158..160
FT /evidence="ECO:0007829|PDB:7LOU"
FT STRAND 163..165
FT /evidence="ECO:0007829|PDB:2BVL"
FT HELIX 168..193
FT /evidence="ECO:0007829|PDB:7LOU"
FT TURN 194..196
FT /evidence="ECO:0007829|PDB:7LOU"
FT HELIX 202..213
FT /evidence="ECO:0007829|PDB:7LOU"
FT HELIX 218..233
FT /evidence="ECO:0007829|PDB:7LOU"
FT TURN 234..236
FT /evidence="ECO:0007829|PDB:7LOU"
FT STRAND 237..239
FT /evidence="ECO:0007829|PDB:7LOU"
FT HELIX 240..242
FT /evidence="ECO:0007829|PDB:7LOU"
FT HELIX 244..248
FT /evidence="ECO:0007829|PDB:7LOU"
FT HELIX 252..260
FT /evidence="ECO:0007829|PDB:7LOU"
FT HELIX 265..280
FT /evidence="ECO:0007829|PDB:7LOU"
FT STRAND 282..285
FT /evidence="ECO:0007829|PDB:7LOU"
FT TURN 295..300
FT /evidence="ECO:0007829|PDB:7LOU"
FT HELIX 309..324
FT /evidence="ECO:0007829|PDB:7LOU"
FT HELIX 335..337
FT /evidence="ECO:0007829|PDB:7LOU"
FT HELIX 340..351
FT /evidence="ECO:0007829|PDB:7LOU"
FT HELIX 356..358
FT /evidence="ECO:0007829|PDB:7LOU"
FT STRAND 374..378
FT /evidence="ECO:0007829|PDB:7LOU"
FT STRAND 381..389
FT /evidence="ECO:0007829|PDB:7LOU"
FT HELIX 394..419
FT /evidence="ECO:0007829|PDB:7LOU"
FT HELIX 424..438
FT /evidence="ECO:0007829|PDB:7LOU"
FT TURN 441..448
FT /evidence="ECO:0007829|PDB:7LOU"
FT HELIX 453..455
FT /evidence="ECO:0007829|PDB:7LOU"
FT TURN 456..458
FT /evidence="ECO:0007829|PDB:7LOU"
FT STRAND 459..461
FT /evidence="ECO:0007829|PDB:6OQ8"
FT HELIX 465..468
FT /evidence="ECO:0007829|PDB:7LOU"
FT HELIX 471..482
FT /evidence="ECO:0007829|PDB:7LOU"
FT HELIX 495..498
FT /evidence="ECO:0007829|PDB:7LOU"
FT HELIX 499..501
FT /evidence="ECO:0007829|PDB:7LOU"
FT HELIX 505..507
FT /evidence="ECO:0007829|PDB:7LOU"
FT HELIX 514..516
FT /evidence="ECO:0007829|PDB:7LOU"
FT HELIX 524..539
FT /evidence="ECO:0007829|PDB:7LOU"
FT STRAND 545..548
FT /evidence="ECO:0007829|PDB:7ML7"
FT HELIX 559..566
FT /evidence="ECO:0007829|PDB:7ML7"
FT STRAND 580..583
FT /evidence="ECO:0007829|PDB:7ML7"
FT HELIX 588..598
FT /evidence="ECO:0007829|PDB:7ML7"
FT TURN 602..604
FT /evidence="ECO:0007829|PDB:7ML7"
FT STRAND 606..609
FT /evidence="ECO:0007829|PDB:7ML7"
FT STRAND 618..621
FT /evidence="ECO:0007829|PDB:7ML7"
FT TURN 623..625
FT /evidence="ECO:0007829|PDB:7ML7"
FT STRAND 626..629
FT /evidence="ECO:0007829|PDB:7ML7"
FT STRAND 632..634
FT /evidence="ECO:0007829|PDB:7ML7"
FT HELIX 638..640
FT /evidence="ECO:0007829|PDB:7ML7"
FT STRAND 644..646
FT /evidence="ECO:0007829|PDB:7ML7"
FT STRAND 649..651
FT /evidence="ECO:0007829|PDB:7ML7"
FT STRAND 656..659
FT /evidence="ECO:0007829|PDB:7ML7"
FT HELIX 668..681
FT /evidence="ECO:0007829|PDB:7ML7"
FT TURN 682..685
FT /evidence="ECO:0007829|PDB:7ML7"
FT STRAND 689..697
FT /evidence="ECO:0007829|PDB:7ML7"
FT STRAND 704..706
FT /evidence="ECO:0007829|PDB:7ML7"
FT HELIX 713..726
FT /evidence="ECO:0007829|PDB:7ML7"
FT STRAND 735..738
FT /evidence="ECO:0007829|PDB:7ML7"
FT STRAND 744..746
FT /evidence="ECO:0007829|PDB:7ML7"
FT STRAND 752..755
FT /evidence="ECO:0007829|PDB:7ML7"
FT STRAND 759..762
FT /evidence="ECO:0007829|PDB:7ML7"
FT HELIX 765..773
FT /evidence="ECO:0007829|PDB:7ML7"
FT STRAND 777..781
FT /evidence="ECO:0007829|PDB:7ML7"
FT TURN 782..785
FT /evidence="ECO:0007829|PDB:7ML7"
FT STRAND 786..790
FT /evidence="ECO:0007829|PDB:7ML7"
FT HELIX 794..807
FT /evidence="ECO:0007829|PDB:7ML7"
FT HELIX 815..832
FT /evidence="ECO:0007829|PDB:7ML7"
FT HELIX 854..875
FT /evidence="ECO:0007829|PDB:7ML7"
FT TURN 1091..1093
FT /evidence="ECO:0007829|PDB:6OQ6"
FT TURN 1097..1101
FT /evidence="ECO:0007829|PDB:6OQ6"
FT STRAND 1105..1114
FT /evidence="ECO:0007829|PDB:6OQ6"
FT HELIX 1117..1127
FT /evidence="ECO:0007829|PDB:6OQ6"
FT HELIX 1129..1132
FT /evidence="ECO:0007829|PDB:6OQ6"
FT STRAND 1135..1139
FT /evidence="ECO:0007829|PDB:6OQ6"
FT TURN 1140..1142
FT /evidence="ECO:0007829|PDB:6OQ6"
FT STRAND 1143..1146
FT /evidence="ECO:0007829|PDB:6OQ6"
FT STRAND 1151..1156
FT /evidence="ECO:0007829|PDB:6OQ6"
FT TURN 1157..1160
FT /evidence="ECO:0007829|PDB:6OQ6"
FT STRAND 1161..1164
FT /evidence="ECO:0007829|PDB:6OQ6"
FT STRAND 1167..1169
FT /evidence="ECO:0007829|PDB:6OQ6"
FT STRAND 1171..1173
FT /evidence="ECO:0007829|PDB:6OQ6"
FT STRAND 1179..1181
FT /evidence="ECO:0007829|PDB:6OQ6"
FT STRAND 1184..1189
FT /evidence="ECO:0007829|PDB:6OQ6"
FT STRAND 1192..1194
FT /evidence="ECO:0007829|PDB:6OQ6"
FT HELIX 1203..1205
FT /evidence="ECO:0007829|PDB:6OQ6"
FT STRAND 1218..1221
FT /evidence="ECO:0007829|PDB:6OQ6"
FT STRAND 1228..1236
FT /evidence="ECO:0007829|PDB:6OQ6"
FT HELIX 1246..1257
FT /evidence="ECO:0007829|PDB:6OQ6"
FT TURN 1258..1261
FT /evidence="ECO:0007829|PDB:6OQ6"
FT STRAND 1264..1268
FT /evidence="ECO:0007829|PDB:6OQ6"
FT STRAND 1271..1279
FT /evidence="ECO:0007829|PDB:6OQ6"
FT STRAND 1286..1291
FT /evidence="ECO:0007829|PDB:6C0B"
FT STRAND 1297..1299
FT /evidence="ECO:0007829|PDB:6C0B"
FT HELIX 1306..1309
FT /evidence="ECO:0007829|PDB:6OQ6"
FT STRAND 1313..1326
FT /evidence="ECO:0007829|PDB:6C0B"
FT STRAND 1333..1337
FT /evidence="ECO:0007829|PDB:6C0B"
FT STRAND 1343..1347
FT /evidence="ECO:0007829|PDB:6C0B"
FT TURN 1349..1351
FT /evidence="ECO:0007829|PDB:6C0B"
FT STRAND 1352..1358
FT /evidence="ECO:0007829|PDB:6C0B"
FT STRAND 1361..1367
FT /evidence="ECO:0007829|PDB:6C0B"
FT HELIX 1371..1374
FT /evidence="ECO:0007829|PDB:6C0B"
FT STRAND 1376..1378
FT /evidence="ECO:0007829|PDB:6C0B"
FT STRAND 1381..1384
FT /evidence="ECO:0007829|PDB:6C0B"
FT STRAND 1387..1393
FT /evidence="ECO:0007829|PDB:6C0B"
FT TURN 1397..1399
FT /evidence="ECO:0007829|PDB:6C0B"
FT STRAND 1401..1409
FT /evidence="ECO:0007829|PDB:6C0B"
FT STRAND 1412..1419
FT /evidence="ECO:0007829|PDB:6C0B"
FT TURN 1420..1423
FT /evidence="ECO:0007829|PDB:6C0B"
FT STRAND 1424..1431
FT /evidence="ECO:0007829|PDB:6C0B"
FT HELIX 1433..1438
FT /evidence="ECO:0007829|PDB:6C0B"
FT HELIX 1440..1449
FT /evidence="ECO:0007829|PDB:6C0B"
FT TURN 1454..1456
FT /evidence="ECO:0007829|PDB:6C0B"
FT STRAND 1458..1465
FT /evidence="ECO:0007829|PDB:6C0B"
FT STRAND 1470..1476
FT /evidence="ECO:0007829|PDB:6C0B"
FT TURN 1477..1479
FT /evidence="ECO:0007829|PDB:6C0B"
FT STRAND 1481..1487
FT /evidence="ECO:0007829|PDB:6C0B"
FT STRAND 1492..1498
FT /evidence="ECO:0007829|PDB:6C0B"
FT STRAND 1506..1512
FT /evidence="ECO:0007829|PDB:6C0B"
FT STRAND 1514..1521
FT /evidence="ECO:0007829|PDB:6C0B"
FT STRAND 1524..1535
FT /evidence="ECO:0007829|PDB:6C0B"
FT STRAND 1537..1546
FT /evidence="ECO:0007829|PDB:6C0B"
FT STRAND 1549..1557
FT /evidence="ECO:0007829|PDB:6C0B"
FT HELIX 1559..1572
FT /evidence="ECO:0007829|PDB:6C0B"
FT HELIX 1580..1587
FT /evidence="ECO:0007829|PDB:6C0B"
FT HELIX 1590..1592
FT /evidence="ECO:0007829|PDB:6C0B"
FT STRAND 1603..1616
FT /evidence="ECO:0007829|PDB:6C0B"
FT STRAND 1619..1625
FT /evidence="ECO:0007829|PDB:6C0B"
FT STRAND 1631..1640
FT /evidence="ECO:0007829|PDB:6C0B"
FT STRAND 1643..1648
FT /evidence="ECO:0007829|PDB:6C0B"
FT TURN 1649..1653
FT /evidence="ECO:0007829|PDB:6C0B"
FT STRAND 1655..1659
FT /evidence="ECO:0007829|PDB:6C0B"
FT STRAND 1664..1668
FT /evidence="ECO:0007829|PDB:7ML7"
FT STRAND 1672..1678
FT /evidence="ECO:0007829|PDB:6C0B"
FT HELIX 1679..1681
FT /evidence="ECO:0007829|PDB:6C0B"
FT TURN 1682..1687
FT /evidence="ECO:0007829|PDB:6C0B"
FT STRAND 1690..1693
FT /evidence="ECO:0007829|PDB:6C0B"
FT STRAND 1701..1705
FT /evidence="ECO:0007829|PDB:6C0B"
FT STRAND 1716..1719
FT /evidence="ECO:0007829|PDB:6C0B"
FT STRAND 1725..1727
FT /evidence="ECO:0007829|PDB:6C0B"
FT STRAND 1729..1733
FT /evidence="ECO:0007829|PDB:6C0B"
FT HELIX 1737..1739
FT /evidence="ECO:0007829|PDB:6C0B"
FT STRAND 1741..1745
FT /evidence="ECO:0007829|PDB:6C0B"
FT STRAND 1748..1752
FT /evidence="ECO:0007829|PDB:6C0B"
FT STRAND 1756..1758
FT /evidence="ECO:0007829|PDB:6C0B"
FT STRAND 1764..1767
FT /evidence="ECO:0007829|PDB:6C0B"
FT TURN 1768..1772
FT /evidence="ECO:0007829|PDB:6C0B"
FT HELIX 1774..1779
FT /evidence="ECO:0007829|PDB:6C0B"
FT STRAND 1780..1783
FT /evidence="ECO:0007829|PDB:6C0B"
FT STRAND 1785..1787
FT /evidence="ECO:0007829|PDB:6C0B"
FT STRAND 1789..1791
FT /evidence="ECO:0007829|PDB:6C0B"
FT HELIX 1792..1798
FT /evidence="ECO:0007829|PDB:6C0B"
FT STRAND 1799..1801
FT /evidence="ECO:0007829|PDB:6C0B"
FT STRAND 1814..1818
FT /evidence="ECO:0007829|PDB:7ML7"
FT STRAND 1821..1825
FT /evidence="ECO:0007829|PDB:7ML7"
FT STRAND 1835..1838
FT /evidence="ECO:0007829|PDB:4NP4"
FT STRAND 1841..1846
FT /evidence="ECO:0007829|PDB:4NP4"
FT TURN 1847..1850
FT /evidence="ECO:0007829|PDB:4NP4"
FT STRAND 1855..1859
FT /evidence="ECO:0007829|PDB:4NP4"
FT STRAND 1862..1867
FT /evidence="ECO:0007829|PDB:4NP4"
FT TURN 1868..1872
FT /evidence="ECO:0007829|PDB:4NP4"
FT STRAND 1877..1881
FT /evidence="ECO:0007829|PDB:4NP4"
FT STRAND 1884..1888
FT /evidence="ECO:0007829|PDB:4NP4"
FT STRAND 1897..1900
FT /evidence="ECO:0007829|PDB:4NP4"
FT STRAND 1902..1909
FT /evidence="ECO:0007829|PDB:4NP4"
FT STRAND 1927..1931
FT /evidence="ECO:0007829|PDB:4NP4"
FT STRAND 1934..1939
FT /evidence="ECO:0007829|PDB:4NP4"
FT TURN 1940..1942
FT /evidence="ECO:0007829|PDB:4NP4"
FT STRAND 1947..1951
FT /evidence="ECO:0007829|PDB:4NP4"
FT STRAND 1954..1958
FT /evidence="ECO:0007829|PDB:4NP4"
FT TURN 1960..1962
FT /evidence="ECO:0007829|PDB:4NP4"
FT STRAND 1968..1972
FT /evidence="ECO:0007829|PDB:4NP4"
FT STRAND 1975..1979
FT /evidence="ECO:0007829|PDB:4NP4"
FT STRAND 1988..1992
FT /evidence="ECO:0007829|PDB:4NP4"
FT STRAND 1995..1999
FT /evidence="ECO:0007829|PDB:4NP4"
FT STRAND 2008..2012
FT /evidence="ECO:0007829|PDB:4NP4"
FT STRAND 2015..2019
FT /evidence="ECO:0007829|PDB:4NP4"
FT STRAND 2028..2032
FT /evidence="ECO:0007829|PDB:4NP4"
FT STRAND 2035..2040
FT /evidence="ECO:0007829|PDB:4NP4"
FT TURN 2044..2046
FT /evidence="ECO:0007829|PDB:4NP4"
FT STRAND 2058..2062
FT /evidence="ECO:0007829|PDB:4NP4"
FT STRAND 2065..2069
FT /evidence="ECO:0007829|PDB:4NP4"
FT STRAND 2073..2075
FT /evidence="ECO:0007829|PDB:4NP4"
FT STRAND 2078..2081
FT /evidence="ECO:0007829|PDB:4NP4"
FT STRAND 2087..2090
FT /evidence="ECO:0007829|PDB:4NP4"
FT TURN 2092..2094
FT /evidence="ECO:0007829|PDB:4NP4"
FT STRAND 2097..2099
FT /evidence="ECO:0007829|PDB:4NP4"
FT STRAND 2254..2258
FT /evidence="ECO:0007829|PDB:4NC2"
FT STRAND 2261..2265
FT /evidence="ECO:0007829|PDB:4NC2"
FT STRAND 2274..2278
FT /evidence="ECO:0007829|PDB:4NC2"
FT STRAND 2281..2285
FT /evidence="ECO:0007829|PDB:4NC2"
FT STRAND 2294..2298
FT /evidence="ECO:0007829|PDB:4NC2"
FT STRAND 2301..2305
FT /evidence="ECO:0007829|PDB:4NC2"
FT STRAND 2324..2328
FT /evidence="ECO:0007829|PDB:4NC2"
FT STRAND 2331..2335
FT /evidence="ECO:0007829|PDB:4NC2"
FT STRAND 2339..2341
FT /evidence="ECO:0007829|PDB:4NC2"
FT STRAND 2344..2348
FT /evidence="ECO:0007829|PDB:4NC2"
FT STRAND 2351..2355
FT /evidence="ECO:0007829|PDB:4NC2"
FT TURN 2357..2359
FT /evidence="ECO:0007829|PDB:4NC2"
SQ SEQUENCE 2366 AA; 269712 MW; E1024BD8B8A56ADF CRC64;
MSLVNRKQLE KMANVRFRTQ EDEYVAILDA LEEYHNMSEN TVVEKYLKLK DINSLTDIYI
DTYKKSGRNK ALKKFKEYLV TEVLELKNNN LTPVEKNLHF VWIGGQINDT AINYINQWKD
VNSDYNVNVF YDSNAFLINT LKKTVVESAI NDTLESFREN LNDPRFDYNK FFRKRMEIIY
DKQKNFINYY KAQREENPEL IIDDIVKTYL SNEYSKEIDE LNTYIEESLN KITQNSGNDV
RNFEEFKNGE SFNLYEQELV ERWNLAAASD ILRISALKEI GGMYLDVDML PGIQPDLFES
IEKPSSVTVD FWEMTKLEAI MKYKEYIPEY TSEHFDMLDE EVQSSFESVL ASKSDKSEIF
SSLGDMEASP LEVKIAFNSK GIINQGLISV KDSYCSNLIV KQIENRYKIL NNSLNPAISE
DNDFNTTTNT FIDSIMAEAN ADNGRFMMEL GKYLRVGFFP DVKTTINLSG PEAYAAAYQD
LLMFKEGSMN IHLIEADLRN FEISKTNISQ STEQEMASLW SFDDARAKAQ FEEYKRNYFE
GSLGEDDNLD FSQNIVVDKE YLLEKISSLA RSSERGYIHY IVQLQGDKIS YEAACNLFAK
TPYDSVLFQK NIEDSEIAYY YNPGDGEIQE IDKYKIPSII SDRPKIKLTF IGHGKDEFNT
DIFAGFDVDS LSTEIEAAID LAKEDISPKS IEINLLGCNM FSYSINVEET YPGKLLLKVK
DKISELMPSI SQDSIIVSAN QYEVRINSEG RRELLDHSGE WINKEESIIK DISSKEYISF
NPKENKITVK SKNLPELSTL LQEIRNNSNS SDIELEEKVM LTECEINVIS NIDTQIVEER
IEEAKNLTSD SINYIKDEFK LIESISDALC DLKQQNELED SHFISFEDIS ETDEGFSIRF
INKETGESIF VETEKTIFSE YANHITEEIS KIKGTIFDTV NGKLVKKVNL DTTHEVNTLN
AAFFIQSLIE YNSSKESLSN LSVAMKVQVY AQLFSTGLNT ITDAAKVVEL VSTALDETID
LLPTLSEGLP IIATIIDGVS LGAAIKELSE TSDPLLRQEI EAKIGIMAVN LTTATTAIIT
SSLGIASGFS ILLVPLAGIS AGIPSLVNNE LVLRDKATKV VDYFKHVSLV ETEGVFTLLD
DKIMMPQDDL VISEIDFNNN SIVLGKCEIW RMEGGSGHTV TDDIDHFFSA PSITYREPHL
SIYDVLEVQK EELDLSKDLM VLPNAPNRVF AWETGWTPGL RSLENDGTKL LDRIRDNYEG
EFYWRYFAFI ADALITTLKP RYEDTNIRIN LDSNTRSFIV PIITTEYIRE KLSYSFYGSG
GTYALSLSQY NMGINIELSE SDVWIIDVDN VVRDVTIESD KIKKGDLIEG ILSTLSIEEN
KIILNSHEIN FSGEVNGSNG FVSLTFSILE GINAIIEVDL LSKSYKLLIS GELKILMLNS
NHIQQKIDYI GFNSELQKNI PYSFVDSEGK ENGFINGSTK EGLFVSELPD VVLISKVYMD
DSKPSFGYYS NNLKDVKVIT KDNVNILTGY YLKDDIKISL SLTLQDEKTI KLNSVHLDES
GVAEILKFMN RKGNTNTSDS LMSFLESMNI KSIFVNFLQS NIKFILDANF IISGTTSIGQ
FEFICDENDN IQPYFIKFNT LETNYTLYVG NRQNMIVEPN YDLDDSGDIS STVINFSQKY
LYGIDSCVNK VVISPNIYTD EINITPVYET NNTYPEVIVL DANYINEKIN VNINDLSIRY
VWSNDGNDFI LMSTSEENKV SQVKIRFVNV FKDKTLANKL SFNFSDKQDV PVSEIILSFT
PSYYEDGLIG YDLGLVSLYN EKFYINNFGM MVSGLIYIND SLYYFKPPVN NLITGFVTVG
DDKYYFNPIN GGAASIGETI IDDKNYYFNQ SGVLQTGVFS TEDGFKYFAP ANTLDENLEG
EAIDFTGKLI IDENIYYFDD NYRGAVEWKE LDGEMHYFSP ETGKAFKGLN QIGDYKYYFN
SDGVMQKGFV SINDNKHYFD DSGVMKVGYT EIDGKHFYFA ENGEMQIGVF NTEDGFKYFA
HHNEDLGNEE GEEISYSGIL NFNNKIYYFD DSFTAVVGWK DLEDGSKYYF DEDTAEAYIG
LSLINDGQYY FNDDGIMQVG FVTINDKVFY FSDSGIIESG VQNIDDNYFY IDDNGIVQIG
VFDTSDGYKY FAPANTVNDN IYGQAVEYSG LVRVGEDVYY FGETYTIETG WIYDMENESD
KYYFNPETKK ACKGINLIDD IKYYFDEKGI MRTGLISFEN NNYYFNENGE MQFGYINIED
KMFYFGEDGV MQIGVFNTPD GFKYFAHQNT LDENFEGESI NYTGWLDLDE KRYYFTDEYI
AATGSVIIDG EEYYFDPDTA QLVISE
