PA2H1_BOTPI
ID PA2H1_BOTPI Reviewed; 121 AA.
AC P58399;
DT 16-NOV-2001, integrated into UniProtKB/Swiss-Prot.
DT 05-DEC-2001, sequence version 2.
DT 25-MAY-2022, entry version 90.
DE RecName: Full=Basic phospholipase A2 homolog piratoxin-1;
DE Short=svPLA2 homolog;
DE AltName: Full=Myotoxin SIV-SP5;
DE AltName: Full=Piratoxin-I {ECO:0000303|PubMed:7660366, ECO:0000303|PubMed:9853687};
DE Short=PrTX-I {ECO:0000303|PubMed:7660366, ECO:0000303|PubMed:9853687};
OS Bothrops pirajai (Piraja's lancehead).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Lepidosauria; Squamata; Bifurcata; Unidentata; Episquamata; Toxicofera;
OC Serpentes; Colubroidea; Viperidae; Crotalinae; Bothrops.
OX NCBI_TaxID=113192;
RN [1]
RP PROTEIN SEQUENCE, TOXIC DOSE, AND SUBCELLULAR LOCATION.
RC TISSUE=Venom;
RX PubMed=9853687; DOI=10.1007/bf02780974;
RA Toyama M.H., Soares A.M., Vieira C.A., Novello J.C., Oliveira B.,
RA Giglio J.R., Marangoni S.;
RT "Amino acid sequence of piratoxin-I, a myotoxin from Bothrops pirajai snake
RT venom, and its biological activity after alkylation with p-bromophenacyl
RT bromide.";
RL J. Protein Chem. 17:713-718(1998).
RN [2]
RP PARTIAL PROTEIN SEQUENCE, FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=7660366; DOI=10.1016/0041-0101(95)00012-b;
RA Mancuso L.C., Correa M.M., Vieira C.A., Cunha O.A., Lachat J.J.,
RA de Araujo H.S., Ownby C.L., Giglio J.R.;
RT "Fractionation of Bothrops pirajai snake venom: isolation and
RT characterization of piratoxin-I, a new myotoxic protein.";
RL Toxicon 33:615-626(1995).
RN [3]
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS).
RX PubMed=9723838; DOI=10.1016/s0041-0101(98)00017-8;
RA de Azevedo W.F. Jr., Ward R.J., Canduri F., Soares A., Giglio J.R.,
RA Arni R.K.;
RT "Crystal structure of piratoxin-I: a calcium-independent, myotoxic
RT phospholipase A2-homologue from Bothrops pirajai venom.";
RL Toxicon 36:1395-1406(1998).
RN [4] {ECO:0000312|PDB:2OK9}
RP X-RAY CRYSTALLOGRAPHY (2.34 ANGSTROMS) OF 1-111 IN COMPLEX WITH THE PLA2
RP INHIBITOR BROMOPHENACYL BROMIDE, AND DISULFIDE BONDS.
RC TISSUE=Venom;
RX PubMed=19616648; DOI=10.1016/j.bbapap.2009.07.005;
RA Marchi-Salvador D.P., Fernandes C.A., Silveira L.B., Soares A.M.,
RA Fontes M.R.;
RT "Crystal structure of a phospholipase A(2) homolog complexed with p-
RT bromophenacyl bromide reveals important structural changes associated with
RT the inhibition of myotoxic activity.";
RL Biochim. Biophys. Acta 1794:1583-1590(2009).
RN [5] {ECO:0000312|PDB:3QNL}
RP X-RAY CRYSTALLOGRAPHY (1.77 ANGSTROMS) IN COMPLEX WITH ROSMARINIC ACID,
RP FUNCTION, AND DISULFIDE BONDS.
RC TISSUE=Venom;
RX PubMed=22205953; DOI=10.1371/journal.pone.0028521;
RA Dos Santos J.I., Cardoso F.F., Soares A.M., Dal Pai Silva M., Gallacci M.,
RA Fontes M.R.;
RT "Structural and functional studies of a bothropic myotoxin complexed to
RT rosmarinic acid: new insights into Lys49-PLA(2) inhibition.";
RL PLoS ONE 6:E28521-E28521(2011).
RN [6] {ECO:0000312|PDB:4YU7, ECO:0000312|PDB:4YZ7}
RP X-RAY CRYSTALLOGRAPHY (1.65 ANGSTROMS) IN COMPLEX WITH CAFFEIC ACID AND
RP ARISTOLOCHIC ACID, AND ACTIVITY REGULATION.
RC TISSUE=Venom;
RX PubMed=26192963; DOI=10.1371/journal.pone.0133370;
RA Fernandes C.A., Cardoso F.F., Cavalcante W.G., Soares A.M., Dal-Pai M.,
RA Gallacci M., Fontes M.R.;
RT "Structural basis for the inhibition of a phospholipase a2-like toxin by
RT caffeic and aristolochic acids.";
RL PLoS ONE 10:E0133370-E0133370(2015).
CC -!- FUNCTION: Snake venom phospholipase A2 (PLA2) homolog that lacks
CC enzymatic activity (PubMed:7660366). Is myotoxic and displays edema-
CC inducing activities (PubMed:7660366). Induces neuromuscular blockage
CC (PubMed:26192963). A model of myotoxic mechanism has been proposed: an
CC apo Lys49-PLA2 is activated by the entrance of a hydrophobic molecule
CC (e.g. fatty acid) at the hydrophobic channel of the protein leading to
CC a reorientation of a monomer (By similarity). This reorientation causes
CC a transition between 'inactive' to 'active' states, causing alignment
CC of C-terminal and membrane-docking sites (MDoS) side-by-side and
CC putting the membrane-disruption sites (MDiS) in the same plane, exposed
CC to solvent and in a symmetric position for both monomers (By
CC similarity). The MDoS region stabilizes the toxin on membrane by the
CC interaction of charged residues with phospholipid head groups (By
CC similarity). Subsequently, the MDiS region destabilizes the membrane
CC 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:22205953, ECO:0000269|PubMed:26192963,
CC ECO:0000269|PubMed:7660366}.
CC -!- ACTIVITY REGULATION: Rosmarinic acid inhibits the myotoxic activity
CC (PubMed:22205953). Bromophenacyl bromide (BPB) inhibits the myotoxic
CC activity through a covalent binding (PubMed:19616648). Caffeic acid and
CC aristolochic acid, two plant compounds used in folk medicine used to
CC treat envenomation, inhibit the myotoxic activity (PubMed:26192963).
CC {ECO:0000269|PubMed:19616648, ECO:0000269|PubMed:22205953,
CC ECO:0000269|PubMed:26192963}.
CC -!- SUBUNIT: Homodimer; non-covalently linked.
CC {ECO:0000269|PubMed:19616648, ECO:0000269|PubMed:22205953}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:7660366,
CC ECO:0000269|PubMed:9853687}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC {ECO:0000305|PubMed:7660366, ECO:0000305|PubMed:9853687}.
CC -!- TOXIC DOSE: LD(50) is 8 mg/kg by intraperitoneal injection into mice.
CC {ECO:0000269|PubMed:9853687}.
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 PDB; 2OK9; X-ray; 2.34 A; A/B=1-121.
DR PDB; 3QNL; X-ray; 1.77 A; A/B=1-121.
DR PDB; 4YU7; X-ray; 1.65 A; A/B=1-121.
DR PDB; 4YZ7; X-ray; 1.96 A; A/B=1-121.
DR PDBsum; 2OK9; -.
DR PDBsum; 3QNL; -.
DR PDBsum; 4YU7; -.
DR PDBsum; 4YZ7; -.
DR AlphaFoldDB; P58399; -.
DR SMR; P58399; -.
DR BRENDA; 3.1.1.4; 8187.
DR EvolutionaryTrace; P58399; -.
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: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; Direct protein sequencing; Disulfide bond; Myotoxin;
KW Neurotoxin; Secreted; Toxin.
FT CHAIN 1..121
FT /note="Basic phospholipase A2 homolog piratoxin-1"
FT /evidence="ECO:0000269|PubMed:9853687"
FT /id="PRO_0000161627"
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 105
FT /note="Important residue of the cationic membrane-docking
FT site (MDoS)"
FT /evidence="ECO:0000250|UniProtKB:I6L8L6"
FT SITE 108
FT /note="Important residue of the cationic membrane-docking
FT site (MDoS)"
FT /evidence="ECO:0000250|UniProtKB:I6L8L6"
FT SITE 111
FT /note="Hydrophobic membrane-disruption site (MDiS)"
FT /evidence="ECO:0000250|UniProtKB:I6L8L6"
FT SITE 112
FT /note="Cationic membrane-docking site (MDoS)"
FT /evidence="ECO:0000250|UniProtKB:I6L8L6"
FT SITE 114
FT /note="Hydrophobic membrane-disruption site (MDiS)"
FT /evidence="ECO:0000250|UniProtKB:I6L8L6"
FT SITE 117
FT /note="Cationic membrane-docking site (MDoS)"
FT /evidence="ECO:0000250|UniProtKB:I6L8L6"
FT DISULFID 26..115
FT /evidence="ECO:0000269|PubMed:19616648,
FT ECO:0000269|PubMed:22205953, ECO:0000269|PubMed:26192963,
FT ECO:0007744|PDB:2OK9, ECO:0007744|PDB:3QNL,
FT ECO:0007744|PDB:4YU7, ECO:0007744|PDB:4YZ7"
FT DISULFID 28..44
FT /evidence="ECO:0000269|PubMed:19616648,
FT ECO:0000269|PubMed:22205953, ECO:0000269|PubMed:26192963,
FT ECO:0007744|PDB:2OK9, ECO:0007744|PDB:3QNL,
FT ECO:0007744|PDB:4YU7, ECO:0007744|PDB:4YZ7"
FT DISULFID 43..95
FT /evidence="ECO:0000269|PubMed:19616648,
FT ECO:0000269|PubMed:22205953, ECO:0000269|PubMed:26192963,
FT ECO:0007744|PDB:2OK9, ECO:0007744|PDB:3QNL,
FT ECO:0007744|PDB:4YU7, ECO:0007744|PDB:4YZ7"
FT DISULFID 49..121
FT /evidence="ECO:0000269|PubMed:19616648,
FT ECO:0000269|PubMed:22205953, ECO:0000269|PubMed:26192963,
FT ECO:0007744|PDB:2OK9, ECO:0007744|PDB:3QNL,
FT ECO:0007744|PDB:4YU7, ECO:0007744|PDB:4YZ7"
FT DISULFID 50..88
FT /evidence="ECO:0000269|PubMed:19616648,
FT ECO:0000269|PubMed:22205953, ECO:0000269|PubMed:26192963,
FT ECO:0007744|PDB:2OK9, ECO:0007744|PDB:3QNL,
FT ECO:0007744|PDB:4YU7, ECO:0007744|PDB:4YZ7"
FT DISULFID 57..81
FT /evidence="ECO:0000269|PubMed:19616648,
FT ECO:0000269|PubMed:22205953, ECO:0000269|PubMed:26192963,
FT ECO:0007744|PDB:2OK9, ECO:0007744|PDB:3QNL,
FT ECO:0007744|PDB:4YU7, ECO:0007744|PDB:4YZ7"
FT DISULFID 75..86
FT /evidence="ECO:0000269|PubMed:19616648,
FT ECO:0000269|PubMed:22205953, ECO:0000269|PubMed:26192963,
FT ECO:0007744|PDB:2OK9, ECO:0007744|PDB:3QNL,
FT ECO:0007744|PDB:4YU7, ECO:0007744|PDB:4YZ7"
FT HELIX 2..13
FT /evidence="ECO:0007829|PDB:4YU7"
FT HELIX 17..21
FT /evidence="ECO:0007829|PDB:4YU7"
FT STRAND 22..24
FT /evidence="ECO:0007829|PDB:2OK9"
FT TURN 25..27
FT /evidence="ECO:0007829|PDB:4YU7"
FT STRAND 28..31
FT /evidence="ECO:0007829|PDB:4YU7"
FT HELIX 39..52
FT /evidence="ECO:0007829|PDB:4YU7"
FT TURN 59..61
FT /evidence="ECO:0007829|PDB:4YU7"
FT STRAND 66..69
FT /evidence="ECO:0007829|PDB:4YU7"
FT STRAND 72..75
FT /evidence="ECO:0007829|PDB:4YU7"
FT HELIX 80..98
FT /evidence="ECO:0007829|PDB:4YU7"
FT HELIX 99..102
FT /evidence="ECO:0007829|PDB:4YU7"
FT HELIX 105..107
FT /evidence="ECO:0007829|PDB:4YU7"
FT HELIX 112..114
FT /evidence="ECO:0007829|PDB:4YU7"
SQ SEQUENCE 121 AA; 13729 MW; B51C1BB79639893B CRC64;
SLFELGKMIL QETGKNPAKS YGAYGCNCGV LGRGKPKDAT DRCCYVHKCC YKKLTGCNPK
KDRYSYSWKD KTIVCGENNP CLKELCECDK AVAICLRENL GTYNKLYRYH LKPFCKKADD
C
