RTXA_KINKI
ID RTXA_KINKI Reviewed; 956 AA.
AC A1YKW7;
DT 25-MAY-2022, integrated into UniProtKB/Swiss-Prot.
DT 06-FEB-2007, sequence version 1.
DT 03-AUG-2022, entry version 59.
DE RecName: Full=Cytolysin RtxA {ECO:0000305};
DE AltName: Full=Repeats in toxin A {ECO:0000303|PubMed:33260488};
GN Name=rtxA {ECO:0000303|PubMed:17098895};
OS Kingella kingae.
OC Bacteria; Proteobacteria; Betaproteobacteria; Neisseriales; Neisseriaceae;
OC Kingella.
OX NCBI_TaxID=504;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RC STRAIN=269-492;
RX PubMed=17098895; DOI=10.1128/jb.01319-06;
RA Kehl-Fie T.E., St Geme J.W. III;
RT "Identification and characterization of an RTX toxin in the emerging
RT pathogen Kingella kingae.";
RL J. Bacteriol. 189:430-436(2007).
RN [2]
RP FUNCTION.
RX PubMed=21248099; DOI=10.1128/jcm.01657-10;
RA Lehours P., Freydiere A.M., Richer O., Burucoa C., Boisset S., Lanotte P.,
RA Prere M.F., Ferroni A., Lafuente C., Vandenesch F., Megraud F., Menard A.;
RT "The rtxA toxin gene of Kingella kingae: a pertinent target for molecular
RT diagnosis of osteoarticular infections.";
RL J. Clin. Microbiol. 49:1245-1250(2011).
RN [3]
RP SUBCELLULAR LOCATION.
RX PubMed=21443941; DOI=10.1016/j.micpath.2011.03.005;
RA Maldonado R., Wei R., Kachlany S.C., Kazi M., Balashova N.V.;
RT "Cytotoxic effects of Kingella kingae outer membrane vesicles on human
RT cells.";
RL Microb. Pathog. 51:22-30(2011).
RN [4]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=24664507; DOI=10.1128/iai.01636-14;
RA Chang D.W., Nudell Y.A., Lau J., Zakharian E., Balashova N.V.;
RT "RTX toxin plays a key role in Kingella kingae virulence in an infant rat
RT model.";
RL Infect. Immun. 82:2318-2328(2014).
RN [5]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=25858109; DOI=10.1016/j.bbamem.2015.03.036;
RA Barcena-Uribarri I., Benz R., Winterhalter M., Zakharian E., Balashova N.;
RT "Pore forming activity of the potent RTX-toxin produced by pediatric
RT pathogen Kingella kingae: Characterization and comparison to other RTX-
RT family members.";
RL Biochim. Biophys. Acta 1848:1536-1544(2015).
RN [6]
RP FUNCTION, SUBCELLULAR LOCATION, MYRISTOYLATION AT LYS-558 AND LYS-689, AND
RP MUTAGENESIS OF TYR-54; TYR-285; TYR-343; TYR-352 AND TYR-448.
RX PubMed=30405113; DOI=10.1038/s41426-018-0179-x;
RA Osickova A., Balashova N., Masin J., Sulc M., Roderova J., Wald T.,
RA Brown A.C., Koufos E., Chang E.H., Giannakakis A., Lally E.T., Osicka R.;
RT "Cytotoxic activity of Kingella kingae RtxA toxin depends on post-
RT translational acylation of lysine residues and cholesterol binding.";
RL Emerg. Microbes Infect. 7:178-178(2018).
RN [7]
RP MYRISTOYLATION AT LYS-558 AND LYS-689.
RX PubMed=32461253; DOI=10.1074/jbc.ra120.014122;
RA Osickova A., Khaliq H., Masin J., Jurnecka D., Sukova A., Fiser R.,
RA Holubova J., Stanek O., Sebo P., Osicka R.;
RT "Acyltransferase-mediated selection of the length of the fatty acyl chain
RT and of the acylation site governs activation of bacterial RTX toxins.";
RL J. Biol. Chem. 295:9268-9280(2020).
RN [8]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=33260488; DOI=10.3390/ijms21239092;
RA Rahman W.U., Osickova A., Klimova N., Lora J., Balashova N., Osicka R.;
RT "Binding of Kingella kingae RtxA Toxin Depends on Cell Surface
RT Oligosaccharides, but Not on beta2 Integrins.";
RL Int. J. Mol. Sci. 21:0-0(2020).
CC -!- FUNCTION: Bacterial cytolysin that attacks host cell membranes and
CC causes cell rupture by forming a pore (PubMed:25858109,
CC PubMed:30405113). Binds and permeabilizes target cells by forming
CC cation-selective pores (PubMed:25858109). Constitutes the key virulence
CC cytotoxin of K.kingae (PubMed:21248099, PubMed:24664507). Binds
CC cholesterol and oligosaccharides on the surface of host cells
CC (PubMed:30405113). Does not bind beta-2 integrin (ITGB2) on the host
CC cell surface (PubMed:33260488). {ECO:0000269|PubMed:21248099,
CC ECO:0000269|PubMed:24664507, ECO:0000269|PubMed:25858109,
CC ECO:0000269|PubMed:30405113, ECO:0000269|PubMed:33260488}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:21443941}. Host cell
CC membrane {ECO:0000269|PubMed:25858109, ECO:0000269|PubMed:30405113,
CC ECO:0000269|PubMed:33260488}; Multi-pass membrane protein
CC {ECO:0000305}.
CC -!- PTM: Myristoylated by RtxC; the toxin only becomes active when modified
CC (PubMed:30405113, PubMed:32461253). Mainly myristoylated; a very minor
CC fraction is acylated with hydroxymyristoyl, lauroyl and palmitoleyl
CC chains fatty acyl groups (PubMed:30405113). Fatty acylation is involved
CC in binding to host membranes and promotes the irreversible insertion of
CC RtxA into the host cell membrane (PubMed:30405113).
CC {ECO:0000269|PubMed:30405113, ECO:0000269|PubMed:32461253}.
CC -!- DISRUPTION PHENOTYPE: Cells lacking RtxA display strongly reduced
CC virulence. {ECO:0000269|PubMed:24664507}.
CC -!- SIMILARITY: Belongs to the RTX prokaryotic toxin (TC 1.C.11) family.
CC {ECO:0000305}.
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DR EMBL; EF067866; ABK58601.1; -; Genomic_DNA.
DR TCDB; 1.C.11.1.8; the pore-forming rtx toxin (rtx-toxin) family.
DR EnsemblBacteria; CRZ19291; CRZ19291; KKKWG1_0115.
DR EnsemblBacteria; CRZ19496; CRZ19496; KKKWG1_0321.
DR GeneID; 61308780; -.
DR KEGG; kki:KKKWG1_0115; -.
DR KEGG; kki:KKKWG1_0321; -.
DR OrthoDB; 50309at2; -.
DR PHI-base; PHI:3596; -.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0033644; C:host cell membrane; IDA:UniProtKB.
DR GO; GO:0020002; C:host cell plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016020; C:membrane; IEA:UniProtKB-KW.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0005261; F:cation channel activity; IDA:UniProtKB.
DR GO; GO:0015485; F:cholesterol binding; IDA:UniProtKB.
DR GO; GO:0090729; F:toxin activity; IMP:UniProtKB.
DR GO; GO:0019835; P:cytolysis; IDA:UniProtKB.
DR Gene3D; 2.150.10.10; -; 1.
DR InterPro; IPR018511; Hemolysin-typ_Ca-bd_CS.
DR InterPro; IPR001343; Hemolysn_Ca-bd.
DR InterPro; IPR013550; RTX_C.
DR InterPro; IPR018504; RTX_N.
DR InterPro; IPR003995; RTX_toxin_determinant-A.
DR InterPro; IPR011049; Serralysin-like_metalloprot_C.
DR Pfam; PF00353; HemolysinCabind; 3.
DR Pfam; PF02382; RTX; 1.
DR Pfam; PF08339; RTX_C; 1.
DR PRINTS; PR01488; RTXTOXINA.
DR SUPFAM; SSF51120; SSF51120; 1.
DR PROSITE; PS00330; HEMOLYSIN_CALCIUM; 3.
PE 1: Evidence at protein level;
KW Cytolysis; Host cell membrane; Host membrane; Lipoprotein; Membrane;
KW Myristate; Repeat; Secreted; Toxin; Virulence.
FT CHAIN 1..956
FT /note="Cytolysin RtxA"
FT /id="PRO_0000455664"
FT REPEAT 613..639
FT /note="Hemolysin-type calcium-binding 1"
FT /evidence="ECO:0000255"
FT REPEAT 722..756
FT /note="Hemolysin-type calcium-binding 2"
FT /evidence="ECO:0000255"
FT REPEAT 757..791
FT /note="Hemolysin-type calcium-binding 3"
FT /evidence="ECO:0000255"
FT REGION 48..58
FT /note="Cholesterol recognition/amino acid consensus (CRAC)
FT region 1"
FT /evidence="ECO:0000305|PubMed:30405113"
FT REGION 280..287
FT /note="Cholesterol recognition/amino acid consensus (CARC)
FT region 1"
FT /evidence="ECO:0000305|PubMed:30405113"
FT REGION 340..348
FT /note="Cholesterol recognition/amino acid consensus (CARC)
FT region 2"
FT /evidence="ECO:0000305|PubMed:30405113"
FT REGION 349..354
FT /note="Cholesterol recognition/amino acid consensus (CRAC)
FT region 2"
FT /evidence="ECO:0000305|PubMed:30405113"
FT REGION 444..453
FT /note="Cholesterol recognition/amino acid consensus (CARC)
FT region 3"
FT /evidence="ECO:0000305|PubMed:30405113"
FT LIPID 558
FT /note="N6-myristoyl lysine"
FT /evidence="ECO:0000269|PubMed:30405113,
FT ECO:0000269|PubMed:32461253"
FT LIPID 689
FT /note="N6-myristoyl lysine"
FT /evidence="ECO:0000269|PubMed:30405113,
FT ECO:0000269|PubMed:32461253"
FT MUTAGEN 54
FT /note="Y->F: Does not affect cytolytic ability."
FT /evidence="ECO:0000269|PubMed:30405113"
FT MUTAGEN 285
FT /note="Y->F: Does not affect cytolytic ability."
FT /evidence="ECO:0000269|PubMed:30405113"
FT MUTAGEN 343
FT /note="Y->F: Reduced cytolytic ability."
FT /evidence="ECO:0000269|PubMed:30405113"
FT MUTAGEN 352
FT /note="Y->F: Reduced cytolytic ability."
FT /evidence="ECO:0000269|PubMed:30405113"
FT MUTAGEN 448
FT /note="Y->F: Does not affect cytolytic ability."
FT /evidence="ECO:0000269|PubMed:30405113"
SQ SEQUENCE 956 AA; 101210 MW; 8948AE160D731014 CRC64;
MNLATTKAKL KSGAQAGVQA LNKAGHAAKT GTVAAGKATV AGAKSLYLTI PKDYDIEKGG
SLNELIKAAD ELGIARLQED ANNIESAKKS IDTVEKLLSF TQTGVAVSAK KLDELLQKYS
SSQLAKSLGS SANIDSKLTK TNHILSTLSS FLGTALAGMD LDSLVKQGDA SATDLAKASL
DLINELVNNI SNSVQSIEAF SEQLGRLGAA ISQTKGLSGL GNKLQNLPNF GKANLALEMI
SGLLSGISAG FTLADKNAST EKKVAAGFEL SNQVIGNVTK AISSYVLAQR AAAGLSTTGA
VASLITASIM LAISPLAFMN AADKFKNASL IDEFAKQFKK FGYDGDSLLA EYQRGAGTIE
ASLTAINTAL GAVSAGVSAA AVGSVVGSPV ALLVAGVTGL ISGILEASKQ AMFESVANRL
QSKILAWEKE NGGKNYFENG YDARHAHYLE RNLKLLSELN KELQAERVIA ITQQRWDANI
GELAGITKLG DRISSGKAYA DAFEDGKKLD GASNVTVDTR TGVVDISNAN GKKTQALHFT
SPLLTAGTET RERVQNGKYS YINQLKFNRV KSWTVKDGEA NSRLDFSKVI QHVAFNDEDG
RLSGKTEEIA LNVNAGSGND DIFAGQGKMN VDGGTGHDRV FYSKDGGLGQ VNVDGTKATE
AGSYTVNRSI NNGSFYHEVI KRQTTQVGKR TETLEYRDFE LKRPEHGYQT TDTLKSVEEI
VGSQFSDTFK GSKFADIFHG GDGNDTLEGN DGDDRLFGGN GDDHLYGGNG DDLLDGGKGN
DVINGGDGND VYISRKGDGN DTLYDSHGSD KLAFADADLS ELTIERTAQG IMIKRNDGSG
SINMAEWYKT LSQQNYHGNA TDDKIEQIIG KNGDYITSEQ IDKLLKDKQT GTITSAQLQQ
LAQENKSKSI DSGNLASTLN KLIESMASFG SRGATASNYL QPAHKSPQNV LAPSAV
