Protein |
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| Protein Name | Multifunctional-autoprocessing repeats-in-toxin | |||||
|---|---|---|---|---|---|---|
| #PDB ID | 1 | |||||
| Organism | Vibrio cholerae serotype O1 (strain ATCC 39315 / El Tor Inaba N16961) | |||||
| Uniprot ID/ACC | Q9KS12 (MARTX_VIBCH) | |||||
| Synonym(s) | - | |||||
| Gene Symbol | rtxA | |||||
| Gene ID | - | |||||
| Sequence | MVFYLIPKRRVWLMGKPFWRSVEYFFTGNYSADDGNNNIVAIGFGGQIHAYGGDDHVTVGSIGATVYTGSGNDTVVGGSAYLKVEDSTGHLIVKGAAGYADINKSGDGNVSFAGAAGGVSIDHLGNHGDVSYGGAAAYNGITRKGLSGNVTFAGAGGYNALWHETNQGNLSFTGAGAGNKLDRTWSNRYQGSHGDVTFDGAGAANSISSRVETGNITFRGAGADNHLVRKGKVGDITLQGAGASNRIERTHQAEDVYTQTRGNIRFEGVGGYNSLYSDVAHGDIHFSGGGAYNTIIRKGSGNDFAKEGMTNAKADEIVLTKAVMSGSWIGQDHHVTAVKSASEPNTYLFAFADSTYTKINKVQLRNDPQTGELKYYSTAWYKEVNHLSNLANQDISDNGGFTAVNINGAYTLSDLKVEHQQSVTVHAVEKSLTEYEWVTYANGAVIDAKEVSLSDAKMGGHAIYADGTKVDVKAVKSNRQPNTYIYAKVLGPYTKIVVVELANDPETGALKYQARSWYKEGDHTANIANQDISSATGYNPMGKGGYSLSDLHYSVNAVRSTSETVADIEEYTDQTLFKPANDSGESSGDVRFNGAGGGNVIKSNVTRGNVHFNGGGIANVILHSSQFGNTEFNGGGAANVIVKSGEEGDLTFRGAGLANVLVHQSEQGKMDVYAGGAVNVLVRLGDGQYLAHLLAYGNISVQKGSGDSRVVMLGGYNTHTQIGSGNGLWLAAGGFNVMTQVGKGDVAAVLAGGANVLTKMGEGELTSGMLGGANVITHISNDDQLSNTTAVALGGANILTKKGKGNTLAVMGGGANVLTHVGDGTTTGVMVGGANILTKVGNGDTTGILLGVGNVLTHVGDGQTLGVMGAAGNIFTKVGDGTSIAVMIGAGNIFTHVGEGNAWALMGGLGNVFTKVGNGDALALMVAEANVFTHIGDGMSVALMLAKGNVATKVGNGTTLAAMVGNVNIFTHIGHGSTFAAMIGQANIMTKVGNDLTAALMVGKANIMTHVGDGTSLGLFAGEVNVMTKVGNGTTLAAMFGKANIMTHVGDGLTGVLALGEANIVTKLGDDFMGVVAAAKANVVTHVGDATTAAVLAGKGNILTKVGEGTTVGLLISDVGNVMTHVGDGTTIGIAKGKANLITKVGDGLGVNVTWGQANVFTQVGDGDRYNFAKGEANLITKVGDGQEVSVVQGEANIITHVGNGDDYTGAWGKANVITKVGHGQNVVLAKGEANIVTQVGDGDSFNALWSKGNIVTKVGDGMQVTAAKGQANITTTVGNGLNVTAAYGDANINTKVGDGVSVNVAWGKYNINTKVGDGLNVAVMKGKANANIHVGDGLNINASYAQNNVAIKVGNGDFYSLAVASSNTSSNKLSALFDNIKQTVLGVGGSQAINYLVQGDEASSSGTHKGRGAIATPEITKLDGFQMDAIKEVSSDLGDSLTGSVTKVDTPDLNKMQHALNVDDSSVQAPNLIVNGDFELGEHGWQSTHGVEASYAGSVYGVEGEGHGARVTELDTYTNTSLYQDLANLAQGEVIAVSFDFAKRAGLSNNEGIEVLWNGEVVFSSSGDESAWQQKNLKLTAQAGSNRIEFKGTGHNDGLGYILDNVVATSESSQQANAIREHATQNPAAQNALSDKERAEADRQRLEQEKQKQLDAVAGSQSQLESTDQQALENNGQAQRDAVKEESEAVTAELAKLAQGLDVLDGQATHTGESGDQWRNDFAGGLLDGVQSQLDDAKQLANDKIAAAKQTLSDNNSKVKESVAKSEAGVAQGEQNRAGVEQDIADAQADAEKRKADALAKGKDAQQAESDAHHAVNNAQSRGDRDVQLAENKANQAQADAQGAKQNEGDRPDRQGVTGSGLSGNAHSVEGAGETDSHVNTDSQTNADGRFSEGLTEQEQEALEGATNAVNRLQINAGIRAKNSVSSMTSMFSETNSKSIVVPTKVSPEPERQEVTRRDVRISGVNLESLSAVQGSQPTGQLASKSVPGFKSHFASTSIGIENELSGLVVVLPKNSAQTFGYVHDSQGNPLFMLTKDMNQGGYSNPVGINDIQGVNNWQTHTIELVTYPSEISDTAAVESRKEAMLWLAKEFTDHINQSNHQSLPHLVSDDGRFTLVISNSKHLIAAGNGTSIDAQGKTIGMTPSGQQATMAISAKEFGTSSSPEVRLLESAPWYQAGLRDEFLANAKNTTLDDPATAQNVYAYLTSVYSKTADLAKEYGIYINDWDPASEGFSPNAQGLTDPKVKNAWSILPRTKPVRMLELLSAEDSRYVRQQIAEKLKGTYSESLAKNVFEYFQYGGEVAGHGINNATTGSVQQPEPAILFEFRSVPSALSDFVPKTASTVKVDVKALDHFDSASRKAIITEVNALVSGSEDFDAWYQEYRASKGQPPVKNPKSSASANHKAEWLMTQHAEQWAKITAPYTDNHETLTSTKLASNDKEELHALGETSNLENNKQQENVASIINTMLNDMLPFYALRTERNLLVQEGDEGFEVRAWPGTEDKSKTIILEDPEDAAQHKAIERFILANFDNFEQMPDELFLVDNKVISHHEGRTHVLAQKVDGAWQYNATVELMSVTELLDAANVTGKIRGESYQQVIDALTDYHASITEHADYEPESVEKLLNLRKKIEGYVLGHPDSGRVEAMNSLLNQVNTRLDEVSLLSVAEQTIQAQNSFSRLYDQLEAANLKESKHLYLDQNGDFVTKGKGNLANIDLLGSREAVLEKVKLTVSNEYGQTVADTIFAGLSAKDLAKDGKGVDIAGLNKVHQAIEQHLSPVSATLYIWKPSDHSALGHAALQIGQGRTQLEGQAAADFNQQNYVSWWPLGSKSSNISNILNVATKDQPDLKLRWSDFSQPAHQNDTLEHDVASEENDGFGLHDGDIKLKRFIEKLNAAKGIDASFKEASEGYASVLLGNPDMLETTSIPAHVFQPFVEQWNDTSYDMMDVAHRFAQELRLQAQRSDDPELLEKRIGNVIRQFAERALEEIETFKASQADQGRVFRINLEGLDVAAMQAEWHRLSNDPDARYQLLTKNCSSTVAKVLKAGGADKLIGHTWLPKFGVWTPTELFNFGQALQEAQLEIAAKKQSHQVTDVLDALSGNEKPKENVAIENDGTPPRDKESLSPLTRFLNNELYGDKEARRKIGEITQTLLDHAVEKGESQKITLQGEAGRLTGYYHQGTAPSEGETSSPSGKVVLFLHGSGSSAEEQASAIRNHYQKQGIDMLAVNLRGYGESDGGPSEKGLYQDARTMFNYLVNDKGIDPSNIIIHGYSMGGPIAADLARYAAQNGQAVSGLLLDRPMPSMTKAITAHEVANPAGIVGAIAKAVNGQFSVEKNLEGLPKETSILLLTDNEGLGNEGEKLRTKLTASGYNVTGEQTFYGHEASNRLMSQYADQIVSGLSSSASVDEDLDQQGLDTTSTKDQGISNKNDHLQVVDSKEALADGKILHNQNVNSWGPITVTPTTDGGETRFDGQIIVQMENDPVVAKAAANLAGKHAESSVVVQLDSDGNYRVVYGDPSKLDGKLRWQLVGHGRDHSETNNTRLSGYSADELAVKLAKFQQSFNQAENINNKPDHISIVGCSLVSDDKQKGFGHQFINAMDANGLRVDVSVRSSELAVDEAGRKHTKDANGDWVQKAENNKVSLSWDAQGEVVAKDERIRNGIAEGDIDLSRIGVNNVDEPARGAIGDNNDVFDAPEKRKPETEVIANSSSSNQFSYSGNIQVNVGEGEFTAVNWGTSNVGIKVGTGGFKSLAFGDNNVMVHIGDGESKHSVDIGGYQALEGAQMFLGNRNVSFNFGHSNDLILMMDKSIPTPPLVNPFDGAARISGVLQGIATSGEGEDWLAAQEQQWTLSGAKKFVKDMSGLDQSSSVDYTTLVELDSQNERDSRGLKHDAEATLNKQYNQWLSGNGNSGTSQLSRADKLRQANEKLAFNFAVGGQGADIQVTTGNWNFMFGDNIQSILDTNLGSLFGLMTQQFTATGQAKTTFTYTPQDLPRQLKNKLLGQLAGVGAETTLADIFGVDYTASGQIVSRNGQAVDGVAILKEMLEVIGEFSGDQLQAFVDPAKLLDSLKAGIDMGADGIKSFAETHGLKEKAPEEEKDNSSVSVNGANVNSAQGATVADGNTETAETQDRAFGFNSLNLPNLFATIFSQDKQKEMKSLVENLKQNLTADLLNMKEKTFDFLRNSGHLQGDGDINISLGNYNFNWGGDGKDLGAYLGDNNNFWGGRGDDVFYATGKSNIFTGGEGNDMGVLMGRENMMFGGDGNDTAVVAGRINHVFLGAGDDQSFVFGEGGEIDTGSGRDYVVTSGNFNRVDTGDDQDYSVTIGNNNQVELGAGNDFANIFGNYNRINAGAGNDVVKLMGYHAVLNGGDGDDHLIATAISKFSQFNGGEGRDLMVLGGYQNTFKGGTDVDSFVVSGDVIDNLVEDIRSEDNIVFNGIDWQKLWFERSGYDLKLSILRDPSNDSDQSKFEHIGSVTFSDYFNGNRAQVVIGMSEKDLSGEREYTMLSDSAIDALVQAMSGFEPQAGDNGFIDSLESKSQAAISMAWSDVVHKKGLMV | |||||
| Protein Class | HYDROLASE | |||||
| Function | Multifunctional-autoprocessing repeats-in-toxin: Precursor of a multifunctional toxin that causes destruction of the actin cytoskeleton by covalent cross-linking of actin and inactivation of Rho GTPases when translocated into the host cytoplasm (PubMed:26185092). Upon translocation into the host cell, undergoes autoprocessing in cis mediated by the peptidase C80 domain (also named CPD domain): the protease activity is activated upon binding inositol hexakisphosphate (InsP6) present at the host cell membrane and delivers the Cysteine protease domain-containing toxin F3 chain to the host cytosol (PubMed:17464284, PubMed:18591243, PubMed:18845756, PubMed:19620709, PubMed:19465933). The Cysteine protease domain-containing toxin F3 chain will then further cleave and release effector toxin chains that cause disassembly of the actin cytoskeleton and enhance V.cholerae colonization of the small intestine, possibly by facilitating evasion of phagocytic cells (PubMed:11553575, PubMed:12045243, PubMed:17698573, PubMed:17698571, PubMed:19812690, PubMed:19620709). Cysteine protease domain-containing toxin F3: Following autocatalytic cleavage in cis at the Leu-3441-Ala-3442 site, this chain mediates processing in trans to release other individual toxin chains to the host cytosol (PubMed:19620709). Released effector toxin chains cause disassembly of the actin cytoskeleton and enhance V.cholerae colonization of the small intestine, possibly by facilitating evasion of phagocytic cells (PubMed:17698573, PubMed:17698571). Actin cross-linking toxin F1: Actin-directed toxin that catalyzes the covalent cross-linking of host cytoplasmic monomeric actin (PubMed:11032799, PubMed:15199181, PubMed:16954226, PubMed:17951576, PubMed:19015515, PubMed:19656298, PubMed:23029200, PubMed:26228148). Mediates the cross-link between 'Lys-50' of one monomer and 'Glu-270' of another actin monomer, resulting in formation of highly toxic actin oligomers that cause cell rounding (PubMed:19015515). The toxin can be highly efficient at very low concentrations by acting on formin homology family proteins: toxic actin oligomers bind with high affinity to formins and adversely affect both nucleation and elongation abilities of formins, causing their potent inhibition in both profilin-dependent and independent manners (PubMed:26228148). Acts as an acid--amino-acid ligase that transfers the gamma-phosphoryl group of ATP to the 'Glu-270' actin residue, resulting in the formation of an activated acyl phosphate intermediate. This intermediate is further hydrolyzed and the energy of hydrolysis is utilized for the formation of the amide bond between actin subunits (PubMed:23029200). Actin cross-linking toxin F4: Actin-directed toxin that catalyzes the covalent cross-linking of host cytoplasmic monomeric actin (PubMed:11032799, PubMed:15199181, PubMed:16954226, PubMed:17951576, PubMed:19015515, PubMed:19656298, PubMed:23029200, PubMed:26228148). Mediates the cross-link between 'Lys-50' of one monomer and 'Glu-270' of another actin monomer, resulting in formation of highly toxic actin oligomers that cause cell rounding (PubMed:19015515). The toxin can be highly efficient at very low concentrations by acting on formin homology family proteins: toxic actin oligomers bind with high affinity to formins and adversely affect both nucleation and elongation abilities of formins, causing their potent inhibition in both profilin-dependent and independent manners (PubMed:26228148). Acts as an acid--amino-acid ligase that transfers the gamma-phosphoryl group of ATP to the 'Glu-270' actin residue, resulting in the formation of an activated acyl phosphate intermediate. This intermediate is further hydrolyzed and the energy of hydrolysis is utilized for the formation of the amide bond between actin subunits (PubMed:23029200). Rho inactivation domain-containing toxin F2: After delivery to the host cytosol, localizes to the host cell membrane where it modifies some cellular signaling resulting in loss of all active GTP-bound Rho and subsequent actin depolymerization. Although both this chain and the Actin cross-linking toxin F4 chain independently affect polymerized actin, the domains are not synergistic (PubMed:17474905, PubMed:19434753, PubMed:23184949). Its similarity with members of the circular permuted thiol peptidase family, suggests that it acts by mediating modification of some protein at the host cell membrane (PubMed:26185092). ABH effector region toxin F5: Indirectly activates the small GTPase CDC42. |
Bound Ligands |
Ligand ID | HET Code | PDB ID | Binding Affinity | Binding Database | Structure | Complex Card |
| COVPDB518 | AZ0 | 3GCD |
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SHOW |