Protein: BXD_CBDP
Sequence: MTWPVKDFNYSDPVNDNDILYLRIPQNKLITTPVKAFMITQNIWVIPERFSSDTNPSLSKPPRPTSKYQSYYDPSYLSTDEQKDTFLKGIIKLFKRINERDIGKKLINYLVVGSPFMGDSSTPEDTFDFTRHTTNIAVEKFENGSWKVTNIITPSVLIFGPLPNILDYTASLTLQGQQSNPSFEGFGTLSILKVAPEFLLTFSDVTSNQSSAVLGKSIFCMDPVIALMHELTHSLHQLYGINIPSDKRIRPQVSEGFFSQDGPNVQFEELYTFGGLDVEIIPQIERSQLREKALGHYKDIAKRLNNINKTIPSSWISNIDKYKKIFSEKYNFDKDNTGNFVVNIDKFNSLYSDLTNVMSEVVYSSQYNVKNRTHYFSRHYLPVFANILDDNIYTIRDGFNLTNKGFNIENSGQNIERNPALQKLSSESVVDLFTKVCLRLTKNSRDDSTCIKVKNNRLPYVADKDSISQEIFENKIITDETNVQNYSDKFSLDESILDGQVPINPEIVDPLLPNVNMEPLNLPGEEIVFYDDITKYVDYLNSYYYLESQKLSNNVENITLTTSVEEALGYSNKIYTFLPSLAEKVNKGVQAGLFLNWANEVVEDFTTNIMKKDTLDKISDVSVIIPYIGPALNIGNSALRGNFNQAFATAGVAFLLEGFPEFTIPALGVFTFYSSIQEREKIIKTIENCLEQRVKRWKDSYQWMVSNWLSRITTQFNHINYQMYDSLSYQADAIKAKIDLEYKKYSGSDKENIKSQVENLKNSLDVKISEAMNNINKFIRECSVTYLFKNMLPKVIDELNKFDLRTKTELINLIDSHNIILVGEVDRLKAKVNESFENTMPFNIFSYTNNSLLKDIINEYFNSINDSKILSLQNKKNALVDTSGYNAEVRVGDNVQLNTIYTNDFKLSSSGDKIIVNLNNNILYSAIYENSSVSFWIKISKDLTNSHNEYTIINSIEQNSGWKLCIRNGNIEWILQDVNRKYKSLIFDYSESLSHTGYTNKWFFVTITNNIMGYMKLYINGELKQSQKIEDLDEVKLDKTIVFGIDENIDENQMLWIRDFNIFSKELSNEDINIVYEGQILRNVIKDYWGNPLKFDTEYYIINDNYIDRYIAPESNVLVLVQYPDRSKLYTGNPITIKSVSDKNPYSRILNGDNIILHMLYNSRKYMIIRDTDTIYATQGGECSQNCVYALKLQSNLGNYGIGIFSIKNIVSKNKYCSQIFSSFRENTMLLADIYKPWRFSFKNAYTPVAVTNYETKLLSTSSFWKFISRDPGWVE
What is the function of this protein?
Responsible for host epithelial cell transcytosis, host nerve cell targeting and translocation of light chain (LC) into eukaryotic host cell cytosol.  Composed of 3 subdomains; the translocation domain (TD), and N-terminus and C-terminus of the receptor-binding domain (RBD).  The RBD is responsible for the adherence of the toxin to the eukaryotic target cell surface.  The N-terminus of the TD wraps an extended belt around the perimeter of the LC, protecting Zn(2+) in the active site; it may also prevent premature LC dissociation from the translocation channel and protect toxin prior to translocation (PubMed:17907800).  The TD inserts into synaptic vesicle membrane to allow translocation into the host cytosol (By similarity).  The RBD binds eukaryotic host phosphatidylethanolamine, which may serve as toxin receptor (PubMed:16115873).  Treatment of synaptosomes with proteinase K does not reduce HC binding, suggesting there is no protein receptor or it is protected from extracellular proteases (PubMed:16115873).  HC significantly decreases uptake and toxicity of whole BoNT/D (PubMed:19650874, PubMed:21483489).  HC also interferes with uptake of tetanus toxin (PubMed:19650874).  Has 2 closely located carbohydrate-binding receptor sites and binds at least 1 GT1b ganglioside (PubMed:20704566).  Bind gangliosides in the order GD2 > GT1b > GD1b (PubMed:21632541).  Interacts with eukaryotic target protein SV2B (synaptic vesicle glycoprotein 2B) (PubMed:21483489).  Expression of SV2A, SV2B or SV2C in mice knocked-out for the SV2 proteins restores entry of BoNT/D and cleavage of VAMP2, suggesting SV2 acts as its receptor (PubMed:21483489).  Unlike BoNT/A and BoNT/E, toxin uptake is not mediated by large extracellular loop 4 of SV2 (PubMed:21483489).  Another group finds very poor interaction with SV2 proteins, suggesting the possible protein receptor may not have been identified (PubMed:21632541).
What are the official names of this protein?
Botulinum neurotoxin type D, BoNT/D, Bontoxilysin-D.
What is the protein family that this protein belongs to?
Belongs to the peptidase M27 family.
What are the subcellular locations of this protein?
[Botulinum neurotoxin type D]: Secreted. SUBCELLULAR LOCATION: [Botulinum neurotoxin D light chain]: Secreted. Note=In animals that have ingested BoNT/D LC acts in the eukaryotic host cytosol (Probable). SUBCELLULAR LOCATION: [Botulinum neurotoxin D heavy chain]: Secreted. Note=Upon incubation with hippocampal cell colocalizes with SV2C, probably in host synaptic vesicles (PubMed:21483489). Upon incubation with primary neurons HC colocalizes with synaptophysin probably in synaptic vesicles of presynaptic cells; a small portion also colocalizes with RAB5 and may be in synaptic vesicle protein sorting endosomes (PubMed:21632541). Probably integrates into the eukaryotic host synaptic vesicle membrane.