ID TCDA_CLODI Reviewed; 2710 AA. AC P16154; M4NKU2; DT 01-APR-1990, integrated into UniProtKB/Swiss-Prot. DT 01-FEB-1996, sequence version 2. DT 24-JAN-2024, entry version 125. DE RecName: Full=Toxin A {ECO:0000303|PubMed:2109310}; DE EC=3.4.22.- {ECO:0000269|PubMed:17334356, ECO:0000269|PubMed:19553670, ECO:0000269|PubMed:27571750}; DE Contains: DE RecName: Full=Glucosyltransferase TcdA {ECO:0000305}; DE EC=2.4.1.- {ECO:0000269|PubMed:22267739, ECO:0000269|PubMed:22747490, ECO:0000269|PubMed:24905543, ECO:0000269|PubMed:30622517, ECO:0000269|PubMed:7775453}; GN Name=tcdA {ECO:0000303|PubMed:24958798}; GN Synonyms=toxA {ECO:0000303|PubMed:2109310}; OS Clostridioides difficile (Peptoclostridium difficile). OC Bacteria; Bacillota; Clostridia; Eubacteriales; Peptostreptococcaceae; OC Clostridioides. OX NCBI_TaxID=1496; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RC STRAIN=ATCC 4325 / VPI 10463; RX PubMed=2109310; DOI=10.1093/nar/18.6.1629; RA Sauerborn M., von Eichel-Streiber C.; RT "Nucleotide sequence of Clostridium difficile toxin A."; RL Nucleic Acids Res. 18:1629-1630(1990). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RC STRAIN=ATCC 4325 / VPI 10463; RX PubMed=2105276; DOI=10.1128/iai.58.2.480-488.1990; RA Dove C.H., Wang S.-Z., Price S.B., Phelps C.J., Lyerly D.M., Wilkins T.D., RA Johnson J.L.; RT "Molecular characterization of the Clostridium difficile toxin A gene."; RL Infect. Immun. 58:480-488(1990). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RC STRAIN=ATCC 4325 / VPI 10463; 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 [4] 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 [5] RP FUNCTION (TOXIN A). RC STRAIN=ATCC 4325 / VPI 10463; RX PubMed=1670930; DOI=10.1128/iai.59.1.73-78.1991; RA Tucker K.D., Wilkins T.D.; RT "Toxin A of Clostridium difficile binds to the human carbohydrate antigens RT I, X, and Y."; RL Infect. Immun. 59:73-78(1991). RN [6] RP FUNCTION (GLUCOSYLTRANSFERASE TCDA), AND CATALYTIC ACTIVITY RP (GLUCOSYLTRANSFERASE TCDA). RC STRAIN=ATCC 4325 / VPI 10463; RX PubMed=7775453; DOI=10.1074/jbc.270.23.13932; RA Just I., Wilm M., Selzer J., Rex G., von Eichel-Streiber C., Mann M., RA Aktories K.; RT "The enterotoxin from Clostridium difficile (ToxA) monoglucosylates the Rho RT proteins."; RL J. Biol. Chem. 270:13932-13936(1995). RN [7] RP FUNCTION (TOXIN A), PROTEOLYTIC CLEAVAGE (TOXIN A), AND ACTIVITY REGULATION RP (TOXIN A). 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 [8] RP CAUTION. RX PubMed=18411291; DOI=10.1128/iai.00326-08; RA Na X., Kim H., Moyer M.P., Pothoulakis C., LaMont J.T.; RT "gp96 is a human colonocyte plasma membrane binding protein for Clostridium RT difficile toxin A."; RL Infect. Immun. 76:2862-2871(2008). RN [9] 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 [10] 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 [11] RP SUBCELLULAR LOCATION (TOXIN A). 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 [12] RP SUBCELLULAR LOCATION (TOXIN A). 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 [13] RP FUNCTION (GLUCOSYLTRANSFERASE TCDA), AND CATALYTIC ACTIVITY RP (GLUCOSYLTRANSFERASE TCDA). 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 [14] 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 [15] RP FUNCTION (TOXIN A). 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 [16] RP FUNCTION (GLUCOSYLTRANSFERASE TCDA), AND CATALYTIC ACTIVITY RP (GLUCOSYLTRANSFERASE TCDA). RC STRAIN=ATCC 4325 / VPI 10463; RX PubMed=30622517; DOI=10.3389/fmicb.2018.03078; RA Genth H., Junemann J., Laemmerhirt C.M., Luecke A.C., Schelle I., Just I., RA Gerhard R., Pich A.; RT "Difference in mono-O-glucosylation of Ras subtype GTPases between toxin A RT and toxin B from Clostridioides difficile strain 10463 and lethal toxin RT from Clostridium sordellii strain 6018."; RL Front. Microbiol. 9:3078-3078(2018). RN [17] 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 [18] RP FUNCTION (TOXIN A), AND INTERACTION WITH HOST LDLR. RC STRAIN=ATCC 4325 / VPI 10463; RX PubMed=31160825; DOI=10.1038/s41564-019-0464-z; RA Tao L., Tian S., Zhang J., Liu Z., Robinson-McCarthy L., Miyashita S.I., RA Breault D.T., Gerhard R., Oottamasathien S., Whelan S.P.J., Dong M.; RT "Sulfated glycosaminoglycans and low-density lipoprotein receptor RT contribute to Clostridium difficile toxin A entry into cells."; RL Nat. Microbiol. 4:1760-1769(2019). RN [19] {ECO:0007744|PDB:2F6E} RP X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) OF 2583-2709. RC STRAIN=ATCC 4325 / VPI 10463; RX PubMed=16344467; DOI=10.1073/pnas.0506391102; RA Ho J.G., Greco A., Rupnik M., Ng K.K.; RT "Crystal structure of receptor-binding C-terminal repeats from Clostridium RT difficile toxin A."; RL Proc. Natl. Acad. Sci. U.S.A. 102:18373-18378(2005). RN [20] {ECO:0007744|PDB:2G7C} RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 2456-2710 IN COMPLEX WITH RP N-LINKED CARBOHYDRATE, FUNCTION (TOXIN A), AND DOMAIN (TOXIN A). RC STRAIN=48489; RX PubMed=16622409; DOI=10.1038/nsmb1084; RA Greco A., Ho J.G., Lin S.J., Palcic M.M., Rupnik M., Ng K.K.; RT "Carbohydrate recognition by Clostridium difficile toxin A."; RL Nat. Struct. Mol. Biol. 13:460-461(2006). RN [21] {ECO:0007744|PDB:3HO6} RP X-RAY CRYSTALLOGRAPHY (1.60 ANGSTROMS) OF 543-809 IN COMPLEX WITH RP 1D-MYO-INOSITOL HEXAKISPHOSPHATE, FUNCTION (TOXIN A), PROTEOLYTIC CLEAVAGE RP (TOXIN A), ACTIVE SITES (PROTEASE ACTIVITY), ACTIVITY REGULATION (TOXIN A), RP AND MUTAGENESIS OF LEU-542; ASP-589; ASP-590; HIS-655 AND CYS-700. RC STRAIN=ATCC 4325 / VPI 10463; RX PubMed=19553670; DOI=10.1074/jbc.m109.018929; RA Pruitt R.N., Chagot B., Cover M., Chazin W.J., Spiller B., Lacy D.B.; RT "Structure-function analysis of inositol hexakisphosphate-induced RT autoprocessing in Clostridium difficile toxin A."; RL J. Biol. Chem. 284:21934-21940(2009). RN [22] {ECO:0007744|PDB:4DMV, ECO:0007744|PDB:4DMW} RP X-RAY CRYSTALLOGRAPHY (1.50 ANGSTROMS) OF 1-541 IN COMPLEX WITH UDP AND RP MANGANESE, COFACTOR, FUNCTION (GLUCOSYLTRANSFERASE TCDA), CATALYTIC RP ACTIVITY (GLUCOSYLTRANSFERASE TCDA), AND BIOPHYSICOCHEMICAL PROPERTIES RP (GLUCOSYLTRANSFERASE TCDA). RC STRAIN=630 / Type X; RX PubMed=22747490; DOI=10.1111/j.1742-4658.2012.08688.x; RA D'Urzo N., Malito E., Biancucci M., Bottomley M.J., Maione D., RA Scarselli M., Martinelli M.; RT "The structure of Clostridium difficile toxin A glucosyltransferase domain RT bound to Mn2+ and UDP provides insights into glucosyltransferase activity RT and product release."; RL FEBS J. 279:3085-3097(2012). RN [23] {ECO:0007744|PDB:3SRZ, ECO:0007744|PDB:3SS1} RP X-RAY CRYSTALLOGRAPHY (2.20 ANGSTROMS) OF 1-542 IN COMPLEX WITH RP UDP-ALPHA-D-GLUCOSE AND MANGANESE, FUNCTION (GLUCOSYLTRANSFERASE TCDA), RP CATALYTIC ACTIVITY (GLUCOSYLTRANSFERASE TCDA), PROTEOLYTIC CLEAVAGE (TOXIN RP A), AND COFACTOR. RX PubMed=22267739; DOI=10.1074/jbc.m111.298414; RA Pruitt R.N., Chumbler N.M., Rutherford S.A., Farrow M.A., Friedman D.B., RA Spiller B., Lacy D.B.; RT "Structural determinants of Clostridium difficile toxin A RT glucosyltransferase activity."; RL J. Biol. Chem. 287:8013-8020(2012). RN [24] {ECO:0007744|PDB:4NBX, ECO:0007744|PDB:4NBZ} RP X-RAY CRYSTALLOGRAPHY (1.75 ANGSTROMS) OF 2573-2709. 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 [25] {ECO:0007744|PDB:4R04} RP X-RAY CRYSTALLOGRAPHY (3.26 ANGSTROMS) OF 1-1832 IN COMPLEX WITH ZINC, RP FUNCTION (TOXIN A), COFACTOR, ACTIVE SITES, AND MUTAGENESIS OF HIS-655; RP CYS-700 AND HIS-759. 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 [26] {ECO:0007744|PDB:5UMI} RP X-RAY CRYSTALLOGRAPHY (3.23 ANGSTROMS) OF 2461-2710. RX PubMed=28705932; DOI=10.1074/jbc.m117.781112; RA Kroh H.K., Chandrasekaran R., Rosenthal K., Woods R., Jin X., Ohi M.D., RA Nyborg A.C., Rainey G.J., Warrener P., Spiller B.W., Lacy D.B.; RT "Use of a neutralizing antibody helps identify structural features critical RT for binding of Clostridium difficile toxin TcdA to the host cell surface."; RL J. Biol. Chem. 292:14401-14412(2017). RN [27] {ECO:0007744|PDB:5UQK, ECO:0007744|PDB:5UQL} RP X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) OF 1-544 IN COMPLEX WITH RP UDP-ALPHA-D-GLUCOSE AND MANGANESE, AND COFACTOR. 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). CC -!- FUNCTION: [Toxin A]: 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). TcdA and TcdB constitute the main toxins that CC mediate 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 TcdB, TcdA is CC less virulent and less important for inducing the host inflammatory and CC innate immune responses (PubMed:19252482). This form constitutes the CC precursor of the toxin: it enters into host cells and mediates CC autoprocessing to release the active toxin (Glucosyltransferase TcdA) CC into the host cytosol (By similarity). Targets colonic epithelia by CC binding to some receptor, and enters host cells via clathrin-mediated CC endocytosis (By similarity). Binding to LDLR, as well as carbohydrates CC and sulfated glycosaminoglycans on host cell surface contribute to CC entry into cells (PubMed:1670930, PubMed:31160825, PubMed:16622409). In CC contrast to TcdB, Frizzled receptors FZD1, FZD2 and FZD7 do not act as CC host receptors in the colonic epithelium for TcdA (PubMed:27680706). CC Once entered into host cells, acidification in the endosome promotes CC the membrane insertion of the translocation region and formation of a CC pore, leading to translocation of the GT44 and peptidase C80 domains CC across the endosomal membrane (By similarity). This activates the CC peptidase C80 domain and autocatalytic processing, releasing the N- CC terminal part (Glucosyltransferase TcdA), which constitutes the active CC part of the toxin, in the cytosol (PubMed:17334356, PubMed:19553670, CC PubMed:27571750). {ECO:0000250|UniProtKB:P18177, CC ECO:0000269|PubMed:16622409, ECO:0000269|PubMed:1670930, CC ECO:0000269|PubMed:17334356, ECO:0000269|PubMed:19252482, CC ECO:0000269|PubMed:19553670, ECO:0000269|PubMed:20844489, CC ECO:0000269|PubMed:27571750, ECO:0000269|PubMed:27680706, CC ECO:0000269|PubMed:31160825}. CC -!- FUNCTION: [Glucosyltransferase TcdA]: Active form of the toxin, which CC is released into the host cytosol following autoprocessing and CC inactivates small GTPases (PubMed:7775453, PubMed:24905543, CC PubMed:30622517, PubMed:22747490, PubMed:22267739). Acts by mediating CC monoglucosylation of small GTPases of the Rho family (Rac1, RhoA, RhoB, CC RhoC, Rap2A and Cdc42) in host cells at the conserved threonine residue CC located in the switch I region ('Thr-37/35'), using UDP-alpha-D-glucose CC as the sugar donor (PubMed:7775453, PubMed:24905543, PubMed:30622517, CC PubMed:22747490, PubMed:22267739). Monoglucosylation of host small CC GTPases completely prevents the recognition of the downstream effector, CC blocking the GTPases in their inactive form, leading to actin CC cytoskeleton disruption and cell death, resulting in the loss of CC colonic epithelial barrier function (PubMed:7775453). Also able to CC catalyze monoglucosylation of some members of the Ras family (H- CC Ras/HRAS, K-Ras/KRAS and N-Ras/NRAS), but with much less efficiency CC than with Rho proteins, suggesting that it does not act on Ras proteins CC in vivo (PubMed:30622517). {ECO:0000269|PubMed:22267739, CC ECO:0000269|PubMed:22747490, ECO:0000269|PubMed:24905543, CC ECO:0000269|PubMed:30622517, ECO:0000269|PubMed:7775453}. CC -!- CATALYTIC ACTIVITY: [Glucosyltransferase TcdA]: 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:22267739, CC ECO:0000269|PubMed:22747490, ECO:0000269|PubMed:24905543, CC ECO:0000269|PubMed:30622517, ECO:0000269|PubMed:7775453}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:64685; CC Evidence={ECO:0000269|PubMed:22267739, ECO:0000269|PubMed:22747490, CC ECO:0000269|PubMed:24905543, ECO:0000269|PubMed:30622517, CC ECO:0000269|PubMed:7775453}; CC -!- COFACTOR: [Toxin A]: CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105; CC Evidence={ECO:0000269|PubMed:27571750}; CC Note=Binds 1 Zn(2+) ion per subunit (PubMed:27571750). Zn(2+) is CC required for autocatalytic cleavage (PubMed:27571750). CC {ECO:0000269|PubMed:27571750}; CC -!- COFACTOR: [Glucosyltransferase TcdA]: CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035; CC Evidence={ECO:0000269|PubMed:22267739, ECO:0000269|PubMed:22747490, CC ECO:0000269|PubMed:28433497}; CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; CC Evidence={ECO:0000250|UniProtKB:P18177}; CC Note=Has higher activity with Mn(2+), but most likely uses Mg(2+) in CC host cells (By similarity). Required for glucosyltransferase activity CC (PubMed:22747490). {ECO:0000250|UniProtKB:P18177, CC ECO:0000269|PubMed:22747490}; CC -!- ACTIVITY REGULATION: [Toxin A]: Protease activity is activated upon CC binding to 1D-myo-inositol hexakisphosphate (InsP6), which induces CC conformational reorganization. {ECO:0000269|PubMed:17334356, CC ECO:0000269|PubMed:19553670}. CC -!- BIOPHYSICOCHEMICAL PROPERTIES: [Glucosyltransferase TcdA]: CC Kinetic parameters: CC KM=43.9 uM for UDP-alpha-D-glucose (in presence of K(+)) CC {ECO:0000269|PubMed:22747490}; CC KM=36.3 uM for UDP-alpha-D-glucose (in presence of NH4(+)) CC {ECO:0000269|PubMed:22747490}; CC KM=51.1 uM for UDP-alpha-D-glucose (in presence of Na(+)) CC {ECO:0000269|PubMed:22747490}; CC Vmax=252.2 pmol/min/ug enzyme with UDP-alpha-D-glucose (in presence CC of K(+)) {ECO:0000269|PubMed:22747490}; CC Vmax=162.8 pmol/min/ug enzyme with UDP-alpha-D-glucose (in presence CC of NH4(+)) {ECO:0000269|PubMed:22747490}; CC Vmax=36.4 pmol/min/ug enzyme with UDP-alpha-D-glucose (in presence of CC Na(+)) {ECO:0000269|PubMed:22747490}; CC -!- SUBUNIT: [Toxin A]: Interacts with host LDLR; LDLR probably does not CC constitute a major receptor but may contribute to entry into cells. CC {ECO:0000269|PubMed:31160825}. CC -!- SUBCELLULAR LOCATION: [Toxin A]: Secreted CC {ECO:0000269|PubMed:22685398}. Host endosome membrane CC {ECO:0000250|UniProtKB:P18177}. Note=Secreted from C.difficile cell CC into the extracellular environment via help of holin-like protein CC TcdE/UtxA (PubMed:22685398). Binds to the cell surface receptors via CC the receptor-binding region and enters the cells via clathrin-mediated CC endocytosis (PubMed:20498856). Acidification in the endosome triggers CC conformational changes that promote the membrane insertion of the CC translocation region, allowing formation of a pore, leading to CC translocation of the GT44 and peptidase C80 domains across the CC endosomal membrane (By similarity). 1D-myo-inositol hexakisphosphate- CC binding (InsP6) activates the peptidase C80 domain and autoprocessing, CC generating the Glucosyltransferase TcdA form, which is released in the CC host cytosol (PubMed:19553670). {ECO:0000250|UniProtKB:P18177, CC ECO:0000269|PubMed:19553670, ECO:0000269|PubMed:20498856, CC ECO:0000269|PubMed:22685398}. CC -!- SUBCELLULAR LOCATION: [Glucosyltransferase TcdA]: Host cytoplasm, host CC cytosol {ECO:0000250|UniProtKB:P18177}. Host cell membrane CC {ECO:0000250|UniProtKB:Q46342}; Peripheral membrane protein CC {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 A]: 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:0000303|PubMed:29146177}. CC -!- DOMAIN: [Toxin A]: 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:0000250|UniProtKB:P18177}. CC -!- DOMAIN: [Toxin A]: The cell wall-binding repeats bind carbohydrates, CC such as Galalpha1-3Galbeta1-4GlcNAc, probably contributing to entry CC into cells. {ECO:0000269|PubMed:16622409, ECO:0000305|PubMed:1670930}. CC -!- DOMAIN: [Glucosyltransferase TcdA]: 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 A]: Undergoes autocatalytic cleavage to release the N- CC terminal part (Glucosyltransferase TcdA), which constitutes the active CC part of the toxin, in the host cytosol (PubMed:17334356, CC PubMed:22267739, PubMed:19553670, PubMed:27571750). 1D-myo-inositol CC hexakisphosphate-binding (InsP6) activates the peptidase C80 domain and CC promotes autoprocessing (PubMed:17334356, PubMed:19553670). CC {ECO:0000269|PubMed:17334356, ECO:0000269|PubMed:19553670, CC ECO:0000269|PubMed:22267739, ECO:0000269|PubMed:27571750}. CC -!- DISRUPTION PHENOTYPE: Cells lacking tcdA display virulence and CC cytotoxity, because of the presence of TcdB (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}. CC -!- CAUTION: Host HSP90B1/gp96 was initially identified as a possible CC receptor for TcdA (PubMed:18411291). However, as HSP90B1/gp96 localizes CC in the endoplasmic reticulum and not at the cell membrane, it probably CC does not act as a receptor for TcdA. {ECO:0000269|PubMed:18411291, CC ECO:0000305}. 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; X51797; CAA36094.1; -; Genomic_DNA. DR EMBL; M30307; AAA23283.1; -; Genomic_DNA. DR EMBL; KC292122; AGG91568.1; -; Genomic_DNA. DR EMBL; X92982; CAA63564.1; -; Genomic_DNA. DR PIR; A37052; A37052. DR RefSeq; WP_009902072.1; NZ_PZRE01000002.1. DR PDB; 2F6E; X-ray; 1.85 A; A=2583-2709. DR PDB; 2G7C; X-ray; 2.00 A; A/B=2456-2710. DR PDB; 2QJ6; X-ray; 2.50 A; A/B=2387-2706. DR PDB; 3HO6; X-ray; 1.60 A; A/B=543-809. DR PDB; 3SRZ; X-ray; 2.58 A; A=1-542. DR PDB; 3SS1; X-ray; 2.20 A; A=1-542. DR PDB; 4DMV; X-ray; 1.50 A; A=1-541. DR PDB; 4DMW; X-ray; 2.50 A; A=1-541. DR PDB; 4NBX; X-ray; 1.75 A; A=2573-2709. DR PDB; 4NBZ; X-ray; 1.75 A; A/C=2573-2709. DR PDB; 4R04; X-ray; 3.26 A; A=1-1832. DR PDB; 5UMI; X-ray; 3.23 A; C=2461-2710. DR PDB; 5UQK; X-ray; 1.85 A; A=1-544. DR PDB; 5UQL; X-ray; 1.97 A; A=1-544. DR PDB; 7POG; EM; 2.83 A; A=1-2710. DR PDB; 7U1Z; X-ray; 3.18 A; A/B=843-2481. DR PDB; 7U2P; X-ray; 2.60 A; A=1-542. DR PDB; 7UBX; X-ray; 1.81 A; A/B=1073-1464. DR PDB; 7UBY; X-ray; 2.10 A; A/B=1-542. DR PDBsum; 2F6E; -. DR PDBsum; 2G7C; -. DR PDBsum; 2QJ6; -. DR PDBsum; 3HO6; -. DR PDBsum; 3SRZ; -. DR PDBsum; 3SS1; -. DR PDBsum; 4DMV; -. DR PDBsum; 4DMW; -. DR PDBsum; 4NBX; -. DR PDBsum; 4NBZ; -. DR PDBsum; 4R04; -. DR PDBsum; 5UMI; -. DR PDBsum; 5UQK; -. DR PDBsum; 5UQL; -. DR PDBsum; 7POG; -. DR PDBsum; 7U1Z; -. DR PDBsum; 7U2P; -. DR PDBsum; 7UBX; -. DR PDBsum; 7UBY; -. DR EMDB; EMD-13574; -. DR SMR; P16154; -. DR BindingDB; P16154; -. DR ChEMBL; CHEMBL3580504; -. DR CAZy; GT44; Glycosyltransferase Family 44. DR MEROPS; C80.002; -. DR TCDB; 1.C.57.1.2; the clostridial cytotoxin (cct) family. DR UniLectin; P16154; -. DR ABCD; P16154; 2 sequenced antibodies. DR BRENDA; 2.4.1.B62; 1473. DR BRENDA; 3.1.4.B4; 1473. DR EvolutionaryTrace; P16154; -. DR PHI-base; PHI:10932; -. DR PHI-base; PHI:9028; -. DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell. DR GO; GO:0044164; C:host cell cytosol; IEA:UniProtKB-SubCell. DR GO; GO:0044175; C:host cell endosome membrane; IEA:UniProtKB-SubCell. DR GO; GO:0020002; C:host cell plasma membrane; IEA:UniProtKB-SubCell. DR GO; GO:0016020; C:membrane; IEA:UniProtKB-KW. DR GO; GO:0008234; F:cysteine-type peptidase activity; IEA:UniProtKB-KW. DR GO; GO:0016757; F:glycosyltransferase activity; IEA:UniProtKB-KW. DR GO; GO:0008289; F:lipid binding; IEA:UniProtKB-KW. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW. DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW. DR CDD; cd20502; C80_toxinA_B-like; 1. DR CDD; cd16840; toxin_MLD; 1. DR Gene3D; 1.10.10.1780; -; 1. DR Gene3D; 1.10.274.80; -; 1. DR Gene3D; 1.10.3730.30; -; 1. DR Gene3D; 1.20.58.1190; -; 1. DR Gene3D; 3.40.50.11050; -; 1. DR Gene3D; 2.10.270.10; Cholin Binding; 12. DR InterPro; IPR018337; Cell_wall/Cho-bd_repeat. DR InterPro; IPR020974; CPD_dom. DR InterPro; IPR038383; CPD_dom_sf. 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; 8. DR Pfam; PF19127; Choline_bind_3; 6. 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; SSF69360; Cell wall binding repeat; 4. DR SUPFAM; SSF53448; Nucleotide-diphospho-sugar transferases; 1. DR PROSITE; PS51771; CGT_MARTX_CPD; 1. DR PROSITE; PS51170; CW; 32. PE 1: Evidence at protein level; KW 3D-structure; Autocatalytic cleavage; Enterotoxin; Glycosyltransferase; KW Host cell membrane; Host cytoplasm; Host endosome; Host membrane; KW Hydrolase; Lipid-binding; Magnesium; Manganese; Membrane; Metal-binding; KW Protease; Repeat; Secreted; Thiol protease; Toxin; Transferase; Virulence; KW Zinc. FT CHAIN 1..2710 FT /note="Toxin A" FT /id="PRO_0000072634" FT CHAIN 1..542 FT /note="Glucosyltransferase TcdA" FT /evidence="ECO:0000305|PubMed:19553670" FT /id="PRO_0000451191" FT DOMAIN 95..467 FT /note="GT44" FT /evidence="ECO:0000255" FT DOMAIN 569..776 FT /note="Peptidase C80" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01107" FT REPEAT 1810..1829 FT /note="Cell wall-binding 1" FT REPEAT 1851..1870 FT /note="Cell wall-binding 2" FT REPEAT 1872..1891 FT /note="Cell wall-binding 3" FT REPEAT 1923..1942 FT /note="Cell wall-binding 4" FT REPEAT 1943..1962 FT /note="Cell wall-binding 5" FT REPEAT 1964..1983 FT /note="Cell wall-binding 6" FT REPEAT 1985..2004 FT /note="Cell wall-binding 7" FT REPEAT 2006..2025 FT /note="Cell wall-binding 8" FT REPEAT 2057..2076 FT /note="Cell wall-binding 9" FT REPEAT 2077..2096 FT /note="Cell wall-binding 10" FT REPEAT 2098..2117 FT /note="Cell wall-binding 11" FT REPEAT 2119..2138 FT /note="Cell wall-binding 12" FT REPEAT 2140..2159 FT /note="Cell wall-binding 13" FT REPEAT 2191..2210 FT /note="Cell wall-binding 14" FT REPEAT 2211..2230 FT /note="Cell wall-binding 15" FT REPEAT 2232..2251 FT /note="Cell wall-binding 16" FT REPEAT 2252..2271 FT /note="Cell wall-binding 17" FT REPEAT 2305..2324 FT /note="Cell wall-binding 18" FT REPEAT 2325..2344 FT /note="Cell wall-binding 19" FT REPEAT 2346..2365 FT /note="Cell wall-binding 20" FT REPEAT 2367..2386 FT /note="Cell wall-binding 21" FT REPEAT 2388..2407 FT /note="Cell wall-binding 22" FT REPEAT 2439..2458 FT /note="Cell wall-binding 23" FT REPEAT 2459..2478 FT /note="Cell wall-binding 24" FT REPEAT 2480..2499 FT /note="Cell wall-binding 25" FT REPEAT 2501..2520 FT /note="Cell wall-binding 26" FT REPEAT 2552..2571 FT /note="Cell wall-binding 27" FT REPEAT 2572..2591 FT /note="Cell wall-binding 28" FT REPEAT 2593..2612 FT /note="Cell wall-binding 29" FT REPEAT 2643..2662 FT /note="Cell wall-binding 30" FT REPEAT 2663..2682 FT /note="Cell wall-binding 31" FT REPEAT 2685..2704 FT /note="Cell wall-binding 32" FT REGION 1..90 FT /note="Four-helical bundle" FT /evidence="ECO:0000305|PubMed:25882477" FT REGION 95..467 FT /note="Glucosyltransferase region" FT /evidence="ECO:0000303|PubMed:29146177" FT REGION 543..801 FT /note="Autoprocessing region" FT /evidence="ECO:0000303|PubMed:29146177" FT REGION 802..1497 FT /note="Translocation region" FT /evidence="ECO:0000303|PubMed:29146177" FT REGION 1832..2483 FT /note="Receptor-binding (CROPS) region" FT /evidence="ECO:0000303|PubMed:29146177" FT ACT_SITE 655 FT /note="For protease activity" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01107, FT ECO:0000269|PubMed:19553670, ECO:0000269|PubMed:27571750" FT ACT_SITE 700 FT /note="Nucleophile; for protease activity" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01107, FT ECO:0000269|PubMed:19553670, ECO:0000269|PubMed:27571750" FT BINDING 100..102 FT /ligand="UDP-alpha-D-glucose" FT /ligand_id="ChEBI:CHEBI:58885" FT /evidence="ECO:0000269|PubMed:22267739, FT ECO:0000269|PubMed:22747490, ECO:0000269|PubMed:28433497, FT ECO:0007744|PDB:3SRZ, ECO:0007744|PDB:4DMV, FT ECO:0007744|PDB:5UQK, ECO:0007744|PDB:5UQL" FT BINDING 138 FT /ligand="UDP-alpha-D-glucose" FT /ligand_id="ChEBI:CHEBI:58885" FT /evidence="ECO:0000269|PubMed:22267739, FT ECO:0000269|PubMed:28433497, ECO:0007744|PDB:3SRZ, FT ECO:0007744|PDB:5UQK, ECO:0007744|PDB:5UQL" FT BINDING 268..272 FT /ligand="UDP-alpha-D-glucose" FT /ligand_id="ChEBI:CHEBI:58885" FT /evidence="ECO:0000269|PubMed:22267739, FT ECO:0000269|PubMed:22747490, ECO:0000269|PubMed:28433497, FT ECO:0007744|PDB:3SRZ, ECO:0007744|PDB:4DMV, FT ECO:0007744|PDB:5UQK, ECO:0007744|PDB:5UQL" FT BINDING 285..287 FT /ligand="UDP-alpha-D-glucose" FT /ligand_id="ChEBI:CHEBI:58885" FT /evidence="ECO:0000269|PubMed:22267739, FT ECO:0000269|PubMed:22747490, ECO:0000269|PubMed:28433497, FT ECO:0007744|PDB:3SRZ, ECO:0007744|PDB:4DMV, FT ECO:0007744|PDB:5UQK, ECO:0007744|PDB:5UQL" FT BINDING 285 FT /ligand="Mn(2+)" FT /ligand_id="ChEBI:CHEBI:29035" FT /evidence="ECO:0000269|PubMed:22267739, FT ECO:0007744|PDB:3SS1" FT BINDING 287 FT /ligand="Mn(2+)" FT /ligand_id="ChEBI:CHEBI:29035" FT /evidence="ECO:0000269|PubMed:22267739, FT ECO:0000269|PubMed:22747490, ECO:0000269|PubMed:28433497, FT ECO:0007744|PDB:3SRZ, ECO:0007744|PDB:3SS1, FT ECO:0007744|PDB:5UQK, ECO:0007744|PDB:5UQL" FT BINDING 514 FT /ligand="Mn(2+)" FT /ligand_id="ChEBI:CHEBI:29035" FT /evidence="ECO:0000269|PubMed:22267739, FT ECO:0000269|PubMed:22747490, ECO:0000269|PubMed:28433497, FT ECO:0007744|PDB:3SRZ, ECO:0007744|PDB:3SS1, FT ECO:0007744|PDB:5UQK, ECO:0007744|PDB:5UQL" FT BINDING 517..519 FT /ligand="UDP-alpha-D-glucose" FT /ligand_id="ChEBI:CHEBI:58885" FT /evidence="ECO:0000269|PubMed:22267739, FT ECO:0000269|PubMed:22747490, ECO:0000269|PubMed:28433497, FT ECO:0007744|PDB:3SRZ, ECO:0007744|PDB:4DMV, FT ECO:0007744|PDB:5UQK, ECO:0007744|PDB:5UQL" FT BINDING 544 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000269|PubMed:27571750, FT ECO:0007744|PDB:4R04" FT BINDING 545 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000269|PubMed:27571750, FT ECO:0007744|PDB:4R04" FT BINDING 551 FT /ligand="1D-myo-inositol hexakisphosphate" FT /ligand_id="ChEBI:CHEBI:58130" FT /evidence="ECO:0000269|PubMed:19553670, FT ECO:0007744|PDB:3HO6" FT BINDING 579 FT /ligand="1D-myo-inositol hexakisphosphate" FT /ligand_id="ChEBI:CHEBI:58130" FT /evidence="ECO:0000269|PubMed:19553670, FT ECO:0007744|PDB:3HO6" FT BINDING 602 FT /ligand="1D-myo-inositol hexakisphosphate" FT /ligand_id="ChEBI:CHEBI:58130" FT /evidence="ECO:0000269|PubMed:19553670, FT ECO:0007744|PDB:3HO6" FT BINDING 649 FT /ligand="1D-myo-inositol hexakisphosphate" FT /ligand_id="ChEBI:CHEBI:58130" FT /evidence="ECO:0000269|PubMed:19553670, FT ECO:0007744|PDB:3HO6" FT BINDING 655 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000269|PubMed:27571750, FT ECO:0007744|PDB:4R04" FT BINDING 753..754 FT /ligand="1D-myo-inositol hexakisphosphate" FT /ligand_id="ChEBI:CHEBI:58130" FT /evidence="ECO:0000269|PubMed:19553670, FT ECO:0007744|PDB:3HO6" FT BINDING 759 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000269|PubMed:27571750, FT ECO:0007744|PDB:4R04" FT BINDING 766 FT /ligand="1D-myo-inositol hexakisphosphate" FT /ligand_id="ChEBI:CHEBI:58130" FT /evidence="ECO:0000269|PubMed:19553670, FT ECO:0007744|PDB:3HO6" FT BINDING 777 FT /ligand="1D-myo-inositol hexakisphosphate" FT /ligand_id="ChEBI:CHEBI:58130" FT /evidence="ECO:0000269|PubMed:19553670, FT ECO:0007744|PDB:3HO6" FT BINDING 794 FT /ligand="1D-myo-inositol hexakisphosphate" FT /ligand_id="ChEBI:CHEBI:58130" FT /evidence="ECO:0000269|PubMed:19553670, FT ECO:0007744|PDB:3HO6" FT BINDING 2540 FT /ligand="alpha-D-galactosyl-(1->3)-beta-D-galactosyl- FT (1->4)-N-acetyl-beta-D-glucosamine" FT /ligand_id="ChEBI:CHEBI:62327" FT /ligand_label="1" FT /evidence="ECO:0000269|PubMed:16622409, FT ECO:0007744|PDB:2G7C" FT BINDING 2547..2550 FT /ligand="alpha-D-galactosyl-(1->3)-beta-D-galactosyl- FT (1->4)-N-acetyl-beta-D-glucosamine" FT /ligand_id="ChEBI:CHEBI:62327" FT /ligand_label="1" FT /evidence="ECO:0000269|PubMed:16622409, FT ECO:0007744|PDB:2G7C" FT BINDING 2567..2570 FT /ligand="alpha-D-galactosyl-(1->3)-beta-D-galactosyl- FT (1->4)-N-acetyl-beta-D-glucosamine" FT /ligand_id="ChEBI:CHEBI:62327" FT /ligand_label="1" FT /evidence="ECO:0000269|PubMed:16622409, FT ECO:0007744|PDB:2G7C" FT BINDING 2631 FT /ligand="alpha-D-galactosyl-(1->3)-beta-D-galactosyl- FT (1->4)-N-acetyl-beta-D-glucosamine" FT /ligand_id="ChEBI:CHEBI:62327" FT /ligand_label="2" FT /evidence="ECO:0000269|PubMed:16622409, FT ECO:0007744|PDB:2G7C" FT BINDING 2638..2641 FT /ligand="alpha-D-galactosyl-(1->3)-beta-D-galactosyl- FT (1->4)-N-acetyl-beta-D-glucosamine" FT /ligand_id="ChEBI:CHEBI:62327" FT /ligand_label="2" FT /evidence="ECO:0000269|PubMed:16622409, FT ECO:0007744|PDB:2G7C" FT BINDING 2658..2661 FT /ligand="alpha-D-galactosyl-(1->3)-beta-D-galactosyl- FT (1->4)-N-acetyl-beta-D-glucosamine" FT /ligand_id="ChEBI:CHEBI:62327" FT /ligand_label="2" FT /evidence="ECO:0000269|PubMed:16622409, FT ECO:0007744|PDB:2G7C" FT SITE 542..543 FT /note="Cleavage; by autolysis" FT /evidence="ECO:0000305|PubMed:19553670" FT MUTAGEN 542 FT /note="L->A: Abolished cleavage." FT /evidence="ECO:0000269|PubMed:19553670" FT MUTAGEN 589 FT /note="D->N: Abolished protease activity and FT autoprocessing." FT /evidence="ECO:0000269|PubMed:19553670" FT MUTAGEN 590 FT /note="D->N: Does not affect protease activity and FT autoprocessing." FT /evidence="ECO:0000269|PubMed:19553670" FT MUTAGEN 655 FT /note="H->A: Abolished protease activity and FT autoprocessing." FT /evidence="ECO:0000269|PubMed:19553670, FT ECO:0000269|PubMed:27571750" FT MUTAGEN 700 FT /note="C->A,S: Abolished protease activity and FT autoprocessing." FT /evidence="ECO:0000269|PubMed:19553670, FT ECO:0000269|PubMed:27571750" FT MUTAGEN 759 FT /note="H->A: Abolished autoprocessing." FT /evidence="ECO:0000269|PubMed:27571750" FT CONFLICT 2080 FT /note="L -> W (in Ref. 3; AGG91568)" FT /evidence="ECO:0000305" FT HELIX 6..12 FT /evidence="ECO:0007829|PDB:4DMV" FT HELIX 21..34 FT /evidence="ECO:0007829|PDB:4DMV" FT STRAND 38..40 FT /evidence="ECO:0007829|PDB:7POG" FT HELIX 41..61 FT /evidence="ECO:0007829|PDB:4DMV" FT HELIX 68..88 FT /evidence="ECO:0007829|PDB:4DMV" FT STRAND 95..100 FT /evidence="ECO:0007829|PDB:4DMV" FT HELIX 108..120 FT /evidence="ECO:0007829|PDB:4DMV" FT TURN 121..123 FT /evidence="ECO:0007829|PDB:5UQK" FT STRAND 124..130 FT /evidence="ECO:0007829|PDB:4DMV" FT STRAND 134..136 FT /evidence="ECO:0007829|PDB:7POG" FT HELIX 137..160 FT /evidence="ECO:0007829|PDB:4DMV" FT STRAND 162..164 FT /evidence="ECO:0007829|PDB:7POG" FT HELIX 167..192 FT /evidence="ECO:0007829|PDB:4DMV" FT STRAND 195..198 FT /evidence="ECO:0007829|PDB:7UBY" FT HELIX 201..212 FT /evidence="ECO:0007829|PDB:4DMV" FT HELIX 217..232 FT /evidence="ECO:0007829|PDB:4DMV" FT TURN 233..235 FT /evidence="ECO:0007829|PDB:4DMV" FT STRAND 236..238 FT /evidence="ECO:0007829|PDB:4DMV" FT TURN 239..243 FT /evidence="ECO:0007829|PDB:4DMV" FT HELIX 248..258 FT /evidence="ECO:0007829|PDB:4DMV" FT TURN 259..261 FT /evidence="ECO:0007829|PDB:4DMV" FT HELIX 264..279 FT /evidence="ECO:0007829|PDB:4DMV" FT STRAND 281..284 FT /evidence="ECO:0007829|PDB:4DMV" FT TURN 294..299 FT /evidence="ECO:0007829|PDB:4DMV" FT STRAND 304..306 FT /evidence="ECO:0007829|PDB:7U2P" FT HELIX 308..323 FT /evidence="ECO:0007829|PDB:4DMV" FT STRAND 325..328 FT /evidence="ECO:0007829|PDB:4R04" FT HELIX 334..336 FT /evidence="ECO:0007829|PDB:4DMV" FT HELIX 339..350 FT /evidence="ECO:0007829|PDB:4DMV" FT HELIX 355..357 FT /evidence="ECO:0007829|PDB:4DMV" FT STRAND 366..368 FT /evidence="ECO:0007829|PDB:4DMW" FT STRAND 373..377 FT /evidence="ECO:0007829|PDB:4DMV" FT STRAND 380..388 FT /evidence="ECO:0007829|PDB:4DMV" FT HELIX 393..417 FT /evidence="ECO:0007829|PDB:4DMV" FT TURN 418..420 FT /evidence="ECO:0007829|PDB:4DMV" FT HELIX 423..435 FT /evidence="ECO:0007829|PDB:4DMV" FT TURN 440..442 FT /evidence="ECO:0007829|PDB:4DMV" FT HELIX 443..449 FT /evidence="ECO:0007829|PDB:4DMV" FT HELIX 452..454 FT /evidence="ECO:0007829|PDB:4DMV" FT TURN 455..457 FT /evidence="ECO:0007829|PDB:4DMV" FT STRAND 458..460 FT /evidence="ECO:0007829|PDB:4R04" FT HELIX 464..467 FT /evidence="ECO:0007829|PDB:4DMV" FT HELIX 470..482 FT /evidence="ECO:0007829|PDB:4DMV" FT HELIX 494..497 FT /evidence="ECO:0007829|PDB:4DMV" FT HELIX 498..500 FT /evidence="ECO:0007829|PDB:4DMV" FT HELIX 504..506 FT /evidence="ECO:0007829|PDB:4DMV" FT HELIX 512..517 FT /evidence="ECO:0007829|PDB:4DMV" FT HELIX 523..536 FT /evidence="ECO:0007829|PDB:4DMV" FT HELIX 544..546 FT /evidence="ECO:0007829|PDB:7POG" FT HELIX 558..563 FT /evidence="ECO:0007829|PDB:3HO6" FT HELIX 565..569 FT /evidence="ECO:0007829|PDB:3HO6" FT STRAND 578..585 FT /evidence="ECO:0007829|PDB:3HO6" FT HELIX 590..602 FT /evidence="ECO:0007829|PDB:3HO6" FT HELIX 604..606 FT /evidence="ECO:0007829|PDB:3HO6" FT STRAND 607..611 FT /evidence="ECO:0007829|PDB:3HO6" FT HELIX 612..617 FT /evidence="ECO:0007829|PDB:3HO6" FT STRAND 619..623 FT /evidence="ECO:0007829|PDB:3HO6" FT STRAND 630..634 FT /evidence="ECO:0007829|PDB:3HO6" FT HELIX 640..642 FT /evidence="ECO:0007829|PDB:3HO6" FT STRAND 646..653 FT /evidence="ECO:0007829|PDB:3HO6" FT STRAND 658..661 FT /evidence="ECO:0007829|PDB:4R04" FT STRAND 663..665 FT /evidence="ECO:0007829|PDB:7POG" FT HELIX 670..684 FT /evidence="ECO:0007829|PDB:3HO6" FT TURN 685..687 FT /evidence="ECO:0007829|PDB:3HO6" FT STRAND 691..701 FT /evidence="ECO:0007829|PDB:3HO6" FT HELIX 709..711 FT /evidence="ECO:0007829|PDB:3HO6" FT HELIX 713..728 FT /evidence="ECO:0007829|PDB:3HO6" FT HELIX 734..736 FT /evidence="ECO:0007829|PDB:3HO6" FT STRAND 737..741 FT /evidence="ECO:0007829|PDB:3HO6" FT STRAND 746..748 FT /evidence="ECO:0007829|PDB:3HO6" FT STRAND 754..757 FT /evidence="ECO:0007829|PDB:3HO6" FT STRAND 761..764 FT /evidence="ECO:0007829|PDB:4R04" FT HELIX 766..771 FT /evidence="ECO:0007829|PDB:3HO6" FT STRAND 778..783 FT /evidence="ECO:0007829|PDB:3HO6" FT TURN 784..787 FT /evidence="ECO:0007829|PDB:3HO6" FT STRAND 788..795 FT /evidence="ECO:0007829|PDB:3HO6" FT HELIX 796..811 FT /evidence="ECO:0007829|PDB:7POG" FT STRAND 812..815 FT /evidence="ECO:0007829|PDB:7POG" FT HELIX 817..839 FT /evidence="ECO:0007829|PDB:7POG" FT HELIX 849..876 FT /evidence="ECO:0007829|PDB:7POG" FT STRAND 882..884 FT /evidence="ECO:0007829|PDB:7POG" FT STRAND 886..892 FT /evidence="ECO:0007829|PDB:7POG" FT TURN 894..896 FT /evidence="ECO:0007829|PDB:7POG" FT STRAND 897..903 FT /evidence="ECO:0007829|PDB:7POG" FT STRAND 905..907 FT /evidence="ECO:0007829|PDB:7POG" FT STRAND 910..915 FT /evidence="ECO:0007829|PDB:7POG" FT HELIX 919..936 FT /evidence="ECO:0007829|PDB:7POG" FT STRAND 942..944 FT /evidence="ECO:0007829|PDB:7POG" FT STRAND 945..949 FT /evidence="ECO:0007829|PDB:7U1Z" FT HELIX 954..971 FT /evidence="ECO:0007829|PDB:7POG" FT HELIX 972..974 FT /evidence="ECO:0007829|PDB:4R04" FT HELIX 978..981 FT /evidence="ECO:0007829|PDB:7POG" FT HELIX 983..996 FT /evidence="ECO:0007829|PDB:7POG" FT HELIX 1000..1002 FT /evidence="ECO:0007829|PDB:7POG" FT HELIX 1006..1018 FT /evidence="ECO:0007829|PDB:7POG" FT STRAND 1027..1030 FT /evidence="ECO:0007829|PDB:7POG" FT HELIX 1044..1053 FT /evidence="ECO:0007829|PDB:7POG" FT HELIX 1056..1064 FT /evidence="ECO:0007829|PDB:7POG" FT STRAND 1068..1070 FT /evidence="ECO:0007829|PDB:7POG" FT HELIX 1081..1086 FT /evidence="ECO:0007829|PDB:7UBX" FT HELIX 1088..1092 FT /evidence="ECO:0007829|PDB:7UBX" FT TURN 1099..1103 FT /evidence="ECO:0007829|PDB:7UBX" FT STRAND 1107..1109 FT /evidence="ECO:0007829|PDB:7UBX" FT STRAND 1112..1116 FT /evidence="ECO:0007829|PDB:7UBX" FT HELIX 1119..1129 FT /evidence="ECO:0007829|PDB:7UBX" FT HELIX 1131..1135 FT /evidence="ECO:0007829|PDB:7UBX" FT STRAND 1137..1141 FT /evidence="ECO:0007829|PDB:7UBX" FT TURN 1142..1144 FT /evidence="ECO:0007829|PDB:7UBX" FT STRAND 1145..1148 FT /evidence="ECO:0007829|PDB:7UBX" FT STRAND 1154..1158 FT /evidence="ECO:0007829|PDB:7UBX" FT TURN 1159..1162 FT /evidence="ECO:0007829|PDB:7UBX" FT STRAND 1163..1166 FT /evidence="ECO:0007829|PDB:7UBX" FT STRAND 1169..1171 FT /evidence="ECO:0007829|PDB:7UBX" FT STRAND 1173..1175 FT /evidence="ECO:0007829|PDB:7UBX" FT STRAND 1181..1183 FT /evidence="ECO:0007829|PDB:7UBX" FT STRAND 1186..1188 FT /evidence="ECO:0007829|PDB:7UBX" FT STRAND 1194..1199 FT /evidence="ECO:0007829|PDB:7UBX" FT STRAND 1201..1203 FT /evidence="ECO:0007829|PDB:4R04" FT HELIX 1204..1208 FT /evidence="ECO:0007829|PDB:7UBX" FT STRAND 1220..1223 FT /evidence="ECO:0007829|PDB:7UBX" FT STRAND 1230..1238 FT /evidence="ECO:0007829|PDB:7UBX" FT HELIX 1242..1244 FT /evidence="ECO:0007829|PDB:7U1Z" FT HELIX 1248..1259 FT /evidence="ECO:0007829|PDB:7UBX" FT TURN 1261..1263 FT /evidence="ECO:0007829|PDB:7UBX" FT STRAND 1266..1283 FT /evidence="ECO:0007829|PDB:7UBX" FT STRAND 1286..1291 FT /evidence="ECO:0007829|PDB:7UBX" FT STRAND 1294..1300 FT /evidence="ECO:0007829|PDB:7UBX" FT HELIX 1307..1310 FT /evidence="ECO:0007829|PDB:7UBX" FT STRAND 1313..1318 FT /evidence="ECO:0007829|PDB:7UBX" FT STRAND 1321..1327 FT /evidence="ECO:0007829|PDB:7UBX" FT STRAND 1334..1339 FT /evidence="ECO:0007829|PDB:7UBX" FT STRAND 1344..1348 FT /evidence="ECO:0007829|PDB:7UBX" FT TURN 1350..1353 FT /evidence="ECO:0007829|PDB:7UBX" FT STRAND 1354..1359 FT /evidence="ECO:0007829|PDB:7UBX" FT STRAND 1362..1368 FT /evidence="ECO:0007829|PDB:7UBX" FT TURN 1370..1375 FT /evidence="ECO:0007829|PDB:7UBX" FT STRAND 1377..1379 FT /evidence="ECO:0007829|PDB:7UBX" FT STRAND 1382..1385 FT /evidence="ECO:0007829|PDB:7UBX" FT STRAND 1388..1395 FT /evidence="ECO:0007829|PDB:7UBX" FT STRAND 1403..1412 FT /evidence="ECO:0007829|PDB:7UBX" FT STRAND 1414..1420 FT /evidence="ECO:0007829|PDB:7UBX" FT TURN 1421..1424 FT /evidence="ECO:0007829|PDB:7UBX" FT STRAND 1425..1432 FT /evidence="ECO:0007829|PDB:7UBX" FT HELIX 1434..1439 FT /evidence="ECO:0007829|PDB:7UBX" FT HELIX 1441..1450 FT /evidence="ECO:0007829|PDB:7UBX" FT STRAND 1456..1462 FT /evidence="ECO:0007829|PDB:7UBX" FT HELIX 1465..1467 FT /evidence="ECO:0007829|PDB:4R04" FT STRAND 1469..1477 FT /evidence="ECO:0007829|PDB:7POG" FT STRAND 1480..1489 FT /evidence="ECO:0007829|PDB:7POG" FT STRAND 1491..1497 FT /evidence="ECO:0007829|PDB:7POG" FT STRAND 1500..1506 FT /evidence="ECO:0007829|PDB:7POG" FT STRAND 1511..1518 FT /evidence="ECO:0007829|PDB:7POG" FT STRAND 1521..1529 FT /evidence="ECO:0007829|PDB:7POG" FT HELIX 1530..1532 FT /evidence="ECO:0007829|PDB:7POG" FT STRAND 1534..1544 FT /evidence="ECO:0007829|PDB:7POG" FT STRAND 1546..1548 FT /evidence="ECO:0007829|PDB:4R04" FT STRAND 1549..1557 FT /evidence="ECO:0007829|PDB:7POG" FT HELIX 1559..1571 FT /evidence="ECO:0007829|PDB:7POG" FT STRAND 1572..1574 FT /evidence="ECO:0007829|PDB:7POG" FT STRAND 1576..1578 FT /evidence="ECO:0007829|PDB:7POG" FT HELIX 1579..1589 FT /evidence="ECO:0007829|PDB:7POG" FT HELIX 1591..1594 FT /evidence="ECO:0007829|PDB:7POG" FT STRAND 1601..1613 FT /evidence="ECO:0007829|PDB:7POG" FT STRAND 1615..1623 FT /evidence="ECO:0007829|PDB:7POG" FT STRAND 1627..1637 FT /evidence="ECO:0007829|PDB:7POG" FT STRAND 1639..1645 FT /evidence="ECO:0007829|PDB:7POG" FT HELIX 1647..1649 FT /evidence="ECO:0007829|PDB:7U1Z" FT STRAND 1651..1657 FT /evidence="ECO:0007829|PDB:7POG" FT STRAND 1670..1676 FT /evidence="ECO:0007829|PDB:7POG" FT TURN 1677..1680 FT /evidence="ECO:0007829|PDB:7POG" FT HELIX 1681..1683 FT /evidence="ECO:0007829|PDB:7POG" FT STRAND 1687..1690 FT /evidence="ECO:0007829|PDB:7POG" FT STRAND 1698..1702 FT /evidence="ECO:0007829|PDB:7POG" FT STRAND 1713..1716 FT /evidence="ECO:0007829|PDB:7POG" FT STRAND 1726..1732 FT /evidence="ECO:0007829|PDB:7POG" FT STRAND 1734..1742 FT /evidence="ECO:0007829|PDB:7POG" FT STRAND 1745..1756 FT /evidence="ECO:0007829|PDB:7POG" FT STRAND 1758..1765 FT /evidence="ECO:0007829|PDB:7POG" FT TURN 1766..1769 FT /evidence="ECO:0007829|PDB:7POG" FT HELIX 1772..1775 FT /evidence="ECO:0007829|PDB:7POG" FT STRAND 1778..1781 FT /evidence="ECO:0007829|PDB:7POG" FT STRAND 1783..1785 FT /evidence="ECO:0007829|PDB:7POG" FT STRAND 1787..1789 FT /evidence="ECO:0007829|PDB:7POG" FT HELIX 1790..1796 FT /evidence="ECO:0007829|PDB:7POG" FT HELIX 1805..1807 FT /evidence="ECO:0007829|PDB:7POG" FT STRAND 1811..1814 FT /evidence="ECO:0007829|PDB:7POG" FT STRAND 1821..1823 FT /evidence="ECO:0007829|PDB:7POG" FT STRAND 1827..1829 FT /evidence="ECO:0007829|PDB:7POG" FT STRAND 1832..1836 FT /evidence="ECO:0007829|PDB:7POG" FT STRAND 1839..1843 FT /evidence="ECO:0007829|PDB:7POG" FT TURN 1845..1847 FT /evidence="ECO:0007829|PDB:7POG" FT STRAND 1853..1857 FT /evidence="ECO:0007829|PDB:7POG" FT STRAND 1860..1864 FT /evidence="ECO:0007829|PDB:7POG" FT TURN 1866..1868 FT /evidence="ECO:0007829|PDB:7POG" FT STRAND 1876..1878 FT /evidence="ECO:0007829|PDB:7POG" FT STRAND 1881..1883 FT /evidence="ECO:0007829|PDB:7POG" FT STRAND 1894..1898 FT /evidence="ECO:0007829|PDB:7POG" FT STRAND 1901..1906 FT /evidence="ECO:0007829|PDB:7POG" FT STRAND 1908..1913 FT /evidence="ECO:0007829|PDB:7U1Z" FT STRAND 1924..1929 FT /evidence="ECO:0007829|PDB:7POG" FT STRAND 1932..1936 FT /evidence="ECO:0007829|PDB:7POG" FT STRAND 1940..1942 FT /evidence="ECO:0007829|PDB:7POG" FT STRAND 1945..1956 FT /evidence="ECO:0007829|PDB:7POG" FT TURN 1958..1960 FT /evidence="ECO:0007829|PDB:7POG" FT STRAND 1966..1970 FT /evidence="ECO:0007829|PDB:7POG" FT STRAND 1973..1977 FT /evidence="ECO:0007829|PDB:7POG" FT TURN 1979..1981 FT /evidence="ECO:0007829|PDB:7POG" FT STRAND 1987..1991 FT /evidence="ECO:0007829|PDB:7POG" FT STRAND 1994..1998 FT /evidence="ECO:0007829|PDB:7POG" FT STRAND 2000..2002 FT /evidence="ECO:0007829|PDB:7POG" FT STRAND 2008..2012 FT /evidence="ECO:0007829|PDB:7POG" FT STRAND 2015..2020 FT /evidence="ECO:0007829|PDB:7POG" FT TURN 2021..2023 FT /evidence="ECO:0007829|PDB:7U1Z" FT STRAND 2028..2032 FT /evidence="ECO:0007829|PDB:7U1Z" FT STRAND 2037..2040 FT /evidence="ECO:0007829|PDB:7POG" FT TURN 2044..2046 FT /evidence="ECO:0007829|PDB:7POG" FT STRAND 2052..2054 FT /evidence="ECO:0007829|PDB:7POG" FT STRAND 2062..2065 FT /evidence="ECO:0007829|PDB:7POG" FT STRAND 2067..2070 FT /evidence="ECO:0007829|PDB:7U1Z" FT STRAND 2079..2083 FT /evidence="ECO:0007829|PDB:7U1Z" FT TURN 2084..2087 FT /evidence="ECO:0007829|PDB:7POG" FT STRAND 2092..2094 FT /evidence="ECO:0007829|PDB:7POG" FT STRAND 2100..2102 FT /evidence="ECO:0007829|PDB:7POG" FT STRAND 2109..2111 FT /evidence="ECO:0007829|PDB:7POG" FT STRAND 2113..2116 FT /evidence="ECO:0007829|PDB:7POG" FT STRAND 2121..2125 FT /evidence="ECO:0007829|PDB:7POG" FT STRAND 2128..2131 FT /evidence="ECO:0007829|PDB:7POG" FT STRAND 2134..2137 FT /evidence="ECO:0007829|PDB:7POG" FT STRAND 2142..2146 FT /evidence="ECO:0007829|PDB:7POG" FT STRAND 2149..2151 FT /evidence="ECO:0007829|PDB:7POG" FT STRAND 2162..2166 FT /evidence="ECO:0007829|PDB:7POG" FT STRAND 2169..2173 FT /evidence="ECO:0007829|PDB:7POG" FT STRAND 2176..2181 FT /evidence="ECO:0007829|PDB:7U1Z" FT STRAND 2192..2199 FT /evidence="ECO:0007829|PDB:7POG" FT STRAND 2201..2204 FT /evidence="ECO:0007829|PDB:7POG" FT STRAND 2206..2210 FT /evidence="ECO:0007829|PDB:7POG" FT STRAND 2213..2215 FT /evidence="ECO:0007829|PDB:7POG" FT HELIX 2217..2219 FT /evidence="ECO:0007829|PDB:7POG" FT STRAND 2222..2224 FT /evidence="ECO:0007829|PDB:7POG" FT TURN 2226..2228 FT /evidence="ECO:0007829|PDB:7POG" FT STRAND 2234..2236 FT /evidence="ECO:0007829|PDB:7POG" FT STRAND 2238..2240 FT /evidence="ECO:0007829|PDB:7POG" FT STRAND 2243..2245 FT /evidence="ECO:0007829|PDB:7POG" FT STRAND 2254..2258 FT /evidence="ECO:0007829|PDB:7POG" FT STRAND 2261..2267 FT /evidence="ECO:0007829|PDB:7POG" FT STRAND 2270..2273 FT /evidence="ECO:0007829|PDB:7POG" FT STRAND 2276..2278 FT /evidence="ECO:0007829|PDB:7POG" FT STRAND 2285..2288 FT /evidence="ECO:0007829|PDB:7POG" FT STRAND 2292..2295 FT /evidence="ECO:0007829|PDB:7POG" FT STRAND 2306..2311 FT /evidence="ECO:0007829|PDB:7U1Z" FT STRAND 2312..2314 FT /evidence="ECO:0007829|PDB:7POG" FT STRAND 2316..2318 FT /evidence="ECO:0007829|PDB:7POG" FT STRAND 2320..2322 FT /evidence="ECO:0007829|PDB:7POG" FT STRAND 2329..2333 FT /evidence="ECO:0007829|PDB:7POG" FT STRAND 2335..2338 FT /evidence="ECO:0007829|PDB:7U1Z" FT STRAND 2340..2342 FT /evidence="ECO:0007829|PDB:7POG" FT STRAND 2348..2352 FT /evidence="ECO:0007829|PDB:7U1Z" FT STRAND 2355..2359 FT /evidence="ECO:0007829|PDB:7U1Z" FT STRAND 2361..2363 FT /evidence="ECO:0007829|PDB:7POG" FT STRAND 2369..2373 FT /evidence="ECO:0007829|PDB:7U1Z" FT STRAND 2374..2376 FT /evidence="ECO:0007829|PDB:7POG" FT TURN 2382..2384 FT /evidence="ECO:0007829|PDB:7U1Z" FT STRAND 2390..2393 FT /evidence="ECO:0007829|PDB:7U1Z" FT STRAND 2395..2397 FT /evidence="ECO:0007829|PDB:2QJ6" FT STRAND 2399..2401 FT /evidence="ECO:0007829|PDB:2QJ6" FT STRAND 2410..2412 FT /evidence="ECO:0007829|PDB:2QJ6" FT STRAND 2417..2421 FT /evidence="ECO:0007829|PDB:7U1Z" FT STRAND 2424..2429 FT /evidence="ECO:0007829|PDB:2QJ6" FT STRAND 2442..2445 FT /evidence="ECO:0007829|PDB:2QJ6" FT STRAND 2448..2451 FT /evidence="ECO:0007829|PDB:2QJ6" FT STRAND 2454..2457 FT /evidence="ECO:0007829|PDB:2QJ6" FT STRAND 2462..2465 FT /evidence="ECO:0007829|PDB:2G7C" FT STRAND 2468..2472 FT /evidence="ECO:0007829|PDB:2G7C" FT STRAND 2474..2478 FT /evidence="ECO:0007829|PDB:2QJ6" FT STRAND 2482..2486 FT /evidence="ECO:0007829|PDB:2G7C" FT STRAND 2489..2493 FT /evidence="ECO:0007829|PDB:2G7C" FT TURN 2495..2497 FT /evidence="ECO:0007829|PDB:2G7C" FT STRAND 2503..2507 FT /evidence="ECO:0007829|PDB:2G7C" FT STRAND 2510..2514 FT /evidence="ECO:0007829|PDB:2G7C" FT STRAND 2523..2527 FT /evidence="ECO:0007829|PDB:2G7C" FT STRAND 2530..2534 FT /evidence="ECO:0007829|PDB:2G7C" FT STRAND 2539..2542 FT /evidence="ECO:0007829|PDB:5UMI" FT STRAND 2553..2558 FT /evidence="ECO:0007829|PDB:2G7C" FT STRAND 2561..2565 FT /evidence="ECO:0007829|PDB:2G7C" FT STRAND 2574..2578 FT /evidence="ECO:0007829|PDB:4NBX" FT STRAND 2581..2585 FT /evidence="ECO:0007829|PDB:4NBX" FT TURN 2587..2589 FT /evidence="ECO:0007829|PDB:4NBX" FT STRAND 2590..2592 FT /evidence="ECO:0007829|PDB:4NBZ" FT STRAND 2595..2599 FT /evidence="ECO:0007829|PDB:4NBX" FT STRAND 2602..2607 FT /evidence="ECO:0007829|PDB:4NBX" FT STRAND 2614..2618 FT /evidence="ECO:0007829|PDB:4NBX" FT STRAND 2621..2626 FT /evidence="ECO:0007829|PDB:4NBX" FT STRAND 2630..2633 FT /evidence="ECO:0007829|PDB:5UMI" FT STRAND 2644..2649 FT /evidence="ECO:0007829|PDB:4NBX" FT STRAND 2652..2656 FT /evidence="ECO:0007829|PDB:4NBX" FT STRAND 2660..2662 FT /evidence="ECO:0007829|PDB:2F6E" FT STRAND 2665..2669 FT /evidence="ECO:0007829|PDB:4NBX" FT STRAND 2672..2676 FT /evidence="ECO:0007829|PDB:4NBX" FT TURN 2678..2680 FT /evidence="ECO:0007829|PDB:4NBX" FT STRAND 2686..2691 FT /evidence="ECO:0007829|PDB:4NBX" FT STRAND 2694..2698 FT /evidence="ECO:0007829|PDB:4NBX" FT STRAND 2700..2702 FT /evidence="ECO:0007829|PDB:5UMI" FT STRAND 2704..2707 FT /evidence="ECO:0007829|PDB:2G7C" SQ SEQUENCE 2710 AA; 308056 MW; 0A6E52CE84C14421 CRC64; MSLISKEELI KLAYSIRPRE NEYKTILTNL DEYNKLTTNN NENKYLQLKK LNESIDVFMN KYKTSSRNRA LSNLKKDILK EVILIKNSNT SPVEKNLHFV WIGGEVSDIA LEYIKQWADI NAEYNIKLWY DSEAFLVNTL KKAIVESSTT EALQLLEEEI QNPQFDNMKF YKKRMEFIYD RQKRFINYYK SQINKPTVPT IDDIIKSHLV SEYNRDETVL ESYRTNSLRK INSNHGIDIR ANSLFTEQEL LNIYSQELLN RGNLAAASDI VRLLALKNFG GVYLDVDMLP GIHSDLFKTI SRPSSIGLDR WEMIKLEAIM KYKKYINNYT SENFDKLDQQ LKDNFKLIIE SKSEKSEIFS KLENLNVSDL EIKIAFALGS VINQALISKQ GSYLTNLVIE QVKNRYQFLN QHLNPAIESD NNFTDTTKIF HDSLFNSATA ENSMFLTKIA PYLQVGFMPE ARSTISLSGP GAYASAYYDF INLQENTIEK TLKASDLIEF KFPENNLSQL TEQEINSLWS FDQASAKYQF EKYVRDYTGG SLSEDNGVDF NKNTALDKNY LLNNKIPSNN VEEAGSKNYV HYIIQLQGDD ISYEATCNLF SKNPKNSIII QRNMNESAKS YFLSDDGESI LELNKYRIPE RLKNKEKVKV TFIGHGKDEF NTSEFARLSV DSLSNEISSF LDTIKLDISP KNVEVNLLGC NMFSYDFNVE ETYPGKLLLS IMDKITSTLP DVNKNSITIG ANQYEVRINS EGRKELLAHS GKWINKEEAI MSDLSSKEYI FFDSIDNKLK AKSKNIPGLA SISEDIKTLL LDASVSPDTK FILNNLKLNI ESSIGDYIYY EKLEPVKNII HNSIDDLIDE FNLLENVSDE LYELKKLNNL DEKYLISFED ISKNNSTYSV RFINKSNGES VYVETEKEIF SKYSEHITKE ISTIKNSIIT DVNGNLLDNI QLDHTSQVNT LNAAFFIQSL IDYSSNKDVL NDLSTSVKVQ LYAQLFSTGL NTIYDSIQLV NLISNAVNDT INVLPTITEG IPIVSTILDG INLGAAIKEL LDEHDPLLKK ELEAKVGVLA INMSLSIAAT VASIVGIGAE VTIFLLPIAG ISAGIPSLVN NELILHDKAT SVVNYFNHLS ESKKYGPLKT EDDKILVPID DLVISEIDFN NNSIKLGTCN ILAMEGGSGH TVTGNIDHFF SSPSISSHIP SLSIYSAIGI ETENLDFSKK IMMLPNAPSR VFWWETGAVP GLRSLENDGT RLLDSIRDLY PGKFYWRFYA FFDYAITTLK PVYEDTNIKI KLDKDTRNFI MPTITTNEIR NKLSYSFDGA GGTYSLLLSS YPISTNINLS KDDLWIFNID NEVREISIEN GTIKKGKLIK DVLSKIDINK NKLIIGNQTI DFSGDIDNKD RYIFLTCELD DKISLIIEIN LVAKSYSLLL SGDKNYLISN LSNTIEKINT LGLDSKNIAY NYTDESNNKY FGAISKTSQK SIIHYKKDSK NILEFYNDST LEFNSKDFIA EDINVFMKDD INTITGKYYV DNNTDKSIDF SISLVSKNQV KVNGLYLNES VYSSYLDFVK NSDGHHNTSN FMNLFLDNIS FWKLFGFENI NFVIDKYFTL VGKTNLGYVE FICDNNKNID IYFGEWKTSS SKSTIFSGNG RNVVVEPIYN PDTGEDISTS LDFSYEPLYG IDRYINKVLI APDLYTSLIN INTNYYSNEY YPEIIVLNPN TFHKKVNINL DSSSFEYKWS TEGSDFILVR YLEESNKKIL QKIRIKGILS NTQSFNKMSI DFKDIKKLSL GYIMSNFKSF NSENELDRDH LGFKIIDNKT YYYDEDSKLV KGLININNSL FYFDPIEFNL VTGWQTINGK KYYFDINTGA ALTSYKIING KHFYFNNDGV MQLGVFKGPD GFEYFAPANT QNNNIEGQAI VYQSKFLTLN GKKYYFDNNS KAVTGWRIIN NEKYYFNPNN AIAAVGLQVI DNNKYYFNPD TAIISKGWQT VNGSRYYFDT DTAIAFNGYK TIDGKHFYFD SDCVVKIGVF STSNGFEYFA PANTYNNNIE GQAIVYQSKF LTLNGKKYYF DNNSKAVTGL QTIDSKKYYF NTNTAEAATG WQTIDGKKYY FNTNTAEAAT GWQTIDGKKY YFNTNTAIAS TGYTIINGKH FYFNTDGIMQ IGVFKGPNGF EYFAPANTDA NNIEGQAILY QNEFLTLNGK KYYFGSDSKA VTGWRIINNK KYYFNPNNAI AAIHLCTINN DKYYFSYDGI LQNGYITIER NNFYFDANNE SKMVTGVFKG PNGFEYFAPA NTHNNNIEGQ AIVYQNKFLT LNGKKYYFDN DSKAVTGWQT IDGKKYYFNL NTAEAATGWQ TIDGKKYYFN LNTAEAATGW QTIDGKKYYF NTNTFIASTG YTSINGKHFY FNTDGIMQIG VFKGPNGFEY FAPANTDANN IEGQAILYQN KFLTLNGKKY YFGSDSKAVT GLRTIDGKKY YFNTNTAVAV TGWQTINGKK YYFNTNTSIA STGYTIISGK HFYFNTDGIM QIGVFKGPDG FEYFAPANTD ANNIEGQAIR YQNRFLYLHD NIYYFGNNSK AATGWVTIDG NRYYFEPNTA MGANGYKTID NKNFYFRNGL PQIGVFKGSN GFEYFAPANT DANNIEGQAI RYQNRFLHLL GKIYYFGNNS KAVTGWQTIN GKVYYFMPDT AMAAAGGLFE IDGVIYFFGV DGVKAPGIYG //