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ProGT64 (TcsH)

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ProGT ID ProGT64 (TcsH)
Organism Information
Organism NamePaeniclostridium sordellii strain VPI 9048
Clinical ImplicationPathogenic
DomainBacteria
PhylumFirmicutes
ClassificationFamily: Clostridiaceae
Order: Clostridiales
Class: Clostridia
Phylum: Firmicutes
Taxonomic ID (NCBI)1505
Genome Information
Gene BankKC814176.1
EMBLKC814176
Gene Information
Gene NametcsH
NCBI Reference SequenceKC814176
Protein information
Protein NameTcsH 
UniProtKB/ SwissProt IDM9ZTT7
UniProtKB Sequence>tr|M9ZTT7|M9ZTT7_PAESO Haemorrhagic Toxin OS=Paeniclostridium sordellii GN=tcsH PE=4 SV=1 MSLISKDELIKLAYSIKPREDEYKTILTNLDEYNKLVTINNKDKYLQLKKLNDSIDIFIN KYKKSSRNRALFNLKKDISKEVILIKNSNISPVEKNLHFVWIGGEVSDTALEYINQWADI NRDYNIRVWYDGEAFLVNTLKKAIVEHSTTDTLQLFEEDIKNPQFDNMKFYKKRMEFIYE RQNRFINYYKSEINKPIKPTIDDIIKSHLVSEYNKNSESLELYRRTSFEKISNNNGVDIR NNNLFTEQELLNIYNQELLDRENLAAASDLVRLLALKDFGGVYLDVDMLPGIQPDLFKTI SRPSSIGVDSWEMIKLEAIMKYKKYIKNYTSKNFDKLDQQLKDDFQITLESKSEKSEIFS KLGNLDVSDLEIKIAFALGSVINQALISKKGSYLTNLVIEQVKNRYKFLNQHLNPAIELG GNFSDTTKNFHDSLFNSATSENSMFLTKIASYLQVGFMPEARATISLSGPGAYSSAYYDF INLQDNTIEKTLNASDLMEFKFPESNLSQFTEQEINSLWSFDQASAKYQFEKYVRDYTQE SLSEDSELDFNKNTVLDKNYLLNNKIPSNNVEETGSKNYVHYIIQLQGDDISYESACNLF SKNPKNSVIIQRNMNESAKSYFLSDNGESISELNKYRIPQRLKNKEKIKVTFIGHGKDEF NTSEFAKLSVDSLSNEISSFLDIMKLDISPKNVEINLLGCNMFSYNVNVEETYPGKLLLN NIDKIISTLPNVNKDNITIGANQYEVRINNEGRKELLDHSGQWLNKEEAIMNDLSSKEYI FFDSIENRPKAKSKNLIELASISDNIKTLLLDTNIDPETKFILNNLKLNIESSIDNNIYY EKLEPVKNIIHNSIDNLTNEFNLIENVSDELYELKKINNLDDNYLISFEDISKNDSTYTI RFINKNSGESVHIQTEKEIFLKYGEHITQEINTIKNNIIIDVNGNLIGNIELEHAPQVNT LNAAFFIQSLIDYSNNKDVLNNLRTSVKVQLYAQLFSTGLNTIYDSIQLVNLISNAINDA INVLPTLTEGVPILATILDGISLGAAIKELSETNDPLLKKELEAKVGIIAINMSLSLASM ISTVIGVGSELAIFLLPIAGISAGIPSLVNNELILHDKATSVVNYFTHLSESKKYGPFKL EDDKILSPIDDLVISEIDFNTDSIKLGTCDILSMEGGSGYTVTNDIDHFFSSPYINSNIP PLSIYPVMNIQTTNLDFSKDLMMLPNAPSRLLWWETGAVPGLRSLETDGTRLLDSIRDFY PGKFYWRFYAWFDFAITTLKPVYENTNIKIKLDKNTRNFIMPTITTDVIRNNLSYSFTGS GGTYSLLLSSHPISTNINLSKDDLWIFNIDNKVREISIQNGTIKKGNLVRNALSNLDINK NKLTIDNQIINFSGDVDNKYRYIFLNCSLDDEISLMIEINLFAKSYNLILSGNKDYLISN LSTIINKINNLGLNSKNISYNYTDEFNNKYFGVISKTNQKSIICYKKGSKNILELYNGNM LLFDSKDFIADDINIFMKDDINTITGKYYIDNNLDISVDFSISLISKNKVKVNGLYLNEY GYASFLEFIKNSDGHHNTSNFINLFLDNIGFWKLFGFNNIEFVIDKYFAITGKTDMGYIE FICDNNKNIDIYFGEWKTSSTKNTIFSGNGRNLIVEPIYDINAGDNISTSIDFSYEYISG IDIYINKILIVPNLYTELVNINTDYSSNKYFPEIIVLNTDTFHDKVNINLDSSSLDYEWA IDGSDFILSRYLEENNRKILQKIRIKDILSNTKSFNKMMIDFKDIKNISLDHIMNNFKSF NSESELDRDHFGFKTIDSKTYYYNEVGKLVKGLININDSLFYFDTIESNLVTGWKTINGK TYYFDINNGVAYIGYKTIDGKNFYFDGNGIMQIGVFKVPDGFKYFAPANTYNNNEEGQTI VYQNKFLTINGKKYYFDNNSKAVTGWQIINGNKYYFDTNTGIAAVGLQIINNNKYYFNPH TAIAATGWQSINNAKYYFDINTYIGTTGYKTIDSKNFYFDSNCIMQIGVFKVSDGFKYFA PANTYNNNEEGQAIVYQNKFLTINGKRYYFDNNSKAVTGWHTIDGKKYYFNPNTAIAATG WHTIDDKKYYFNPDTAIAATGWHTIDDKKYYFNPNTGITSTGETTINNKSFYFNDKGIMQ IGVFKVPDGFKYFAPANTHNNNLEGQAIVYQNKFLTINGKKYYFDNNSKAITGWQVIDDK KYYFNSNTAVADTNLCTINNEKYYFSYDGILQNGYITIGRLNFYFDSNNDSKMTTGVFKG PNGFEYFAPANTYNNNLEGQAIVYQNKFLTINGKKYYFDNKSKAVTGWQTIDGKKYYFNP NTAIAAMGWQAIDGKKYYFNPNTAIATTGWQTIDGKKYYFNPNTAIAATGWQAIDGKKYY FNPNTATTSIGYTTINSKNFYFNNDGIMQLGVFKGPDGFEYFAPANTHNNNEEGQSITYQ NKFLIFNEDVYYFDSSSKAVTGWRTIDDHRFYFEPNTGIGANGYKTLDGKNFYFRNGLPQ FGVFKGPDGFEYFAPANTHNNNEEGQSITYQNKFLVFLGNRYYFDSSSKAVTGWQTINGN TYYFMPDTAIAAAGGFFTIDGAIYFFGIDGVKQPGIYG
EMBL CDSAGK40891
Sequence length2618 AA
Subcellular LocationHost cell plasma membrane
Function in Native Organism 1) It is a secretory glycosyltransferase which glycosylates the Rho family protein of host.
Potential Application1) Potential veterinary vaccine candidate against Clostridium sordellii infections.
Additional Information1) According to sequence similarity, TcsH is highly related to Toxin B (TcdB) from C. difficile
2) In vitro studies show that it glycosylate Rho-GTPases and Ras-GTPases of host protein during infection.
3) Recombinant LCGT transferase domains (rN) rN-TcsH-9048 glucosylated preferably Rho-GTPases but also Ras-GTPases to some extent.
4) rN-TcsH-9048 differ from the respective full-length TcsH-9048, which exclusively glucosylate Rho-GTPases.
5) Vero cells treated with full-length TcsH-9048 showed glucosylation of Ras, albeit to a lower extent than of Rho-GTPases.
Glycosyltransferase Information
Glycosylation TypeO- (Thr) linked 
CAZY FamilyGT44
EC Number (BRENDA)2.4.1.B62.13625.
Mechanism of Glycan TransferSequential
Donor TypeNucleotide activated sugars
Donor SpecificityUDP-Glc and UDP-GlcNAc
Glycan Information
Glycan transferredMonosaccharides (GlcNAc and Glc) 
Experimental_strategiesIn vitro 
Acceptor Subtrate Information
Acceptor Substrate name RhoA
Acceptor Substrate name Rac1
Acceptor Substrate name Ras
Acceptor Substrate name Cdc42Hs
Litrature
Year Of Validation2013 
Reference Thiele, T. L., Stuber, T. P., & Hauer, P. J. (2013). Detection of Clostridium sordellii strains expressing hemorrhagic toxin (TcsH) and implications for diagnostics and regulation of veterinary vaccines. Vaccine, 31(44), 5082-5087.

Authors Thiele, T. L., Stuber, T. P., & Hauer, P. J.
Research groupsCenter for Veterinary Biologics, Animal and Plant Health Inspection Service, United States Department of Agriculture, 1920 Dayton Avenue, Ames, IA 50010, USA
Corresponding Author Hauer, P. J.
ContactsCenter for Veterinary Biologics, Animal and Plant Health Inspection Service, United States Department of Agriculture, 1920 Dayton Avenue, Ames, IA 50010, USA
Reference Genth, H., Pauillac, S., Schelle, I., Bouvet, P., Bouchier, C., Varela?Chavez, C., Just, I. & Popoff, M. R. (2014). Haemorrhagic toxin and lethal toxin from C lostridium sordellii strain vpi9048: molecular characterization and comparative analysis of substrate specificity of the large clostridial glucosylating toxins. Cellular microbiology, 16(11), 1706-1721.

Authors Genth, H., Pauillac, S., Schelle, I., Bouvet, P., Bouchier, C., Varela?Chavez, C., Just, I. & Popoff, M. R.
Research groupsInstitute of Toxicology, Medical School Hannover, Hannover, Germany.
Corresponding Author Popoff, M. R.
ContactsInstitute of Toxicology, Medical School Hannover, Hannover, Germany.
Reference Ziegler, M. O., Jank, T., Aktories, K., & Schulz, G. E. (2008). Conformational changes and reaction of clostridial glycosylating toxins. Journal of molecular biology, 377(5), 1346-1356.

Authors Ziegler, M. O., Jank, T., Aktories, K., & Schulz, G. E.
Research groupsInstitute of Organic Chemistry and Biochemistry, Albert-Ludwigs-University, Albertstr. 21, D-79104 Freiburg im Breisgau, Germany.
Corresponding Author Schulz, G. E.
ContactsInstitute of Organic Chemistry and Biochemistry, Albert-Ludwigs-University, Albertstr. 21, D-79104 Freiburg im Breisgau, Germany.
Reference Huelsenbeck, S. C., Klose, I., Reichenbach, M., Huelsenbeck, J., & Genth, H. (2009). Distinct kinetics of (H/K/N) Ras glucosylation and Rac1 glucosylation catalysed by Clostridium sordellii lethal toxin. FEBS letters, 583(19), 3133-3139.

Authors Huelsenbeck, S. C., Klose, I., Reichenbach, M., Huelsenbeck, J., & Genth, H.
Research groupsInstitute of Toxicology, Hannover Medical School, D-30625 Hannover, Germany
Corresponding Author Genth, H.
ContactsInstitute of Toxicology, Hannover Medical School, D-30625 Hannover, Germany