Protein: TCSL1_PAESO
Sequence: MNLVNKAQLQKMVYVKFRIQEDEYVAILNALEEYHNMSESSVVEKYLKLKDINNLTDNYLNTYKKSGRNKALKKFKEYLTMEVLELKNNSLTPVEKNLHFIWIGGQINDTAINYINQWKDVNSDYTVKVFYDSNAFLINTLKKTIVESATNNTLESFRENLNDPEFDYNKFYRKRMEIIYDKQKHFIDYYKSQIEENPEFIIDNIIKTYLSNEYSKDLEALNKYIEESLNKITANNGNDIRNLEKFADEDLVRLYNQELVERWNLAAASDILRISMLKEDGGVYLDVDILPGIQPDLFKSINKPDSITNTSWEMIKLEAIMKYKEYIPGYTSKNFDMLDEEVQRSFESALSSKSDKSEIFLPLDDIKVSPLEVKIAFANNSVINQALISLKDSYCSDLVINQIKNRYKILNDNLNPSINEGTDFNTTMKIFSDKLASISNEDNMMFMIKITNYLKVGFAPDVRSTINLSGPGVYTGAYQDLLMFKDNSTNIHLLEPELRNFEFPKTKISQLTEQEITSLWSFNQARAKSQFEEYKKGYFEGALGEDDNLDFAQNTVLDKDYVSKKILSSMKTRNKEYIHYIVQLQGDKISYEASCNLFSKDPYSSILYQKNIEGSETAYYYYVADAEIKEIDKYRIPYQISNKRNIKLTFIGHGKSEFNTDTFANLDVDSLSSEIETILNLAKADISPKYIEINLLGCNMFSYSISAEETYPGKLLLKIKDRVSELMPSISQDSITVSANQYEVRINEEGKREILDHSGKWINKEESIIKDISSKEYISFNPKENKIIVKSKYLHELSTLLQEIRNNANSSDIDLEKKVMLTECEINVASNIDRQIVEGRIEEAKNLTSDSINYIKNEFKLIESISDSLYDLKHQNGLDDSHFISFEDISKTENGFRIRFINKETGNSIFIETEKEIFSEYATHISKEISNIKDTIFDNVNGKLVKKVNLDAAHEVNTLNSAFFIQSLIEYNTTKESLSNLSVAMKVQVYAQLFSTGLNTITDASKVVELVSTALDETIDLLPTLSEGLPIIATIIDGVSLGAAIKELSETNDPLLRQEIEAKIGIMAVNLTAASTAIVTSALGIASGFSILLVPLAGISAGIPSLVNNELILQDKATKVIDYFKHISLAETEGAFTLLDDKIIMPQDDLVLSEIDFNNNSITLGKCEIWRAEGGSGHTLTDDIDHFFSSPSITYRKPWLSIYDVLNIKKEKIDFSKDLMVLPNAPNRVFGYEMGWTPGFRSLDNDGTKLLDRIRDHYEGQFYWRYFAFIADALITKLKPRYEDTNVRINLDGNTRSFIVPVITTEQIRKNLSYSFYGSGGSYSLSLSPYNMNIDLNLVENDTWVIDVDNVVKNITIESDEIQKGELIENILSKLNIEDNKIILNNHTINFYGDINESNRFISLTFSILEDINIIIEIDLVSKSYKILLSGNCMKLIENSSDIQQKIDHIGFNGEHQKYIPYSYIDNETKYNGFIDYSKKEGLFTAEFSNESIIRNIYMPDSNNLFIYSSKDLKDIRIINKGDVKLLIGNYFKDDMKVSLSFTIEDTNTIKLNGVYLDENGVAQILKFMNNAKSALNTSNSLMNFLESINIKNIFYNNLDPNIEFILDTNFIISGSNSIGQFELICDKDKNIQPYFINFKIKETSYTLYVGNRQNLIVEPSYHLDDSGNISSTVINFSQKYLYGIDRYVNKVIIAPNLYTDEINITPVYKPNYICPEVIILDANYINEKINVNINDLSIRYVWDNDGSDLILIANSEEDNQPQVKIRFVNVFKSDTAADKLSFNFSDKQDVSVSKIISTFSLAAYSDGFFDYEFGLVSLDNDYFYINSFGNMVSGLIYINDSLYYFKPPKNNLITGFTTIDGNKYYFDPTKSGAASIGEITIDGKDYYFNKQGILQVGVINTSDGLKYFAPAGTLDENLEGESVNFIGKLNIDGKIYYFEDNYRAAVEWKLLDDETYYFNPKTGEALKGLHQIGDNKYYFDDNGIMQTGFITINDKVFYFNNDGVMQVGYIEVNGKYFYFGKNGERQLGVFNTPDGFKFFGPKDDDLGTEEGELTLYNGILNFNGKIYFFDISNTAVVGWGTLDDGSTYYFDDNRAEACIGLTVINDCKYYFDDNGIRQLGFITINDNIFYFSESGKIELGYQNINGNYFYIDESGLVLIGVFDTPDGYKYFAPLNTVNDNIYGQAVKYSGLVRVNEDVYYFGETYKIETGWIENETDKYYFDPETKKAYKGINVVDDIKYYFDENGIMRTGLISFENNNYYFNEDGKMQFGYLNIKDKMFYFGKDGKMQIGVFNTPDGFKYFAHQNTLDENFEGESINYTGWLDLDGKRYYFTDEYIAATGSLTIDGYNYYFDPDTAELVVSE
What is the function of this protein?
Active form of the toxin, which is released into the host cytosol following autoprocessing and inactivates small GTPases (PubMed:8626575, PubMed:8626586, PubMed:9632667, PubMed:17901056, PubMed:19744486, PubMed:24905543, PubMed:24919149, PubMed:27303685, PubMed:27023605, PubMed:30622517).  Acts by mediating monoglucosylation of small GTPases of the Ras (H-Ras/HRAS, K-Ras/KRAS, N-Ras/NRAS and Ral/RALA) family 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:8858106, PubMed:8626575, PubMed:8626586, PubMed:9632667, PubMed:17901056, PubMed:19744486, PubMed:24905543, PubMed:24919149, PubMed:27023605, PubMed:30622517).  Also able to catalyze monoglucosylation of some members of the Rho family (Rac1 and Rap2A), but with less efficiency than with Ras proteins (PubMed:8626586, PubMed:9632667, PubMed:19744486, PubMed:24905543).  Monoglucosylation of host small GTPases completely prevents the recognition of the downstream effector, blocking the GTPases in their inactive form and leading to apoptosis (PubMed:8626586, PubMed:9632667, PubMed:17910886).  Induces an anti-inflammatory effect, mainly by inactivating Ras proteins which results in blockage of the cell cycle and killing of immune cells (PubMed:17910886, PubMed:24919149).  The absence or moderate local inflammatory response allows C. sordellii spreading in deep tissues, production of toxin which is released in the general circulation and causes a toxic shock syndrome (PubMed:24919149, PubMed:29146177).
What are the official names of this protein?
Cytotoxin-L, Lethal toxin, LT.
What is the protein family that this protein belongs to?
Belongs to the clostridial glucosylating toxin (LCGT) family.
What are the subcellular locations of this protein?
[Cytotoxin-L]: Secreted. Host endosome membrane. Note=Secreted from P.sordellii 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 (By similarity). 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 Glucosyltransferase TcsL form, which is released in the host cytosol (PubMed:17334356). SUBCELLULAR LOCATION: [Glucosyltransferase TcsL]: 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).