The following text describes a protein:
Function:
[Toxin A]: 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; [N-acetylglucosaminyltransferase TcdA]: Active form of the toxin, which is released into the host cytosol following autoprocessing and inactivates small GTPases. Acts by mediating monoglycosylation of small GTPases of the Rho family (Rac1, RhoA, RhoG and Cdc42) in host cells at the conserved threonine residue located in the switch I region ('Thr-37/35'), using UDP-N-acetyl-alpha-D-glucosamine as the sugar donor. Monoglycosylation of host small GTPases completely prevents the recognition of the downstream effector, blocking the GTPases in their inactive form, leading to actin cytoskeleton disruption and cell death.
Subcellular Localization:
[Toxin A]: Secreted. Host endosome membrane. 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. 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); [N-acetylglucosaminyltransferase TcdA]: Host cytoplasm, host cytosol. Host cell membrane; Peripheral membrane protein; Cytoplasmic side. 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).
Domain:
[Toxin A]: Consists of 4 functional domains: (1) the N-terminal GT44 domain (glycosyltransferase, also named GTD), which mediates glucosylation of host small GTPases, (2) an autoprocessing region that catalyzes autoprocessing to release the N-terminal GT44 domain in the host cytosol, (3) the translocation region that forms a pore to promote translocation of the GT44 and peptidase C80 domains across the endosomal membrane and (4) the receptor-binding (CROPS) region that mediates binding to host cells and contribute to entry into cells; [Toxin A]: The receptor-binding (CROPS) region is dynamic and can have open and closed conformations depending of the pH: has an open conformation at endosomal pH and a closed conformation at neutral pH; [Toxin A]: The cell wall-binding repeats bind carbohydrates, probably contributing to entry into cells; [N-acetylglucosaminyltransferase TcdA]: The four-helical bundle region mediates binding to phospholipids, such as phosphatidylserine and phosphatidic acid (By similarity). This promotes localization to the inner face of the cell membrane close to small GTPases (By similarity).
Sequence:
MLITREQLMKIASIPLKRKEPEYNLILDALENFNRDIEGTSVKEIYSKLSKLNELVDNYQTKYPSSGRNLALENFRDSLYSELRELIKNSRTSTIASKNLSFIWIGGPISDQSLEYYNMWKMFNKDYNIRLFYDKNSLLVNTLKTAIIQESSKVIIEQNQSNILDGTYGHNKFYSDRMKLIYRYKRELKMLYENMKQNNSVDDIIINFLSNYFKYDIGKLNNQKENNNNKMIAIGATDINTENILTNKLKSYYYQELIQTNNLAAASDILRIAILKKYGGVYCDLDFLPGVNLSLFNDISKPNGMDSNYWEAAIFEAIANEKKLMNNYPYKYMEQVPSEIKERILSFVRNHDINDLILPLGDIKISQLEILLSRLKAATGKKTFSNAFIISNNDSLTLNNLISQLENRYEILNSIIQEKFKICETYDSYINSVSELVLETTPKNLSMDGSSFYQQIIGYLSSGFKPEVNSTVFFSGPNIYSSATCDTYHFIKNTFDMLSSQNQEIFEASNNLYFSKTHDEFKSSWLLRSNIAEKEFQKLIKTYIGRTLNYEDGLNFNKWKRVTTSELLKVIEEVNSTKIYENYDLNMILQIQGDDISYESAVNVFGKNPNKSILIQGVDDFANVFYFENGIVQSDNINNILSRFNDIKKIKLTLIGHGENVFNPKLFGGKTVNDLYTNIIKPKLQHLLEREGVILKNKYLKINILGCYMFTPKVDINSTFVGKLFNKISRDLQPKGFSKNQLEISANKYAIRINREGKREVLDYFGKWVSNTDLIAEQISNKYVVYWNEVENTLSARVEQLNKVAEFAKDINSIIQTTNNQELKQSLVNTYADLITTLYSELLKEDIPFELDNIQIKERIILNEISRLHDFSNIILDFYQKNNISNNMIILFDSIIKEKDYYNVKLANKITGETSVIKTYSDSLWNFTNKYKKIVDDIKGIIVKDINGEFIKKADFEIEQNPSLLNSAMLMQLLIDYKPYTEILTNMNTSLKVQAYAQIFQLSIGAIQEATEIVTIISDALNANFNILSKLKVGSSVASVIIDGINLIAALTELKNVKTNFERKLIEAKVGMYSIGFILESSSLISGLLGATAVSEILGVISVPVAGILVGLPSLVNNILVLGEKYNQILDYFSKFYPIVGKNPFSIQDNIIIPYDDIAITELNFKYNKFKYGYAKISGLKVGLVTHIGENIDHYFSAPSLDHYIELSIYPALKLNDTNLPKGNVVLLPSGLNKVYKPEISAIAGANSQEGNGVEVLNLIRNYYVDSNGNTKFPWKYEAPFEYSFSYMRVEYFDTKVNVILDNENKTLIIPVLTIDEMRNKISYEILGDGGQYNVILPVNQTNINIVSNKNDIWNFDVSYIVKESKIEDNKFVLDGFINNIFSTLKVSNDGFKIGKQFISIKNTPRAINLSFKINNNIVIVSIYLNHEKSNSITIISSDLNDIKNNFDNLLDNINYIGLGSISDNTINCIVRNDEVYMEGKIFLNEKKLVFIQNELELHLYDSVNKDSQYLINNPINNVVKYKDGYIVEGTFLINSTENKYSLYIENNKIMLKGLYLESSVFKTIQDKIYSKEKVNDYILSLIKKFFTVNIQLCPFMIVSGVDENNRYLEYMLSTNNKWIINGGYWENDFNNYKIVDFEKCNVIVSGSNKLNSEGDLADTIDVLDKDLENLYIDSVIIIPKVYTKKIIIHPIPNNPQINIINTQSIHDKCHLIIDSVLTNNYHWESDGDDLIITNGLDINIRILQGLSFGFKYKNIYLKFSNYDELSLNDFLLQNYNVKGLYYINGELHYKNIPGDTFEYGWINIDSRWYFFDSINLIAKKGYQEIEGERYYFNPNTGVQESGVFLTPNGLEYFTNKHASSKRWGRAINYTGWLTLDGNKYYFQSNSKAVTGLQKISDKYYYFNDNGQMQIKWQIINNNKYYFDGNTGEAIIGWFNNNKERYYFDSEGRLLTGYQVIGDKSYYFSDNINGNWEEGSGVLKSGIFKTPSGFKLFSSEGDKSAINYKGWLDLNGNKYYFNSDSIAVTGSYNIKGIQYYFNPKTAVLTNGWYTLDNNNYYVSNGHNVLGYQDIDGKGYYFDPSTGIQKAGVFPTPNGLRYFTMKPIDGQRWGQCIDYTGWLHLNGNKYYFGYYNSAVTGWRVLGGKRYFFNIKTGAATTGLLTLSGKRYYFNEKGEQLTLV