ID   LKA11_MANHA             Reviewed;         953 AA.
AC   P55118;
DT   01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-1996, sequence version 1.
DT   25-MAY-2022, entry version 92.
DE   RecName: Full=Leukotoxin;
DE            Short=Lkt;
GN   Name=lktA;
OS   Mannheimia haemolytica (Pasteurella haemolytica).
OC   Bacteria; Proteobacteria; Gammaproteobacteria; Pasteurellales;
OC   Pasteurellaceae; Mannheimia.
OX   NCBI_TaxID=75985;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   STRAIN=Serotype A11;
RX   PubMed=8225575; DOI=10.1128/iai.61.12.5001-5007.1993;
RA   Burrows L.L., Olah-Winfield E., Lo R.Y.C.;
RT   "Molecular analysis of the leukotoxin determinants from Pasteurella
RT   haemolytica serotypes 1 to 16.";
RL   Infect. Immun. 61:5001-5007(1993).
CC   -!- FUNCTION: Pasteurella leukotoxins are exotoxins that attack host
CC       leukocytes and especially polymorphonuclear cells, by causing cell
CC       rupture. The leukotoxin binds to the host LFA-1 integrin and induces a
CC       signaling cascade leading to many biological effects, including
CC       tyrosine phosphorylation of the CD18 tail, elevation of the
CC       intracellular Ca(2+) and lysis of the host cell (By similarity). This
CC       leukotoxin is a major contributor to the pathogenesis of lung injury in
CC       ovine pneumonic pasteurellosis. It has also weak hemolytic activity.
CC       {ECO:0000250}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250}. Host cell membrane
CC       {ECO:0000250}; Multi-pass membrane protein {ECO:0000250}.
CC   -!- DOMAIN: The transmembrane domains are believed to be involved in pore
CC       formation in target cells. {ECO:0000250}.
CC   -!- DOMAIN: The Gly-rich region is probably involved in calcium binding,
CC       which is required for target cell-binding and cytolytic activity.
CC       {ECO:0000250}.
CC   -!- DOMAIN: The C-terminal domain contains an export signal that is
CC       recognized by the ABC transporter complex LktBD. {ECO:0000250}.
CC   -!- PTM: Acylated by LktC. The toxin only becomes active when modified (By
CC       similarity). {ECO:0000250}.
CC   -!- MISCELLANEOUS: The lktCABD operon has a complex mosaic structure that
CC       has been derived by extensive inter- and intraspecies horizontal DNA
CC       transfer and intragenic recombination events.
CC   -!- SIMILARITY: Belongs to the RTX prokaryotic toxin (TC 1.C.11) family.
CC       {ECO:0000305}.
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DR   EMBL; U01215; AAB36689.1; -; Unassigned_DNA.
DR   AlphaFoldDB; P55118; -.
DR   SMR; P55118; -.
DR   GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR   GO; GO:0020002; C:host cell plasma membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR   GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR   GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR   GO; GO:0044179; P:hemolysis in another organism; IEA:UniProtKB-KW.
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; 4.
PE   3: Inferred from homology;
KW   Calcium; Cytolysis; Hemolysis; Host cell membrane; Host membrane;
KW   Lipoprotein; Membrane; Repeat; Secreted; Toxin; Transmembrane;
KW   Transmembrane helix; Virulence.
FT   CHAIN           1..953
FT                   /note="Leukotoxin"
FT                   /id="PRO_0000196230"
FT   TRANSMEM        230..250
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        297..317
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        381..401
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   REPEAT          715..732
FT                   /note="Hemolysin-type calcium-binding 1"
FT   REPEAT          733..750
FT                   /note="Hemolysin-type calcium-binding 2"
FT   REPEAT          751..768
FT                   /note="Hemolysin-type calcium-binding 3"
FT   REPEAT          769..786
FT                   /note="Hemolysin-type calcium-binding 4"
FT   REPEAT          789..806
FT                   /note="Hemolysin-type calcium-binding 5"
SQ   SEQUENCE   953 AA;  102206 MW;  927FF56CFC884F12 CRC64;
     MGNKLTNIST NLKSSWLTAK SGLNRTGQSL AKAGQSLKTG AKKIILYIPK DYQYDTEKGN
     GLQDLVKAAE ELGIEVQKEE GNDIAKAQTS LGTIQNVLGL TERGIVLSAP QLDKLLQKTK
     VGQAIGSAEN LTKGFSNAKT VLSGIQSILG SVLAGMDLDE ALQKNSNELT LAKAGLELTN
     SLIENIANSV KTLDAFGDQI NQLGSKLQNV KGLSSLGDKL KGLSGFDKTS LGLDVVSGLL
     SGATAALVLA DKNASTSRKV GAGFELANQV VGNITKAVSS YILAQRVAAG LSSTGPVAAL
     IASTVSLAIS PLAFAGIADK FNHAKSLESY AERFKKLGYD GDNLLAEYQR GTGTIDRSVT
     AINTALAAIA GGVSAAGRGS VIASPIALLV SGITGVISTI LQYSKQAMFE HVANKIHNKI
     VEWEKNNHGK NYFENGYDAR YLANLQDNMK FLLNLNKELQ AERVIAITQQ QWDNNIGDLA
     GISRLGEKVL SGKAYVDAFE EGKHLKADKL VQLDSANGII DVSNSGKAKT QDILFRTPLL
     TPGTDDRERV QTGKYEYITK LNINRVDSWK ITDGAASSTF DLTNVVQRIG IELDNAGNVT
     KTKETKIVAK LGAGDDNVFV GSGTTEIDGG EGYDRVHYSR GNYGALTIDA TKETEQGSYT
     VNRFVETGKA LHEGTSTHTA LVGNREEKIE YRHSNNQHHA GYYTKDTLKA VEEIIGTSHN
     DIFKGSKFND AFNGGDGVDT IDGKDGNDRL FGGKGDDIID GGNGDDFIDG GKGNDLLHGG
     KGDDIFVHRQ GDGNDIITDS DGNDKLSFSD SNLKDLTFEK VKHNLVITNS RKEKVTIQDW
     FREADFAKEV RNYKATKDEK IEEIIGQNGE RITSKQVDDL IAKGNGKITQ DELSKVVDNY
     ELLKHSKNVT NSLDKLISSA SAFTSSNDSR NVLVAPTSML DQSLSSLQFA RAA