PA2H3_BOTPI
ID PA2H3_BOTPI Reviewed; 120 AA.
AC P58464;
DT 13-DEC-2001, integrated into UniProtKB/Swiss-Prot.
DT 13-DEC-2001, sequence version 1.
DT 25-MAY-2022, entry version 100.
DE RecName: Full=Basic phospholipase A2 homolog piratoxin-3;
DE Short=svPLA2 homolog;
DE AltName: Full=MP-III 4R {ECO:0000303|PubMed:10395455};
DE AltName: Full=Piratoxin-III {ECO:0000303|PubMed:12554936};
DE Short=PrTX-III {ECO:0000303|PubMed:12554936};
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, FUNCTION, AND SUBCELLULAR LOCATION.
RC TISSUE=Venom;
RX PubMed=10395455; DOI=10.1023/a:1021051831740;
RA Toyama M.H., Costa P.D., Novello J.C., de Oliveira B., Giglio J.R.,
RA da Cruz-Hofling M.A., Marangoni S.;
RT "Purification and amino acid sequence of MP-III 4R D49 phospholipase A2
RT from Bothrops pirajai snake venom, a toxin with moderate PLA2 and
RT anticoagulant activities and high myotoxic activity.";
RL J. Protein Chem. 18:371-378(1999).
RN [2]
RP IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=23385358; DOI=10.1016/j.jprot.2013.01.021;
RA Bernardes C.P., Menaldo D.L., Camacho E., Rosa J.C., Escalante T.,
RA Rucavado A., Lomonte B., Gutierrez J.M., Sampaio S.V.;
RT "Proteomic analysis of Bothrops pirajai snake venom and characterization of
RT BpirMP, a new P-I metalloproteinase.";
RL J. Proteomics 80:250-267(2013).
RN [3] {ECO:0000312|PDB:1GMZ}
RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 1-106, AND DISULFIDE BONDS.
RX PubMed=12554936; DOI=10.1107/s0907444902021467;
RA Rigden D.J., Hwa L.W., Marangoni S., Toyama M.H., Polikarpov I.;
RT "The structure of the D49 phospholipase A2 piratoxin III from Bothrops
RT pirajai reveals unprecedented structural displacement of the calcium-
RT binding loop: possible relationship to cooperative substrate binding.";
RL Acta Crystallogr. D 59:255-262(2003).
CC -!- FUNCTION: Snake venom phospholipase A2 (PLA2) that lacks enzymatic
CC activity. Shows high myotoxin activities (PubMed:10395455). Also has
CC anticoagulant activity (PubMed:10395455). A model of myotoxic mechanism
CC has 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:10395455}.
CC -!- SUBUNIT: Homodimer; non-covalently linked (probable alternative/compact
CC dimer conformation). {ECO:0000250|UniProtKB:P45881,
CC ECO:0000269|PubMed:12554936}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:10395455}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC {ECO:0000305|PubMed:10395455}.
CC -!- SIMILARITY: Belongs to the phospholipase A2 family. Group II subfamily.
CC D49 sub-subfamily. {ECO:0000305}.
CC -!- CAUTION: Shows no or low enzymatic activity even tough it conserves the
CC catalytic residues. This may be due to the distorsion of the calcium
CC binding loop. {ECO:0000305|PubMed:12554936}.
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DR PDB; 1GMZ; X-ray; 2.40 A; A/B=1-120.
DR PDBsum; 1GMZ; -.
DR AlphaFoldDB; P58464; -.
DR SMR; P58464; -.
DR EvolutionaryTrace; P58464; -.
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 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; Blood coagulation cascade inhibiting toxin;
KW Direct protein sequencing; Disulfide bond; Hemostasis impairing toxin;
KW Myotoxin; Secreted; Toxin.
FT CHAIN 1..120
FT /note="Basic phospholipase A2 homolog piratoxin-3"
FT /id="PRO_0000161629"
FT REGION 104..115
FT /note="Important for membrane-damaging activities in
FT eukaryotes and bacteria; heparin-binding"
FT /evidence="ECO:0000250|UniProtKB:P24605"
FT SITE 3
FT /note="Putative membrane-disrupting site (MDiS)"
FT /evidence="ECO:0000250|UniProtKB:P20474"
FT SITE 10
FT /note="Putative membrane-disrupting site (MDiS)"
FT /evidence="ECO:0000250|UniProtKB:P20474"
FT SITE 15
FT /note="Putative membrane-disrupting site (MDiS)"
FT /evidence="ECO:0000250|UniProtKB:P20474"
FT SITE 16
FT /note="Putative membrane-disrupting site (MDiS)"
FT /evidence="ECO:0000250|UniProtKB:P20474"
FT SITE 63
FT /note="Putative cationic membrane-docking site (MDoS)"
FT /evidence="ECO:0000250|UniProtKB:P20474"
FT SITE 104
FT /note="Important residue of the cationic membrane-docking
FT site (MDoS)"
FT /evidence="ECO:0000250|UniProtKB:I6L8L6"
FT SITE 107
FT /note="Important residue of the cationic membrane-docking
FT site (MDoS)"
FT /evidence="ECO:0000250|UniProtKB:I6L8L6"
FT SITE 110
FT /note="Hydrophobic membrane-disruption site (MDiS)"
FT /evidence="ECO:0000250|UniProtKB:I6L8L6"
FT SITE 111
FT /note="Cationic membrane-docking site (MDoS)"
FT /evidence="ECO:0000250|UniProtKB:I6L8L6"
FT DISULFID 26..113
FT /evidence="ECO:0000269|PubMed:12554936,
FT ECO:0007744|PDB:1GMZ"
FT DISULFID 28..44
FT /evidence="ECO:0000269|PubMed:12554936,
FT ECO:0007744|PDB:1GMZ"
FT DISULFID 43..94
FT /evidence="ECO:0000269|PubMed:12554936,
FT ECO:0007744|PDB:1GMZ"
FT DISULFID 49..120
FT /evidence="ECO:0000269|PubMed:12554936,
FT ECO:0007744|PDB:1GMZ"
FT DISULFID 50..87
FT /evidence="ECO:0000269|PubMed:12554936,
FT ECO:0007744|PDB:1GMZ"
FT DISULFID 57..81
FT /evidence="ECO:0000269|PubMed:12554936,
FT ECO:0007744|PDB:1GMZ"
FT DISULFID 75..85
FT /evidence="ECO:0000269|PubMed:12554936,
FT ECO:0007744|PDB:1GMZ"
FT HELIX 2..13
FT /evidence="ECO:0007829|PDB:1GMZ"
FT HELIX 17..20
FT /evidence="ECO:0007829|PDB:1GMZ"
FT TURN 21..23
FT /evidence="ECO:0007829|PDB:1GMZ"
FT TURN 25..27
FT /evidence="ECO:0007829|PDB:1GMZ"
FT HELIX 28..30
FT /evidence="ECO:0007829|PDB:1GMZ"
FT HELIX 39..52
FT /evidence="ECO:0007829|PDB:1GMZ"
FT TURN 58..60
FT /evidence="ECO:0007829|PDB:1GMZ"
FT HELIX 80..97
FT /evidence="ECO:0007829|PDB:1GMZ"
FT HELIX 99..101
FT /evidence="ECO:0007829|PDB:1GMZ"
FT HELIX 104..106
FT /evidence="ECO:0007829|PDB:1GMZ"
SQ SEQUENCE 120 AA; 13834 MW; 47604E612E824592 CRC64;
DLWQFGQMIL KETGKLPFPY YTYGGCYCGV GGRRGLGTKD DRCCYVHDCC YKKLTGCPKT
DDRYSYSWLD LTIVCGEDDP CKELCECDKA IAVCFRENLG TYNKKYRYHL KPCKKADKPC
