MARTX_VIBCH
ID MARTX_VIBCH Reviewed; 4558 AA.
AC Q9KS12; Q9X4W2;
DT 14-OCT-2015, integrated into UniProtKB/Swiss-Prot.
DT 14-OCT-2015, sequence version 2.
DT 03-AUG-2022, entry version 135.
DE RecName: Full=Multifunctional-autoprocessing repeats-in-toxin {ECO:0000303|PubMed:26185092};
DE Short=MARTX {ECO:0000303|PubMed:26185092};
DE EC=3.4.22.- {ECO:0000269|PubMed:17464284};
DE Contains:
DE RecName: Full=Actin cross-linking toxin F1 {ECO:0000305|PubMed:19620709};
DE EC=6.3.2.- {ECO:0000269|PubMed:23029200};
DE Contains:
DE RecName: Full=Actin cross-linking toxin F4 {ECO:0000305|PubMed:19620709};
DE EC=6.3.2.- {ECO:0000269|PubMed:23029200};
DE Contains:
DE RecName: Full=N-epsilon-fatty acyltransferase F2;
DE EC=2.3.1.- {ECO:0000269|PubMed:29074776};
DE AltName: Full=Rho inactivation domain-containing toxin F2 {ECO:0000305|PubMed:19620709};
DE Short=RIDvc {ECO:0000303|PubMed:29074776};
DE Contains:
DE RecName: Full=ABH effector region toxin F5 {ECO:0000305|PubMed:19620709};
DE Contains:
DE RecName: Full=Cysteine protease domain-containing toxin F3 {ECO:0000305|PubMed:19620709};
DE EC=3.4.22.- {ECO:0000269|PubMed:17464284};
DE Flags: Precursor;
GN Name=rtxA {ECO:0000303|PubMed:11032799};
GN Synonyms=rtx {ECO:0000303|PubMed:9927695};
GN OrderedLocusNames=VC_1451 {ECO:0000312|EMBL:AAF94608.1};
OS Vibrio cholerae serotype O1 (strain ATCC 39315 / El Tor Inaba N16961).
OC Bacteria; Proteobacteria; Gammaproteobacteria; Vibrionales; Vibrionaceae;
OC Vibrio.
OX NCBI_TaxID=243277;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=ATCC 39315 / El Tor Inaba N16961;
RX PubMed=9927695; DOI=10.1073/pnas.96.3.1071;
RA Lin W., Fullner K.J., Clayton R., Sexton J.A., Rogers M.B., Calia K.E.,
RA Calderwood S.B., Fraser C., Mekalanos J.J.;
RT "Identification of a vibrio cholerae RTX toxin gene cluster that is tightly
RT linked to the cholera toxin prophage.";
RL Proc. Natl. Acad. Sci. U.S.A. 96:1071-1076(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 39315 / El Tor Inaba N16961
RC {ECO:0000312|Proteomes:UP000000584};
RX PubMed=10952301; DOI=10.1038/35020000;
RA Heidelberg J.F., Eisen J.A., Nelson W.C., Clayton R.A., Gwinn M.L.,
RA Dodson R.J., Haft D.H., Hickey E.K., Peterson J.D., Umayam L.A., Gill S.R.,
RA Nelson K.E., Read T.D., Tettelin H., Richardson D.L., Ermolaeva M.D.,
RA Vamathevan J.J., Bass S., Qin H., Dragoi I., Sellers P., McDonald L.A.,
RA Utterback T.R., Fleischmann R.D., Nierman W.C., White O., Salzberg S.L.,
RA Smith H.O., Colwell R.R., Mekalanos J.J., Venter J.C., Fraser C.M.;
RT "DNA sequence of both chromosomes of the cholera pathogen Vibrio
RT cholerae.";
RL Nature 406:477-483(2000).
RN [3]
RP FUNCTION (ACTIN CROSS-LINKING TOXIN F1 AND ACTIN CROSS-LINKING TOXIN F4),
RP AND SUBCELLULAR LOCATION.
RX PubMed=11032799; DOI=10.1093/emboj/19.20.5315;
RA Fullner K.J., Mekalanos J.J.;
RT "In vivo covalent cross-linking of cellular actin by the Vibrio cholerae
RT RTX toxin.";
RL EMBO J. 19:5315-5323(2000).
RN [4]
RP FUNCTION (MULTIFUNCTIONAL-AUTOPROCESSING REPEATS-IN-TOXIN).
RX PubMed=11553575; DOI=10.1128/iai.69.10.6310-6317.2001;
RA Fullner K.J., Lencer W.I., Mekalanos J.J.;
RT "Vibrio cholerae-induced cellular responses of polarized T84 intestinal
RT epithelial cells are dependent on production of cholera toxin and the RTX
RT toxin.";
RL Infect. Immun. 69:6310-6317(2001).
RN [5]
RP FUNCTION (MULTIFUNCTIONAL-AUTOPROCESSING REPEATS-IN-TOXIN).
RX PubMed=12045243; DOI=10.1084/jem.20020318;
RA Fullner K.J., Boucher J.C., Hanes M.A., Haines G.K. III, Meehan B.M.,
RA Walchle C., Sansonetti P.J., Mekalanos J.J.;
RT "The contribution of accessory toxins of Vibrio cholerae O1 El Tor to the
RT proinflammatory response in a murine pulmonary cholera model.";
RL J. Exp. Med. 195:1455-1462(2002).
RN [6]
RP SUBCELLULAR LOCATION (MULTIFUNCTIONAL-AUTOPROCESSING REPEATS-IN-TOXIN).
RX PubMed=15547287; DOI=10.1128/jb.186.23.8137-8143.2004;
RA Boardman B.K., Satchell K.J.;
RT "Vibrio cholerae strains with mutations in an atypical type I secretion
RT system accumulate RTX toxin intracellularly.";
RL J. Bacteriol. 186:8137-8143(2004).
RN [7]
RP FUNCTION (ACTIN CROSS-LINKING TOXIN F1 AND ACTIN CROSS-LINKING TOXIN F4).
RX PubMed=15199181; DOI=10.1073/pnas.0401104101;
RA Sheahan K.L., Cordero C.L., Satchell K.J.;
RT "Identification of a domain within the multifunctional Vibrio cholerae RTX
RT toxin that covalently cross-links actin.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:9798-9803(2004).
RN [8]
RP FUNCTION (ACTIN CROSS-LINKING TOXIN F1 AND ACTIN CROSS-LINKING TOXIN F4),
RP AND COFACTOR.
RX PubMed=16954226; DOI=10.1074/jbc.m605275200;
RA Cordero C.L., Kudryashov D.S., Reisler E., Satchell K.J.;
RT "The Actin cross-linking domain of the Vibrio cholerae RTX toxin directly
RT catalyzes the covalent cross-linking of actin.";
RL J. Biol. Chem. 281:32366-32374(2006).
RN [9]
RP FUNCTION (N-EPSILON-FATTY ACYLTRANSFERASE F2).
RX PubMed=17474905; DOI=10.1111/j.1462-5822.2006.00876.x;
RA Sheahan K.L., Satchell K.J.;
RT "Inactivation of small Rho GTPases by the multifunctional RTX toxin from
RT Vibrio cholerae.";
RL Cell. Microbiol. 9:1324-1335(2007).
RN [10]
RP FUNCTION (MULTIFUNCTIONAL-AUTOPROCESSING REPEATS-IN-TOXIN), ACTIVE SITE,
RP CLEAVAGE SITE, ACTIVITY REGULATION, AND MUTAGENESIS OF HIS-3532; GLU-3551
RP AND CYS-3581.
RX PubMed=17464284; DOI=10.1038/sj.emboj.7601700;
RA Sheahan K.L., Cordero C.L., Satchell K.J.;
RT "Autoprocessing of the Vibrio cholerae RTX toxin by the cysteine protease
RT domain.";
RL EMBO J. 26:2552-2561(2007).
RN [11]
RP FUNCTION (MULTIFUNCTIONAL-AUTOPROCESSING REPEATS-IN-TOXIN AND CYSTEINE
RP PROTEASE DOMAIN-CONTAINING TOXIN F3).
RX PubMed=17698573; DOI=10.1128/iai.00506-07;
RA Olivier V., Haines G.K. III, Tan Y., Satchell K.J.;
RT "Hemolysin and the multifunctional autoprocessing RTX toxin are virulence
RT factors during intestinal infection of mice with Vibrio cholerae El Tor O1
RT strains.";
RL Infect. Immun. 75:5035-5042(2007).
RN [12]
RP FUNCTION (MULTIFUNCTIONAL-AUTOPROCESSING REPEATS-IN-TOXIN AND CYSTEINE
RP PROTEASE DOMAIN-CONTAINING TOXIN F3).
RX PubMed=17698571; DOI=10.1128/iai.00508-07;
RA Olivier V., Salzman N.H., Satchell K.J.;
RT "Prolonged colonization of mice by Vibrio cholerae El Tor O1 depends on
RT accessory toxins.";
RL Infect. Immun. 75:5043-5051(2007).
RN [13]
RP FUNCTION (ACTIN CROSS-LINKING TOXIN F1 AND ACTIN CROSS-LINKING TOXIN F4).
RX PubMed=17951576; DOI=10.1074/jbc.m703910200;
RA Kudryashov D.S., Cordero C.L., Reisler E., Satchell K.J.;
RT "Characterization of the enzymatic activity of the actin cross-linking
RT domain from the Vibrio cholerae MARTX Vc toxin.";
RL J. Biol. Chem. 283:445-452(2008).
RN [14]
RP FUNCTION (MULTIFUNCTIONAL-AUTOPROCESSING REPEATS-IN-TOXIN), ACTIVITY
RP REGULATION, CLEAVAGE SITE, AND MUTAGENESIS OF PRO-3462; ARG-3470; ILE-3476;
RP GLN-3478; GLU-3480; ASP-3482; ALA-3488; LEU-3492; LYS-3495;
RP 3499-SER-SER-3500; LYS-3524; ARG-3526; HIS-3532; ARG-3534; SER-3537;
RP LEU-3552; LYS-3572; CYS-3581; ARG-3606; VAL-3609; ARG-3612; ARG-3623;
RP LYS-3624 AND LYS-3641.
RX PubMed=18591243; DOI=10.1074/jbc.m803334200;
RA Prochazkova K., Satchell K.J.;
RT "Structure-function analysis of inositol hexakisphosphate-induced
RT autoprocessing of the Vibrio cholerae multifunctional autoprocessing RTX
RT toxin.";
RL J. Biol. Chem. 283:23656-23664(2008).
RN [15]
RP FUNCTION (ACTIN CROSS-LINKING TOXIN F1 AND ACTIN CROSS-LINKING TOXIN F4).
RX PubMed=19015515; DOI=10.1073/pnas.0808082105;
RA Kudryashov D.S., Durer Z.A., Ytterberg A.J., Sawaya M.R., Pashkov I.,
RA Prochazkova K., Yeates T.O., Loo R.R., Loo J.A., Satchell K.J., Reisler E.;
RT "Connecting actin monomers by iso-peptide bond is a toxicity mechanism of
RT the Vibrio cholerae MARTX toxin.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:18537-18542(2008).
RN [16]
RP FUNCTION (ACTIN CROSS-LINKING TOXIN F1 AND ACTIN CROSS-LINKING TOXIN F4),
RP AND MUTAGENESIS OF GLU-2003; GLU-2005; LEU-2035; ASP-2038; GLY-2055;
RP GLU-2065; THR-2068; LEU-2089; HIS-2096; LEU-2117; GLN-2149; ALA-2153;
RP TRP-2175; LEU-2206; VAL-2209; TRP-2250; VAL-2259; GLU-2326 AND ARG-2328.
RX PubMed=19656298; DOI=10.1111/j.1365-2958.2009.06810.x;
RA Geissler B., Bonebrake A., Sheahan K.L., Walker M.E., Satchell K.J.;
RT "Genetic determination of essential residues of the Vibrio cholerae actin
RT cross-linking domain reveals functional similarity with glutamine
RT synthetases.";
RL Mol. Microbiol. 73:858-868(2009).
RN [17]
RP FUNCTION (MULTIFUNCTIONAL-AUTOPROCESSING REPEATS-IN-TOXIN).
RX PubMed=19812690; DOI=10.1371/journal.pone.0007352;
RA Olivier V., Queen J., Satchell K.J.;
RT "Successful small intestine colonization of adult mice by Vibrio cholerae
RT requires ketamine anesthesia and accessory toxins.";
RL PLoS ONE 4:E7352-E7352(2009).
RN [18]
RP FUNCTION (N-EPSILON-FATTY ACYLTRANSFERASE F2).
RX PubMed=19434753; DOI=10.1002/prot.22447;
RA Pei J., Grishin N.V.;
RT "The Rho GTPase inactivation domain in Vibrio cholerae MARTX toxin has a
RT circularly permuted papain-like thiol protease fold.";
RL Proteins 77:413-419(2009).
RN [19]
RP SUBCELLULAR LOCATION (N-EPSILON-FATTY ACYLTRANSFERASE F2), AND MUTAGENESIS
RP OF TYR-2596; SER-2641 AND ARG-2643.
RX PubMed=20212166; DOI=10.1073/pnas.0908700107;
RA Geissler B., Tungekar R., Satchell K.J.;
RT "Identification of a conserved membrane localization domain within numerous
RT large bacterial protein toxins.";
RL Proc. Natl. Acad. Sci. U.S.A. 107:5581-5586(2010).
RN [20]
RP SUBCELLULAR LOCATION (N-EPSILON-FATTY ACYLTRANSFERASE F2).
RX PubMed=22044757; DOI=10.1111/j.1462-5822.2011.01718.x;
RA Geissler B., Ahrens S., Satchell K.J.;
RT "Plasma membrane association of three classes of bacterial toxins is
RT mediated by a basic-hydrophobic motif.";
RL Cell. Microbiol. 14:286-298(2012).
RN [21]
RP FUNCTION (ACTIN CROSS-LINKING TOXIN F1 AND ACTIN CROSS-LINKING TOXIN F4),
RP BIOPHYSICOCHEMICAL PROPERTIES, AND COFACTOR.
RX PubMed=23029200; DOI=10.1371/journal.pone.0045721;
RA Kudryashova E., Kalda C., Kudryashov D.S.;
RT "Glutamyl phosphate is an activated intermediate in actin crosslinking by
RT actin crosslinking domain (ACD) toxin.";
RL PLoS ONE 7:E45721-E45721(2012).
RN [22]
RP FUNCTION (N-EPSILON-FATTY ACYLTRANSFERASE F2), AND MUTAGENESIS OF GLU-2734;
RP TYR-2735; ASP-2760; LEU-2764; LYS-2766; HIS-2768; GLU-2772; SER-2776;
RP SER-2779; THR-2781; LYS-2786; SER-2788; HIS-2790; SER-2791; LEU-2793;
RP HIS-2795; LEU-2798; ARG-2804; TYR-2820; SER-2822; LYS-2829; SER-2830;
RP ARG-2850; LEU-2864; ASP-2867; GLU-2871; GLU-2872; ASP-2874; ARG-2887;
RP LEU-2914; ARG-2950; ARG-2956; ARG-2961; ARG-2971; ARG-2977; GLU-2981;
RP ARG-2982; LYS-2991; SER-2993; ASP-2996; ARG-2999; ARG-3002; LEU-3005;
RP LEU-3008; GLU-3016; ARG-3019; ARG-3027; TYR-3028; LEU-3031; CYS-3035;
RP SER-3036; SER-3037; LEU-3043; LYS-3044; ASP-3049; HIS-3054; THR-3064 AND
RP GLU-3077.
RX PubMed=23184949; DOI=10.1074/jbc.m112.396309;
RA Ahrens S., Geissler B., Satchell K.J.;
RT "Identification of a His-Asp-Cys catalytic triad essential for function of
RT the Rho inactivation domain (RID) of Vibrio cholerae MARTX toxin.";
RL J. Biol. Chem. 288:1397-1408(2013).
RN [23]
RP REVIEW.
RX PubMed=26185092; DOI=10.1128/microbiolspec.ve-0002-2014;
RA Satchell K.J.;
RT "Multifunctional-autoprocessing repeats-in-toxin (MARTX) Toxins of
RT Vibrios.";
RL Microbiol. Spectr. 3:0-0(2015).
RN [24]
RP FUNCTION (ABH EFFECTOR REGION TOXIN F5).
RX PubMed=25427654; DOI=10.1111/mmi.12879;
RA Dolores J.S., Agarwal S., Egerer M., Satchell K.J.;
RT "Vibrio cholerae MARTX toxin heterologous translocation of beta-lactamase
RT and roles of individual effector domains on cytoskeleton dynamics.";
RL Mol. Microbiol. 95:590-604(2015).
RN [25]
RP FUNCTION (ACTIN CROSS-LINKING TOXIN F1 AND ACTIN CROSS-LINKING TOXIN F4).
RX PubMed=26228148; DOI=10.1126/science.aab4090;
RA Heisler D.B., Kudryashova E., Grinevich D.O., Suarez C., Winkelman J.D.,
RA Birukov K.G., Kotha S.R., Parinandi N.L., Vavylonis D., Kovar D.R.,
RA Kudryashov D.S.;
RT "ACD toxin-produced actin oligomers poison formin-controlled actin
RT polymerization.";
RL Science 349:535-539(2015).
RN [26]
RP FUNCTION (N-EPSILON-FATTY ACYLTRANSFERASE F2), CATALYTIC ACTIVITY
RP (N-EPSILON-FATTY ACYLTRANSFERASE F2), AND MUTAGENESIS OF HIS-2795 AND
RP CYS-3035.
RX PubMed=29074776; DOI=10.1126/science.aam8659;
RA Zhou Y., Huang C., Yin L., Wan M., Wang X., Li L., Liu Y., Wang Z., Fu P.,
RA Zhang N., Chen S., Liu X., Shao F., Zhu Y.;
RT "Nepsilon-fatty acylation of Rho GTPases by a MARTX toxin effector.";
RL Science 358:528-531(2017).
RN [27] {ECO:0007744|PDB:3EEB}
RP X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) OF 3442-3650 IN COMPLEX WITH
RP INOSITOL HEXAKISPHOSPHATE, FUNCTION (MULTIFUNCTIONAL-AUTOPROCESSING
RP REPEATS-IN-TOXIN), ACTIVITY REGULATION, AND MUTAGENESIS OF ASP-3619;
RP GLU-3620; ARG-3623; LYS-3624; ASP-3632; TRP-3633 AND LYS-3636.
RX PubMed=18845756; DOI=10.1126/science.1162403;
RA Lupardus P.J., Shen A., Bogyo M., Garcia K.C.;
RT "Small molecule-induced allosteric activation of the Vibrio cholerae RTX
RT cysteine protease domain.";
RL Science 322:265-268(2008).
RN [28] {ECO:0007744|PDB:3FZY}
RP X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) OF 3440-3650 IN COMPLEX WITH
RP INOSITOL HEXAKISPHOSPHATE, PARTIAL PROTEIN SEQUENCE, SUBCELLULAR LOCATION,
RP FUNCTION (MULTIFUNCTIONAL-AUTOPROCESSING REPEATS-IN-TOXIN AND CYSTEINE
RP PROTEASE DOMAIN-CONTAINING TOXIN F3), ACTIVITY REGULATION, AND CLEAVAGE
RP SITES.
RX PubMed=19620709; DOI=10.1074/jbc.m109.025510;
RA Prochazkova K., Shuvalova L.A., Minasov G., Voburka Z., Anderson W.F.,
RA Satchell K.J.;
RT "Structural and molecular mechanism for autoprocessing of MARTX toxin of
RT Vibrio cholerae at multiple sites.";
RL J. Biol. Chem. 284:26557-26568(2009).
RN [29] {ECO:0007744|PDB:3GCD}
RP X-RAY CRYSTALLOGRAPHY (2.35 ANGSTROMS) OF 3442-3650 IN COMPLEX WITH
RP INOSITOL HEXAKISPHOSPHATE AND INHIBITOR, FUNCTION
RP (MULTIFUNCTIONAL-AUTOPROCESSING REPEATS-IN-TOXIN), ACTIVITY REGULATION,
RP CLEAVAGE SITES, AND MUTAGENESIS OF LEU-2447; LEU-3098; LEU-3441 AND
RP CYS-3581.
RX PubMed=19465933; DOI=10.1038/nchembio.178;
RA Shen A., Lupardus P.J., Albrow V.E., Guzzetta A., Powers J.C., Garcia K.C.,
RA Bogyo M.;
RT "Mechanistic and structural insights into the proteolytic activation of
RT Vibrio cholerae MARTX toxin.";
RL Nat. Chem. Biol. 5:469-478(2009).
CC -!- FUNCTION: [Multifunctional-autoprocessing repeats-in-toxin]: Precursor
CC of a multifunctional toxin that causes destruction of the actin
CC cytoskeleton by covalent cross-linking of actin and inactivation of Rho
CC GTPases when translocated into the host cytoplasm (PubMed:26185092).
CC Upon translocation into the host cell, undergoes autoprocessing in cis
CC mediated by the peptidase C80 domain (also named CPD domain): the
CC protease activity is activated upon binding inositol hexakisphosphate
CC (InsP6) present at the host cell membrane and delivers the Cysteine
CC protease domain-containing toxin F3 chain to the host cytosol
CC (PubMed:17464284, PubMed:18591243, PubMed:18845756, PubMed:19620709,
CC PubMed:19465933). The Cysteine protease domain-containing toxin F3
CC chain will then further cleave and release effector toxin chains that
CC cause disassembly of the actin cytoskeleton and enhance V.cholerae
CC colonization of the small intestine, possibly by facilitating evasion
CC of phagocytic cells (PubMed:11553575, PubMed:12045243, PubMed:17698573,
CC PubMed:17698571, PubMed:19812690, PubMed:19620709).
CC {ECO:0000269|PubMed:11553575, ECO:0000269|PubMed:12045243,
CC ECO:0000269|PubMed:17464284, ECO:0000269|PubMed:18591243,
CC ECO:0000269|PubMed:18845756, ECO:0000269|PubMed:19465933,
CC ECO:0000269|PubMed:19620709, ECO:0000269|PubMed:19812690,
CC ECO:0000303|PubMed:26185092}.
CC -!- FUNCTION: [Cysteine protease domain-containing toxin F3]: Following
CC autocatalytic cleavage in cis at the Leu-3441-Ala-3442 site, this chain
CC mediates processing in trans to release other individual toxin chains
CC to the host cytosol (PubMed:19620709). Released effector toxin chains
CC cause disassembly of the actin cytoskeleton and enhance V.cholerae
CC colonization of the small intestine, possibly by facilitating evasion
CC of phagocytic cells (PubMed:17698573, PubMed:17698571).
CC {ECO:0000269|PubMed:17698571, ECO:0000269|PubMed:17698573,
CC ECO:0000269|PubMed:19620709}.
CC -!- FUNCTION: [Actin cross-linking toxin F1]: Actin-directed toxin that
CC catalyzes the covalent cross-linking of host cytoplasmic monomeric
CC actin (PubMed:11032799, PubMed:15199181, PubMed:16954226,
CC PubMed:17951576, PubMed:19015515, PubMed:19656298, PubMed:23029200,
CC PubMed:26228148). Mediates the cross-link between 'Lys-50' of one
CC monomer and 'Glu-270' of another actin monomer, resulting in formation
CC of highly toxic actin oligomers that cause cell rounding
CC (PubMed:19015515). The toxin can be highly efficient at very low
CC concentrations by acting on formin homology family proteins: toxic
CC actin oligomers bind with high affinity to formins and adversely affect
CC both nucleation and elongation abilities of formins, causing their
CC potent inhibition in both profilin-dependent and independent manners
CC (PubMed:26228148). Acts as an acid--amino-acid ligase that transfers
CC the gamma-phosphoryl group of ATP to the 'Glu-270' actin residue,
CC resulting in the formation of an activated acyl phosphate intermediate.
CC This intermediate is further hydrolyzed and the energy of hydrolysis is
CC utilized for the formation of the amide bond between actin subunits
CC (PubMed:23029200). {ECO:0000269|PubMed:11032799,
CC ECO:0000269|PubMed:15199181, ECO:0000269|PubMed:16954226,
CC ECO:0000269|PubMed:17951576, ECO:0000269|PubMed:19015515,
CC ECO:0000269|PubMed:19656298, ECO:0000269|PubMed:23029200,
CC ECO:0000269|PubMed:26228148}.
CC -!- FUNCTION: [Actin cross-linking toxin F4]: Actin-directed toxin that
CC catalyzes the covalent cross-linking of host cytoplasmic monomeric
CC actin (PubMed:11032799, PubMed:15199181, PubMed:16954226,
CC PubMed:17951576, PubMed:19015515, PubMed:19656298, PubMed:23029200,
CC PubMed:26228148). Mediates the cross-link between 'Lys-50' of one
CC monomer and 'Glu-270' of another actin monomer, resulting in formation
CC of highly toxic actin oligomers that cause cell rounding
CC (PubMed:19015515). The toxin can be highly efficient at very low
CC concentrations by acting on formin homology family proteins: toxic
CC actin oligomers bind with high affinity to formins and adversely affect
CC both nucleation and elongation abilities of formins, causing their
CC potent inhibition in both profilin-dependent and independent manners
CC (PubMed:26228148). Acts as an acid--amino-acid ligase that transfers
CC the gamma-phosphoryl group of ATP to the 'Glu-270' actin residue,
CC resulting in the formation of an activated acyl phosphate intermediate.
CC This intermediate is further hydrolyzed and the energy of hydrolysis is
CC utilized for the formation of the amide bond between actin subunits
CC (PubMed:23029200). {ECO:0000269|PubMed:11032799,
CC ECO:0000269|PubMed:15199181, ECO:0000269|PubMed:16954226,
CC ECO:0000269|PubMed:17951576, ECO:0000269|PubMed:19015515,
CC ECO:0000269|PubMed:19656298, ECO:0000269|PubMed:23029200,
CC ECO:0000269|PubMed:26228148}.
CC -!- FUNCTION: [N-epsilon-fatty acyltransferase F2]: N-epsilon-fatty
CC acyltransferase that mediates lysine-palmitoylation of host Rho GTPase
CC proteins, with a strong preference for host Rac1 (PubMed:29074776).
CC After delivery to the host cytosol, localizes to the host cell membrane
CC where it palmitoylates host Rho GTPase proteins, resulting in loss of
CC all active GTP-bound Rho and subsequent actin depolymerization
CC (PubMed:17474905, PubMed:19434753, PubMed:23184949, PubMed:29074776).
CC Prenylation of host Rac1 at the C-terminus is required for lysine-
CC palmitoylation (PubMed:29074776). {ECO:0000269|PubMed:17474905,
CC ECO:0000269|PubMed:19434753, ECO:0000269|PubMed:23184949,
CC ECO:0000269|PubMed:29074776}.
CC -!- FUNCTION: [ABH effector region toxin F5]: Indirectly activates the
CC small GTPase CDC42. {ECO:0000269|PubMed:25427654}.
CC -!- CATALYTIC ACTIVITY: [N-epsilon-fatty acyltransferase F2]:
CC Reaction=hexadecanoyl-CoA + L-lysyl-/S-(2E,6E,10E)-geranylgeranyl-L-
CC cysteinyl-[protein] = CoA + H(+) + N(6)-hexadecanoyl-L-lysyl-/S-
CC (2E,6E,10E)-geranylgeranyl-L-cysteinyl-[protein];
CC Xref=Rhea:RHEA:59768, Rhea:RHEA-COMP:17936, Rhea:RHEA-COMP:17953,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:29969, ChEBI:CHEBI:57287,
CC ChEBI:CHEBI:57379, ChEBI:CHEBI:86021, ChEBI:CHEBI:138936;
CC Evidence={ECO:0000269|PubMed:29074776};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:59769;
CC Evidence={ECO:0000269|PubMed:29074776};
CC -!- CATALYTIC ACTIVITY: [N-epsilon-fatty acyltransferase F2]:
CC Reaction=dodecanoyl-CoA + L-lysyl-/S-(2E,6E,10E)-geranylgeranyl-L-
CC cysteinyl-[protein] = CoA + H(+) + N(6)-dodecanoyl-L-lysyl-/S-
CC (2E,6E,10E)-geranylgeranyl-L-cysteinyl-[protein];
CC Xref=Rhea:RHEA:59796, Rhea:RHEA-COMP:17936, Rhea:RHEA-COMP:17954,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:29969, ChEBI:CHEBI:57287,
CC ChEBI:CHEBI:57375, ChEBI:CHEBI:86021, ChEBI:CHEBI:143221;
CC Evidence={ECO:0000269|PubMed:29074776};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:59797;
CC Evidence={ECO:0000269|PubMed:29074776};
CC -!- CATALYTIC ACTIVITY: [N-epsilon-fatty acyltransferase F2]:
CC Reaction=decanoyl-CoA + L-lysyl-/S-(2E,6E,10E)-geranylgeranyl-L-
CC cysteinyl-[protein] = CoA + H(+) + N(6)-decanoyl-L-lysyl-/S-
CC (2E,6E,10E)-geranylgeranyl-L-cysteinyl-[protein];
CC Xref=Rhea:RHEA:59800, Rhea:RHEA-COMP:17936, Rhea:RHEA-COMP:17955,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:29969, ChEBI:CHEBI:57287,
CC ChEBI:CHEBI:61430, ChEBI:CHEBI:86021, ChEBI:CHEBI:143222;
CC Evidence={ECO:0000269|PubMed:29074776};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:59801;
CC Evidence={ECO:0000269|PubMed:29074776};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:16954226, ECO:0000269|PubMed:23029200};
CC Note=Binds 2 Mg(2+) ions per subunit. Mg(2+) is required for actin
CC cross-linking activity. Can also use Mn(2+) ions instead of Mg(2+).
CC {ECO:0000250|UniProtKB:A0A0H3AIG7};
CC -!- ACTIVITY REGULATION: Protease activity is inhibited by N-ethylmaleimide
CC but not other protease inhibitors (PubMed:17464284). Protease activity
CC is inhibited by aza-leucine epoxide (PubMed:19465933). Protease
CC activity is activated upon binding inositol hexakisphosphate (InsP6)
CC via an allosteric mechanism: the active site is disordered or occluded
CC in the absence of InsP6, protecting the protease active-site sulfhydryl
CC until the toxin enters a eukaryotic cell (PubMed:18845756,
CC PubMed:19620709). Upon processing at the Leu-3441-Ala-3442 site, the
CC peptidase C80 domain is converted to a form with much reduced affinity
CC for InsP6, but is reactivated for high affinity binding of InsP6 by
CC cooperative binding of both a new substrate and InsP6. Reactivation
CC allows cleavage at other sites, specifically at Leu residues between
CC the effector domains (PubMed:19620709). {ECO:0000269|PubMed:17464284,
CC ECO:0000269|PubMed:18845756, ECO:0000269|PubMed:19465933,
CC ECO:0000269|PubMed:19620709}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=7.8 uM for ATP (for actin cross-linking activity)
CC {ECO:0000269|PubMed:23029200};
CC KM=49.9 uM for GTP (for actin cross-linking activity)
CC {ECO:0000269|PubMed:23029200};
CC pH dependence:
CC Optimum pH is 7.0-9.0. {ECO:0000269|PubMed:23029200};
CC -!- INTERACTION:
CC Q9KS12; P68135: ACTA1; Xeno; NbExp=4; IntAct=EBI-15741102, EBI-367540;
CC -!- SUBCELLULAR LOCATION: [Multifunctional-autoprocessing repeats-in-
CC toxin]: Secreted {ECO:0000269|PubMed:11032799,
CC ECO:0000269|PubMed:15547287}. Host cytoplasm, host cytosol
CC {ECO:0000303|PubMed:26185092}. Note=Secreted via the type I secretion
CC system. {ECO:0000269|PubMed:11032799}.
CC -!- SUBCELLULAR LOCATION: [N-epsilon-fatty acyltransferase F2]: Host cell
CC membrane {ECO:0000269|PubMed:20212166, ECO:0000269|PubMed:22044757}.
CC Note=Targeted to the host cell membrane via the membrane localization
CC region (MLD). {ECO:0000269|PubMed:20212166}.
CC -!- SUBCELLULAR LOCATION: [Actin cross-linking toxin F1]: Host cytoplasm,
CC host cytosol {ECO:0000305|PubMed:19620709}.
CC -!- SUBCELLULAR LOCATION: [Actin cross-linking toxin F4]: Host cytoplasm,
CC host cytosol {ECO:0000305|PubMed:19620709}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAD21057.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AF119150; AAD21057.1; ALT_INIT; Genomic_DNA.
DR EMBL; AE003852; AAF94608.1; -; Genomic_DNA.
DR PIR; C82199; C82199.
DR RefSeq; NP_231094.1; NC_002505.1.
DR PDB; 3EEB; X-ray; 2.10 A; A/B=3442-3650.
DR PDB; 3FZY; X-ray; 1.95 A; A/B=3440-3650.
DR PDB; 3GCD; X-ray; 2.35 A; A/B/C/D=3442-3650.
DR PDB; 6EN3; X-ray; 2.90 A; A=3444-3649.
DR PDBsum; 3EEB; -.
DR PDBsum; 3FZY; -.
DR PDBsum; 3GCD; -.
DR PDBsum; 6EN3; -.
DR SMR; Q9KS12; -.
DR DIP; DIP-48626N; -.
DR IntAct; Q9KS12; 2.
DR STRING; 243277.VC_1451; -.
DR SwissLipids; SLP:000001953; -.
DR ESTHER; vibch-rtxAABH; 6_AlphaBeta_hydrolase.
DR MEROPS; C80.001; -.
DR TCDB; 1.C.57.3.5; the clostridial cytotoxin (cct) family.
DR PRIDE; Q9KS12; -.
DR EnsemblBacteria; AAF94608; AAF94608; VC_1451.
DR KEGG; vch:VC_1451; -.
DR PATRIC; fig|243277.26.peg.1381; -.
DR eggNOG; COG1073; Bacteria.
DR eggNOG; COG2931; Bacteria.
DR eggNOG; COG3064; Bacteria.
DR HOGENOM; CLU_000137_1_0_6; -.
DR BioCyc; VCHO:VC1451-MON; -.
DR SABIO-RK; Q9KS12; -.
DR EvolutionaryTrace; Q9KS12; -.
DR Proteomes; UP000000584; Chromosome 1.
DR GO; GO:0005576; C:extracellular region; IDA:UniProtKB.
DR GO; GO:0044164; C:host cell cytosol; IEA:UniProtKB-SubCell.
DR GO; GO:0020002; C:host cell plasma membrane; IDA:UniProtKB.
DR GO; GO:0016020; C:membrane; IEA:UniProtKB-KW.
DR GO; GO:0016881; F:acid-amino acid ligase activity; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IDA:UniProtKB.
DR GO; GO:0140772; F:CoA-dependent peptidyl-lysine N6-palmitoyltransferase activity; IEA:RHEA.
DR GO; GO:0004197; F:cysteine-type endopeptidase activity; IDA:UniProtKB.
DR GO; GO:0008234; F:cysteine-type peptidase activity; IEA:UniProtKB-KW.
DR GO; GO:0000822; F:inositol hexakisphosphate binding; IDA:UniProtKB.
DR GO; GO:0016874; F:ligase activity; IEA:UniProtKB-KW.
DR GO; GO:0008289; F:lipid binding; IEA:UniProtKB-KW.
DR GO; GO:0000287; F:magnesium ion binding; IDA:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0018031; F:peptidyl-lysine N6-palmitoyltransferase activity; IDA:UniProtKB.
DR GO; GO:0090729; F:toxin activity; IDA:UniProtKB.
DR GO; GO:0030042; P:actin filament depolymerization; IDA:UniProtKB.
DR GO; GO:0090527; P:actin filament reorganization; IEA:InterPro.
DR GO; GO:0018262; P:isopeptide cross-linking; IDA:UniProtKB.
DR GO; GO:0018153; P:isopeptide cross-linking via N6-(L-isoglutamyl)-L-lysine; IDA:UniProtKB.
DR GO; GO:0016540; P:protein autoprocessing; IDA:UniProtKB.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR Gene3D; 3.40.50.11050; -; 1.
DR Gene3D; 3.40.50.1820; -; 1.
DR InterPro; IPR029058; AB_hydrolase.
DR InterPro; IPR032074; ACD_dom.
DR InterPro; IPR020974; CPD_dom.
DR InterPro; IPR038383; CPD_dom_sf.
DR InterPro; IPR020972; Dermonecrotic/RTX_toxin_MLD.
DR InterPro; IPR022742; Hydrolase_4.
DR InterPro; IPR011509; RtxA_toxin.
DR InterPro; IPR011049; Serralysin-like_metalloprot_C.
DR Pfam; PF16671; ACD; 1.
DR Pfam; PF12146; Hydrolase_4; 1.
DR Pfam; PF11647; MLD; 1.
DR Pfam; PF11713; Peptidase_C80; 1.
DR Pfam; PF07634; RtxA; 37.
DR SUPFAM; SSF51120; SSF51120; 2.
DR SUPFAM; SSF53474; SSF53474; 1.
DR PROSITE; PS51772; ACD; 1.
DR PROSITE; PS51771; CGT_MARTX_CPD; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acyltransferase; ATP-binding; Autocatalytic cleavage;
KW Direct protein sequencing; Host cell membrane; Host cytoplasm;
KW Host membrane; Hydrolase; Ligase; Lipid-binding; Magnesium; Membrane;
KW Metal-binding; Multifunctional enzyme; Nucleotide-binding; Protease;
KW Reference proteome; Repeat; Secreted; Signal; Thiol protease; Toxin;
KW Transferase; Virulence.
FT SIGNAL 1..32
FT /evidence="ECO:0000255"
FT CHAIN 33..4558
FT /note="Multifunctional-autoprocessing repeats-in-toxin"
FT /id="PRO_0000434113"
FT CHAIN 33..2447
FT /note="Actin cross-linking toxin F1"
FT /evidence="ECO:0000305|PubMed:19620709"
FT /id="PRO_0000434114"
FT CHAIN 1972..2447
FT /note="Actin cross-linking toxin F4"
FT /evidence="ECO:0000305|PubMed:19620709"
FT /id="PRO_0000434115"
FT CHAIN 2448..3098
FT /note="N-epsilon-fatty acyltransferase F2"
FT /evidence="ECO:0000305|PubMed:19620709"
FT /id="PRO_0000434116"
FT CHAIN 3099..3441
FT /note="ABH effector region toxin F5"
FT /evidence="ECO:0000305|PubMed:19620709"
FT /id="PRO_0000434117"
FT CHAIN 3442..4558
FT /note="Cysteine protease domain-containing toxin F3"
FT /evidence="ECO:0000305|PubMed:19620709"
FT /id="PRO_0000434118"
FT REPEAT 114..131
FT /note="RtxA 1"
FT /evidence="ECO:0000255"
FT REPEAT 134..151
FT /note="RtxA 2"
FT /evidence="ECO:0000255"
FT REPEAT 154..170
FT /note="RtxA 3"
FT /evidence="ECO:0000255"
FT REPEAT 174..197
FT /note="RtxA 4"
FT /evidence="ECO:0000255"
FT REPEAT 200..217
FT /note="RtxA 5"
FT /evidence="ECO:0000255"
FT REPEAT 220..237
FT /note="RtxA 6"
FT /evidence="ECO:0000255"
FT REPEAT 268..285
FT /note="RtxA 7"
FT /evidence="ECO:0000255"
FT REPEAT 288..304
FT /note="RtxA 8"
FT /evidence="ECO:0000255"
FT REPEAT 594..611
FT /note="RtxA 9"
FT /evidence="ECO:0000255"
FT REPEAT 614..630
FT /note="RtxA 10"
FT /evidence="ECO:0000255"
FT REPEAT 634..651
FT /note="RtxA 11"
FT /evidence="ECO:0000255"
FT REPEAT 654..668
FT /note="RtxA 12"
FT /evidence="ECO:0000255"
FT REPEAT 751..763
FT /note="RtxA 13"
FT /evidence="ECO:0000255"
FT REPEAT 769..781
FT /note="RtxA 14"
FT /evidence="ECO:0000255"
FT REPEAT 792..808
FT /note="RtxA 15"
FT /evidence="ECO:0000255"
FT REPEAT 811..826
FT /note="RtxA 16"
FT /evidence="ECO:0000255"
FT REPEAT 830..845
FT /note="RtxA 17"
FT /evidence="ECO:0000255"
FT REPEAT 851..865
FT /note="RtxA 18"
FT /evidence="ECO:0000255"
FT REPEAT 868..885
FT /note="RtxA 19"
FT /evidence="ECO:0000255"
FT REPEAT 887..901
FT /note="RtxA 20"
FT /evidence="ECO:0000255"
FT REPEAT 906..920
FT /note="RtxA 21"
FT /evidence="ECO:0000255"
FT REPEAT 925..942
FT /note="RtxA 22"
FT /evidence="ECO:0000255"
FT REPEAT 944..960
FT /note="RtxA 23"
FT /evidence="ECO:0000255"
FT REPEAT 982..994
FT /note="RtxA 24"
FT /evidence="ECO:0000255"
FT REPEAT 1001..1016
FT /note="RtxA 25"
FT /evidence="ECO:0000255"
FT REPEAT 1041..1053
FT /note="RtxA 26"
FT /evidence="ECO:0000255"
FT REPEAT 1077..1089
FT /note="RtxA 27"
FT /evidence="ECO:0000255"
FT REPEAT 1097..1112
FT /note="RtxA 28"
FT /evidence="ECO:0000255"
FT REPEAT 1120..1132
FT /note="RtxA 29"
FT /evidence="ECO:0000255"
FT REPEAT 1135..1152
FT /note="RtxA 30"
FT /evidence="ECO:0000255"
FT REPEAT 1155..1169
FT /note="RtxA 31"
FT /evidence="ECO:0000255"
FT REPEAT 1173..1189
FT /note="RtxA 32"
FT /evidence="ECO:0000255"
FT REPEAT 1194..1209
FT /note="RtxA 33"
FT /evidence="ECO:0000255"
FT REPEAT 1211..1227
FT /note="RtxA 34"
FT /evidence="ECO:0000255"
FT REPEAT 1230..1246
FT /note="RtxA 35"
FT /evidence="ECO:0000255"
FT REPEAT 1252..1266
FT /note="RtxA 36"
FT /evidence="ECO:0000255"
FT REPEAT 1268..1285
FT /note="RtxA 37"
FT /evidence="ECO:0000255"
FT REPEAT 1306..1323
FT /note="RtxA 38"
FT /evidence="ECO:0000255"
FT REPEAT 1325..1342
FT /note="RtxA 39"
FT /evidence="ECO:0000255"
FT DOMAIN 1988..2422
FT /note="ACD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01108,
FT ECO:0000305|PubMed:15199181"
FT DOMAIN 3462..3646
FT /note="Peptidase C80"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01107"
FT REGION 1623..1688
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1752..1779
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1791..1890
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2574..2658
FT /note="Membrane localization region (MLD)"
FT /evidence="ECO:0000269|PubMed:20212166"
FT REGION 2734..3098
FT /note="Rho inactivation domain (RID)"
FT /evidence="ECO:0000305"
FT REGION 3195..3310
FT /note="ABH effector region"
FT /evidence="ECO:0000305"
FT REGION 3404..3426
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1636..1653
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1655..1678
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1791..1811
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1812..1844
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1875..1890
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 3532
FT /note="For cysteine protease activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01107,
FT ECO:0000269|PubMed:17698571"
FT ACT_SITE 3581
FT /note="Nucleophile; for cysteine protease activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01107,
FT ECO:0000269|PubMed:17698571"
FT BINDING 1999..2003
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:A0A0H3AIG7"
FT BINDING 2003
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /ligand_note="catalytic; for actin cross-linking activity"
FT /evidence="ECO:0000250|UniProtKB:A0A0H3AIG7"
FT BINDING 2003
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /ligand_note="catalytic; for actin cross-linking activity"
FT /evidence="ECO:0000250|UniProtKB:A0A0H3AIG7"
FT BINDING 2065
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /ligand_note="catalytic; for actin cross-linking activity"
FT /evidence="ECO:0000250|UniProtKB:A0A0H3AIG7"
FT BINDING 2149
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /ligand_note="catalytic; for actin cross-linking activity"
FT /evidence="ECO:0000250|UniProtKB:A0A0H3AIG7"
FT BINDING 2255
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:A0A0H3AIG7"
FT BINDING 2326
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /ligand_note="catalytic; for actin cross-linking activity"
FT /evidence="ECO:0000250|UniProtKB:A0A0H3AIG7"
FT BINDING 3468..3470
FT /ligand="1D-myo-inositol hexakisphosphate"
FT /ligand_id="ChEBI:CHEBI:58130"
FT /evidence="ECO:0000269|PubMed:18845756,
FT ECO:0000269|PubMed:19465933, ECO:0000269|PubMed:19620709,
FT ECO:0007744|PDB:3EEB, ECO:0007744|PDB:3FZY,
FT ECO:0007744|PDB:3GCD"
FT BINDING 3495..3496
FT /ligand="1D-myo-inositol hexakisphosphate"
FT /ligand_id="ChEBI:CHEBI:58130"
FT /evidence="ECO:0000269|PubMed:18845756,
FT ECO:0000269|PubMed:19465933, ECO:0000269|PubMed:19620709,
FT ECO:0007744|PDB:3EEB, ECO:0007744|PDB:3FZY,
FT ECO:0007744|PDB:3GCD"
FT BINDING 3526
FT /ligand="1D-myo-inositol hexakisphosphate"
FT /ligand_id="ChEBI:CHEBI:58130"
FT /evidence="ECO:0000269|PubMed:18845756,
FT ECO:0000269|PubMed:19465933, ECO:0000269|PubMed:19620709,
FT ECO:0007744|PDB:3EEB, ECO:0007744|PDB:3FZY,
FT ECO:0007744|PDB:3GCD"
FT BINDING 3577
FT /ligand="1D-myo-inositol hexakisphosphate"
FT /ligand_id="ChEBI:CHEBI:58130"
FT /evidence="ECO:0000269|PubMed:18845756,
FT ECO:0000269|PubMed:19465933, ECO:0000269|PubMed:19620709,
FT ECO:0007744|PDB:3EEB, ECO:0007744|PDB:3FZY,
FT ECO:0007744|PDB:3GCD"
FT BINDING 3610..3612
FT /ligand="1D-myo-inositol hexakisphosphate"
FT /ligand_id="ChEBI:CHEBI:58130"
FT /evidence="ECO:0000269|PubMed:18845756,
FT ECO:0000269|PubMed:19465933, ECO:0000269|PubMed:19620709,
FT ECO:0007744|PDB:3EEB, ECO:0007744|PDB:3FZY,
FT ECO:0007744|PDB:3GCD"
FT BINDING 3623..3624
FT /ligand="1D-myo-inositol hexakisphosphate"
FT /ligand_id="ChEBI:CHEBI:58130"
FT /evidence="ECO:0000269|PubMed:18845756,
FT ECO:0000269|PubMed:19465933, ECO:0000269|PubMed:19620709,
FT ECO:0007744|PDB:3EEB, ECO:0007744|PDB:3FZY,
FT ECO:0007744|PDB:3GCD"
FT BINDING 3636
FT /ligand="1D-myo-inositol hexakisphosphate"
FT /ligand_id="ChEBI:CHEBI:58130"
FT /evidence="ECO:0000269|PubMed:18845756,
FT ECO:0000269|PubMed:19465933, ECO:0000269|PubMed:19620709,
FT ECO:0007744|PDB:3EEB, ECO:0007744|PDB:3FZY,
FT ECO:0007744|PDB:3GCD"
FT BINDING 3641
FT /ligand="1D-myo-inositol hexakisphosphate"
FT /ligand_id="ChEBI:CHEBI:58130"
FT /evidence="ECO:0000269|PubMed:18845756,
FT ECO:0000269|PubMed:19465933, ECO:0000269|PubMed:19620709,
FT ECO:0007744|PDB:3EEB, ECO:0007744|PDB:3FZY,
FT ECO:0007744|PDB:3GCD"
FT SITE 1971..1972
FT /note="Cleavage; by autolysis"
FT /evidence="ECO:0000269|PubMed:19620709"
FT SITE 2447..2448
FT /note="Cleavage; by autolysis"
FT /evidence="ECO:0000269|PubMed:19465933,
FT ECO:0000269|PubMed:19620709"
FT SITE 3098..3099
FT /note="Cleavage; by autolysis"
FT /evidence="ECO:0000269|PubMed:19465933,
FT ECO:0000269|PubMed:19620709"
FT SITE 3441..3442
FT /note="Cleavage; by autolysis"
FT /evidence="ECO:0000269|PubMed:17464284,
FT ECO:0000269|PubMed:18591243, ECO:0000269|PubMed:19465933,
FT ECO:0000269|PubMed:19620709"
FT MUTAGEN 2003
FT /note="E->A: Abolished actin cross-linking activity and
FT ability to round host cells."
FT /evidence="ECO:0000269|PubMed:19656298"
FT MUTAGEN 2005
FT /note="E->A: Impaired actin cross-linking activity and
FT ability to round host cells."
FT /evidence="ECO:0000269|PubMed:19656298"
FT MUTAGEN 2005
FT /note="E->G: Reduced actin cross-linking activity."
FT /evidence="ECO:0000269|PubMed:19656298"
FT MUTAGEN 2035
FT /note="L->P: Reduced actin cross-linking activity."
FT /evidence="ECO:0000269|PubMed:19656298"
FT MUTAGEN 2038
FT /note="D->A: Impaired actin cross-linking activity and
FT ability to round host cells."
FT /evidence="ECO:0000269|PubMed:19656298"
FT MUTAGEN 2055
FT /note="G->E: Reduced actin cross-linking activity."
FT /evidence="ECO:0000269|PubMed:19656298"
FT MUTAGEN 2065
FT /note="E->A: Abolished actin cross-linking activity."
FT /evidence="ECO:0000269|PubMed:19656298"
FT MUTAGEN 2065
FT /note="E->G: Reduced actin cross-linking activity."
FT /evidence="ECO:0000269|PubMed:19656298"
FT MUTAGEN 2068
FT /note="T->P: Reduced actin cross-linking activity."
FT /evidence="ECO:0000269|PubMed:19656298"
FT MUTAGEN 2089
FT /note="L->P: Reduced actin cross-linking activity."
FT /evidence="ECO:0000269|PubMed:19656298"
FT MUTAGEN 2096
FT /note="H->A: Abolished actin cross-linking activity."
FT /evidence="ECO:0000269|PubMed:19656298"
FT MUTAGEN 2117
FT /note="L->P: Reduced actin cross-linking activity."
FT /evidence="ECO:0000269|PubMed:19656298"
FT MUTAGEN 2149
FT /note="Q->R: Reduced actin cross-linking activity."
FT /evidence="ECO:0000269|PubMed:19656298"
FT MUTAGEN 2153
FT /note="A->T: Reduced actin cross-linking activity."
FT /evidence="ECO:0000269|PubMed:19656298"
FT MUTAGEN 2175
FT /note="W->R: Reduced actin cross-linking activity."
FT /evidence="ECO:0000269|PubMed:19656298"
FT MUTAGEN 2206
FT /note="L->P: Reduced actin cross-linking activity."
FT /evidence="ECO:0000269|PubMed:19656298"
FT MUTAGEN 2209
FT /note="V->A: Reduced actin cross-linking activity."
FT /evidence="ECO:0000269|PubMed:19656298"
FT MUTAGEN 2250
FT /note="W->R: Reduced actin cross-linking activity."
FT /evidence="ECO:0000269|PubMed:19656298"
FT MUTAGEN 2259
FT /note="V->I: Reduced actin cross-linking activity."
FT /evidence="ECO:0000269|PubMed:19656298"
FT MUTAGEN 2326
FT /note="E->A: Abolished actin cross-linking activity."
FT /evidence="ECO:0000269|PubMed:19656298"
FT MUTAGEN 2328
FT /note="R->A: Impaired actin cross-linking activity and
FT ability to round host cells."
FT /evidence="ECO:0000269|PubMed:19656298"
FT MUTAGEN 2328
FT /note="R->H: Reduced actin cross-linking activity."
FT /evidence="ECO:0000269|PubMed:19656298"
FT MUTAGEN 2447
FT /note="L->A: Impaired cleavage of the Rho inactivation
FT domain-containing toxin F2 chain; when associated with A-
FT 3098."
FT /evidence="ECO:0000269|PubMed:19465933"
FT MUTAGEN 2596
FT /note="Y->F: Abolished localization to the host cell
FT membrane."
FT /evidence="ECO:0000269|PubMed:20212166"
FT MUTAGEN 2641
FT /note="S->T: Abolished localization to the host cell
FT membrane."
FT /evidence="ECO:0000269|PubMed:20212166"
FT MUTAGEN 2643
FT /note="R->K: Abolished localization to the host cell
FT membrane."
FT /evidence="ECO:0000269|PubMed:20212166"
FT MUTAGEN 2734
FT /note="E->A: Does not affect the activity of the Rho
FT inactivation domain-containing toxin F2 chain."
FT /evidence="ECO:0000269|PubMed:23184949"
FT MUTAGEN 2735
FT /note="Y->A: Does not affect the activity of the Rho
FT inactivation domain-containing toxin F2 chain."
FT /evidence="ECO:0000269|PubMed:23184949"
FT MUTAGEN 2760
FT /note="D->A: Does not affect the activity of the Rho
FT inactivation domain-containing toxin F2 chain."
FT /evidence="ECO:0000269|PubMed:23184949"
FT MUTAGEN 2764
FT /note="L->A: Does not affect the activity of the Rho
FT inactivation domain-containing toxin F2 chain."
FT /evidence="ECO:0000269|PubMed:23184949"
FT MUTAGEN 2766
FT /note="K->A: Does not affect the activity of the Rho
FT inactivation domain-containing toxin F2 chain."
FT /evidence="ECO:0000269|PubMed:23184949"
FT MUTAGEN 2768
FT /note="H->A: Does not affect the activity of the Rho
FT inactivation domain-containing toxin F2 chain."
FT /evidence="ECO:0000269|PubMed:23184949"
FT MUTAGEN 2772
FT /note="E->A: Does not affect the activity of the Rho
FT inactivation domain-containing toxin F2 chain."
FT /evidence="ECO:0000269|PubMed:23184949"
FT MUTAGEN 2776
FT /note="S->A: Does not affect the activity of the Rho
FT inactivation domain-containing toxin F2 chain."
FT /evidence="ECO:0000269|PubMed:23184949"
FT MUTAGEN 2779
FT /note="S->A: Does not affect the activity of the Rho
FT inactivation domain-containing toxin F2 chain."
FT /evidence="ECO:0000269|PubMed:23184949"
FT MUTAGEN 2781
FT /note="T->A: Does not affect the activity of the Rho
FT inactivation domain-containing toxin F2 chain."
FT /evidence="ECO:0000269|PubMed:23184949"
FT MUTAGEN 2786
FT /note="K->A: Does not affect the activity of the Rho
FT inactivation domain-containing toxin F2 chain."
FT /evidence="ECO:0000269|PubMed:23184949"
FT MUTAGEN 2788
FT /note="S->A: Does not affect the activity of the Rho
FT inactivation domain-containing toxin F2 chain."
FT /evidence="ECO:0000269|PubMed:23184949"
FT MUTAGEN 2790
FT /note="H->A: Does not affect the activity of the Rho
FT inactivation domain-containing toxin F2 chain."
FT /evidence="ECO:0000269|PubMed:23184949"
FT MUTAGEN 2791
FT /note="S->A: Does not affect the activity of the Rho
FT inactivation domain-containing toxin F2 chain."
FT /evidence="ECO:0000269|PubMed:23184949"
FT MUTAGEN 2793
FT /note="L->A: Does not affect the activity of the Rho
FT inactivation domain-containing toxin F2 chain."
FT /evidence="ECO:0000269|PubMed:23184949"
FT MUTAGEN 2795
FT /note="H->A: Abolished lysine-palmitoyltransferase activity
FT and ability to inactivate host Rho GTPases."
FT /evidence="ECO:0000269|PubMed:23184949,
FT ECO:0000269|PubMed:29074776"
FT MUTAGEN 2798
FT /note="L->A: Does not affect the activity of the Rho
FT inactivation domain-containing toxin F2 chain."
FT /evidence="ECO:0000269|PubMed:23184949"
FT MUTAGEN 2804
FT /note="R->A: Does not affect the activity of the Rho
FT inactivation domain-containing toxin F2 chain."
FT /evidence="ECO:0000269|PubMed:23184949"
FT MUTAGEN 2820
FT /note="Y->A: Impaired activity of the Rho inactivation
FT domain-containing toxin F2 chain."
FT /evidence="ECO:0000269|PubMed:23184949"
FT MUTAGEN 2820
FT /note="Y->F: Does not affect the activity of the Rho
FT inactivation domain-containing toxin F2 chain."
FT /evidence="ECO:0000269|PubMed:23184949"
FT MUTAGEN 2822
FT /note="S->A: Does not affect the activity of the Rho
FT inactivation domain-containing toxin F2 chain."
FT /evidence="ECO:0000269|PubMed:23184949"
FT MUTAGEN 2829
FT /note="K->A: Does not affect the activity of the Rho
FT inactivation domain-containing toxin F2 chain."
FT /evidence="ECO:0000269|PubMed:23184949"
FT MUTAGEN 2830
FT /note="S->A: Does not affect the activity of the Rho
FT inactivation domain-containing toxin F2 chain."
FT /evidence="ECO:0000269|PubMed:23184949"
FT MUTAGEN 2850
FT /note="R->A: Does not affect the activity of the Rho
FT inactivation domain-containing toxin F2 chain."
FT /evidence="ECO:0000269|PubMed:23184949"
FT MUTAGEN 2864
FT /note="L->A: Impaired activity of the Rho inactivation
FT domain-containing toxin F2 chain."
FT /evidence="ECO:0000269|PubMed:23184949"
FT MUTAGEN 2867
FT /note="D->A: Impaired activity of the Rho inactivation
FT domain-containing toxin F2 chain."
FT /evidence="ECO:0000269|PubMed:23184949"
FT MUTAGEN 2871
FT /note="E->A: Does not affect the activity of the Rho
FT inactivation domain-containing toxin F2 chain."
FT /evidence="ECO:0000269|PubMed:23184949"
FT MUTAGEN 2872
FT /note="E->A: Does not affect the activity of the Rho
FT inactivation domain-containing toxin F2 chain."
FT /evidence="ECO:0000269|PubMed:23184949"
FT MUTAGEN 2874
FT /note="D->A: Does not affect the activity of the Rho
FT inactivation domain-containing toxin F2 chain."
FT /evidence="ECO:0000269|PubMed:23184949"
FT MUTAGEN 2887
FT /note="R->A: Does not affect the activity of the Rho
FT inactivation domain-containing toxin F2 chain."
FT /evidence="ECO:0000269|PubMed:23184949"
FT MUTAGEN 2914
FT /note="L->A: Does not affect the activity of the Rho
FT inactivation domain-containing toxin F2 chain."
FT /evidence="ECO:0000269|PubMed:23184949"
FT MUTAGEN 2950
FT /note="R->A: Does not affect the activity of the Rho
FT inactivation domain-containing toxin F2 chain."
FT /evidence="ECO:0000269|PubMed:23184949"
FT MUTAGEN 2956
FT /note="R->A: Does not affect the activity of the Rho
FT inactivation domain-containing toxin F2 chain."
FT /evidence="ECO:0000269|PubMed:23184949"
FT MUTAGEN 2961
FT /note="R->A: Does not affect the activity of the Rho
FT inactivation domain-containing toxin F2 chain."
FT /evidence="ECO:0000269|PubMed:23184949"
FT MUTAGEN 2971
FT /note="R->A: Does not affect the activity of the Rho
FT inactivation domain-containing toxin F2 chain."
FT /evidence="ECO:0000269|PubMed:23184949"
FT MUTAGEN 2977
FT /note="R->A: Does not affect the activity of the Rho
FT inactivation domain-containing toxin F2 chain."
FT /evidence="ECO:0000269|PubMed:23184949"
FT MUTAGEN 2981
FT /note="E->A: Does not affect the activity of the Rho
FT inactivation domain-containing toxin F2 chain."
FT /evidence="ECO:0000269|PubMed:23184949"
FT MUTAGEN 2982
FT /note="R->A: Does not affect the activity of the Rho
FT inactivation domain-containing toxin F2 chain."
FT /evidence="ECO:0000269|PubMed:23184949"
FT MUTAGEN 2991
FT /note="K->A: Does not affect the activity of the Rho
FT inactivation domain-containing toxin F2 chain."
FT /evidence="ECO:0000269|PubMed:23184949"
FT MUTAGEN 2993
FT /note="S->A: Does not affect the activity of the Rho
FT inactivation domain-containing toxin F2 chain."
FT /evidence="ECO:0000269|PubMed:23184949"
FT MUTAGEN 2996
FT /note="D->A: Does not affect the activity of the Rho
FT inactivation domain-containing toxin F2 chain."
FT /evidence="ECO:0000269|PubMed:23184949"
FT MUTAGEN 2999
FT /note="R->A: Does not affect the activity of the Rho
FT inactivation domain-containing toxin F2 chain."
FT /evidence="ECO:0000269|PubMed:23184949"
FT MUTAGEN 3002
FT /note="R->A: Does not affect the activity of the Rho
FT inactivation domain-containing toxin F2 chain."
FT /evidence="ECO:0000269|PubMed:23184949"
FT MUTAGEN 3005
FT /note="L->A: Does not affect the activity of the Rho
FT inactivation domain-containing toxin F2 chain."
FT /evidence="ECO:0000269|PubMed:23184949"
FT MUTAGEN 3008
FT /note="L->A: Does not affect the activity of the Rho
FT inactivation domain-containing toxin F2 chain."
FT /evidence="ECO:0000269|PubMed:23184949"
FT MUTAGEN 3016
FT /note="E->A: Does not affect the activity of the Rho
FT inactivation domain-containing toxin F2 chain."
FT /evidence="ECO:0000269|PubMed:23184949"
FT MUTAGEN 3019
FT /note="R->A: Does not affect the activity of the Rho
FT inactivation domain-containing toxin F2 chain."
FT /evidence="ECO:0000269|PubMed:23184949"
FT MUTAGEN 3027
FT /note="R->A: Does not affect the activity of the Rho
FT inactivation domain-containing toxin F2 chain."
FT /evidence="ECO:0000269|PubMed:23184949"
FT MUTAGEN 3028
FT /note="Y->A: Impaired activity of the Rho inactivation
FT domain-containing toxin F2 chain."
FT /evidence="ECO:0000269|PubMed:23184949"
FT MUTAGEN 3028
FT /note="Y->F: Does not affect the activity of the Rho
FT inactivation domain-containing toxin F2 chain."
FT /evidence="ECO:0000269|PubMed:23184949"
FT MUTAGEN 3031
FT /note="L->A: Does not affect the activity of the Rho
FT inactivation domain-containing toxin F2 chain."
FT /evidence="ECO:0000269|PubMed:23184949"
FT MUTAGEN 3035
FT /note="C->A,S: Abolished lysine-palmitoyltransferase
FT activity and ability to inactivate host Rho GTPases."
FT /evidence="ECO:0000269|PubMed:23184949"
FT MUTAGEN 3036
FT /note="S->A: Does not affect the activity of the Rho
FT inactivation domain-containing toxin F2 chain."
FT /evidence="ECO:0000269|PubMed:23184949"
FT MUTAGEN 3037
FT /note="S->A: Does not affect the activity of the Rho
FT inactivation domain-containing toxin F2 chain."
FT /evidence="ECO:0000269|PubMed:23184949"
FT MUTAGEN 3043
FT /note="L->A: Does not affect the activity of the Rho
FT inactivation domain-containing toxin F2 chain."
FT /evidence="ECO:0000269|PubMed:23184949"
FT MUTAGEN 3044
FT /note="K->A: Does not affect the activity of the Rho
FT inactivation domain-containing toxin F2 chain."
FT /evidence="ECO:0000269|PubMed:23184949"
FT MUTAGEN 3049
FT /note="D->A: Does not affect the activity of the Rho
FT inactivation domain-containing toxin F2 chain."
FT /evidence="ECO:0000269|PubMed:23184949"
FT MUTAGEN 3054
FT /note="H->A: Does not affect the activity of the Rho
FT inactivation domain-containing toxin F2 chain."
FT /evidence="ECO:0000269|PubMed:23184949"
FT MUTAGEN 3064
FT /note="T->A: Does not affect the activity of the Rho
FT inactivation domain-containing toxin F2 chain."
FT /evidence="ECO:0000269|PubMed:23184949"
FT MUTAGEN 3077
FT /note="E->A: Does not affect the activity of the Rho
FT inactivation domain-containing toxin F2 chain."
FT /evidence="ECO:0000269|PubMed:23184949"
FT MUTAGEN 3098
FT /note="L->A: Impaired cleavage of the Rho inactivation
FT domain-containing toxin F2 chain; when associated with A-
FT 2447."
FT /evidence="ECO:0000269|PubMed:19465933"
FT MUTAGEN 3441
FT /note="L->A: Modified autocatalytic cleavage site, leading
FT to cleavage at another site."
FT /evidence="ECO:0000269|PubMed:19465933"
FT MUTAGEN 3462
FT /note="P->A: No effect in autocatalytic cleavage."
FT /evidence="ECO:0000269|PubMed:18591243"
FT MUTAGEN 3470
FT /note="R->A: Decreased autocatalytic cleavage."
FT /evidence="ECO:0000269|PubMed:18591243"
FT MUTAGEN 3476
FT /note="I->A: No effect in autocatalytic cleavage."
FT /evidence="ECO:0000269|PubMed:18591243"
FT MUTAGEN 3478
FT /note="Q->A: No effect in autocatalytic cleavage."
FT /evidence="ECO:0000269|PubMed:18591243"
FT MUTAGEN 3480
FT /note="E->A: No effect in autocatalytic cleavage. Impaired
FT autocatalytic cleavage; when associated with A-3482."
FT /evidence="ECO:0000269|PubMed:18591243"
FT MUTAGEN 3482
FT /note="D->A: No effect in autocatalytic cleavage. Impaired
FT autocatalytic cleavage; when associated with A-3480."
FT /evidence="ECO:0000269|PubMed:18591243"
FT MUTAGEN 3488
FT /note="A->I: Decreased autocatalytic cleavage."
FT /evidence="ECO:0000269|PubMed:18591243"
FT MUTAGEN 3492
FT /note="L->D: Decreased autocatalytic cleavage."
FT /evidence="ECO:0000269|PubMed:18591243"
FT MUTAGEN 3495
FT /note="K->A: Decreased autocatalytic cleavage."
FT /evidence="ECO:0000269|PubMed:18591243"
FT MUTAGEN 3499..3500
FT /note="SS->AA: No effect in autocatalytic cleavage."
FT /evidence="ECO:0000269|PubMed:18591243"
FT MUTAGEN 3524
FT /note="K->A: No effect in autocatalytic cleavage."
FT /evidence="ECO:0000269|PubMed:18591243"
FT MUTAGEN 3526
FT /note="R->A: Decreased autocatalytic cleavage."
FT /evidence="ECO:0000269|PubMed:18591243"
FT MUTAGEN 3532
FT /note="H->A: Abolishes autocatalytic cleavage."
FT /evidence="ECO:0000269|PubMed:17464284,
FT ECO:0000269|PubMed:18591243"
FT MUTAGEN 3534
FT /note="R->A: Increased autocatalytic cleavage."
FT /evidence="ECO:0000269|PubMed:18591243"
FT MUTAGEN 3537
FT /note="S->A: No effect in autocatalytic cleavage."
FT /evidence="ECO:0000269|PubMed:18591243"
FT MUTAGEN 3551
FT /note="E->A: Does not affect autocatalytic cleavage."
FT /evidence="ECO:0000269|PubMed:17464284"
FT MUTAGEN 3552
FT /note="L->A: No effect in autocatalytic cleavage."
FT /evidence="ECO:0000269|PubMed:18591243"
FT MUTAGEN 3572
FT /note="K->A: No effect in autocatalytic cleavage."
FT /evidence="ECO:0000269|PubMed:18591243"
FT MUTAGEN 3581
FT /note="C->S,A: Abolishes autocatalytic cleavage."
FT /evidence="ECO:0000269|PubMed:17464284,
FT ECO:0000269|PubMed:18591243, ECO:0000269|PubMed:19465933"
FT MUTAGEN 3606
FT /note="R->A: Increased autocatalytic cleavage."
FT /evidence="ECO:0000269|PubMed:18591243"
FT MUTAGEN 3609
FT /note="V->A: No effect in autocatalytic cleavage."
FT /evidence="ECO:0000269|PubMed:18591243"
FT MUTAGEN 3612
FT /note="R->A: Decreased autocatalytic cleavage."
FT /evidence="ECO:0000269|PubMed:18591243"
FT MUTAGEN 3619
FT /note="D->A,N: Slightly reduced inositol hexakisphosphate-
FT binding and strongly decreased autocatalytic cleavage."
FT /evidence="ECO:0000269|PubMed:18845756"
FT MUTAGEN 3620
FT /note="E->A: Does not affect inositol hexakisphosphate-
FT binding."
FT /evidence="ECO:0000269|PubMed:18845756"
FT MUTAGEN 3623
FT /note="R->A: Decreased autocatalytic cleavage."
FT /evidence="ECO:0000269|PubMed:18591243"
FT MUTAGEN 3623
FT /note="R->Q: Slightly reduced inositol hexakisphosphate-
FT binding and strongly decreased autocatalytic cleavage."
FT /evidence="ECO:0000269|PubMed:18845756"
FT MUTAGEN 3624
FT /note="K->A: Decreased autocatalytic cleavage."
FT /evidence="ECO:0000269|PubMed:18591243"
FT MUTAGEN 3624
FT /note="K->N: Abolishes inositol hexakisphosphate-binding
FT and autocatalytic cleavage."
FT /evidence="ECO:0000269|PubMed:18845756"
FT MUTAGEN 3632
FT /note="D->A: Does not affect inositol hexakisphosphate-
FT binding."
FT /evidence="ECO:0000269|PubMed:18845756"
FT MUTAGEN 3633
FT /note="W->A: Reduced inositol hexakisphosphate-binding and
FT autocatalytic cleavage."
FT /evidence="ECO:0000269|PubMed:18845756"
FT MUTAGEN 3633
FT /note="W->F: Slightly reduced inositol hexakisphosphate-
FT binding and strongly decreased autocatalytic cleavage."
FT /evidence="ECO:0000269|PubMed:18845756"
FT MUTAGEN 3636
FT /note="K->N: Abolishes inositol hexakisphosphate-binding
FT and autocatalytic cleavage."
FT /evidence="ECO:0000269|PubMed:18845756"
FT MUTAGEN 3641
FT /note="K->A: Decreased autocatalytic cleavage."
FT /evidence="ECO:0000269|PubMed:18591243"
FT HELIX 3452..3454
FT /evidence="ECO:0007829|PDB:3FZY"
FT STRAND 3472..3478
FT /evidence="ECO:0007829|PDB:3FZY"
FT HELIX 3483..3495
FT /evidence="ECO:0007829|PDB:3FZY"
FT HELIX 3496..3499
FT /evidence="ECO:0007829|PDB:3FZY"
FT STRAND 3500..3505
FT /evidence="ECO:0007829|PDB:3FZY"
FT STRAND 3511..3516
FT /evidence="ECO:0007829|PDB:3FZY"
FT HELIX 3518..3520
FT /evidence="ECO:0007829|PDB:3FZY"
FT STRAND 3523..3530
FT /evidence="ECO:0007829|PDB:3FZY"
FT STRAND 3533..3535
FT /evidence="ECO:0007829|PDB:3FZY"
FT HELIX 3549..3567
FT /evidence="ECO:0007829|PDB:3FZY"
FT STRAND 3574..3582
FT /evidence="ECO:0007829|PDB:3FZY"
FT STRAND 3588..3591
FT /evidence="ECO:0007829|PDB:3FZY"
FT HELIX 3592..3602
FT /evidence="ECO:0007829|PDB:3FZY"
FT STRAND 3608..3614
FT /evidence="ECO:0007829|PDB:3FZY"
FT STRAND 3616..3618
FT /evidence="ECO:0007829|PDB:3FZY"
FT STRAND 3624..3627
FT /evidence="ECO:0007829|PDB:3FZY"
FT STRAND 3629..3631
FT /evidence="ECO:0007829|PDB:3FZY"
FT STRAND 3633..3636
FT /evidence="ECO:0007829|PDB:3FZY"
FT HELIX 3638..3640
FT /evidence="ECO:0007829|PDB:3FZY"
FT STRAND 3641..3644
FT /evidence="ECO:0007829|PDB:3FZY"
SQ SEQUENCE 4558 AA; 485355 MW; 800DD5D1D119AE19 CRC64;
MVFYLIPKRR VWLMGKPFWR SVEYFFTGNY SADDGNNNIV AIGFGGQIHA YGGDDHVTVG
SIGATVYTGS GNDTVVGGSA YLKVEDSTGH LIVKGAAGYA DINKSGDGNV SFAGAAGGVS
IDHLGNHGDV SYGGAAAYNG ITRKGLSGNV TFAGAGGYNA LWHETNQGNL SFTGAGAGNK
LDRTWSNRYQ GSHGDVTFDG AGAANSISSR VETGNITFRG AGADNHLVRK GKVGDITLQG
AGASNRIERT HQAEDVYTQT RGNIRFEGVG GYNSLYSDVA HGDIHFSGGG AYNTIIRKGS
GNDFAKEGMT NAKADEIVLT KAVMSGSWIG QDHHVTAVKS ASEPNTYLFA FADSTYTKIN
KVQLRNDPQT GELKYYSTAW YKEVNHLSNL ANQDISDNGG FTAVNINGAY TLSDLKVEHQ
QSVTVHAVEK SLTEYEWVTY ANGAVIDAKE VSLSDAKMGG HAIYADGTKV DVKAVKSNRQ
PNTYIYAKVL GPYTKIVVVE LANDPETGAL KYQARSWYKE GDHTANIANQ DISSATGYNP
MGKGGYSLSD LHYSVNAVRS TSETVADIEE YTDQTLFKPA NDSGESSGDV RFNGAGGGNV
IKSNVTRGNV HFNGGGIANV ILHSSQFGNT EFNGGGAANV IVKSGEEGDL TFRGAGLANV
LVHQSEQGKM DVYAGGAVNV LVRLGDGQYL AHLLAYGNIS VQKGSGDSRV VMLGGYNTHT
QIGSGNGLWL AAGGFNVMTQ VGKGDVAAVL AGGANVLTKM GEGELTSGML GGANVITHIS
NDDQLSNTTA VALGGANILT KKGKGNTLAV MGGGANVLTH VGDGTTTGVM VGGANILTKV
GNGDTTGILL GVGNVLTHVG DGQTLGVMGA AGNIFTKVGD GTSIAVMIGA GNIFTHVGEG
NAWALMGGLG NVFTKVGNGD ALALMVAEAN VFTHIGDGMS VALMLAKGNV ATKVGNGTTL
AAMVGNVNIF THIGHGSTFA AMIGQANIMT KVGNDLTAAL MVGKANIMTH VGDGTSLGLF
AGEVNVMTKV GNGTTLAAMF GKANIMTHVG DGLTGVLALG EANIVTKLGD DFMGVVAAAK
ANVVTHVGDA TTAAVLAGKG NILTKVGEGT TVGLLISDVG NVMTHVGDGT TIGIAKGKAN
LITKVGDGLG VNVTWGQANV FTQVGDGDRY NFAKGEANLI TKVGDGQEVS VVQGEANIIT
HVGNGDDYTG AWGKANVITK VGHGQNVVLA KGEANIVTQV GDGDSFNALW SKGNIVTKVG
DGMQVTAAKG QANITTTVGN GLNVTAAYGD ANINTKVGDG VSVNVAWGKY NINTKVGDGL
NVAVMKGKAN ANIHVGDGLN INASYAQNNV AIKVGNGDFY SLAVASSNTS SNKLSALFDN
IKQTVLGVGG SQAINYLVQG DEASSSGTHK GRGAIATPEI TKLDGFQMDA IKEVSSDLGD
SLTGSVTKVD TPDLNKMQHA LNVDDSSVQA PNLIVNGDFE LGEHGWQSTH GVEASYAGSV
YGVEGEGHGA RVTELDTYTN TSLYQDLANL AQGEVIAVSF DFAKRAGLSN NEGIEVLWNG
EVVFSSSGDE SAWQQKNLKL TAQAGSNRIE FKGTGHNDGL GYILDNVVAT SESSQQANAI
REHATQNPAA QNALSDKERA EADRQRLEQE KQKQLDAVAG SQSQLESTDQ QALENNGQAQ
RDAVKEESEA VTAELAKLAQ GLDVLDGQAT HTGESGDQWR NDFAGGLLDG VQSQLDDAKQ
LANDKIAAAK QTLSDNNSKV KESVAKSEAG VAQGEQNRAG VEQDIADAQA DAEKRKADAL
AKGKDAQQAE SDAHHAVNNA QSRGDRDVQL AENKANQAQA DAQGAKQNEG DRPDRQGVTG
SGLSGNAHSV EGAGETDSHV NTDSQTNADG RFSEGLTEQE QEALEGATNA VNRLQINAGI
RAKNSVSSMT SMFSETNSKS IVVPTKVSPE PERQEVTRRD VRISGVNLES LSAVQGSQPT
GQLASKSVPG FKSHFASTSI GIENELSGLV VVLPKNSAQT FGYVHDSQGN PLFMLTKDMN
QGGYSNPVGI NDIQGVNNWQ THTIELVTYP SEISDTAAVE SRKEAMLWLA KEFTDHINQS
NHQSLPHLVS DDGRFTLVIS NSKHLIAAGN GTSIDAQGKT IGMTPSGQQA TMAISAKEFG
TSSSPEVRLL ESAPWYQAGL RDEFLANAKN TTLDDPATAQ NVYAYLTSVY SKTADLAKEY
GIYINDWDPA SEGFSPNAQG LTDPKVKNAW SILPRTKPVR MLELLSAEDS RYVRQQIAEK
LKGTYSESLA KNVFEYFQYG GEVAGHGINN ATTGSVQQPE PAILFEFRSV PSALSDFVPK
TASTVKVDVK ALDHFDSASR KAIITEVNAL VSGSEDFDAW YQEYRASKGQ PPVKNPKSSA
SANHKAEWLM TQHAEQWAKI TAPYTDNHET LTSTKLASND KEELHALGET SNLENNKQQE
NVASIINTML NDMLPFYALR TERNLLVQEG DEGFEVRAWP GTEDKSKTII LEDPEDAAQH
KAIERFILAN FDNFEQMPDE LFLVDNKVIS HHEGRTHVLA QKVDGAWQYN ATVELMSVTE
LLDAANVTGK IRGESYQQVI DALTDYHASI TEHADYEPES VEKLLNLRKK IEGYVLGHPD
SGRVEAMNSL LNQVNTRLDE VSLLSVAEQT IQAQNSFSRL YDQLEAANLK ESKHLYLDQN
GDFVTKGKGN LANIDLLGSR EAVLEKVKLT VSNEYGQTVA DTIFAGLSAK DLAKDGKGVD
IAGLNKVHQA IEQHLSPVSA TLYIWKPSDH SALGHAALQI GQGRTQLEGQ AAADFNQQNY
VSWWPLGSKS SNISNILNVA TKDQPDLKLR WSDFSQPAHQ NDTLEHDVAS EENDGFGLHD
GDIKLKRFIE KLNAAKGIDA SFKEASEGYA SVLLGNPDML ETTSIPAHVF QPFVEQWNDT
SYDMMDVAHR FAQELRLQAQ RSDDPELLEK RIGNVIRQFA ERALEEIETF KASQADQGRV
FRINLEGLDV AAMQAEWHRL SNDPDARYQL LTKNCSSTVA KVLKAGGADK LIGHTWLPKF
GVWTPTELFN FGQALQEAQL EIAAKKQSHQ VTDVLDALSG NEKPKENVAI ENDGTPPRDK
ESLSPLTRFL NNELYGDKEA RRKIGEITQT LLDHAVEKGE SQKITLQGEA GRLTGYYHQG
TAPSEGETSS PSGKVVLFLH GSGSSAEEQA SAIRNHYQKQ GIDMLAVNLR GYGESDGGPS
EKGLYQDART MFNYLVNDKG IDPSNIIIHG YSMGGPIAAD LARYAAQNGQ AVSGLLLDRP
MPSMTKAITA HEVANPAGIV GAIAKAVNGQ FSVEKNLEGL PKETSILLLT DNEGLGNEGE
KLRTKLTASG YNVTGEQTFY GHEASNRLMS QYADQIVSGL SSSASVDEDL DQQGLDTTST
KDQGISNKND HLQVVDSKEA LADGKILHNQ NVNSWGPITV TPTTDGGETR FDGQIIVQME
NDPVVAKAAA NLAGKHAESS VVVQLDSDGN YRVVYGDPSK LDGKLRWQLV GHGRDHSETN
NTRLSGYSAD ELAVKLAKFQ QSFNQAENIN NKPDHISIVG CSLVSDDKQK GFGHQFINAM
DANGLRVDVS VRSSELAVDE AGRKHTKDAN GDWVQKAENN KVSLSWDAQG EVVAKDERIR
NGIAEGDIDL SRIGVNNVDE PARGAIGDNN DVFDAPEKRK PETEVIANSS SSNQFSYSGN
IQVNVGEGEF TAVNWGTSNV GIKVGTGGFK SLAFGDNNVM VHIGDGESKH SVDIGGYQAL
EGAQMFLGNR NVSFNFGHSN DLILMMDKSI PTPPLVNPFD GAARISGVLQ GIATSGEGED
WLAAQEQQWT LSGAKKFVKD MSGLDQSSSV DYTTLVELDS QNERDSRGLK HDAEATLNKQ
YNQWLSGNGN SGTSQLSRAD KLRQANEKLA FNFAVGGQGA DIQVTTGNWN FMFGDNIQSI
LDTNLGSLFG LMTQQFTATG QAKTTFTYTP QDLPRQLKNK LLGQLAGVGA ETTLADIFGV
DYTASGQIVS RNGQAVDGVA ILKEMLEVIG EFSGDQLQAF VDPAKLLDSL KAGIDMGADG
IKSFAETHGL KEKAPEEEKD NSSVSVNGAN VNSAQGATVA DGNTETAETQ DRAFGFNSLN
LPNLFATIFS QDKQKEMKSL VENLKQNLTA DLLNMKEKTF DFLRNSGHLQ GDGDINISLG
NYNFNWGGDG KDLGAYLGDN NNFWGGRGDD VFYATGKSNI FTGGEGNDMG VLMGRENMMF
GGDGNDTAVV AGRINHVFLG AGDDQSFVFG EGGEIDTGSG RDYVVTSGNF NRVDTGDDQD
YSVTIGNNNQ VELGAGNDFA NIFGNYNRIN AGAGNDVVKL MGYHAVLNGG DGDDHLIATA
ISKFSQFNGG EGRDLMVLGG YQNTFKGGTD VDSFVVSGDV IDNLVEDIRS EDNIVFNGID
WQKLWFERSG YDLKLSILRD PSNDSDQSKF EHIGSVTFSD YFNGNRAQVV IGMSEKDLSG
EREYTMLSDS AIDALVQAMS GFEPQAGDNG FIDSLESKSQ AAISMAWSDV VHKKGLMV
