PA2H1_BOTJR
ID PA2H1_BOTJR Reviewed; 137 AA.
AC Q90249; Q7LZ25; Q804D7;
DT 05-DEC-2001, integrated into UniProtKB/Swiss-Prot.
DT 22-JUL-2008, sequence version 3.
DT 03-AUG-2022, entry version 111.
DE RecName: Full=Basic phospholipase A2 homolog bothropstoxin-I {ECO:0000303|PubMed:11018293, ECO:0000303|PubMed:11732689, ECO:0000303|PubMed:14505937, ECO:0000303|PubMed:18160090, ECO:0000303|PubMed:20371382, ECO:0000303|PubMed:8427634};
DE Short=Bothropstoxin I {ECO:0000303|PubMed:7758974};
DE Short=BthTx-I {ECO:0000303|PubMed:11018293, ECO:0000303|PubMed:31906173};
DE Short=BtxtxI;
DE Short=svPLA2 homolog;
DE AltName: Full=BOJU-I;
DE AltName: Full=Myotoxic phospholipase A2-like;
DE AltName: Full=Phospholipase A2 homolog 1;
DE Flags: Precursor;
OS Bothrops jararacussu (Jararacussu).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Lepidosauria; Squamata; Bifurcata; Unidentata; Episquamata; Toxicofera;
OC Serpentes; Colubroidea; Viperidae; Crotalinae; Bothrops.
OX NCBI_TaxID=8726;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Venom gland;
RX PubMed=15134836; DOI=10.1016/j.biochi.2004.02.002;
RA Kashima S., Roberto P.G., Soares A.M., Astolfi-Filho S., Pereira J.O.,
RA Giuliati S., Faria M. Jr., Xavier M.A.S., Fontes M.R.M., Giglio J.R.,
RA Franca S.C.;
RT "Analysis of Bothrops jararacussu venomous gland transcriptome focusing on
RT structural and functional aspects: I -- gene expression profile of highly
RT expressed phospholipases A2.";
RL Biochimie 86:211-219(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Venom gland;
RA Hayashi M.A.F., Queiroz G.P., Radis-Baptista G., Yamane T., Camargo A.C.M.;
RT "Bothrops jararacussu myotoxic phospholipase A2-like mRNA.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP PROTEIN SEQUENCE OF 17-137.
RC TISSUE=Venom;
RX PubMed=8427634; DOI=10.1007/bf01024915;
RA Cintra A.C.O., Marangoni S., Oliveira B., Giglio J.R.;
RT "Bothropstoxin-I: amino acid sequence and function.";
RL J. Protein Chem. 12:57-64(1993).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 17-137.
RC TISSUE=Venom gland;
RX PubMed=7758974; DOI=10.1016/0378-1119(95)00099-r;
RA Ward R.J., Monesi N., Arni R.K., Larson R.E., Paco-Larson M.L.;
RT "Sequence of a cDNA encoding bothropstoxin I, a myotoxin from the venom of
RT Bothrops jararacussu.";
RL Gene 156:305-306(1995).
RN [5]
RP SEQUENCE REVISION.
RA Ward R.J.;
RL Submitted (SEP-2004) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP PROTEIN SEQUENCE OF 17-137, AND DISULFIDE BONDS.
RC TISSUE=Venom;
RX PubMed=11732689; DOI=10.1023/a:1012228703756;
RA Cintra A.C.O., Sampaio S.V., Raghuvir A.K., Giglio J.R.;
RT "Assignment of the disulfide bridges in bothropstoxin-I, a myonecrotic
RT Lys49 PLA2 homolog from Bothrops jararacussu snake venom.";
RL J. Protein Chem. 20:377-382(2001).
RN [7]
RP PROTEIN SEQUENCE OF 17-26, FUNCTION, TOXIC DOSE, AND SUBCELLULAR LOCATION.
RC TISSUE=Venom;
RX PubMed=3176051; DOI=10.1016/0041-0101(88)90244-9;
RA Homsi-Brandeburgo M.I., Queiroz L.S., Santo-Neto H., Rodrigues-Simioni L.,
RA Giglio J.R.;
RT "Fractionation of Bothrops jararacussu snake venom: partial chemical
RT characterization and biological activity of bothropstoxin.";
RL Toxicon 26:615-627(1988).
RN [8]
RP FUNCTION, BIOASSAY, AND TOXIC DOSE.
RC TISSUE=Venom;
RX PubMed=11018293; DOI=10.1016/s0300-9084(00)01150-0;
RA Andriao-Escarso S.H., Soares A.M., Rodrigues V.M., Angulo Y., Diaz C.,
RA Lomonte B., Gutierrez J.M., Giglio J.R.;
RT "Myotoxic phospholipases A(2) in bothrops snake venoms: effect of chemical
RT modifications on the enzymatic and pharmacological properties of
RT bothropstoxins from Bothrops jararacussu.";
RL Biochimie 82:755-763(2000).
RN [9]
RP FUNCTION, BIOASSAY, AND MUTAGENESIS OF HIS-63; LYS-64 AND LYS-128.
RX PubMed=11829743; DOI=10.1042/0264-6021:3620089;
RA Ward R.J., Chioato L., de Oliveira A.H., Ruller R., Sa J.M.;
RT "Active-site mutagenesis of a Lys49-phospholipase A2: biological and
RT membrane-disrupting activities in the absence of catalysis.";
RL Biochem. J. 362:89-96(2002).
RN [10]
RP FUNCTION, BIOASSAY, AND MUTAGENESIS OF LYS-121; LYS-122; TYR-123; ARG-124;
RP TYR-125; LYS-128; PHE-130; LYS-132 AND LYS-133.
RX PubMed=12079495; DOI=10.1042/bj20020092;
RA Chioato L., De Oliveira A.H., Ruller R., Sa J.M., Ward R.J.;
RT "Distinct sites for myotoxic and membrane-damaging activities in the C-
RT terminal region of a Lys49-phospholipase A2.";
RL Biochem. J. 366:971-976(2002).
RN [11]
RP FUNCTION, AND ACTIVITY REGULATION.
RX PubMed=14505937; DOI=10.1016/s0041-0101(03)00166-1;
RA de Oliveira M., Cavalcante W.L., Arruda E.Z., Melo P.A., Dal-Pai Silva M.,
RA Gallacci M.;
RT "Antagonism of myotoxic and paralyzing activities of bothropstoxin-I by
RT suramin.";
RL Toxicon 42:373-379(2003).
RN [12]
RP SUBUNIT, AND PROBABLE ACTIVITY REGULATION.
RX PubMed=16197992; DOI=10.1016/j.ijbiomac.2005.08.003;
RA Bugs M.R., Bortoleto-Bugs R.K., Cornelio M.L.;
RT "The interaction between heparin and Lys49 phospholipase A2 reveals the
RT natural binding of heparin on the enzyme.";
RL Int. J. Biol. Macromol. 37:21-27(2005).
RN [13]
RP FUNCTION, BIOASSAY, AND MUTAGENESIS OF LYS-23; LYS-31; LYS-51; PRO-52;
RP LYS-53; ASP-54; ARG-58; TYR-61; HIS-63; LYS-68; LYS-69; THR-71; LYS-87;
RP GLU-93; LYS-99; LYS-106; THR-118; ASN-120; LYS-121; LYS-122; TYR-123;
RP ARG-124; TYR-125; HIS-126; LEU-127; LYS-128; PHE-130; LYS-132 AND LYS-133.
RX PubMed=17346668; DOI=10.1016/j.bbamem.2007.01.023;
RA Chioato L., Aragao E.A., Lopes Ferreira T., Medeiros A.I., Faccioli L.H.,
RA Ward R.J.;
RT "Mapping of the structural determinants of artificial and biological
RT membrane damaging activities of a Lys49 phospholipase A2 by scanning
RT alanine mutagenesis.";
RL Biochim. Biophys. Acta 1768:1247-1257(2007).
RN [14]
RP FUNCTION, AND MUTAGENESIS OF HIS-63; LYS-121; TYR-123; ARG-124; LYS-128;
RP PHE-130 AND LYS-133.
RC TISSUE=Venom;
RX PubMed=18160090; DOI=10.1016/j.toxicon.2007.11.004;
RA Aragao E.A., Chioato L., Ward R.J.;
RT "Permeabilization of E. coli K12 inner and outer membranes by
RT bothropstoxin-I, a Lys49 phospholipase A2 from Bothrops jararacussu.";
RL Toxicon 51:538-546(2008).
RN [15]
RP FUNCTION.
RX PubMed=31906173; DOI=10.3390/toxins12010022;
RA Boeno C.N., Paloschi M.V., Lopes J.A., Pires W.L., Setubal S.D.S.,
RA Evangelista J.R., Soares A.M., Zuliani J.P.;
RT "Inflammasome activation induced by a snake venom Lys49-phospholipase A2
RT homologue.";
RL Toxins 12:0-0(2019).
RN [16] {ECO:0000312|PDB:2H8I}
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 17-137, FUNCTION, SUBUNIT, AND
RP DISULFIDE BONDS.
RC TISSUE=Venom;
RX PubMed=17157889; DOI=10.1016/j.toxicon.2006.10.011;
RA Murakami M.T., Vicoti M.M., Abrego J.R.B., Lourenzoni M.R., Cintra A.C.O.,
RA Arruda E.Z., Tomaz M.A., Melo P.A., Arni R.K.;
RT "Interfacial surface charge and free accessibility to the PLA2-active site-
RT like region are essential requirements for the activity of Lys49 PLA2
RT homologues.";
RL Toxicon 49:378-387(2007).
RN [17] {ECO:0000312|PDB:3CXI}
RP X-RAY CRYSTALLOGRAPHY (1.83 ANGSTROMS) OF 17-137 IN COMPLEX WITH
RP ALPHA-TOCOPHEROL, SUBUNIT, AND DISULFIDE BONDS.
RX PubMed=19401234; DOI=10.1016/j.jsb.2009.04.003;
RA dos Santos J.I., Soares A.M., Fontes M.R.;
RT "Comparative structural studies on Lys49-phospholipases A(2) from Bothrops
RT genus reveal their myotoxic site.";
RL J. Struct. Biol. 167:106-116(2009).
RN [18] {ECO:0000312|PDB:3HZD, ECO:0000312|PDB:3HZW, ECO:0000312|PDB:3I03, ECO:0000312|PDB:3I3I, ECO:0000312|PDB:3IQ3}
RP X-RAY CRYSTALLOGRAPHY (1.48 ANGSTROMS) OF 17-137 IN COMPLEX WITH THE PLA2
RP INHIBITOR BROMOPHENACYL BROMIDE (BPB), SUBUNIT, AND DISULFIDE BONDS.
RC TISSUE=Venom;
RX PubMed=20371382; DOI=10.1016/j.jsb.2010.03.019;
RA Fernandes C.A., Marchi-Salvador D.P., Salvador G.M., Silva M.C.,
RA Costa T.R., Soares A.M., Fontes M.R.;
RT "Comparison between apo and complexed structures of bothropstoxin-I reveals
RT the role of Lys122 and Ca(2+)-binding loop region for the catalytically
RT inactive Lys49-PLA(2)s.";
RL J. Struct. Biol. 171:31-43(2010).
RN [19] {ECO:0000312|PDB:4WTB}
RP X-RAY CRYSTALLOGRAPHY (2.16 ANGSTROMS) OF 17-137 IN COMPLEX WITH ZINC IONS,
RP ACTIVITY REGULATION, AND SUBUNIT.
RC TISSUE=Venom;
RX PubMed=27531710; DOI=10.1016/j.bbagen.2016.08.003;
RA Borges R.J., Cardoso F.F., Fernandes C.A.H., Dreyer T.R., de Moraes D.S.,
RA Floriano R.S., Rodrigues-Simioni L., Fontes M.R.M.;
RT "Functional and structural studies of a phospholipase A2-like protein
RT complexed to zinc ions: insights on its myotoxicity and inhibition
RT mechanism.";
RL Biochim. Biophys. Acta 1861:3199-3209(2017).
RN [20] {ECO:0000312|PDB:6DIK}
RP X-RAY CRYSTALLOGRAPHY (1.93 ANGSTROMS) OF 17-137 IN COMPLEX WITH CHICORIC
RP ACID, AND ACTIVITY REGULATION.
RX PubMed=30251662; DOI=10.1016/j.bbagen.2018.08.002;
RA Cardoso F.F., Borges R.J., Dreyer T.R., Salvador G.H.M., Cavalcante W.L.G.,
RA Pai M.D., Gallacci M., Fontes M.R.M.;
RT "Structural basis of phospholipase A2-like myotoxin inhibition by chicoric
RT acid, a novel potent inhibitor of ophidian toxins.";
RL Biochim. Biophys. Acta 1862:2728-2737(2018).
CC -!- FUNCTION: Snake venom phospholipase A2 homolog that lacks enzymatic
CC activity. Shows local myotoxic activity (PubMed:11018293,
CC PubMed:12079495, PubMed:31906173). Induces inflammation, since it
CC induces edema and leukocytes infiltration (PubMed:11018293,
CC PubMed:31906173). In addition, it induces NLRP3 NLRP3, ASC (PYCARD),
CC caspase-1 (CASP1), and IL-1beta (IL1B) gene expression in the
CC gastrocnemius muscle, showing that it is able to activate NLRP3
CC inflammasome (PubMed:31906173). It also damages artificial and myoblast
CC membranes by a calcium-independent mechanism, has bactericidal
CC activity, and induces neuromuscular blockade (PubMed:27531710). A model
CC of myotoxic mechanism has been proposed: an apo Lys49-PLA2 is activated
CC by the entrance of a hydrophobic molecule (e.g. fatty acid) at the
CC hydrophobic channel of the protein leading to a reorientation of a
CC monomer (PubMed:27531710) (By similarity). This reorientation causes a
CC transition between 'inactive' to 'active' states, causing alignment of
CC C-terminal and membrane-docking sites (MDoS) side-by-side and putting
CC the membrane-disruption sites (MDiS) in the same plane, exposed to
CC solvent and in a symmetric position for both monomers (PubMed:27531710)
CC (By similarity). The MDoS region stabilizes the toxin on membrane by
CC the interaction of charged residues with phospholipid head groups
CC (PubMed:27531710) (By similarity). Subsequently, the MDiS region
CC destabilizes the membrane with penetration of hydrophobic residues
CC (PubMed:27531710) (By similarity). This insertion causes a
CC disorganization of the membrane, allowing an uncontrolled influx of
CC ions (i.e. calcium and sodium), and eventually triggering irreversible
CC intracellular alterations and cell death (PubMed:27531710) (By
CC similarity). {ECO:0000250|UniProtKB:I6L8L6,
CC ECO:0000269|PubMed:11018293, ECO:0000269|PubMed:11829743,
CC ECO:0000269|PubMed:12079495, ECO:0000269|PubMed:17157889,
CC ECO:0000269|PubMed:17346668, ECO:0000269|PubMed:18160090,
CC ECO:0000269|PubMed:27531710, ECO:0000269|PubMed:3176051,
CC ECO:0000269|PubMed:31906173}.
CC -!- ACTIVITY REGULATION: Suramin inhibits both myotoxic and muscle-
CC paralyzing activities (PubMed:14505937). Chicoric acid inhibits
CC myotoxic activity (PubMed:30251662). Zinc ions inhibits the myotoxic
CC activity and the neuromuscular blockade (PubMed:27531710). Heparin
CC inhibits myotoxic activity (PubMed:16197992).
CC {ECO:0000269|PubMed:14505937, ECO:0000269|PubMed:27531710,
CC ECO:0000269|PubMed:30251662, ECO:0000305|PubMed:16197992}.
CC -!- SUBUNIT: Homodimer; non-covalently linked (probable alternative/compact
CC dimer conformation in solution) (PubMed:17157889, PubMed:19401234,
CC PubMed:20371382, PubMed:27531710, PubMed:30251662). Binds to heparin
CC (PubMed:16197992). {ECO:0000269|PubMed:16197992,
CC ECO:0000269|PubMed:17157889, ECO:0000269|PubMed:19401234,
CC ECO:0000269|PubMed:20371382, ECO:0000269|PubMed:27531710,
CC ECO:0000269|PubMed:30251662}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:3176051}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC {ECO:0000305|PubMed:3176051}.
CC -!- TOXIC DOSE: LD(50) is 7.5-8.5 mg/kg by intraperitoneal injection into
CC mice. {ECO:0000269|PubMed:11018293, ECO:0000269|PubMed:3176051}.
CC -!- TOXIC DOSE: LD(50) is 4.8 mg/kg by intravenous injection into mice.
CC {ECO:0000269|PubMed:3176051}.
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 64, which corresponds to 'Lys-49' in the
CC current nomenclature). However, the hydrolytic activity is not restored
CC by the mutant containing an Asp-64, indicating that other residues play
CC a key role in hydrolytic activity (PubMed:11829743).
CC {ECO:0000305|PubMed:11829743}.
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DR EMBL; AY185200; AAO27453.1; -; mRNA.
DR EMBL; AY299391; AAP57527.1; -; mRNA.
DR EMBL; X78599; CAA55334.2; -; mRNA.
DR PIR; A30823; A30823.
DR PIR; PC4024; PC4024.
DR PDB; 2H8I; X-ray; 1.90 A; A/B=17-137.
DR PDB; 3CXI; X-ray; 1.83 A; A/B=17-137.
DR PDB; 3HZD; X-ray; 1.91 A; A/B=17-137.
DR PDB; 3HZW; X-ray; 2.28 A; A/B=17-127.
DR PDB; 3I03; X-ray; 1.48 A; A=17-137.
DR PDB; 3I3H; X-ray; 2.17 A; A/B=17-137.
DR PDB; 3I3I; X-ray; 1.82 A; A=17-137.
DR PDB; 3IQ3; X-ray; 1.55 A; A/B=17-137.
DR PDB; 4WTB; X-ray; 2.16 A; A/B=17-137.
DR PDB; 6DIK; X-ray; 1.93 A; A/B=17-137.
DR PDBsum; 2H8I; -.
DR PDBsum; 3CXI; -.
DR PDBsum; 3HZD; -.
DR PDBsum; 3HZW; -.
DR PDBsum; 3I03; -.
DR PDBsum; 3I3H; -.
DR PDBsum; 3I3I; -.
DR PDBsum; 3IQ3; -.
DR PDBsum; 4WTB; -.
DR PDBsum; 6DIK; -.
DR AlphaFoldDB; Q90249; -.
DR SMR; Q90249; -.
DR ABCD; Q90249; 12 sequenced antibodies.
DR EvolutionaryTrace; Q90249; -.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0008201; F:heparin binding; IEA:UniProtKB-KW.
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: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; Heparin-binding; Myotoxin; Secreted; Signal; Toxin.
FT SIGNAL 1..16
FT /evidence="ECO:0000269|PubMed:11732689,
FT ECO:0000269|PubMed:3176051, ECO:0000269|PubMed:8427634"
FT CHAIN 17..137
FT /note="Basic phospholipase A2 homolog bothropstoxin-I"
FT /id="PRO_0000161622"
FT REGION 121..133
FT /note="Important for membrane-damaging activities in
FT eukaryotes and bacteria; heparin-binding"
FT /evidence="ECO:0000250|UniProtKB:P24605"
FT SITE 121
FT /note="Important residue of the cationic membrane-docking
FT site (MDoS)"
FT /evidence="ECO:0000250|UniProtKB:I6L8L6"
FT SITE 124
FT /note="Important residue of the cationic membrane-docking
FT site (MDoS)"
FT /evidence="ECO:0000250|UniProtKB:I6L8L6"
FT SITE 127
FT /note="Hydrophobic membrane-disruption site (MDiS)"
FT /evidence="ECO:0000250|UniProtKB:I6L8L6"
FT SITE 128
FT /note="Cationic membrane-docking site (MDoS)"
FT /evidence="ECO:0000250|UniProtKB:I6L8L6"
FT SITE 130
FT /note="Hydrophobic membrane-disruption site (MDiS)"
FT /evidence="ECO:0000250|UniProtKB:I6L8L6"
FT SITE 133
FT /note="Cationic membrane-docking site (MDoS)"
FT /evidence="ECO:0000250|UniProtKB:I6L8L6"
FT DISULFID 42..131
FT /evidence="ECO:0000269|PubMed:11732689,
FT ECO:0000269|PubMed:17157889, ECO:0000269|PubMed:19401234,
FT ECO:0000269|PubMed:20371382, ECO:0007744|PDB:2H8I,
FT ECO:0007744|PDB:3CXI, ECO:0007744|PDB:3HZD"
FT DISULFID 44..60
FT /evidence="ECO:0000269|PubMed:11732689,
FT ECO:0000269|PubMed:17157889, ECO:0000269|PubMed:19401234,
FT ECO:0000269|PubMed:20371382, ECO:0007744|PDB:2H8I,
FT ECO:0007744|PDB:3CXI, ECO:0007744|PDB:3HZD"
FT DISULFID 59..111
FT /evidence="ECO:0000269|PubMed:11732689,
FT ECO:0000269|PubMed:17157889, ECO:0000269|PubMed:19401234,
FT ECO:0000269|PubMed:20371382, ECO:0007744|PDB:2H8I,
FT ECO:0007744|PDB:3CXI, ECO:0007744|PDB:3HZD"
FT DISULFID 65..137
FT /evidence="ECO:0000269|PubMed:11732689,
FT ECO:0000269|PubMed:17157889, ECO:0000269|PubMed:19401234,
FT ECO:0000269|PubMed:20371382, ECO:0007744|PDB:2H8I,
FT ECO:0007744|PDB:3CXI, ECO:0007744|PDB:3HZD"
FT DISULFID 66..104
FT /evidence="ECO:0000269|PubMed:11732689,
FT ECO:0000269|PubMed:17157889, ECO:0000269|PubMed:19401234,
FT ECO:0000269|PubMed:20371382, ECO:0007744|PDB:2H8I,
FT ECO:0007744|PDB:3CXI, ECO:0007744|PDB:3HZD"
FT DISULFID 73..97
FT /evidence="ECO:0000269|PubMed:11732689,
FT ECO:0000269|PubMed:17157889, ECO:0000269|PubMed:19401234,
FT ECO:0000269|PubMed:20371382, ECO:0007744|PDB:2H8I,
FT ECO:0007744|PDB:3CXI, ECO:0007744|PDB:3HZD"
FT DISULFID 91..102
FT /evidence="ECO:0000269|PubMed:11732689,
FT ECO:0000269|PubMed:17157889, ECO:0000269|PubMed:19401234,
FT ECO:0000269|PubMed:20371382, ECO:0007744|PDB:2H8I,
FT ECO:0007744|PDB:3CXI, ECO:0007744|PDB:3HZD"
FT VARIANT 19
FT /note="F -> L"
FT VARIANT 37
FT /note="Y -> H"
FT VARIANT 136
FT /note="P -> A"
FT MUTAGEN 23
FT /note="K->A: No change in myotoxicity when injected into
FT mice. No change in myoblast membrane permeabilizing
FT activities. Important decrease in bactericidal activity. No
FT change in calcium-independent damaging activity against
FT EYPC:DPPG liposomes. Decrease in calcium-independent
FT damaging activity against EYPC:DMPA liposomes."
FT /evidence="ECO:0000269|PubMed:17346668"
FT MUTAGEN 31
FT /note="K->A: No change in myotoxicity when injected into
FT mice. No change in myoblast membrane permeabilizing
FT activities. No change in bactericidal activity. No change
FT in calcium-independent damaging activity against EYPC:DPPG
FT liposomes. Decrease in calcium-independent damaging
FT activity against EYPC:DMPA liposomes."
FT /evidence="ECO:0000269|PubMed:17346668"
FT MUTAGEN 51
FT /note="K->A: No change in myotoxicity when injected into
FT mice. No change in myoblast membrane permeabilizing
FT activities. No change in bactericidal activity. Decrease in
FT calcium-independent damaging activity against EYPC:DPPG
FT liposomes. Decrease in calcium-independent damaging
FT activity against EYPC:DMPA liposomes."
FT /evidence="ECO:0000269|PubMed:17346668"
FT MUTAGEN 52
FT /note="P->A: Important decrease in myotoxicity when
FT injected into mice. Decrease in membrane permeabilization
FT of cultured myoblasts. No change in bactericidal activity.
FT No change in calcium-independent damaging activity against
FT EYPC:DPPG liposomes. Increase in calcium-independent
FT damaging activity against EYPC:DMPA liposomes."
FT /evidence="ECO:0000269|PubMed:17346668"
FT MUTAGEN 53
FT /note="K->A: No change in myotoxicity when injected into
FT mice. Decrease in myoblast membrane permeabilizing
FT activities. No change in bactericidal activity. Important
FT decrease in calcium-independent damaging activity against
FT EYPC:DPPG liposomes. Important decrease in calcium-
FT independent damaging activity against EYPC:DMPA liposomes."
FT /evidence="ECO:0000269|PubMed:17346668"
FT MUTAGEN 54
FT /note="D->A: No change in myoblast membrane permeabilizing
FT activities."
FT /evidence="ECO:0000269|PubMed:17346668"
FT MUTAGEN 58
FT /note="R->A: No change in myotoxicity when injected into
FT mice. No change in myoblast membrane permeabilizing
FT activities. No change in bactericidal activity. Decrease in
FT calcium-independent damaging activity against EYPC:DPPG
FT liposomes. Decrease in calcium-independent damaging
FT activity against EYPC:DMPA liposomes."
FT /evidence="ECO:0000269|PubMed:17346668"
FT MUTAGEN 61
FT /note="Y->A: No change in myotoxicity when injected into
FT mice. No change in myoblast membrane permeabilizing
FT activities. No change in bactericidal activity. Decrease in
FT calcium-independent damaging activity against EYPC:DPPG
FT liposomes. No change in calcium-independent damaging
FT activity against EYPC:DMPA liposomes."
FT /evidence="ECO:0000269|PubMed:17346668"
FT MUTAGEN 63
FT /note="H->Q: No change in myotoxic activities. No change in
FT myoblast membrane permeabilizing activities. No change in
FT bactericidal activity. No change in calcium-independent
FT membrane-damaging activities. Shows no hydrolytic
FT activity."
FT /evidence="ECO:0000269|PubMed:11829743,
FT ECO:0000269|PubMed:17346668, ECO:0000269|PubMed:18160090"
FT MUTAGEN 64
FT /note="K->D: No change in myotoxic activities. No change in
FT calcium-independent membrane-damaging and myotoxic
FT activities. Shows no hydrolytic activity."
FT /evidence="ECO:0000269|PubMed:11829743"
FT MUTAGEN 68
FT /note="K->A: No change in myotoxicity when injected into
FT mice. No change in myoblast membrane permeabilizing
FT activities. No change in bactericidal activity. Decrease in
FT calcium-independent damaging activity against EYPC:DPPG
FT liposomes. Decrease in calcium-independent damaging
FT activity against EYPC:DMPA liposomes."
FT /evidence="ECO:0000269|PubMed:17346668"
FT MUTAGEN 69
FT /note="K->A: Increase in myotoxicity when injected into
FT mice. Increase in myoblast membrane permeabilizing
FT activities. No change in bactericidal activity. No change
FT in calcium-independent damaging activity against EYPC:DPPG
FT liposomes. Decrease in calcium-independent damaging
FT activity against EYPC:DMPA liposomes."
FT /evidence="ECO:0000269|PubMed:17346668"
FT MUTAGEN 71
FT /note="T->TKR: No change in myotoxicity when injected into
FT mice. No change in myoblast membrane permeabilizing
FT activities. No change in bactericidal activity. No change
FT in calcium-independent damaging activity against EYPC:DPPG
FT liposomes. No change in calcium-independent damaging
FT activity against EYPC:DMPA liposomes."
FT /evidence="ECO:0000269|PubMed:17346668"
FT MUTAGEN 87
FT /note="K->A: No change in myotoxicity when injected into
FT mice. No change in myoblast membrane permeabilizing
FT activities. No change in bactericidal activity. No change
FT in calcium-independent damaging activity against EYPC:DPPG
FT liposomes. Decrease in calcium-independent damaging
FT activity against EYPC:DMPA liposomes."
FT /evidence="ECO:0000269|PubMed:17346668"
FT MUTAGEN 93
FT /note="E->G: No change in myotoxicity when injected into
FT mice. Important decrease in bactericidal activity. No
FT change in calcium-independent damaging activity against
FT EYPC:DPPG liposomes. No change in calcium-independent
FT damaging activity against EYPC:DMPA liposomes."
FT /evidence="ECO:0000269|PubMed:17346668"
FT MUTAGEN 99
FT /note="K->A: No change in myotoxicity when injected into
FT mice. No change in myoblast membrane permeabilizing
FT activities. No change in bactericidal activity. No change
FT in calcium-independent damaging activity against EYPC:DPPG
FT liposomes. No change in calcium-independent damaging
FT activity against EYPC:DMPA liposomes."
FT /evidence="ECO:0000269|PubMed:17346668"
FT MUTAGEN 106
FT /note="K->A: Increase in myotoxicity when injected into
FT mice. No change in myoblast membrane permeabilizing
FT activities. Decrease in bactericidal activity. No change in
FT calcium-independent damaging activity against EYPC:DPPG
FT liposomes. Decrease in calcium-independent damaging
FT activity against EYPC:DMPA liposomes."
FT /evidence="ECO:0000269|PubMed:17346668"
FT MUTAGEN 118
FT /note="T->A: No change in myoblast membrane permeabilizing
FT activities. No change in calcium-independent damaging
FT activity against EYPC:DPPG liposomes. No change in calcium-
FT independent damaging activity against EYPC:DMPA liposomes."
FT /evidence="ECO:0000269|PubMed:17346668"
FT MUTAGEN 120
FT /note="N->A: No change in myotoxicity when injected into
FT mice. Increase in myoblast membrane permeabilizing
FT activities. No change in bactericidal activity. No change
FT in calcium-independent damaging activity against EYPC:DPPG
FT liposomes. No change in calcium-independent damaging
FT activity against EYPC:DMPA liposomes."
FT /evidence="ECO:0000269|PubMed:17346668"
FT MUTAGEN 121
FT /note="K->A: No change in myotoxicity when injected into
FT mice. Decrease in myoblast membrane permeabilizing
FT activities. Important decrease in bactericidal activity.
FT Important decrease in calcium-independent damaging activity
FT against EYPC:DPPG liposomes. Important decrease in calcium-
FT independent damaging activity against EYPC:DMPA liposomes."
FT /evidence="ECO:0000269|PubMed:12079495,
FT ECO:0000269|PubMed:17346668, ECO:0000269|PubMed:18160090"
FT MUTAGEN 122
FT /note="K->A: No change in myotoxicity when injected into
FT mice. Decrease in myoblast membrane permeabilizing
FT activities. Decrease in bactericidal activity. Important
FT decrease in calcium-independent damaging activity against
FT EYPC:DPPG liposomes. Decrease in calcium-independent
FT damaging activity against EYPC:DMPA liposomes."
FT /evidence="ECO:0000269|PubMed:12079495,
FT ECO:0000269|PubMed:17346668"
FT MUTAGEN 123
FT /note="Y->A: Important decrease in myotoxicity when
FT injected into mice. Important decrease in myoblast membrane
FT permeabilizing activities. Important decrease in
FT bactericidal activity. Decrease in calcium-independent
FT damaging activity against EYPC:DPPG liposomes. Decrease in
FT calcium-independent damaging activity against EYPC:DMPA
FT liposomes."
FT /evidence="ECO:0000269|PubMed:12079495,
FT ECO:0000269|PubMed:17346668, ECO:0000269|PubMed:18160090"
FT MUTAGEN 123
FT /note="Y->W: No change (PubMed:17346668) or important
FT decrease (PubMed:12079495) in myotoxicity when injected
FT into mice. No change in myoblast membrane permeabilizing
FT activities. Decrease in bactericidal activity. No change in
FT calcium-independent damaging activity against EYPC:DPPG
FT liposomes. Important increase in calcium-independent
FT damaging activity against EYPC:DMPA liposomes."
FT /evidence="ECO:0000269|PubMed:12079495,
FT ECO:0000269|PubMed:17346668, ECO:0000269|PubMed:18160090"
FT MUTAGEN 124
FT /note="R->A: Important decrease in myotoxicity when
FT injected into mice. Decrease in myoblast membrane
FT permeabilizing activities. Important decrease in
FT bactericidal activity. Important decrease in calcium-
FT independent damaging activity against EYPC:DPPG liposomes.
FT No change in calcium-independent damaging activity against
FT EYPC:DMPA liposomes."
FT /evidence="ECO:0000269|PubMed:12079495,
FT ECO:0000269|PubMed:17346668, ECO:0000269|PubMed:18160090"
FT MUTAGEN 125
FT /note="Y->A: Important decrease in myotoxicity when
FT injected into mice. Decrease in myoblast membrane
FT permeabilizing activities. Decrease in bactericidal
FT activity. Important decrease in calcium-independent
FT damaging activity against EYPC:DPPG liposomes. Important
FT decrease in calcium-independent damaging activity against
FT EYPC:DMPA liposomes."
FT /evidence="ECO:0000269|PubMed:12079495,
FT ECO:0000269|PubMed:17346668"
FT MUTAGEN 125
FT /note="Y->W: No change in myotoxicity when injected into
FT mice. No change in myoblast membrane permeabilizing
FT activities. Decrease in bactericidal activity. No change in
FT calcium-independent damaging activity against EYPC:DPPG
FT liposomes. No change in calcium-independent damaging
FT activity against EYPC:DMPA liposomes."
FT /evidence="ECO:0000269|PubMed:12079495,
FT ECO:0000269|PubMed:17346668"
FT MUTAGEN 126
FT /note="H->A: No change in myotoxicity when injected into
FT mice. No change in myoblast membrane permeabilizing
FT activities. Important decrease in bactericidal activity.
FT Decrease in calcium-independent damaging activity against
FT EYPC:DPPG liposomes. Decrease in calcium-independent
FT damaging activity against EYPC:DMPA liposomes."
FT /evidence="ECO:0000269|PubMed:17346668"
FT MUTAGEN 127
FT /note="L->A: No change in myotoxicity when injected into
FT mice. No change in myoblast membrane permeabilizing
FT activities. Decrease in bactericidal activity. Important
FT decrease in calcium-independent damaging activity against
FT EYPC:DPPG liposomes. Important decrease in calcium-
FT independent damaging activity against EYPC:DMPA liposomes."
FT /evidence="ECO:0000269|PubMed:17346668"
FT MUTAGEN 128
FT /note="K->A: Important decrease in myotoxicity when
FT injected into mice. Important decrease in myoblast membrane
FT permeabilizing activities. Important decrease in
FT bactericidal activity. Important decrease in calcium-
FT independent damaging activity against EYPC:DPPG liposomes.
FT Important decrease in calcium-independent damaging activity
FT against EYPC:DMPA liposomes. Shows no hydrolytic activity."
FT /evidence="ECO:0000269|PubMed:11829743,
FT ECO:0000269|PubMed:12079495, ECO:0000269|PubMed:17346668,
FT ECO:0000269|PubMed:18160090"
FT MUTAGEN 130
FT /note="F->A: Important decrease in myotoxicity when
FT injected into mice. Decrease in myoblast membrane
FT permeabilizing activities. Decrease in bactericidal
FT activity. Important decrease in calcium-independent
FT damaging activity against EYPC:DPPG liposomes. Important
FT decrease in calcium-independent damaging activity against
FT EYPC:DMPA liposomes."
FT /evidence="ECO:0000269|PubMed:12079495,
FT ECO:0000269|PubMed:17346668, ECO:0000269|PubMed:18160090"
FT MUTAGEN 130
FT /note="F->W: No change in myotoxicity when injected into
FT mice. No change in myoblast membrane permeabilizing
FT activities. Decrease in bactericidal activity. No change in
FT calcium-independent damaging activity against EYPC:DPPG
FT liposomes. Decrease (PubMed:17346668) or important decrease
FT (PubMed:12079495) in calcium-independent damaging activity
FT against EYPC:DMPA liposomes."
FT /evidence="ECO:0000269|PubMed:12079495,
FT ECO:0000269|PubMed:17346668, ECO:0000269|PubMed:18160090"
FT MUTAGEN 132
FT /note="K->A: No change in myotoxicity when injected into
FT mice. Important decrease in calcium-independent damaging
FT activity against EYPC:DPPG liposomes. No change in calcium-
FT independent damaging activity against EYPC:DMPA liposomes."
FT /evidence="ECO:0000269|PubMed:12079495,
FT ECO:0000269|PubMed:17346668"
FT MUTAGEN 133
FT /note="K->A: No change in myotoxicity when injected into
FT mice. No change in myoblast membrane permeabilizing
FT activities. Decrease in bactericidal activity. No change in
FT calcium-independent damaging activity against EYPC:DPPG
FT liposomes. No change in calcium-independent damaging
FT activity against EYPC:DMPA liposomes."
FT /evidence="ECO:0000269|PubMed:12079495,
FT ECO:0000269|PubMed:17346668, ECO:0000269|PubMed:18160090"
FT CONFLICT 23
FT /note="K -> H (in Ref. 7; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 74
FT /note="D -> N (in Ref. 3; AA sequence)"
FT /evidence="ECO:0000305"
FT HELIX 18..29
FT /evidence="ECO:0007829|PDB:3I03"
FT HELIX 33..37
FT /evidence="ECO:0007829|PDB:3I03"
FT STRAND 38..40
FT /evidence="ECO:0007829|PDB:3CXI"
FT TURN 41..43
FT /evidence="ECO:0007829|PDB:3I03"
FT STRAND 44..47
FT /evidence="ECO:0007829|PDB:3I03"
FT HELIX 55..67
FT /evidence="ECO:0007829|PDB:3I03"
FT TURN 75..77
FT /evidence="ECO:0007829|PDB:3I03"
FT STRAND 82..85
FT /evidence="ECO:0007829|PDB:3I03"
FT STRAND 88..91
FT /evidence="ECO:0007829|PDB:3I03"
FT HELIX 96..114
FT /evidence="ECO:0007829|PDB:3I03"
FT HELIX 116..118
FT /evidence="ECO:0007829|PDB:3I03"
FT HELIX 121..123
FT /evidence="ECO:0007829|PDB:3I03"
FT HELIX 128..130
FT /evidence="ECO:0007829|PDB:3I03"
SQ SEQUENCE 137 AA; 15497 MW; 7BE006BABC4DFC39 CRC64;
MRTLWIMAVL LVGVEGSLFE LGKMILQETG KNPAKSYGAY GCNCGVLGRG KPKDATDRCC
YVHKCCYKKL TGCDPKKDRY SYSWKDKTIV CGENNPCLKE LCECDKAVAI CLRENLGTYN
KKYRYHLKPF CKKADPC
