Protein: Toxin A (EC 3.4.22.-) [Cleaved into: N-acetylglucosaminyltransferase TcdA (EC 2.4.1.-)] (Q46149)
Organism: Clostridium novyi
Function: Precursor of a cytotoxin, which enters into host cells and mediates autoprocessing to release the active toxin (N-acetylglucosaminyltransferase TcdA) into the host cytosol (By similarity). Once entered into host cells, acidification in the endosome promotes the membrane insertion of the translocation region and formation of a pore, leading to translocation of the GT44 and peptidase C80 domains across the endosomal membrane (By similarity). This activates the peptidase C80 domain and autocatalytic processing, releasing the N-terminal part (N-acetylglucosaminyltransferase TcdA), which constitutes the active part of the toxin, in the cytosol.
Subcellular location: [Toxin A]: Secreted {ECO:0000250|UniProtKB:P18177}. Host endosome membrane {ECO:0000305|PubMed:20498856}. Note=Secreted from C.novyi cell into the extracellular environment via help of holin-like protein TcdE/UtxA (By similarity). Binds to the cell surface receptors via the receptor-binding region and enters the cells via clathrin-mediated endocytosis (PubMed:20498856). Acidification in the endosome triggers conformational changes that promote the membrane insertion of the translocation region, allowing formation of a pore, leading to translocation of the GT44 and peptidase C80 domains across the endosomal membrane (By similarity). 1D-myo-inositol hexakisphosphate-binding (InsP6) activates the peptidase C80 domain and autoprocessing, generating the N-acetylglucosaminyltransferase TcdA form, which is released in the host cytosol (By similarity). {ECO:0000250|UniProtKB:P18177, ECO:0000269|PubMed:20498856}.; SUBCELLULAR LOCATION: [N-acetylglucosaminyltransferase TcdA]: Host cytoplasm, host cytosol {ECO:0000250|UniProtKB:P18177}. Host cell membrane {ECO:0000250|UniProtKB:Q46342}; Peripheral membrane protein {ECO:0000250|UniProtKB:Q46342}; Cytoplasmic side {ECO:0000250|UniProtKB:Q46342}. Note=Binding to phospholipids, such as phosphatidylserine and phosphatidic acid promotes localization to the inner face of the cell membrane close to its membrane anchored substrates (small GTPases). {ECO:0000250|UniProtKB:Q46342}.
Interaction partners:
Sequence:
MLITREQLMKIASIPLKRKEPEYNLILDALENFNRDIEGTSVKEIYSKLSKLNELVDNYQTKYPSSGRNLALENFRDSLYSELRELIKNSRTSTIASKNLSFIWIGGPISDQSLEYYNMWKMFNKDYNIRLFYDKNSLLVNTLKTAIIQESSKVIIEQNQSNILDGTYGHNKFYSDRMKLIYRYKRELKMLYENMKQNNSVDDIIINFLSNYFKYDIGKLNNQKENNNNKMIAIGATDINTENILTNKLKSYYYQELIQTNNLAAASDILRIAILKKYGGVYCDLDFLPGVNLSLFNDISKPNGMDSNYWEAAIFEAIANEKKLMNNYPYKYMEQVPSEIKERILSFVRNHDINDLILPLGDIKISQLEILLSRLKAATGKKTFSNAFIISNNDSLTLNNLISQLENRYEILNSIIQEKFKICETYDSYINSVSELVLETTPKNLSMDGSSFYQQIIGYLSSGFKPEVNSTVFFSGPNIYSSATCDTYHFIKNTFDMLSSQNQEIFEASNNLYFSKTHDEFKSSWLLRSNIAEKEFQKLIKTYIGRTLNYEDGLNFNKWKRVTTSELLKVIEEVNSTKIYENYDLNMILQIQGDDISYESAVNVFGKNPNKSILIQGVDDFANVFYFENGIVQSDNINNILSRFNDIKKIKLTLIGHGENVFNPKLFGGKTVNDLYTNIIKPKLQHLLEREGVILKNKYLKINILGCYMFTPKVDINSTFVGKLFNKISRDLQPKGFSKNQLEISANKYAIRINREGKREVLDYFGKWVSNTDLIAEQISNKYVVYWNEVENTLSARVEQLNKVAEFAKDINSIIQTTNNQELKQSLVNTYADLITTLYSELLKEDIPFELDNIQIKERIILNEISRLHDFSNIILDFYQKNNISNNMIILFDSIIKEKDYYNVKLANKITGETSVIKTYSDSLWNFTNKYKKIVDDIKGIIVKDINGEFIKKADFEIEQNPSLLNSAMLMQLLIDYKPYTEILTNMNTSLKVQAYAQIFQLSIGAIQEATEIVTIISDALNANFNILSKLKVGSSVASVIIDGINLIAALTELKNVKTNFERKLIEAKVGMYSIGFILESSSLISGLLGATAVSEILGVISVPVAGILVGLPSLVNNILVLGEKYNQILDYFSKFYPIVGKNPFSIQDNIIIPYDDIAITELNFKYNKFKYGYAKISGLKVGLVTHIGENIDHYFSAPSLDHYIELSIYPALKLNDTNLPKGNVVLLPSGLNKVYKPEISAIAGANSQEGNGVEVLNLIRNYYVDSNGNTKFPWKYEAPFEYSFSYMRVEYFDTKVNVILDNENKTLIIPVLTIDEMRNKISYEILGDGGQYNVILPVNQTNINIVSNKNDIWNFDVSYIVKESKIEDNKFVLDGFINNIFSTLKVSNDGFKIGKQFISIKNTPRAINLSFKINNNIVIVSIYLNHEKSNSITIISSDLNDIKNNFDNLLDNINYIGLGSISDNTINCIVRNDEVYMEGKIFLNEKKLVFIQNELELHLYDSVNKDSQYLINNPINNVVKYKDGYIVEGTFLINSTENKYSLYIENNKIMLKGLYLESSVFKTIQDKIYSKEKVNDYILSLIKKFFTVNIQLCPFMIVSGVDENNRYLEYMLSTNNKWIINGGYWENDFNNYKIVDFEKCNVIVSGSNKLNSEGDLADTIDVLDKDLENLYIDSVIIIPKVYTKKIIIHPIPNNPQINIINTQSIHDKCHLIIDSVLTNNYHWESDGDDLIITNGLDINIRILQGLSFGFKYKNIYLKFSNYDELSLNDFLLQNYNVKGLYYINGELHYKNIPGDTFEYGWINIDSRWYFFDSINLIAKKGYQEIEGERYYFNPNTGVQESGVFLTPNGLEYFTNKHASSKRWGRAINYTGWLTLDGNKYYFQSNSKAVTGLQKISDKYYYFNDNGQMQIKWQIINNNKYYFDGNTGEAIIGWFNNNKERYYFDSEGRLLTGYQVIGDKSYYFSDNINGNWEEGSGVLKSGIFKTPSGFKLFSSEGDKSAINYKGWLDLNGNKYYFNSDSIAVTGSYNIKGIQYYFNPKTAVLTNGWYTLDNNNYYVSNGHNVLGYQDIDGKGYYFDPSTGIQKAGVFPTPNGLRYFTMKPIDGQRWGQCIDYTGWLHLNGNKYYFGYYNSAVTGWRVLGGKRYFFNIKTGAATTGLLTLSGKRYYFNEKGEQLTLV