PA2H2_BOTMO
ID PA2H2_BOTMO Reviewed; 122 AA.
AC Q9I834;
DT 13-DEC-2001, integrated into UniProtKB/Swiss-Prot.
DT 13-DEC-2001, sequence version 2.
DT 25-MAY-2022, entry version 98.
DE RecName: Full=Basic phospholipase A2 homolog myotoxin II {ECO:0000303|PubMed:15760708, ECO:0000303|PubMed:23810946, ECO:0000303|PubMed:9637370, ECO:0000303|Ref.4};
DE Short=MjTX-II {ECO:0000303|PubMed:15760708, ECO:0000303|PubMed:23810946, ECO:0000303|PubMed:26457430, ECO:0000303|PubMed:29287778, ECO:0000303|PubMed:30679550};
DE Short=svPLA2 homolog;
DE AltName: Full=Basic phospholipase A2 homolog 2;
DE AltName: Full=M-VI;
OS Bothrops moojeni (Lance-headed viper) (Caissaca).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Lepidosauria; Squamata; Bifurcata; Unidentata; Episquamata; Toxicofera;
OC Serpentes; Colubroidea; Viperidae; Crotalinae; Bothrops.
OX NCBI_TaxID=98334;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND ACTIVITY REGULATION.
RC TISSUE=Venom, and Venom gland;
RX PubMed=16442348; DOI=10.1016/j.cbpc.2005.11.020;
RA Stabeli R.G., Amui S.F., Sant'Ana C.D., Pires M.G., Nomizo A.,
RA Monteiro M.C., Romao P.R.T., Guerra-Sa R., Vieira C.A., Giglio J.R.,
RA Fontes M.R.M., Soares A.M.;
RT "Bothrops moojeni myotoxin-II, a Lys49-phospholipase A2 homologue: an
RT example of function versatility of snake venom proteins.";
RL Comp. Biochem. Physiol. 142:371-381(2006).
RN [2]
RP PROTEIN SEQUENCE OF 1-52, FUNCTION, AND SUBCELLULAR LOCATION.
RC TISSUE=Venom;
RX PubMed=9637370; DOI=10.1016/s0041-0101(97)00133-5;
RA Soares A.M., Rodrigues V.M., Homsi-Brandeburgo M.I., Toyama M.H.,
RA Lombardi F.R., Arni R.K., Giglio J.R.;
RT "A rapid procedure for the isolation of the Lys-49 myotoxin II from
RT Bothrops moojeni (caissaca) venom: biochemical characterization,
RT crystallization, myotoxic and edematogenic activity.";
RL Toxicon 36:503-514(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 15-122.
RC TISSUE=Venom gland;
RA Soares A.M., Ward R.J., Rodrigues-Simioni L., Lomonte B., Gutierrez J.M.,
RA Guerra-Sa R., Rodrigues V., Fontes M.R.M., Arni R.K., Giglio J.R.;
RL Submitted (APR-1999) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS), AND SUBUNIT.
RC TISSUE=Venom;
RA de Azevedo W.F. Jr., Ward R.J., Lombardi F.R., Giglio J.R., Soares A.M.,
RA Fontes M.R.M., Arni R.K.;
RT "Crystal structure of myotoxin-II: a myotoxic phospholipase A2 homologue
RT from Bothrops moojeni venom.";
RL Protein Pept. Lett. 4:329-334(1997).
RN [5] {ECO:0000312|PDB:1XXS}
RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 1-122, AND DISULFIDE BONDS.
RX PubMed=15760708; DOI=10.1016/j.biochi.2004.11.005;
RA Watanabe L., Soares A.M., Ward R.J., Fontes M.R., Arni R.K.;
RT "Structural insights for fatty acid binding in a Lys49-phospholipase A2:
RT crystal structure of myotoxin II from Bothrops moojeni complexed with
RT stearic acid.";
RL Biochimie 87:161-167(2005).
RN [6] {ECO:0000312|PDB:4KF3}
RP X-RAY CRYSTALLOGRAPHY (1.92 ANGSTROMS) OF 1-122, FUNCTION, AND DISULFIDE
RP BONDS.
RX PubMed=23810946; DOI=10.1016/j.toxicon.2013.06.013;
RA Salvador G.H., Cavalcante W.L., Dos Santos J.I., Gallacci M., Soares A.M.,
RA Fontes M.R.;
RT "Structural and functional studies with mytoxin II from Bothrops moojeni
RT reveal remarkable similarities and differences compared to other
RT catalytically inactive phospholipases A(2)-like.";
RL Toxicon 72:52-63(2013).
RN [7] {ECO:0000312|PDB:4YV5}
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 1-122 IN COMPLEX WITH SURAMIN,
RP FUNCTION, ACTIVITY REGULATION, SUBUNIT, AND DISULFIDE BONDS.
RX PubMed=26457430; DOI=10.1107/s1399004715014443;
RA Salvador G.H., Dreyer T.R., Cavalcante W.L., Matioli F.F., Dos Santos J.I.,
RA Velazquez-Campoy A., Gallacci M., Fontes M.R.;
RT "Structural and functional evidence for membrane docking and disruption
RT sites on phospholipase A2-like proteins revealed by complexation with the
RT inhibitor suramin.";
RL Acta Crystallogr. D 71:2066-2078(2015).
RN [8] {ECO:0000312|PDB:6B80, ECO:0000312|PDB:6B81, ECO:0000312|PDB:6B83, ECO:0000312|PDB:6B84}
RP X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 1-122 ALONE AND IN COMPLEX WITH
RP FATTY ACIDS, DISULFIDE BONDS, AND SUBUNIT.
RX PubMed=29287778; DOI=10.1016/j.bbapap.2017.12.008;
RA Salvador G.H.M., Dos Santos J.I., Borges R.J., Fontes M.R.M.;
RT "Structural evidence for a fatty acid-independent myotoxic mechanism for a
RT phospholipase A2-like toxin.";
RL Biochim. Biophys. Acta 1866:473-481(2018).
RN [9] {ECO:0000312|PDB:6MQD, ECO:0000312|PDB:6MQF}
RP X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) OF 1-122 IN COMPLEX WITH
RP ACETYLSALICYLIC ACID AND ROSMARINIC ACID, FUNCTION, ACTIVITY REGULATION,
RP SUBUNIT, AND DISULFIDE BONDS.
RX PubMed=30679550; DOI=10.1038/s41598-018-36839-6;
RA Salvador G.H.M., Cardoso F.F., Gomes A.A., Cavalcante W.L.G., Gallacci M.,
RA Fontes M.R.M.;
RT "Search for efficient inhibitors of myotoxic activity induced by ophidian
RT phospholipase A2-like proteins using functional, structural and
RT bioinformatics approaches.";
RL Sci. Rep. 9:510-510(2019).
RN [10] {ECO:0000312|PDB:6PWH}
RP X-RAY CRYSTALLOGRAPHY (1.75 ANGSTROMS) IN COMPLEX WITH VARESPLADIB,
RP FUNCTION, AND DISULFIDE BONDS.
RX PubMed=31748642; DOI=10.1038/s41598-019-53755-5;
RA Salvador G.H.M., Gomes A.A.S., Bryan-Quiros W., Fernandez J., Lewin M.R.,
RA Gutierrez J.M., Lomonte B., Fontes M.R.M.;
RT "Structural basis for phospholipase A2-like toxin inhibition by the
RT synthetic compound Varespladib (LY315920).";
RL Sci. Rep. 9:17203-17203(2019).
CC -!- FUNCTION: Snake venom phospholipase A2 (PLA2) homolog that lacks
CC enzymatic activity. Shows high myotoxin activities (PubMed:16442348,
CC PubMed:9637370, PubMed:31748642). Also shows neurotoxicity, since it
CC induces muscle paralysis when tested on mouse phrenic-diaphragm
CC preparations (PubMed:16442348, PubMed:23810946, PubMed:26457430,
CC PubMed:30679550). Displays edema-inducing activities (PubMed:9637370,
CC PubMed:16442348, PubMed:26457430). Also displays antimicrobial activity
CC against E.coli and C.albicans, as well as antitumoral activity against
CC some human and mice cell lines (PubMed:16442348). In addition, it is
CC effective as parasiticidal agent against Leishmania sp. and S.mansoni
CC (PubMed:16442348). It also disrupts negatively charged liposomes in a
CC dose- and temperature-dependent manner and shows toxicity by
CC intraperitoneal route (PubMed:16442348). In contrast to other
CC phospholipase A2-like toxins, this myotoxin does not require fatty acid
CC binding to be active (PubMed:29287778). {ECO:0000269|PubMed:16442348,
CC ECO:0000269|PubMed:23810946, ECO:0000269|PubMed:26457430,
CC ECO:0000269|PubMed:30679550, ECO:0000269|PubMed:9637370,
CC ECO:0000305|PubMed:29287778}.
CC -!- ACTIVITY REGULATION: Myotoxic activity is inhibited by suramin and
CC rosmarinic acid (PubMed:26457430, PubMed:30679550). Cytotoxic and
CC myotoxic activities are inhibited by pre-incubation with varespladib
CC (PubMed:31748642). Suramin inhibits this myotoxin by (i) direct
CC blockage of the MDoS and MDiS, preventing the toxin/membrane
CC interaction and disruption and (ii) formation of an oligomeric complex,
CC resulting in a tetrameric configuration for which both MDoS and MDiS
CC becomes physically inaccessible, thus avoiding any possibility of
CC toxin-membrane interaction or disruption (PubMed:26457430). Heparin
CC completely inhibits the cytotoxic and bactericidal activities, but only
CC partially the myotoxic, edema-inducing and lethal effects
CC (PubMed:9637370). {ECO:0000269|PubMed:26457430,
CC ECO:0000269|PubMed:30679550, ECO:0000269|PubMed:9637370}.
CC -!- SUBUNIT: Homodimer; non-covalently linked (probable alternative/compact
CC dimer conformation) (Ref.4, PubMed:26457430, PubMed:29287778,
CC PubMed:30679550). {ECO:0000269|PubMed:26457430,
CC ECO:0000269|PubMed:29287778, ECO:0000269|PubMed:30679550,
CC ECO:0000269|Ref.4}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:9637370}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC {ECO:0000305|PubMed:9637370}.
CC -!- MISCELLANEOUS: Lacks hemorrhagic, anticoagulant and coagulant
CC activities. {ECO:0000269|PubMed:9637370}.
CC -!- SIMILARITY: Belongs to the phospholipase A2 family. Group II subfamily.
CC K49 sub-subfamily. {ECO:0000305}.
CC -!- CAUTION: Does not bind calcium as one of the calcium-binding sites is
CC lost (Asp->Lys in position 48, which corresponds to 'Lys-49' in the
CC current nomenclature). {ECO:0000305}.
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DR EMBL; AF145759; AAF66702.1; -; mRNA.
DR PDB; 1XXS; X-ray; 1.80 A; A/B=1-122.
DR PDB; 4KF3; X-ray; 1.92 A; A/B=1-122.
DR PDB; 4YV5; X-ray; 1.90 A; A/B=1-122.
DR PDB; 6B80; X-ray; 1.95 A; A/B=1-122.
DR PDB; 6B81; X-ray; 1.76 A; A/B=1-122.
DR PDB; 6B83; X-ray; 1.70 A; A/B=1-122.
DR PDB; 6B84; X-ray; 2.00 A; A/B=1-122.
DR PDB; 6MQD; X-ray; 1.60 A; A/B=1-122.
DR PDB; 6MQF; X-ray; 1.69 A; A/B=1-122.
DR PDB; 6PWH; X-ray; 1.75 A; A/B=1-122.
DR PDBsum; 1XXS; -.
DR PDBsum; 4KF3; -.
DR PDBsum; 4YV5; -.
DR PDBsum; 6B80; -.
DR PDBsum; 6B81; -.
DR PDBsum; 6B83; -.
DR PDBsum; 6B84; -.
DR PDBsum; 6MQD; -.
DR PDBsum; 6MQF; -.
DR PDBsum; 6PWH; -.
DR AlphaFoldDB; Q9I834; -.
DR SMR; Q9I834; -.
DR EvolutionaryTrace; Q9I834; -.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0004623; F:phospholipase A2 activity; IEA:InterPro.
DR GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR GO; GO:0050482; P:arachidonic acid secretion; IEA:InterPro.
DR GO; GO:0042742; P:defense response to bacterium; IEA:UniProtKB-KW.
DR GO; GO:0050832; P:defense response to fungus; IEA:UniProtKB-KW.
DR GO; GO:0031640; P:killing of cells of another organism; IEA:UniProtKB-KW.
DR GO; GO:0016042; P:lipid catabolic process; IEA:InterPro.
DR GO; GO:0006644; P:phospholipid metabolic process; IEA:InterPro.
DR CDD; cd00125; PLA2c; 1.
DR Gene3D; 1.20.90.10; -; 1.
DR InterPro; IPR001211; PLipase_A2.
DR InterPro; IPR033112; PLipase_A2_Asp_AS.
DR InterPro; IPR016090; PLipase_A2_dom.
DR InterPro; IPR036444; PLipase_A2_dom_sf.
DR InterPro; IPR033113; PLipase_A2_His_AS.
DR PANTHER; PTHR11716; PTHR11716; 1.
DR Pfam; PF00068; Phospholip_A2_1; 1.
DR PRINTS; PR00389; PHPHLIPASEA2.
DR SMART; SM00085; PA2c; 1.
DR SUPFAM; SSF48619; SSF48619; 1.
DR PROSITE; PS00119; PA2_ASP; 1.
DR PROSITE; PS00118; PA2_HIS; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Antibiotic; Antimicrobial; Direct protein sequencing;
KW Disulfide bond; Fungicide; Myotoxin; Neurotoxin; Postsynaptic neurotoxin;
KW Secreted; Toxin.
FT CHAIN 1..122
FT /note="Basic phospholipase A2 homolog myotoxin II"
FT /evidence="ECO:0000305|PubMed:16442348"
FT /id="PRO_0000161624"
FT REGION 105..118
FT /note="Important for membrane-damaging activities in
FT eukaryotes and bacteria; heparin-binding"
FT /evidence="ECO:0000250|UniProtKB:P24605"
FT SITE 15
FT /note="Cationic membrane-docking site (MDoS)"
FT /evidence="ECO:0000305|PubMed:29287778"
FT SITE 19
FT /note="Cationic membrane-docking site (MDoS)"
FT /evidence="ECO:0000305|PubMed:29287778"
FT SITE 105
FT /note="Important residue of the cationic membrane-docking
FT site (MDoS)"
FT /evidence="ECO:0000250|UniProtKB:I6L8L6,
FT ECO:0000305|PubMed:29287778"
FT SITE 108
FT /note="Important residue of the cationic membrane-docking
FT site (MDoS)"
FT /evidence="ECO:0000250|UniProtKB:I6L8L6,
FT ECO:0000305|PubMed:29287778"
FT SITE 112
FT /note="Hydrophobic membrane-disruption site (MDiS)"
FT /evidence="ECO:0000250|UniProtKB:I6L8L6"
FT SITE 113
FT /note="Cationic membrane-docking site (MDoS)"
FT /evidence="ECO:0000250|UniProtKB:I6L8L6"
FT SITE 115
FT /note="Hydrophobic membrane-disruption site (MDiS)"
FT /evidence="ECO:0000250|UniProtKB:I6L8L6"
FT SITE 118
FT /note="Cationic membrane-docking site (MDoS)"
FT /evidence="ECO:0000250|UniProtKB:I6L8L6"
FT DISULFID 26..116
FT /evidence="ECO:0000269|PubMed:15760708,
FT ECO:0000269|PubMed:23810946, ECO:0000269|PubMed:26457430,
FT ECO:0000269|PubMed:29287778, ECO:0000269|PubMed:30679550,
FT ECO:0000269|PubMed:31748642, ECO:0007744|PDB:1XXS,
FT ECO:0007744|PDB:4KF3, ECO:0007744|PDB:4YV5,
FT ECO:0007744|PDB:6B80, ECO:0007744|PDB:6B81,
FT ECO:0007744|PDB:6B83, ECO:0007744|PDB:6B84,
FT ECO:0007744|PDB:6MQD, ECO:0007744|PDB:6MQF,
FT ECO:0007744|PDB:6PWH"
FT DISULFID 28..44
FT /evidence="ECO:0000269|PubMed:15760708,
FT ECO:0000269|PubMed:23810946, ECO:0000269|PubMed:26457430,
FT ECO:0000269|PubMed:29287778, ECO:0000269|PubMed:30679550,
FT ECO:0000269|PubMed:31748642, ECO:0007744|PDB:1XXS,
FT ECO:0007744|PDB:4KF3, ECO:0007744|PDB:4YV5,
FT ECO:0007744|PDB:6B80, ECO:0007744|PDB:6B81,
FT ECO:0007744|PDB:6B83, ECO:0007744|PDB:6B84,
FT ECO:0007744|PDB:6MQD, ECO:0007744|PDB:6MQF,
FT ECO:0007744|PDB:6PWH"
FT DISULFID 43..95
FT /evidence="ECO:0000269|PubMed:15760708,
FT ECO:0000269|PubMed:23810946, ECO:0000269|PubMed:26457430,
FT ECO:0000269|PubMed:29287778, ECO:0000269|PubMed:30679550,
FT ECO:0000269|PubMed:31748642, ECO:0007744|PDB:1XXS,
FT ECO:0007744|PDB:4KF3, ECO:0007744|PDB:4YV5,
FT ECO:0007744|PDB:6B80, ECO:0007744|PDB:6B81,
FT ECO:0007744|PDB:6B83, ECO:0007744|PDB:6B84,
FT ECO:0007744|PDB:6MQD, ECO:0007744|PDB:6MQF,
FT ECO:0007744|PDB:6PWH"
FT DISULFID 49..122
FT /evidence="ECO:0000269|PubMed:15760708,
FT ECO:0000269|PubMed:23810946, ECO:0000269|PubMed:26457430,
FT ECO:0000269|PubMed:29287778, ECO:0000269|PubMed:30679550,
FT ECO:0000269|PubMed:31748642, ECO:0007744|PDB:1XXS,
FT ECO:0007744|PDB:4KF3, ECO:0007744|PDB:4YV5,
FT ECO:0007744|PDB:6B80, ECO:0007744|PDB:6B81,
FT ECO:0007744|PDB:6B83, ECO:0007744|PDB:6B84,
FT ECO:0007744|PDB:6MQD, ECO:0007744|PDB:6MQF,
FT ECO:0007744|PDB:6PWH"
FT DISULFID 50..88
FT /evidence="ECO:0000269|PubMed:15760708,
FT ECO:0000269|PubMed:23810946, ECO:0000269|PubMed:26457430,
FT ECO:0000269|PubMed:29287778, ECO:0000269|PubMed:30679550,
FT ECO:0000269|PubMed:31748642, ECO:0007744|PDB:1XXS,
FT ECO:0007744|PDB:4KF3, ECO:0007744|PDB:4YV5,
FT ECO:0007744|PDB:6B80, ECO:0007744|PDB:6B81,
FT ECO:0007744|PDB:6B83, ECO:0007744|PDB:6B84,
FT ECO:0007744|PDB:6MQD, ECO:0007744|PDB:6MQF,
FT ECO:0007744|PDB:6PWH"
FT DISULFID 57..81
FT /evidence="ECO:0000269|PubMed:15760708,
FT ECO:0000269|PubMed:23810946, ECO:0000269|PubMed:26457430,
FT ECO:0000269|PubMed:29287778, ECO:0000269|PubMed:30679550,
FT ECO:0000269|PubMed:31748642, ECO:0007744|PDB:1XXS,
FT ECO:0007744|PDB:4KF3, ECO:0007744|PDB:4YV5,
FT ECO:0007744|PDB:6B80, ECO:0007744|PDB:6B81,
FT ECO:0007744|PDB:6B83, ECO:0007744|PDB:6B84,
FT ECO:0007744|PDB:6MQD, ECO:0007744|PDB:6MQF,
FT ECO:0007744|PDB:6PWH"
FT DISULFID 75..86
FT /evidence="ECO:0000269|PubMed:15760708,
FT ECO:0000269|PubMed:23810946, ECO:0000269|PubMed:26457430,
FT ECO:0000269|PubMed:29287778, ECO:0000269|PubMed:30679550,
FT ECO:0000269|PubMed:31748642, ECO:0007744|PDB:1XXS,
FT ECO:0007744|PDB:4KF3, ECO:0007744|PDB:4YV5,
FT ECO:0007744|PDB:6B80, ECO:0007744|PDB:6B81,
FT ECO:0007744|PDB:6B83, ECO:0007744|PDB:6B84,
FT ECO:0007744|PDB:6MQD, ECO:0007744|PDB:6MQF,
FT ECO:0007744|PDB:6PWH"
FT CONFLICT 18
FT /note="A -> V (in Ref. 3; AAF66702)"
FT /evidence="ECO:0000305"
FT HELIX 2..13
FT /evidence="ECO:0007829|PDB:6MQD"
FT HELIX 17..21
FT /evidence="ECO:0007829|PDB:6MQD"
FT TURN 25..27
FT /evidence="ECO:0007829|PDB:6MQD"
FT STRAND 28..31
FT /evidence="ECO:0007829|PDB:6MQD"
FT HELIX 39..53
FT /evidence="ECO:0007829|PDB:6MQD"
FT TURN 59..61
FT /evidence="ECO:0007829|PDB:6MQD"
FT STRAND 66..69
FT /evidence="ECO:0007829|PDB:6MQD"
FT STRAND 72..75
FT /evidence="ECO:0007829|PDB:6MQD"
FT HELIX 80..98
FT /evidence="ECO:0007829|PDB:6MQD"
FT HELIX 99..102
FT /evidence="ECO:0007829|PDB:6MQD"
FT HELIX 105..107
FT /evidence="ECO:0007829|PDB:6MQD"
FT HELIX 113..115
FT /evidence="ECO:0007829|PDB:6MQD"
SQ SEQUENCE 122 AA; 13887 MW; 120AA53FAB3009CB CRC64;
SLFELGKMIL QETGKNPAKS YGVYGCNCGV GGRGKPKDAT DRCCYVHKCC YKKLTGCDPK
KDRYSYSWKD KTIVCGENNS CLKELCECDK AVAICLRENL DTYNKKYRYN YLKPFCKKAD
PC
