Protein: Toxin PAU_02230 (Photorhabdus asymbiotica toxin) (PaTox) [Includes: Protein N-acetylglucosaminyltransferase (Protein O-GlcNAc transferase) (EC 2.4.1.-) (PaToxG) (Tyrosine glycosyltransferase); Protein-glutamine amidohydrolase (EC 3.5.1.44) (Glutamine deamidase) (PaToxD) (Protein-glutamine glutaminase)] (C7BKP9)
Organism: Photorhabdus asymbiotica subsp. asymbiotica (strain ATCC 43949 / 3105-77) (Xenorhabdus luminescens (strain 2))
Function: Toxin that acts on host cells by modifying Rho proteins by tyrosine GlcNAcylation and heterotrimeric G alpha proteins by deamidation. Catalyzes the mono-O-GlcNAcylation of small GTPases of the Rho family (RhoA, RhoB, RhoC, Rac1, Rac2, Rac3, Cdc42) in eukaryotic host cells at the conserved tyrosine residue located in the switch I region (Tyr-32/34), using UDP-N-acetylglucosamine (UDP-GlcNAc) as the sugar donor; other GTPases of the Rho, Ras or Rab families are not substrates. Tyrosine glycosylation inhibits Rho activation and prevents interaction with downstream effectors, resulting in actin disassembly, inhibition of phagocytosis, cell rounding, and toxicity toward insects and mammalian cells. Also catalyzes the deamidation of the catalytic glutamine in heterotrimeric G alpha proteins (Gi, Gq/11), which blocks GTP hydrolysis and arrests the G proteins in a permanent active state leading to activation of Rho GTPases. Thus, PaTox hijacks host GTPase signaling in a bidirectional manner by deamidation-induced activation and glycosylation-induced inactivation of GTPases.
Subcellular location: Secreted {ECO:0000305}. Host cell membrane {ECO:0000269|PubMed:25782990}; Peripheral membrane protein {ECO:0000269|PubMed:25782990}; Cytoplasmic side {ECO:0000269|PubMed:25782990}. Note=Associates with the negatively charged inner leaflet of the plasma membrane via interaction with phosphatidylserine and phosphatidylinositolphosphates. Plasma membrane localization of PaTox is essential for cytotoxicity. The glycosyltransferase domain alone is sufficient to localize at the plasma membrane. {ECO:0000269|PubMed:25782990}.
Interaction partners:
- Insecticidal toxin complex protein tcda5
- Uncharacterized protein
- Pvc16 N-terminal domain-containing protein
- Baseplate protein J-like domain-containing protein
- Nucleotidyl transferase AbiEii/AbiGii toxin family protein
- Pvc16 N-terminal domain-containing protein
- Pvc16 N-terminal domain-containing protein
- Uncharacterized protein
- Uncharacterized protein
- Insecticidal toxin complex protein tccc3
Sequence:
MKGIEGVIMLSHDILPEKLLVSEKKHENVGSYFSDDIGEQSEQTEVSHFNLSLDDAFDIYADISIENQQELKNKDNNTNIWSSLGRGDDDHNLKKIINDAFKEKLPQLMEYRRKGYNVIGLDKEGIKKLEGMLKAVPPEIQQPTMKNLYSAAQELLNTLKQHPLLPENQDMIQQSNLVIRNLSDALEAINAVSKVNQVEWWEEVHKTNKAQSDRLIAATLEELFFKVKDKRLPGSNDDYCQQEREETERKIKDLLLYDGYQLTAEHFKFGRLRKSLLAESRVTRLKLAEYLEKKSVGILTAARDAKMYAMKILLAQTRNNGFNAKDLINAGQVNDRLLSFQQYARHIRAVDGEIDGIILSNPLVVACIKETNDEPAHIKIARAILPVSEELGTVSKVLRETKEKVQPSKPKEELNHPHQDWWNRGDELWKYIKKTSWNIKETSVHVTQMVGYEASKTASRAKHKLKESSYSESINGAVKGTALLLLDEIQQAENRIRQIPQFAWDVQEAVEQHSSVIQRTAYPDELPELSELLNEQLKHEEARWQAVKKQSRDKLQELIAPITRLAQEKWAQDLYFQLGEELRKERQDRWKDIQQFDEIMAEAVGQFAEMARELDSEAVRLAEHGHSGGKELQEKVAKWLRDLSKLKGKVKAGVAKITGTSLDNFSRSGMLARGMSEWAEDLKQSYLQETLQEGSAVAAELFERTLMEVVEENRTHFAKESDPEAERFLKRLALALKHAAENTTVYPPTPEEILAGSRSLPEDIRHWAEKKVVSGAISAAFRGGFKLVTGTFSLPVRVVIRGAKTGGTLYRGVRAINRSVRLGQGPATQVKSKFINQELSKTAFRLTLSLSPLVAWGMAASITAGRLYNEKDYPEKIIKNIVIDLPEELLWIGGYAGINAAIRAHAEKAIQQAIQHALDEQADKLALRINKEIAGKSADVNVEIIPQETSVSPAETAQSTPEPLSDFASTSQLTMPELIDIQDNNSAQQPKVRRKRDVSVESEISIDNLNIINANTREDKVNSEIKSELRSELKRFENSDANSPMSDVERAIFIDLFLYKNKYEVSESQQDYKNTWLKFRRELESQENKEIKEYLRFRSIIEAYEIYDKKRLDDDTIPEAGTIIKEVIDFFQKLKKENPITFMKLAEAMVKFQYYYEEEDENEDRYFKMAEIYYFLNKTENEKKSKTFHLDIIDKYPNENNRLLDEFFLNKNNNNPDLDEIIYKLQSMQEKYRESYEMLSKVENIHQVLSDDSKNEENIFLDNRIIAAQVFDGSINISLQDKKKWLNRYDQIRNEEGSDGWKLMHIESILINLRRINTAINLTAMKSESALLLIDKLLNFQKKARENILHISETPHEDFTSYSQFKTRKELGNDDSKYYAQFDNYKDNHDAEKEAKEILSQVVARASLSFSELFDKVESIKLFSFVYKNRDGGAPLAAPGRTVVIKFPGKDTGGLVISNLFLRNHVKRISTKEMEDLKPLTEGMYTRATQHRSLGSYYHIGSQSEHTNALEILSGMNKEELKTHLKKQGIWFGEPALFSNEYPKQENTGHLENTTLKNAIIGVSTIQNNAAANYLRSTMYESTGWEKLGDRFIPFYEIGRRKHYDREYEINSEQLTLDIITSIAIAYPAARGIVATIRSSAIPSILKSGLRGSALFKSLSLELGKMGFNASKVFGGAVYELIEPYPINSHLNRHNVFNKVKDTAWEFHTDVGLKGGGLKDFIDRFTKEPKEITISGYKFKRIKYNQENFDTMQRMALDYAYNPDSKGKIAQAQQAYKTGKEDYNAPQYDNFNGLSLDKKIERYISPDTDATTKGVLAGKMNESIKDINAFQTAKDAQSWKKSANKANKVVLTPQNLYLKGKPSECLPESVLMGWALQSSQDAKLSKMLMGIYSSNDITSNPLYKSLKELHANGNASKFNASATSISNINVSNLATSETKLFPTEISSVRVDAPKHTMLISKIKNRENKIKYVFYDPNYGMAYFDKHSDMAAFFQKKMQQYDFPDDSVSFHPLDYSNVSDIKISGRNLNEIIDGEIPLLYKQEGVQLEGITPRDGIYRVPPKNTLGVQETKHYIIVNNDIYQVEWDQTNNTWRVFDPSNTNRSRPTVPVKQDTNGEWFKHSETGLKGGGPIDDIRKYIARKSAIKIFNQSINYSATKWPPEPIDKNIHMIWIGTKNISEKNIKLSIDTAKKNPDYNTSIIYDSGISGHEGAKKFMLEKFQDSNVNIIDFRKKSYFSQLKQEPSFAYYEQVIAENKYAQASDILRLLVLKYEGGIYKDIDDIQVKGFGSLTFPKGIGVMREYAPEAGKATAFPNTPIAVTKNNPIINKTLDLAVSNYQRGEKNVLKLAGPDVFTQALYQEIPGLDSKVLNAQLYQLELAKRQALGVPLEKPKNFADEQLTSAEKEKINRPYQSIRGLSGYVENGADHSWAVDTNIPSTSTQTSTIVTPLAPKTEMLPPVPSSSTKSSTSAPVLQEKISYNLATDIDATDYLNQLKQKTNINNKISSPAGQCESLMKPVSDFMRENGFTDIRYRGMFIWNNATEQIPMNHFVVVGKKVGKDYVFDVSAHQFENKGMPDLNGPLILAAEDWAKKYRGATTRKLIYYSDFKNASTATNTYNALPRELVLESMEGKTFITSPNWYQTFKRTHNIHPEVTVSDPATFSLNYSVNPTAENLSPPPPPPIPSHGQVPKTVTPPPPPMRSPLSLSQPLERLPANKTKPIGFNPGENKASFSKLEEAGKHYYKDDKSRQAAPVNTMSDFDNRYLSHTTEAPAPSNVAHLAPGNIYNTKVTAKGAEKPAYDIYISKDGESLITSSSYKVDDITTDSKFGKPLPYSEIMFNSLKKSGVDPKNLKRSVQASIENKVTQDVISAIGTRIQRGQVIRVSPTENPDAFYTLLGTDNCKATLHMLNQHAEEFGHKVVTSIEFKGTGYLVMNIGTSTQTSTIVTPPPMPGTSQLVQ