PA2B3_BOTAS
ID PA2B3_BOTAS Reviewed; 138 AA.
AC P20474;
DT 01-FEB-1991, integrated into UniProtKB/Swiss-Prot.
DT 15-JAN-2008, sequence version 2.
DT 03-AUG-2022, entry version 118.
DE RecName: Full=Basic phospholipase A2 myotoxin I {ECO:0000303|PubMed:28034717};
DE Short=MT-I {ECO:0000303|PubMed:28034717};
DE Short=svPLA2;
DE EC=3.1.1.4 {ECO:0000269|PubMed:2327788};
DE AltName: Full=Myotoxic phospholipase {ECO:0000303|PubMed:2327788, ECO:0000303|PubMed:6426093};
DE AltName: Full=Myotoxin III {ECO:0000303|PubMed:11240369, ECO:0000303|PubMed:8218369, ECO:0000303|PubMed:8456450};
DE AltName: Full=Phosphatidylcholine 2-acylhydrolase;
DE Flags: Precursor;
OS Bothrops asper (Terciopelo).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Lepidosauria; Squamata; Bifurcata; Unidentata; Episquamata; Toxicofera;
OC Serpentes; Colubroidea; Viperidae; Crotalinae; Bothrops.
OX NCBI_TaxID=8722;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Venom gland;
RX PubMed=11240369; DOI=10.1016/s1357-2725(00)00073-x;
RA Lizano S., Lambeau G., Lazdunski M.;
RT "Cloning and cDNA sequence analysis of Lys(49) and Asp(49) basic
RT phospholipase A(2) myotoxin isoforms from Bothrops asper.";
RL Int. J. Biochem. Cell Biol. 33:127-132(2001).
RN [2]
RP PROTEIN SEQUENCE OF 17-138, FUNCTION, CATALYTIC ACTIVITY, SUBUNIT,
RP SUBCELLULAR LOCATION, AND TOXIC DOSE.
RC TISSUE=Venom;
RX PubMed=2327788; DOI=10.1016/0003-9861(90)90266-2;
RA Kaiser I.I., Gutierrez J.M., Plummer D., Aird S.D., Odell G.V.;
RT "The amino acid sequence of a myotoxic phospholipase from the venom of
RT Bothrops asper.";
RL Arch. Biochem. Biophys. 278:319-325(1990).
RN [3]
RP PROTEIN SEQUENCE OF 17-26, AND FUNCTION.
RC TISSUE=Venom;
RX PubMed=25276503; DOI=10.7717/peerj.569;
RA Mora-Obando D., Diaz C., Angulo Y., Gutierrez J.M., Lomonte B.;
RT "Role of enzymatic activity in muscle damage and cytotoxicity induced by
RT Bothrops asper Asp49 phospholipase A2 myotoxins: are there additional
RT effector mechanisms involved?";
RL PeerJ 2:E569-E569(2014).
RN [4]
RP FUNCTION.
RX PubMed=6426093; DOI=10.1016/0041-0101(84)90144-2;
RA Gutierrez J.M., Ownby C.L., Odell G.V.;
RT "Isolation of a myotoxin from Bothrops asper venom: partial
RT characterization and action on skeletal muscle.";
RL Toxicon 22:115-128(1984).
RN [5]
RP FUNCTION, AND TOXIC DOSE.
RX PubMed=2873948; DOI=10.1016/0742-8413(86)90183-0;
RA Gutierrez J.M., Lomonte B., Chaves F., Moreno E., Cerdas L.;
RT "Pharmacological activities of a toxic phospholipase A isolated from the
RT venom of the snake Bothrops asper.";
RL Comp. Biochem. Physiol. 84C:159-164(1986).
RN [6]
RP FUNCTION.
RX PubMed=8218369; DOI=10.1016/0167-4889(93)90080-9;
RA Butron E., Ghelestam M., Gutierrez J.M.;
RT "Effects on cultured mammalian cells of myotoxin III, a phospholipase A2
RT isolated from Bothrops asper (terciopelo) venom.";
RL Biochim. Biophys. Acta 1179:253-259(1993).
RN [7]
RP FUNCTION.
RX PubMed=8456450; DOI=10.1016/0041-0101(93)90289-u;
RA Bultron E., Gutierrez J.M., Thelestam M.;
RT "Effects of Bothrops asper (terciopelo) myotoxin III, a basic phospholipase
RT A2, on liposomes and mouse gastrocnemius muscle.";
RL Toxicon 31:217-222(1993).
RN [8]
RP FUNCTION TOWARDS BACTERIA.
RC TISSUE=Venom;
RX PubMed=9654096; DOI=10.1046/j.1432-1327.1998.2530452.x;
RA Paramo L., Lomonte B., Pizarro-Cerda J., Bengoechea J.A., Gorvel J.P.,
RA Moreno E.;
RT "Bactericidal activity of Lys49 and Asp49 myotoxic phospholipases A2 from
RT Bothrops asper snake venom--synthetic Lys49 myotoxin II-(115-129)-peptide
RT identifies its bactericidal region.";
RL Eur. J. Biochem. 253:452-461(1998).
RN [9]
RP FUNCTION IN EDEMA.
RX PubMed=9839670; DOI=10.1016/s0041-0101(98)00107-x;
RA Chaves F., Leon G., Alvarado V.H., Gutierrez J.M.;
RT "Pharmacological modulation of edema induced by Lys-49 and Asp-49 myotoxic
RT phospholipases A2 isolated from the venom of the snake Bothrops asper
RT (terciopelo).";
RL Toxicon 36:1861-1869(1998).
RN [10]
RP FUNCTION IN CYTOTOXICITY.
RC TISSUE=Venom;
RX PubMed=9920486; DOI=10.1016/s0041-0101(98)00171-8;
RA Lomonte B., Angulo Y., Rufini S., Cho W., Giglio J.R., Ohno M.,
RA Daniele J.J., Geoghegan P., Gutierrez J.M.;
RT "Comparative study of the cytolytic activity of myotoxic phospholipases A2
RT on mouse endothelial (tEnd) and skeletal muscle (C2C12) cells in vitro.";
RL Toxicon 37:145-158(1999).
RN [11]
RP ACTIVITY REGULATION BY MEMBRANE CHOLESTEROL.
RC TISSUE=Venom;
RX PubMed=21506137; DOI=10.1002/cbf.1758;
RA Rangel J., Quesada O., Gutierrez J.M., Angulo Y., Lomonte B.;
RT "Membrane cholesterol modulates the cytolytic mechanism of myotoxin II, a
RT Lys49 phospholipase A2 homologue from the venom of Bothrops asper.";
RL Cell Biochem. Funct. 29:365-370(2011).
RN [12]
RP X-RAY CRYSTALLOGRAPHY (2.54 ANGSTROMS) OF 17-138, AND DISULFIDE BONDS.
RC TISSUE=Venom;
RX PubMed=28034717; DOI=10.1016/j.biochi.2016.12.015;
RA Salvador G.H., Dos Santos J.I., Lomonte B., Fontes M.R.;
RT "Crystal structure of a phospholipase A2 from Bothrops asper venom:
RT insights into a new putative 'myotoxic cluster'.";
RL Biochimie 133:95-102(2017).
CC -!- FUNCTION: Snake venom phospholipase A2 (PLA2) that displays local
CC myotoxic activity. It also displays anticoagulant action in plasma and
CC edema-inducing activities (PubMed:2327788, PubMed:9839670). In
CC addition, it shows cytotoxic activity to a variety of cell types and
CC bactericidal activity to a variety of Gram-negative and Gram-positive
CC bacteria (PubMed:9654096, PubMed:9920486). PLA2 catalyzes the calcium-
CC dependent hydrolysis of the 2-acyl groups in 3-sn-phosphoglycerides.
CC {ECO:0000250|UniProtKB:P24605, ECO:0000269|PubMed:2327788,
CC ECO:0000269|PubMed:6426093, ECO:0000269|PubMed:8218369,
CC ECO:0000269|PubMed:8456450, ECO:0000269|PubMed:9654096,
CC ECO:0000269|PubMed:9839670, ECO:0000269|PubMed:9920486}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 1,2-diacyl-sn-glycero-3-phosphocholine + H2O = a 1-acyl-sn-
CC glycero-3-phosphocholine + a fatty acid + H(+); Xref=Rhea:RHEA:15801,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:28868,
CC ChEBI:CHEBI:57643, ChEBI:CHEBI:58168; EC=3.1.1.4;
CC Evidence={ECO:0000269|PubMed:2327788};
CC -!- COFACTOR:
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108; Evidence={ECO:0000250};
CC Note=Binds 1 Ca(2+) ion. {ECO:0000250};
CC -!- ACTIVITY REGULATION: High level of membrane cholesterol content reduces
CC cytolytic activity, whereas low level of membrane cholesterol content
CC increases cytolytic activity (PubMed:21506137).
CC {ECO:0000269|PubMed:21506137}.
CC -!- SUBUNIT: Monomer (PubMed:2327788). Homodimer; non-covalently linked
CC (alternative/compact dimer conformation) (PubMed:28034717).
CC {ECO:0000269|PubMed:2327788, ECO:0000269|PubMed:28034717}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:2327788}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC {ECO:0000305|PubMed:2327788}.
CC -!- TOXIC DOSE: LD(50) is 5.6 mg/kg (95 ug/16-18 g) by intravenous
CC injection into mice (PubMed:2873948). LD(50) is 25 ug/kg (0.42 ug/16-18
CC g) by intracerebroventricular injection into mice (PubMed:2873948).
CC LD(50) is 8 mg/kg by intravenous injection into mice (PubMed:2327788).
CC {ECO:0000269|PubMed:2327788, ECO:0000269|PubMed:2873948}.
CC -!- SIMILARITY: Belongs to the phospholipase A2 family. Group II subfamily.
CC D49 sub-subfamily. {ECO:0000305}.
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DR PIR; S09314; S09314.
DR PDB; 5TFV; X-ray; 2.54 A; A/B=17-138.
DR PDBsum; 5TFV; -.
DR AlphaFoldDB; P20474; -.
DR SMR; P20474; -.
DR BRENDA; 3.1.1.4; 909.
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:UniProtKB-EC.
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:UniProtKB-KW.
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; Calcium;
KW Direct protein sequencing; Disulfide bond; Hydrolase; Lipid degradation;
KW Lipid metabolism; Metal-binding; Myotoxin; Secreted; Signal; Toxin.
FT SIGNAL 1..16
FT /evidence="ECO:0000269|PubMed:2327788"
FT CHAIN 17..138
FT /note="Basic phospholipase A2 myotoxin I"
FT /evidence="ECO:0000269|PubMed:2327788"
FT /id="PRO_0000161617"
FT ACT_SITE 63
FT /evidence="ECO:0000250"
FT ACT_SITE 105
FT /evidence="ECO:0000250"
FT BINDING 43
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250"
FT BINDING 45
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250"
FT BINDING 47
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250"
FT BINDING 64
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250"
FT DISULFID 42..131
FT /evidence="ECO:0000269|PubMed:28034717,
FT ECO:0007744|PDB:5TFV"
FT DISULFID 44..60
FT /evidence="ECO:0000269|PubMed:28034717,
FT ECO:0007744|PDB:5TFV"
FT DISULFID 59..111
FT /evidence="ECO:0000269|PubMed:28034717,
FT ECO:0007744|PDB:5TFV"
FT DISULFID 65..138
FT /evidence="ECO:0000269|PubMed:28034717,
FT ECO:0007744|PDB:5TFV"
FT DISULFID 66..104
FT /evidence="ECO:0000269|PubMed:28034717,
FT ECO:0007744|PDB:5TFV"
FT DISULFID 73..97
FT /evidence="ECO:0000269|PubMed:28034717,
FT ECO:0007744|PDB:5TFV"
FT DISULFID 91..102
FT /evidence="ECO:0000269|PubMed:28034717,
FT ECO:0007744|PDB:5TFV"
FT HELIX 18..29
FT /evidence="ECO:0007829|PDB:5TFV"
FT HELIX 33..36
FT /evidence="ECO:0007829|PDB:5TFV"
FT TURN 37..39
FT /evidence="ECO:0007829|PDB:5TFV"
FT TURN 41..48
FT /evidence="ECO:0007829|PDB:5TFV"
FT HELIX 55..68
FT /evidence="ECO:0007829|PDB:5TFV"
FT TURN 75..77
FT /evidence="ECO:0007829|PDB:5TFV"
FT STRAND 82..85
FT /evidence="ECO:0007829|PDB:5TFV"
FT STRAND 88..91
FT /evidence="ECO:0007829|PDB:5TFV"
FT HELIX 96..114
FT /evidence="ECO:0007829|PDB:5TFV"
FT TURN 115..118
FT /evidence="ECO:0007829|PDB:5TFV"
FT HELIX 121..123
FT /evidence="ECO:0007829|PDB:5TFV"
FT HELIX 128..130
FT /evidence="ECO:0007829|PDB:5TFV"
SQ SEQUENCE 138 AA; 15751 MW; 822EAD31537AC536 CRC64;
MRTLWIMAVL LVGVEGSLIE FAKMILEETK RLPFPYYTTY GCYCGWGGQG QPKDATDRCC
FVHDCCYGKL SNCKPKTDRY SYSRKSGVII CGEGTPCEKQ ICECDKAAAV CFRENLRTYK
KRYMAYPDLL CKKPAEKC
