PA2H_BOTPA
ID PA2H_BOTPA Reviewed; 121 AA.
AC Q9IAT9;
DT 25-NOV-2002, integrated into UniProtKB/Swiss-Prot.
DT 26-FEB-2020, sequence version 3.
DT 25-MAY-2022, entry version 93.
DE RecName: Full=Basic phospholipase A2 homolog BnSP-7 {ECO:0000303|PubMed:10860537, ECO:0000303|PubMed:28751219, ECO:0000303|PubMed:9972319};
DE Short=svPLA2 homolog;
DE AltName: Full=Phospholipase A2 II;
OS Bothrops pauloensis (Neuwied's lancehead) (Bothrops neuwiedi pauloensis).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Lepidosauria; Squamata; Bifurcata; Unidentata; Episquamata; Toxicofera;
OC Serpentes; Colubroidea; Viperidae; Crotalinae; Bothrops.
OX NCBI_TaxID=1042543;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 3-121, PROTEIN SEQUENCE OF 1-40, FUNCTION,
RP TOXIC DOSE, AND SUBCELLULAR LOCATION.
RC TISSUE=Venom gland;
RX PubMed=10860537; DOI=10.1006/abbi.2000.1790;
RA Soares A.M., Guerra-Sa R., Borja-Oliveira C.R., Rodrigues V.M.,
RA Rodrigues-Simioni L., Rodrigues V., Fontes M.R.M., Lomonte B.,
RA Gutierrez J.M., Giglio J.R.;
RT "Structural and functional characterization of BnSP-7, a Lys49 myotoxic
RT phospholipase A(2) homologue from Bothrops neuwiedi pauloensis venom.";
RL Arch. Biochem. Biophys. 378:201-209(2000).
RN [2]
RP PROTEIN SEQUENCE OF 1-30, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Venom;
RX PubMed=22480909; DOI=10.1016/j.jprot.2012.03.028;
RA Rodrigues R.S., Boldrini-Franca J., Fonseca F.P., de la Torre P.,
RA Henrique-Silva F., Sanz L., Calvete J.J., Rodrigues V.M.;
RT "Combined snake venomics and venom gland transcriptomic analysis of
RT Bothropoides pauloensis.";
RL J. Proteomics 75:2707-2720(2012).
RN [3]
RP FUNCTION, TOXIC DOSE, AND AMINO ACID COMPOSITION.
RC TISSUE=Venom;
RX PubMed=9972319; DOI=10.1016/s1095-6433(98)10136-8;
RA Rodrigues V.M., Soares A.M., Mancin A.C., Fontes M.R.M.,
RA Homsi-Brandeburgo M.I., Giglio J.R.;
RT "Geographic variations in the composition of myotoxins from Bothrops
RT neuwiedi snake venoms: biochemical characterization and biological
RT activity.";
RL Comp. Biochem. Physiol. 121A:215-222(1998).
RN [4]
RP FUNCTION.
RC TISSUE=Venom;
RX PubMed=19673103; DOI=10.1016/j.toxicon.2008.12.025;
RA De Freitas Oliveira C., Da Silva Lopes D., Mendes M.M.,
RA Homsi-Brandeburgo M.I., Hamaguchi A., de Alcantara T.M., Clissa P.B.,
RA Rodrigues V.D.M.;
RT "Insights of local tissue damage and regeneration induced by BnSP-7, a
RT myotoxin isolated from Bothrops (neuwiedi) pauloensis snake venom.";
RL Toxicon 53:560-569(2009).
RN [5]
RP CRYSTALLIZATION.
RC TISSUE=Venom;
RX PubMed=10407160; DOI=10.1016/s0167-4838(99)00120-x;
RA Fontes M.R.M., Soares A.M., Rodrigues V.M., Fernandes A.C., Da Silva R.J.,
RA Giglio J.R.;
RT "Crystallization and preliminary X-ray diffraction analysis of a myotoxic
RT phospholipase A(2) homologue from Bothrops neuwiedi pauloensis venom.";
RL Biochim. Biophys. Acta 1432:393-395(1999).
RN [6] {ECO:0000312|PDB:1PA0, ECO:0000312|PDB:1PC9}
RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS), SUBUNIT, AND DISULFIDE BONDS.
RX PubMed=14623331; DOI=10.1016/j.bbrc.2003.10.047;
RA Magro A.J., Soares A.M., Giglio J.R., Fontes M.R.M.;
RT "Crystal structures of BnSP-7 and BnSP-6, two Lys49-phospholipases A2:
RT quaternary structure and inhibition mechanism insights.";
RL Biochem. Biophys. Res. Commun. 311:713-720(2003).
RN [7] {ECO:0000312|PDB:3MLM}
RP X-RAY CRYSTALLOGRAPHY (2.21 ANGSTROMS) IN COMPLEX WITH MYRISTIC ACID.
RX PubMed=21108987; DOI=10.1016/j.biochi.2010.11.003;
RA Delatorre P., Rocha B.A., Santi-Gadelha T., Gadelha C.A., Toyama M.H.,
RA Cavada B.S.;
RT "Crystal structure of Bn IV in complex with myristic acid: a Lys49 myotoxic
RT phospholipase A(2) from Bothrops neuwiedi venom.";
RL Biochimie 93:513-518(2011).
RN [8] {ECO:0000312|PDB:5VFH, ECO:0000312|PDB:5VFJ, ECO:0000312|PDB:5VFM, ECO:0000312|PDB:5VFN}
RP X-RAY CRYSTALLOGRAPHY (1.59 ANGSTROMS) IN COMPLEX WITH 4'-HYDROXYCINNAMIC
RP ACID; HYDROCINNAMIC ACID AND CAFFEIC ACID.
RC TISSUE=Venom;
RX PubMed=28751219; DOI=10.1016/j.biochi.2017.07.009;
RA de Lima L.F.G., Borges R.J., Viviescas M.A., Fernandes C.A.H.,
RA Fontes M.R.M.;
RT "Structural studies with BnSP-7 reveal an atypical oligomeric conformation
RT compared to phospholipases A2-like toxins.";
RL Biochimie 142:11-21(2017).
CC -!- FUNCTION: Snake venom phospholipase A2 (PLA2) that lacks enzymatic
CC activity (PubMed:10860537). Is myotoxic and displays edema-inducing
CC activity (PubMed:10860537, PubMed:9972319). Displays bactericidal
CC activity and promotes the blockage of the neuromuscular contraction of
CC the chick biventer cervicis muscle (PubMed:10860537, PubMed:9972319).
CC Also disrupts artificial membranes, and provokes tissue damages
CC characterized by edema, necrosis and inflammation (PubMed:10860537,
CC PubMed:9972319). May act as pro-inflammatory mediators, inducing
CC metalloproteinase and cytokine production from the inflammatory and
CC satellite cells (PubMed:19673103). A model of myotoxic mechanism has
CC been proposed: an apo Lys49-PLA2 is activated by the entrance of a
CC hydrophobic molecule (e.g. fatty acid) at the hydrophobic channel of
CC the protein leading to a reorientation of a monomer (By similarity).
CC This reorientation causes a transition between 'inactive' to 'active'
CC states, causing alignment of C-terminal and membrane-docking sites
CC (MDoS) side-by-side and putting the membrane-disruption sites (MDiS) in
CC the same plane, exposed to solvent and in a symmetric position for both
CC monomers (By similarity). The MDoS region stabilizes the toxin on
CC membrane by the interaction of charged residues with phospholipid head
CC groups (By similarity). Subsequently, the MDiS region destabilizes the
CC membrane with penetration of hydrophobic residues (By similarity). This
CC insertion causes a disorganization of the membrane, allowing an
CC uncontrolled influx of ions (i.e. calcium and sodium), and eventually
CC triggering irreversible intracellular alterations and cell death (By
CC similarity). {ECO:0000250|UniProtKB:I6L8L6,
CC ECO:0000269|PubMed:10860537, ECO:0000269|PubMed:19673103,
CC ECO:0000269|PubMed:9972319}.
CC -!- ACTIVITY REGULATION: Heparin inhibits the neuromuscular effect,
CC myotoxin activity and edema-inducing effects (PubMed:10860537).
CC Bromophenacyl bromide (BPB) inhibits the neuromuscular effect, the
CC myotoxin activity and edema-inducing effects (PubMed:10860537).
CC {ECO:0000269|PubMed:10860537}.
CC -!- SUBUNIT: Homodimer; non-covalently linked (probable alternative/compact
CC dimer conformation in solution). {ECO:0000269|PubMed:14623331,
CC ECO:0000269|PubMed:28751219}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:10860537}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC {ECO:0000305|PubMed:10860537}.
CC -!- TOXIC DOSE: LD(50) is 7.8 mg/kg by intraperitoneal injection into mice
CC (PubMed:10860537). LD(50) is 7.75 mg/kg by intraperitoneal injection
CC into mice (PubMed:9972319). {ECO:0000269|PubMed:10860537,
CC ECO:0000269|PubMed:9972319}.
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; AF145781; AAF66703.1; -; mRNA.
DR PDB; 1PA0; X-ray; 2.20 A; A/B=1-121.
DR PDB; 1PC9; X-ray; 2.50 A; A/B=1-121.
DR PDB; 3MLM; X-ray; 2.21 A; A/B=1-121.
DR PDB; 5VFH; X-ray; 1.59 A; A/B=1-121.
DR PDB; 5VFJ; X-ray; 2.08 A; A/B=1-121.
DR PDB; 5VFM; X-ray; 2.06 A; A/B=1-121.
DR PDB; 5VFN; X-ray; 2.39 A; A/B=1-121.
DR PDBsum; 1PA0; -.
DR PDBsum; 1PC9; -.
DR PDBsum; 3MLM; -.
DR PDBsum; 5VFH; -.
DR PDBsum; 5VFJ; -.
DR PDBsum; 5VFM; -.
DR PDBsum; 5VFN; -.
DR AlphaFoldDB; Q9IAT9; -.
DR SMR; Q9IAT9; -.
DR ChEMBL; CHEMBL2146345; -.
DR EvolutionaryTrace; Q9IAT9; -.
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: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; Myotoxin; Neurotoxin; Secreted; Toxin.
FT CHAIN 1..121
FT /note="Basic phospholipase A2 homolog BnSP-7"
FT /evidence="ECO:0000305|PubMed:10860537"
FT /id="PRO_0000161625"
FT REGION 105..117
FT /note="Important for membrane-damaging activities in
FT eukaryotes and bacteria; heparin-binding"
FT /evidence="ECO:0000250|UniProtKB:P24605"
FT SITE 16
FT /note="Cationic membrane-docking site (MDoS)"
FT /evidence="ECO:0000305|PubMed:28751219"
FT SITE 19
FT /note="Cationic membrane-docking site (MDoS)"
FT /evidence="ECO:0000250|UniProtKB:I6L8L6,
FT ECO:0000305|PubMed:28751219"
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:28751219"
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:28751219"
FT SITE 111
FT /note="Hydrophobic membrane-disruption site (MDiS)"
FT /evidence="ECO:0000250|UniProtKB:I6L8L6,
FT ECO:0000305|PubMed:28751219"
FT SITE 114
FT /note="Hydrophobic membrane-disruption site (MDiS)"
FT /evidence="ECO:0000250|UniProtKB:I6L8L6,
FT ECO:0000305|PubMed:28751219"
FT DISULFID 26..115
FT /evidence="ECO:0000269|PubMed:14623331,
FT ECO:0000269|PubMed:21108987, ECO:0000269|PubMed:28751219,
FT ECO:0007744|PDB:1PA0, ECO:0007744|PDB:1PC9,
FT ECO:0007744|PDB:3MLM, ECO:0007744|PDB:5VFH"
FT DISULFID 28..44
FT /evidence="ECO:0000269|PubMed:14623331,
FT ECO:0000269|PubMed:21108987, ECO:0000269|PubMed:28751219,
FT ECO:0007744|PDB:1PA0, ECO:0007744|PDB:1PC9,
FT ECO:0007744|PDB:3MLM, ECO:0007744|PDB:5VFH"
FT DISULFID 43..95
FT /evidence="ECO:0000269|PubMed:14623331,
FT ECO:0000269|PubMed:21108987, ECO:0000269|PubMed:28751219,
FT ECO:0007744|PDB:1PA0, ECO:0007744|PDB:1PC9,
FT ECO:0007744|PDB:3MLM, ECO:0007744|PDB:5VFH"
FT DISULFID 49..121
FT /evidence="ECO:0000269|PubMed:14623331,
FT ECO:0000269|PubMed:21108987, ECO:0000269|PubMed:28751219,
FT ECO:0007744|PDB:1PA0, ECO:0007744|PDB:1PC9,
FT ECO:0007744|PDB:3MLM, ECO:0007744|PDB:5VFH"
FT DISULFID 50..88
FT /evidence="ECO:0000269|PubMed:14623331,
FT ECO:0000269|PubMed:21108987, ECO:0000269|PubMed:28751219,
FT ECO:0007744|PDB:1PA0, ECO:0007744|PDB:1PC9,
FT ECO:0007744|PDB:3MLM, ECO:0007744|PDB:5VFH"
FT DISULFID 57..81
FT /evidence="ECO:0000269|PubMed:14623331,
FT ECO:0000269|PubMed:21108987, ECO:0000269|PubMed:28751219,
FT ECO:0007744|PDB:1PA0, ECO:0007744|PDB:1PC9,
FT ECO:0007744|PDB:3MLM, ECO:0007744|PDB:5VFH"
FT DISULFID 75..86
FT /evidence="ECO:0000269|PubMed:14623331,
FT ECO:0000269|PubMed:21108987, ECO:0000269|PubMed:28751219,
FT ECO:0007744|PDB:1PA0, ECO:0007744|PDB:1PC9,
FT ECO:0007744|PDB:3MLM, ECO:0007744|PDB:5VFH"
FT VARIANT 35
FT /note="Q -> G (in BnSP-6 and Bn-IV)"
FT /evidence="ECO:0000269|PubMed:14623331,
FT ECO:0000269|PubMed:21108987"
FT VARIANT 54
FT /note="L -> I (in Bn-IV)"
FT /evidence="ECO:0000269|PubMed:21108987"
FT CONFLICT 2
FT /note="Missing (in Ref. 1; AA sequence)"
FT /evidence="ECO:0000305|PubMed:10860537"
FT HELIX 3..13
FT /evidence="ECO:0007829|PDB:5VFH"
FT HELIX 17..21
FT /evidence="ECO:0007829|PDB:5VFH"
FT TURN 25..27
FT /evidence="ECO:0007829|PDB:5VFH"
FT STRAND 28..31
FT /evidence="ECO:0007829|PDB:5VFH"
FT HELIX 39..52
FT /evidence="ECO:0007829|PDB:5VFH"
FT TURN 59..61
FT /evidence="ECO:0007829|PDB:5VFH"
FT STRAND 66..68
FT /evidence="ECO:0007829|PDB:5VFH"
FT STRAND 73..75
FT /evidence="ECO:0007829|PDB:5VFH"
FT HELIX 80..98
FT /evidence="ECO:0007829|PDB:5VFH"
FT HELIX 99..102
FT /evidence="ECO:0007829|PDB:5VFH"
FT HELIX 105..107
FT /evidence="ECO:0007829|PDB:5VFH"
FT HELIX 112..114
FT /evidence="ECO:0007829|PDB:5VFH"
SQ SEQUENCE 121 AA; 13727 MW; E0106F42CC3999FD CRC64;
SLFELGKMIL QETGKNPAKS YGAYGCNCGV LGRGQPKDAT DRCCYVHKCC YKKLTGCDPK
KDRYSYSWKD KTIVCGENNP CLKELCECDK AVAICLRENL GTYNKKYRYH LKPFCKKADP
C
