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Entry version 132 (02 Jun 2021)
Sequence version 3 (23 Jan 2007)
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Protein

Toxin B

Gene

tcdB

Organism
Clostridioides difficile (Peptoclostridium difficile)
Status
Reviewed-Annotation score:

Annotation score:5 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
-Experimental evidence at protein leveli <p>This indicates the type of evidence that supports the existence of the protein. Note that the 'protein existence' evidence does not give information on the accuracy or correctness of the sequence(s) displayed.<p><a href='/help/protein_existence' target='_top'>More...</a></p>

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

Precursor of a cytotoxin that targets and disrupts the colonic epithelium, inducing the host inflammatory and innate immune responses and resulting in diarrhea and pseudomembranous colitis (PubMed:20844489, PubMed:24919149).

TcdB constitutes the main toxin that mediates the pathology of C.difficile infection, an opportunistic pathogen that colonizes the colon when the normal gut microbiome is disrupted (PubMed:19252482, PubMed:20844489).

Compared to TcdA, TcdB is more virulent and more important for inducing the host inflammatory and innate immune responses (PubMed:19252482, PubMed:24919149).

This form constitutes the precursor of the toxin: it enters into host cells and mediates autoprocessing to release the active toxin (Glucosyltransferase TcdB) into the host cytosol (PubMed:10768933, PubMed:11152463, PubMed:12941936, PubMed:17334356, PubMed:20498856).

Targets colonic epithelia by binding to the frizzled receptors FZD1, FZD2 and FZD7, and enters host cells via clathrin-mediated endocytosis (PubMed:27680706).

Frizzled receptors constitute the major host receptors in the colonic epithelium, but other receptors, such as CSPG4 or NECTIN3/PVRL3, have been identified (PubMed:25547119, PubMed:26038560, PubMed:27680706).

Binding to carbohydrates and sulfated glycosaminoglycans on host cells suface also contribute to entry into cells (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 (PubMed:11152463, PubMed:12941936, PubMed:24567384).

This activates the peptidase C80 domain and autocatalytic processing, releasing the N-terminal part (Glucosyltransferase TcdB), which constitutes the active part of the toxin, in the cytosol (PubMed:17334356, PubMed:27571750).

By similarity13 Publications

Active form of the toxin, which is released into the host cytosol following autoprocessing and inactivates small GTPases (PubMed:8144660, PubMed:7777059, PubMed:16157585, PubMed:17901056, PubMed:24905543, PubMed:24919149).

Acts by mediating monoglucosylation of small GTPases of the Rho family (Rac1, RhoA, RhoB, RhoC, RhoG and Cdc42) in host cells at the conserved threonine residue located in the switch I region ('Thr-37/35'), using UDP-alpha-D-glucose as the sugar donor (PubMed:7777059, PubMed:16157585, PubMed:17901056, PubMed:24905543, PubMed:24919149).

Monoglucosylation 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, resulting in the loss of colonic epithelial barrier function (PubMed:7777059, PubMed:24919149).

6 Publications

<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> section describes the catalytic activity of an enzyme, i.e. a chemical reaction that the enzyme catalyzes.<p><a href='/help/catalytic_activity' target='_top'>More...</a></p>Catalytic activityi

<p>This subsection of the 'Function' section provides information relevant to cofactors. A cofactor is any non-protein substance required for a protein to be catalytically active. Some cofactors are inorganic, such as the metal atoms zinc, iron, and copper in various oxidation states. Others, such as most vitamins, are organic.<p><a href='/help/cofactor' target='_top'>More...</a></p>Cofactori

Glucosyltransferase TcdB:
Mn2+1 Publication3 Publications, Mg2+1 PublicationNote: Has higher activity with Mn2+, but most likely uses Mg2+ in host cells (PubMed:16054646, PubMed:28433497). Mn2+ or Mg2+ are required for glucosyltransferase activity (PubMed:27089365).3 Publications
Toxin B:
Zn2+2 PublicationsNote: Binds 1 Zn2+ ion per subunit (PubMed:27571750, PubMed:31308519). Zn2+ is required for autocatalytic cleavage (PubMed:27571750).2 Publications

<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> section describes regulatory mechanisms for enzymes, transporters or microbial transcription factors, and reports the components which regulate (by activation or inhibition) the reaction.<p><a href='/help/activity_regulation' target='_top'>More...</a></p>Activity regulationi

Protease activity is activated upon binding to 1D-myo-inositol hexakisphosphate (InsP6), which induces conformational reorganization (PubMed:17334356). Inhibited by bezlotoxumab, also named Zinplava, a monoclonal antibody approved by the Food and Drug Administration (FDA), which specifically targets TcdB (PubMed:24821719).2 Publications

<p>This subsection of the 'Function' section describes biophysical and chemical properties, such as maximal absorption, kinetic parameters, pH dependence, redox potentials and temperature dependence.<p><a href='/help/biophysicochemical_properties' target='_top'>More...</a></p>Kineticsi

kcat is 2120 hour(-1) with UDP-alpha-D-glucose as substrate (PubMed:16157585). kcat is 11 hour(-1) with UDP-N-acetyl-alpha-D-glucosamine as substrate (PubMed:16157585).1 Publication
  1. KM=6 µM for UDP-alpha-D-glucose1 Publication
  2. KM=4.3 µM for UDP-alpha-D-glucose1 Publication
  3. KM=960 µM for UDP-N-acetyl-alpha-D-glucosamine1 Publication

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    <p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> section describes the interaction between a single amino acid and another chemical entity. Priority is given to the annotation of physiological ligands.<p><a href='/help/binding' target='_top'>More...</a></p>Binding sitei139UDP-alpha-D-glucoseCombined sources2 Publications1
    <p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> section indicates at which position the protein binds a given metal ion. The nature of the metal is indicated in the 'Description' field.<p><a href='/help/metal' target='_top'>More...</a></p>Metal bindingi286Magnesium or manganeseCombined sources1 Publication1
    Metal bindingi288Magnesium or manganeseCombined sources1 Publication2 Publications1
    Metal bindingi515Magnesium or manganeseCombined sources1 Publication2 Publications1
    Metal bindingi545Zinc; via carbonyl oxygenBy similarity1
    Metal bindingi546ZincCombined sources1 Publication1
    Binding sitei5771D-myo-inositol hexakisphosphateBy similarity1
    Binding sitei6001D-myo-inositol hexakisphosphateBy similarity1
    Binding sitei6471D-myo-inositol hexakisphosphateBy similarity1
    <p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> section is used for enzymes and indicates the residues directly involved in catalysis.<p><a href='/help/act_site' target='_top'>More...</a></p>Active sitei653For protease activityPROSITE-ProRule annotation1 Publication1
    Metal bindingi653ZincCombined sources1 Publication1
    Active sitei698Nucleophile; for protease activityPROSITE-ProRule annotation1 Publication1
    Metal bindingi757ZincCombined sources1 Publication1 Publication1
    Binding sitei7641D-myo-inositol hexakisphosphateBy similarity1
    Binding sitei7751D-myo-inositol hexakisphosphateBy similarity1
    Binding sitei7921D-myo-inositol hexakisphosphateBy similarity1

    <p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

    GO - Biological processi

    <p>UniProtKB Keywords constitute a <a href="http://www.uniprot.org/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>Keywordsi

    Molecular functionEnterotoxin, Glycosyltransferase, Hydrolase, Protease, Thiol protease, Toxin, Transferase
    Biological processVirulence
    LigandLipid-binding, Magnesium, Manganese, Metal-binding, Zinc

    Enzyme and pathway databases

    BRENDA Comprehensive Enzyme Information System

    More...
    BRENDAi
    2.4.1.B62, 1473
    3.1.4.B4, 1473

    Protein family/group databases

    Carbohydrate-Active enZymes

    More...
    CAZyi
    GT44, Glycosyltransferase Family 44

    MEROPS protease database

    More...
    MEROPSi
    C80.003

    Transport Classification Database

    More...
    TCDBi
    1.C.57.1.1, the clostridial cytotoxin (cct) family

    <p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

    <p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section provides an exhaustive list of all names of the protein, from commonly used to obsolete, to allow unambiguous identification of a protein.<p><a href='/help/protein_names' target='_top'>More...</a></p>Protein namesi
    Recommended name:
    Toxin B2 Publications (EC:3.4.22.-2 Publications)
    Cleaved into the following chain:
    Glucosyltransferase TcdBCurated (EC:2.4.1.-5 Publications)
    <p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section indicates the name(s) of the gene(s) that code for the protein sequence(s) described in the entry. Four distinct tokens exist: 'Name', 'Synonyms', 'Ordered locus names' and 'ORF names'.<p><a href='/help/gene_name' target='_top'>More...</a></p>Gene namesi
    Name:tcdB1 Publication
    Synonyms:toxB2 Publications
    <p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section provides information on the name(s) of the organism that is the source of the protein sequence.<p><a href='/help/organism-name' target='_top'>More...</a></p>OrganismiClostridioides difficile (Peptoclostridium difficile)
    <p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section shows the unique identifier assigned by the NCBI to the source organism of the protein. This is known as the 'taxonomic identifier' or 'taxid'.<p><a href='/help/taxonomic_identifier' target='_top'>More...</a></p>Taxonomic identifieri1496 [NCBI]
    <p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section contains the taxonomic hierarchical classification lineage of the source organism. It lists the nodes as they appear top-down in the taxonomic tree, with the more general grouping listed first.<p><a href='/help/taxonomic_lineage' target='_top'>More...</a></p>Taxonomic lineageiBacteriaFirmicutesClostridiaEubacterialesPeptostreptococcaceaeClostridioides

    <p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

    Keywords - Cellular componenti

    Host cell membrane, Host cytoplasm, Host endosome, Host membrane, Membrane, Secreted

    <p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

    <p>This subsection of the 'Pathology and Biotech' section describes the in vivo effects caused by ablation of the gene (or one or more transcripts) coding for the protein described in the entry. This includes gene knockout and knockdown, provided experiments have been performed in the context of a whole organism or a specific tissue, and not at the single-cell level.<p><a href='/help/disruption_phenotype' target='_top'>More...</a></p>Disruption phenotypei

    Cells lacking tcdB display virulence and cytotoxicity, because of the presence of TcdA (PubMed:20844489). Cells lacking both tcdA and tcdB display a strongly reduced virulence (PubMed:20844489).1 Publication

    Mutagenesis

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    <p>This subsection of the <a href="http://www.uniprot.org/manual/pathology%5Fand%5Fbiotech%5Fsection">'Pathology and Biotech'</a> section describes the effect of the experimental mutation of one or more amino acid(s) on the biological properties of the protein.<p><a href='/help/mutagen' target='_top'>More...</a></p>Mutagenesisi102W → A: Abolished glucosyltransferase activity and ability to induce the host inflammatory and innate immune responses; when associated with N-288. 1 Publication1
    Mutagenesisi270D → A: Does not affect ability to form a pore in the membrane of host endosomes at low pH to translocate the GT44 and peptidase C80 domains across the endosomal membrane. Strongly reduced glucosyltransferase activity. 2 Publications1
    Mutagenesisi273R → A: Strongly reduced glucosyltransferase activity. 1 Publication1
    Mutagenesisi284Y → A: Strongly reduced glucosyltransferase activity. 1 Publication1
    Mutagenesisi288D → N: Abolished glucosyltransferase activity and ability to induce the host inflammatory and innate immune responses; when associated with A-102. 1 Publication1
    Mutagenesisi383 – 385INQ → SNN: Changes substrate preference and promotes N-acetylglucosaminyltransferase activity instead of glucosyltransferase activity. 1 Publication3
    Mutagenesisi384N → A: Strongly reduced glucosyltransferase activity. 1 Publication1
    Mutagenesisi455R → E: Impaired ability to recognize RhoA substrate. 1 Publication1
    Mutagenesisi461D → R: Impaired ability to recognize RhoA substrate. 1 Publication1
    Mutagenesisi463K → E: Impaired ability to recognize RhoA substrate. 1 Publication1
    Mutagenesisi472E → R: Impaired ability to recognize RhoA substrate. 1 Publication1
    Mutagenesisi520W → A: Strongly reduced glucosyltransferase activity. 1 Publication1
    Mutagenesisi653H → A: Abolished protease activity and autoprocessing. 1 Publication1
    Mutagenesisi698C → A: Abolished protease activity and autoprocessing. 1 Publication1
    Mutagenesisi757H → A: Abolished autoprocessing. 1 Publication1
    Mutagenesisi1035I → C or K: Reduced ability to form a pore in the membrane of host endosomes to translocate the GT44 and peptidase C80 domains across the endosomal membrane. 1 Publication1
    Mutagenesisi1037D → K: Slightly reduced ability to form a pore in the membrane of host endosomes to translocate the GT44 and peptidase C80 domains across the endosomal membrane. 1 Publication1
    Mutagenesisi1038G → K: Slightly reduced ability to form a pore in the membrane of host endosomes to translocate the GT44 and peptidase C80 domains across the endosomal membrane. 1 Publication1
    Mutagenesisi1041L → K: Reduced ability to form a pore in the membrane of host endosomes to translocate the GT44 and peptidase C80 domains across the endosomal membrane. 1 Publication1
    Mutagenesisi1095P → K: Reduced ability to form a pore in the membrane of host endosomes to translocate the GT44 and peptidase C80 domains across the endosomal membrane. 1 Publication1
    Mutagenesisi1098G → K: Reduced ability to form a pore in the membrane of host endosomes to translocate the GT44 and peptidase C80 domains across the endosomal membrane. 1 Publication1
    Mutagenesisi1099I → K: Reduced ability to form a pore in the membrane of host endosomes to translocate the GT44 and peptidase C80 domains across the endosomal membrane. 1 Publication1
    Mutagenesisi1106L → C: Reduced ability to form a pore in the membrane of host endosomes to translocate the GT44 and peptidase C80 domains across the endosomal membrane. 1 Publication1
    Mutagenesisi1106L → K: Strongly reduced ability to form a pore in the membrane of host endosomes to translocate the GT44 and peptidase C80 domains across the endosomal membrane. 1 Publication1
    Mutagenesisi1107V → K: Reduced ability to form a pore in the membrane of host endosomes to translocate the GT44 and peptidase C80 domains across the endosomal membrane. 1 Publication1
    Mutagenesisi1433 – 1437LKILM → DKILD: Abolished interaction with host FZD2; when associated with A-1493. 1 Publication5
    Mutagenesisi1437M → D: Abolished interaction with host FZD2; when associated with A-1493. 1 Publication1
    Mutagenesisi1493L → A: Abolished interaction with host FZD2; when associated with D-1437 or 1433-D--D-1437. 1 Publication1
    Mutagenesisi1501D → A: Strongly reduced interaction with host FZD2. 1 Publication1
    Mutagenesisi1509 – 1511YSN → ASA: Strongly reduced interaction with host FZD2. 1 Publication3
    Mutagenesisi1509Y → A: Strongly reduced interaction with host FZD2; when associated with A-1599. 1 Publication1
    Mutagenesisi1597F → D: Abolished interaction with host FZD2. 1 Publication1
    Mutagenesisi1597F → G or D: Abolished interaction with host FZD2. 1 Publication1
    Mutagenesisi1599Q → A: Strongly reduced interaction with host FZD2; when associated with A-1509. 1 Publication1

    Miscellaneous databases

    Pathogen-Host Interaction database

    More...
    PHI-basei
    PHI:2619
    PHI:4964
    PHI:5010
    PHI:6499
    PHI:7473
    PHI:9029

    Chemistry databases

    ChEMBL database of bioactive drug-like small molecules

    More...
    ChEMBLi
    CHEMBL3580505

    Drug and drug target database

    More...
    DrugBanki
    DB13140, Bezlotoxumab

    DrugCentral

    More...
    DrugCentrali
    P18177

    <p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    <p>This subsection of the <a href="http://www.uniprot.org/help/ptm%5Fprocessing%5Fsection">PTM / Processing</a> section indicates that the initiator methionine is cleaved from the mature protein.<p><a href='/help/init_met' target='_top'>More...</a></p>Initiator methionineiRemoved2 Publications
    <p>This subsection of the 'PTM / Processing' section describes the extent of a polypeptide chain in the mature protein following processing or proteolytic cleavage.<p><a href='/help/chain' target='_top'>More...</a></p>ChainiPRO_00000726362 – 2366Toxin BAdd BLAST2365
    ChainiPRO_00004511942 – 543Glucosyltransferase TcdB1 PublicationAdd BLAST542

    <p>This subsection of the <a href="http://www.uniprot.org/help/ptm%5Fprocessing%5Fsection">PTM/processing</a> section describes post-translational modifications (PTMs). This subsection <strong>complements</strong> the information provided at the sequence level or describes modifications for which <strong>position-specific data is not yet available</strong>.<p><a href='/help/post-translational_modification' target='_top'>More...</a></p>Post-translational modificationi

    Undergoes autocatalytic cleavage to release the N-terminal part (Glucosyltransferase TcdB), which constitutes the active part of the toxin, in the host cytosol (PubMed:12941936, PubMed:17334356, PubMed:27571750). 1D-myo-inositol hexakisphosphate-binding (InsP6) activates the peptidase C80 domain and promotes autoprocessing (PubMed:17334356).3 Publications

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    <p>This subsection describes interesting single amino acid sites on the sequence that are not defined in any other subsection. This subsection can be displayed in different sections ('Function', 'PTM / Processing', 'Pathology and Biotech') according to its content.<p><a href='/help/site' target='_top'>More...</a></p>Sitei543 – 544Cleavage; by autolysis1 Publication2

    Keywords - PTMi

    Autocatalytic cleavage

    <p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

    <p>This subsection of the <a href="http://www.uniprot.org/help/interaction%5Fsection">'Interaction'</a> section provides information about the protein quaternary structure and interaction(s) with other proteins or protein complexes (with the exception of physiological receptor-ligand interactions which are annotated in the <a href="http://www.uniprot.org/help/function%5Fsection">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>Subunit structurei

    Interacts with host FZD1 (PubMed:27680706).

    Interacts with host FZD2; interaction promotes toxin entry into host cell and occupies the binding site for Wnt-adducted palmitoleate in FZD2, leading to prevent Wnt-binding and downstream Wnt signaling (PubMed:27680706, PubMed:31233493, PubMed:29748286).

    Interacts with host FZD7 (PubMed:27680706).

    Interacts with host CSPG4 (PubMed:25547119, PubMed:31233493).

    Interacts with host NECTIN3/PVRL3 (PubMed:26038560).

    5 Publications

    Protein-protein interaction databases

    Protein interaction database and analysis system

    More...
    IntActi
    P18177, 5 interactors

    Molecular INTeraction database

    More...
    MINTi
    P18177

    Chemistry databases

    BindingDB database of measured binding affinities

    More...
    BindingDBi
    P18177

    <p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

    Secondary structure

    12366
    Legend: HelixTurnBeta strandPDB Structure known for this area
    Show more details

    3D structure databases

    SWISS-MODEL Repository - a database of annotated 3D protein structure models

    More...
    SMRi
    P18177

    Database of comparative protein structure models

    More...
    ModBasei
    Search...

    Protein Data Bank in Europe - Knowledge Base

    More...
    PDBe-KBi
    Search...

    Miscellaneous databases

    Relative evolutionary importance of amino acids within a protein sequence

    More...
    EvolutionaryTracei
    P18177

    <p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    <p>This subsection of the <a href="http://www.uniprot.org/help/family%5Fand%5Fdomains%5Fsection">Family and Domains</a> section describes the position and type of a domain, which is defined as a specific combination of secondary structures organized into a characteristic three-dimensional structure or fold.<p><a href='/help/domain' target='_top'>More...</a></p>Domaini96 – 468GT44Sequence analysisAdd BLAST373
    Domaini567 – 774Peptidase C80PROSITE-ProRule annotationAdd BLAST208
    <p>This subsection of the 'Family and Domains' section indicates the positions and types of repeated sequence motifs or repeated domains within the protein.<p><a href='/help/repeat' target='_top'>More...</a></p>Repeati1832 – 1851Cell wall-binding 1Add BLAST20
    Repeati1853 – 1872Cell wall-binding 2Add BLAST20
    Repeati1875 – 1894Cell wall-binding 3Add BLAST20
    Repeati1925 – 1944Cell wall-binding 4Add BLAST20
    Repeati1966 – 1985Cell wall-binding 5Add BLAST20
    Repeati1986 – 2005Cell wall-binding 6Add BLAST20
    Repeati2006 – 2025Cell wall-binding 7Add BLAST20
    Repeati2056 – 2075Cell wall-binding 8Add BLAST20
    Repeati2076 – 2096Cell wall-binding 9Add BLAST21
    Repeati2098 – 2117Cell wall-binding 10Add BLAST20
    Repeati2118 – 2137Cell wall-binding 11Add BLAST20
    Repeati2138 – 2157Cell wall-binding 12Add BLAST20
    Repeati2208 – 2230Cell wall-binding 13Add BLAST23
    Repeati2232 – 2251Cell wall-binding 14Add BLAST20
    Repeati2252 – 2271Cell wall-binding 15Add BLAST20
    Repeati2272 – 2291Cell wall-binding 16Add BLAST20
    Repeati2322 – 2341Cell wall-binding 17Add BLAST20
    Repeati2342 – 2361Cell wall-binding 18Add BLAST20

    Region

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    <p>This subsection of the 'Family and Domains' section describes a region of interest that cannot be described in other subsections.<p><a href='/help/region' target='_top'>More...</a></p>Regioni2 – 91Four-helical bundle1 PublicationAdd BLAST90
    Regioni96 – 468Glucosyltransferase region1 PublicationAdd BLAST373
    Regioni101 – 103UDP-alpha-D-glucose bindingCombined sources3 Publications3
    Regioni269 – 273UDP-alpha-D-glucose bindingCombined sources3 Publications5
    Regioni286 – 288UDP-alpha-D-glucose bindingCombined sources3 Publications3
    Regioni518 – 520UDP-alpha-D-glucose bindingCombined sources3 Publications3
    Regioni544 – 799Autoprocessing region1 PublicationAdd BLAST256
    Regioni800 – 1500Translocation region1 PublicationAdd BLAST701
    Regioni1433 – 1438Interaction with host frizzled receptors FZD1, FZD2 and FZD71 Publication6
    Regioni1486 – 1511Interaction with host frizzled receptors FZD1, FZD2 and FZD71 PublicationAdd BLAST26
    Regioni1597 – 1599Interaction with host frizzled receptors FZD1, FZD2 and FZD71 Publication3
    Regioni1834 – 2366Receptor-binding (CROPS) region1 PublicationAdd BLAST533

    <p>This subsection of the 'Family and domains' section provides general information on the biological role of a domain. The term 'domain' is intended here in its wide acceptation, it may be a structural domain, a transmembrane region or a functional domain. Several domains are described in this subsection.<p><a href='/help/domain_cc' target='_top'>More...</a></p>Domaini

    Consists of 4 functional domains: (1) the N-terminal GT44 domain (glucosyltransferase, 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.1 Publication1 Publication
    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.1 Publication
    The cell wall-binding repeats bind carbohydrates, probably contributing to entry into cells.By similarity
    The four-helical bundle region mediates binding to phospholipids, such as phosphatidylserine and phosphatidic acid (PubMed:25882477). This promotes localization to the inner face of the cell membrane close to small GTPases (By similarity).By similarity1 Publication

    <p>This subsection of the 'Family and domains' section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesi

    Keywords - Domaini

    Repeat

    Family and domain databases

    Gene3D Structural and Functional Annotation of Protein Families

    More...
    Gene3Di
    3.40.50.11050, 1 hit

    Integrated resource of protein families, domains and functional sites

    More...
    InterProi
    View protein in InterPro
    IPR018337, Cell_wall/Cho-bd_repeat
    IPR020974, CPD_dom
    IPR038383, CPD_dom_sf
    IPR029044, Nucleotide-diphossugar_trans
    IPR024770, TcdA/TcdB_cat
    IPR024772, TcdA/TcdB_N
    IPR024769, TcdA/TcdB_pore_forming

    Pfam protein domain database

    More...
    Pfami
    View protein in Pfam
    PF01473, Choline_bind_1, 2 hits
    PF19127, Choline_bind_3, 2 hits
    PF11713, Peptidase_C80, 1 hit
    PF12919, TcdA_TcdB, 1 hit
    PF12920, TcdA_TcdB_pore, 1 hit
    PF12918, TcdB_N, 1 hit

    Superfamily database of structural and functional annotation

    More...
    SUPFAMi
    SSF53448, SSF53448, 1 hit

    PROSITE; a protein domain and family database

    More...
    PROSITEi
    View protein in PROSITE
    PS51771, CGT_MARTX_CPD, 1 hit
    PS51170, CW, 18 hits

    <p>This section displays by default the canonical protein sequence and upon request all isoforms described in the entry. It also includes information pertinent to the sequence(s), including <a href="http://www.uniprot.org/help/sequence%5Flength">length</a> and <a href="http://www.uniprot.org/help/sequences">molecular weight</a>. The information is filed in different subsections. The current subsections and their content are listed below:<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequencei

    <p>This subsection of the <a href="http://www.uniprot.org/help/sequences%5Fsection">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">canonical sequence</a> displayed by default in the entry is complete or not.<p><a href='/help/sequence_status' target='_top'>More...</a></p>Sequence statusi: Complete.

    <p>This subsection of the <a href="http://www.uniprot.org/help/sequences%5Fsection">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">canonical sequence</a> displayed by default in the entry is in its mature form or if it represents the precursor.<p><a href='/help/sequence_processing' target='_top'>More...</a></p>Sequence processingi: The displayed sequence is further processed into a mature form.

    P18177-1 [UniParc]FASTAAdd to basket
    « Hide
            10         20         30         40         50
    MSLVNRKQLE KMANVRFRTQ EDEYVAILDA LEEYHNMSEN TVVEKYLKLK
    60 70 80 90 100
    DINSLTDIYI DTYKKSGRNK ALKKFKEYLV TEVLELKNNN LTPVEKNLHF
    110 120 130 140 150
    VWIGGQINDT AINYINQWKD VNSDYNVNVF YDSNAFLINT LKKTVVESAI
    160 170 180 190 200
    NDTLESFREN LNDPRFDYNK FFRKRMEIIY DKQKNFINYY KAQREENPEL
    210 220 230 240 250
    IIDDIVKTYL SNEYSKEIDE LNTYIEESLN KITQNSGNDV RNFEEFKNGE
    260 270 280 290 300
    SFNLYEQELV ERWNLAAASD ILRISALKEI GGMYLDVDML PGIQPDLFES
    310 320 330 340 350
    IEKPSSVTVD FWEMTKLEAI MKYKEYIPEY TSEHFDMLDE EVQSSFESVL
    360 370 380 390 400
    ASKSDKSEIF SSLGDMEASP LEVKIAFNSK GIINQGLISV KDSYCSNLIV
    410 420 430 440 450
    KQIENRYKIL NNSLNPAISE DNDFNTTTNT FIDSIMAEAN ADNGRFMMEL
    460 470 480 490 500
    GKYLRVGFFP DVKTTINLSG PEAYAAAYQD LLMFKEGSMN IHLIEADLRN
    510 520 530 540 550
    FEISKTNISQ STEQEMASLW SFDDARAKAQ FEEYKRNYFE GSLGEDDNLD
    560 570 580 590 600
    FSQNIVVDKE YLLEKISSLA RSSERGYIHY IVQLQGDKIS YEAACNLFAK
    610 620 630 640 650
    TPYDSVLFQK NIEDSEIAYY YNPGDGEIQE IDKYKIPSII SDRPKIKLTF
    660 670 680 690 700
    IGHGKDEFNT DIFAGFDVDS LSTEIEAAID LAKEDISPKS IEINLLGCNM
    710 720 730 740 750
    FSYSINVEET YPGKLLLKVK DKISELMPSI SQDSIIVSAN QYEVRINSEG
    760 770 780 790 800
    RRELLDHSGE WINKEESIIK DISSKEYISF NPKENKITVK SKNLPELSTL
    810 820 830 840 850
    LQEIRNNSNS SDIELEEKVM LTECEINVIS NIDTQIVEER IEEAKNLTSD
    860 870 880 890 900
    SINYIKDEFK LIESISDALC DLKQQNELED SHFISFEDIS ETDEGFSIRF
    910 920 930 940 950
    INKETGESIF VETEKTIFSE YANHITEEIS KIKGTIFDTV NGKLVKKVNL
    960 970 980 990 1000
    DTTHEVNTLN AAFFIQSLIE YNSSKESLSN LSVAMKVQVY AQLFSTGLNT
    1010 1020 1030 1040 1050
    ITDAAKVVEL VSTALDETID LLPTLSEGLP IIATIIDGVS LGAAIKELSE
    1060 1070 1080 1090 1100
    TSDPLLRQEI EAKIGIMAVN LTTATTAIIT SSLGIASGFS ILLVPLAGIS
    1110 1120 1130 1140 1150
    AGIPSLVNNE LVLRDKATKV VDYFKHVSLV ETEGVFTLLD DKIMMPQDDL
    1160 1170 1180 1190 1200
    VISEIDFNNN SIVLGKCEIW RMEGGSGHTV TDDIDHFFSA PSITYREPHL
    1210 1220 1230 1240 1250
    SIYDVLEVQK EELDLSKDLM VLPNAPNRVF AWETGWTPGL RSLENDGTKL
    1260 1270 1280 1290 1300
    LDRIRDNYEG EFYWRYFAFI ADALITTLKP RYEDTNIRIN LDSNTRSFIV
    1310 1320 1330 1340 1350
    PIITTEYIRE KLSYSFYGSG GTYALSLSQY NMGINIELSE SDVWIIDVDN
    1360 1370 1380 1390 1400
    VVRDVTIESD KIKKGDLIEG ILSTLSIEEN KIILNSHEIN FSGEVNGSNG
    1410 1420 1430 1440 1450
    FVSLTFSILE GINAIIEVDL LSKSYKLLIS GELKILMLNS NHIQQKIDYI
    1460 1470 1480 1490 1500
    GFNSELQKNI PYSFVDSEGK ENGFINGSTK EGLFVSELPD VVLISKVYMD
    1510 1520 1530 1540 1550
    DSKPSFGYYS NNLKDVKVIT KDNVNILTGY YLKDDIKISL SLTLQDEKTI
    1560 1570 1580 1590 1600
    KLNSVHLDES GVAEILKFMN RKGNTNTSDS LMSFLESMNI KSIFVNFLQS
    1610 1620 1630 1640 1650
    NIKFILDANF IISGTTSIGQ FEFICDENDN IQPYFIKFNT LETNYTLYVG
    1660 1670 1680 1690 1700
    NRQNMIVEPN YDLDDSGDIS STVINFSQKY LYGIDSCVNK VVISPNIYTD
    1710 1720 1730 1740 1750
    EINITPVYET NNTYPEVIVL DANYINEKIN VNINDLSIRY VWSNDGNDFI
    1760 1770 1780 1790 1800
    LMSTSEENKV SQVKIRFVNV FKDKTLANKL SFNFSDKQDV PVSEIILSFT
    1810 1820 1830 1840 1850
    PSYYEDGLIG YDLGLVSLYN EKFYINNFGM MVSGLIYIND SLYYFKPPVN
    1860 1870 1880 1890 1900
    NLITGFVTVG DDKYYFNPIN GGAASIGETI IDDKNYYFNQ SGVLQTGVFS
    1910 1920 1930 1940 1950
    TEDGFKYFAP ANTLDENLEG EAIDFTGKLI IDENIYYFDD NYRGAVEWKE
    1960 1970 1980 1990 2000
    LDGEMHYFSP ETGKAFKGLN QIGDYKYYFN SDGVMQKGFV SINDNKHYFD
    2010 2020 2030 2040 2050
    DSGVMKVGYT EIDGKHFYFA ENGEMQIGVF NTEDGFKYFA HHNEDLGNEE
    2060 2070 2080 2090 2100
    GEEISYSGIL NFNNKIYYFD DSFTAVVGWK DLEDGSKYYF DEDTAEAYIG
    2110 2120 2130 2140 2150
    LSLINDGQYY FNDDGIMQVG FVTINDKVFY FSDSGIIESG VQNIDDNYFY
    2160 2170 2180 2190 2200
    IDDNGIVQIG VFDTSDGYKY FAPANTVNDN IYGQAVEYSG LVRVGEDVYY
    2210 2220 2230 2240 2250
    FGETYTIETG WIYDMENESD KYYFNPETKK ACKGINLIDD IKYYFDEKGI
    2260 2270 2280 2290 2300
    MRTGLISFEN NNYYFNENGE MQFGYINIED KMFYFGEDGV MQIGVFNTPD
    2310 2320 2330 2340 2350
    GFKYFAHQNT LDENFEGESI NYTGWLDLDE KRYYFTDEYI AATGSVIIDG
    2360
    EEYYFDPDTA QLVISE
    Length:2,366
    Mass (Da):269,712
    Last modified:January 23, 2007 - v3
    <p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.</p> <p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.</p> <p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).</p> <p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x<sup>64</sup> + x<sup>4</sup> + x<sup>3</sup> + x + 1. The algorithm is described in the ISO 3309 standard. </p> <p class="publication">Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.<br /> <strong>Cyclic redundancy and other checksums</strong><br /> <a href="http://www.nrbook.com/b/bookcpdf.php">Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993)</a>)</p> Checksum:iE1024BD8B8A56ADF
    GO

    Sequence databases

    Select the link destinations:

    EMBL nucleotide sequence database

    More...
    EMBLi

    GenBank nucleotide sequence database

    More...
    GenBanki

    DNA Data Bank of Japan; a nucleotide sequence database

    More...
    DDBJi
    Links Updated
    X53138 Genomic DNA Translation: CAA37298.1
    KC292194 Genomic DNA Translation: AGG91640.1
    KC292155 Genomic DNA Translation: AGG91601.1
    KC292159 Genomic DNA Translation: AGG91605.1
    KC292162 Genomic DNA Translation: AGG91608.1
    KC292138 Genomic DNA Translation: AGG91584.1
    X92982 Genomic DNA Translation: CAA63562.1
    X60984 Genomic DNA Translation: CAA43299.1

    Protein sequence database of the Protein Information Resource

    More...
    PIRi
    A27636
    S10317

    NCBI Reference Sequences

    More...
    RefSeqi
    WP_009902069.1, NZ_SRKJ01000018.1

    <p>This section provides links to proteins that are similar to the protein sequence(s) described in this entry at different levels of sequence identity thresholds (100%, 90% and 50%) based on their membership in UniProt Reference Clusters (<a href="http://www.uniprot.org/help/uniref">UniRef</a>).<p><a href='/help/similar_proteins_section' target='_top'>More...</a></p>Similar proteinsi

    <p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    X53138 Genomic DNA Translation: CAA37298.1
    KC292194 Genomic DNA Translation: AGG91640.1
    KC292155 Genomic DNA Translation: AGG91601.1
    KC292159 Genomic DNA Translation: AGG91605.1
    KC292162 Genomic DNA Translation: AGG91608.1
    KC292138 Genomic DNA Translation: AGG91584.1
    X92982 Genomic DNA Translation: CAA63562.1
    X60984 Genomic DNA Translation: CAA43299.1
    PIRiA27636
    S10317
    RefSeqiWP_009902069.1, NZ_SRKJ01000018.1

    3D structure databases

    Select the link destinations:

    Protein Data Bank Europe

    More...
    PDBei

    Protein Data Bank RCSB

    More...
    RCSB PDBi

    Protein Data Bank Japan

    More...
    PDBji
    Links Updated
    PDB entryMethodResolution (Å)ChainPositionsPDBsum
    2BVLX-ray2.20A2-541[»]
    2BVMX-ray2.55A2-542[»]
    4NC2X-ray2.50A2248-2366[»]
    4NP4X-ray2.89A1834-2099[»]
    5UQMX-ray2.03A1-543[»]
    5UQNX-ray2.06A1-543[»]
    5UQTX-ray2.75A/B1-543[»]
    6AR6electron microscopy9.00A4-2099[»]
    6C0BX-ray2.50A1285-1804[»]
    6OQ5X-ray3.87A1-2366[»]
    6OQ6X-ray2.97A1071-1432[»]
    6OQ7X-ray2.39A1-543[»]
    6OQ8X-ray2.20A/B1-542[»]
    SMRiP18177
    ModBaseiSearch...
    PDBe-KBiSearch...

    Protein-protein interaction databases

    IntActiP18177, 5 interactors
    MINTiP18177

    Chemistry databases

    BindingDBiP18177
    ChEMBLiCHEMBL3580505
    DrugBankiDB13140, Bezlotoxumab
    DrugCentraliP18177

    Protein family/group databases

    CAZyiGT44, Glycosyltransferase Family 44
    MEROPSiC80.003
    TCDBi1.C.57.1.1, the clostridial cytotoxin (cct) family

    Protocols and materials databases

    ABCD curated depository of sequenced antibodies

    More...
    ABCDi
    P18177, 5 sequenced antibodies

    Enzyme and pathway databases

    BRENDAi2.4.1.B62, 1473
    3.1.4.B4, 1473

    Miscellaneous databases

    EvolutionaryTraceiP18177
    PHI-baseiPHI:2619
    PHI:4964
    PHI:5010
    PHI:6499
    PHI:7473
    PHI:9029

    Family and domain databases

    Gene3Di3.40.50.11050, 1 hit
    InterProiView protein in InterPro
    IPR018337, Cell_wall/Cho-bd_repeat
    IPR020974, CPD_dom
    IPR038383, CPD_dom_sf
    IPR029044, Nucleotide-diphossugar_trans
    IPR024770, TcdA/TcdB_cat
    IPR024772, TcdA/TcdB_N
    IPR024769, TcdA/TcdB_pore_forming
    PfamiView protein in Pfam
    PF01473, Choline_bind_1, 2 hits
    PF19127, Choline_bind_3, 2 hits
    PF11713, Peptidase_C80, 1 hit
    PF12919, TcdA_TcdB, 1 hit
    PF12920, TcdA_TcdB_pore, 1 hit
    PF12918, TcdB_N, 1 hit
    SUPFAMiSSF53448, SSF53448, 1 hit
    PROSITEiView protein in PROSITE
    PS51771, CGT_MARTX_CPD, 1 hit
    PS51170, CW, 18 hits

    MobiDB: a database of protein disorder and mobility annotations

    More...
    MobiDBi
    Search...

    <p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationi

    <p>This subsection of the 'Entry information' section provides a mnemonic identifier for a UniProtKB entry, but it is not a stable identifier. Each reviewed entry is assigned a unique entry name upon integration into UniProtKB/Swiss-Prot.<p><a href='/help/entry_name' target='_top'>More...</a></p>Entry nameiTCDB_CLODI
    <p>This subsection of the 'Entry information' section provides one or more accession number(s). These are stable identifiers and should be used to cite UniProtKB entries. Upon integration into UniProtKB, each entry is assigned a unique accession number, which is called 'Primary (citable) accession number'.<p><a href='/help/accession_numbers' target='_top'>More...</a></p>AccessioniPrimary (citable) accession number: P18177
    Secondary accession number(s): M4NW36
    <p>This subsection of the 'Entry information' section shows the date of integration of the entry into UniProtKB, the date of the last sequence update and the date of the last annotation modification ('Last modified'). The version number for both the entry and the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">canonical sequence</a> are also displayed.<p><a href='/help/entry_history' target='_top'>More...</a></p>Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1990
    Last sequence update: January 23, 2007
    Last modified: June 2, 2021
    This is version 132 of the entry and version 3 of the sequence. See complete history.
    <p>This subsection of the 'Entry information' section indicates whether the entry has been manually annotated and reviewed by UniProtKB curators or not, in other words, if the entry belongs to the Swiss-Prot section of UniProtKB (<strong>reviewed</strong>) or to the computer-annotated TrEMBL section (<strong>unreviewed</strong>).<p><a href='/help/entry_status' target='_top'>More...</a></p>Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programProkaryotic Protein Annotation Program

    <p>This section contains any relevant information that doesn't fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousi

    Keywords - Technical termi

    3D-structure, Direct protein sequencing

    Documents

    1. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    2. SIMILARITY comments
      Index of protein domains and families
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