PA2H2_BOTPI
ID PA2H2_BOTPI Reviewed; 121 AA.
AC P82287;
DT 16-NOV-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 25-MAY-2022, entry version 100.
DE RecName: Full=Basic phospholipase A2 homolog piratoxin-2;
DE Short=svPLA2 homolog;
DE AltName: Full=Piratoxin-II {ECO:0000303|PubMed:10863008};
DE Short=PrTX-II {ECO:0000303|PubMed:10863008};
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=10863008; DOI=10.1016/s0300-9084(00)00202-9;
RA Toyama M.H., Soares A.M., Lee W.-H., Polikarpov I., Giglio J.R.,
RA Marangoni S.;
RT "Amino acid sequence of piratoxin-II, a myotoxic Lys49 phospholipase A2
RT homologue from Bothrops piraja venom.";
RL Biochimie 82:245-250(2000).
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:1QLL}
RP X-RAY CRYSTALLOGRAPHY (2.04 ANGSTROMS) OF 1-119 IN COMPLEX WITH FATTY ACID,
RP AND DISULFIDE BONDS.
RX PubMed=11141053; DOI=10.1021/bi0010470;
RA Lee W.-H., da Silva Giotto M.T., Marangoni S., Toyama M.H., Polikarpov I.,
RA Garratt R.C.;
RT "Structural basis for low catalytic activity in Lys49 phospholipases A2
RT -- a hypothesis: the crystal structure of piratoxin II complexed to fatty
RT acid.";
RL Biochemistry 40:28-36(2001).
RN [4] {ECO:0000312|PDB:2Q2J, ECO:0000312|PDB:3CYL}
RP X-RAY CRYSTALLOGRAPHY (1.65 ANGSTROMS) ALONE AND IN COMPLEX WITH
RP ALPHA-TOCOPHEROL (VITAMIN E), 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).
CC -!- FUNCTION: Snake venom phospholipase A2 (PLA2) homolog that lacks
CC enzymatic activity (PubMed:10863008). Shows myotoxic activity and
CC edema-inducing activities in vivo (PubMed:10863008). A model of
CC myotoxic mechanism has been proposed: an apo Lys49-PLA2 is activated by
CC 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 (By similarity). This reorientation causes a transition between
CC 'inactive' to 'active' states, causing alignment of C-terminal and
CC membrane-docking sites (MDoS) side-by-side and putting the membrane-
CC disruption sites (MDiS) in the same plane, exposed to solvent and in a
CC symmetric position for both monomers (By similarity). The MDoS region
CC stabilizes the toxin on membrane by the interaction of charged residues
CC with phospholipid head groups (By similarity). Subsequently, the MDiS
CC region destabilizes the membrane with penetration of hydrophobic
CC residues (By similarity). This insertion causes a disorganization of
CC the membrane, allowing an uncontrolled influx of ions (i.e. calcium and
CC sodium), and eventually triggering irreversible intracellular
CC alterations and cell death (By similarity).
CC {ECO:0000250|UniProtKB:I6L8L6, ECO:0000269|PubMed:10863008}.
CC -!- SUBUNIT: Homodimer; non-covalently linked. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:10863008}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC {ECO:0000305|PubMed:10863008}.
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}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR PDB; 1QLL; X-ray; 2.04 A; A/B=1-119.
DR PDB; 2Q2J; X-ray; 1.65 A; A/B=1-121.
DR PDB; 3CYL; X-ray; 1.87 A; A/B=1-121.
DR PDBsum; 1QLL; -.
DR PDBsum; 2Q2J; -.
DR PDBsum; 3CYL; -.
DR AlphaFoldDB; P82287; -.
DR SMR; P82287; -.
DR EvolutionaryTrace; P82287; -.
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 Secreted; Toxin.
FT CHAIN 1..121
FT /note="Basic phospholipase A2 homolog piratoxin-2"
FT /id="PRO_0000161628"
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 DISULFID 26..115
FT /evidence="ECO:0000269|PubMed:11141053,
FT ECO:0000269|PubMed:19401234, ECO:0007744|PDB:1QLL,
FT ECO:0007744|PDB:2Q2J"
FT DISULFID 28..44
FT /evidence="ECO:0000269|PubMed:11141053,
FT ECO:0000269|PubMed:19401234, ECO:0007744|PDB:1QLL,
FT ECO:0007744|PDB:2Q2J"
FT DISULFID 43..95
FT /evidence="ECO:0000269|PubMed:11141053,
FT ECO:0000269|PubMed:19401234, ECO:0007744|PDB:1QLL,
FT ECO:0007744|PDB:2Q2J"
FT DISULFID 49..121
FT /evidence="ECO:0000269|PubMed:11141053,
FT ECO:0000269|PubMed:19401234, ECO:0007744|PDB:1QLL,
FT ECO:0007744|PDB:2Q2J"
FT DISULFID 50..88
FT /evidence="ECO:0000269|PubMed:11141053,
FT ECO:0000269|PubMed:19401234, ECO:0007744|PDB:1QLL,
FT ECO:0007744|PDB:2Q2J"
FT DISULFID 57..81
FT /evidence="ECO:0000269|PubMed:11141053,
FT ECO:0000269|PubMed:19401234, ECO:0007744|PDB:1QLL,
FT ECO:0007744|PDB:2Q2J"
FT DISULFID 75..86
FT /evidence="ECO:0000269|PubMed:11141053,
FT ECO:0000269|PubMed:19401234, ECO:0007744|PDB:1QLL,
FT ECO:0007744|PDB:2Q2J"
FT HELIX 2..13
FT /evidence="ECO:0007829|PDB:2Q2J"
FT HELIX 17..21
FT /evidence="ECO:0007829|PDB:2Q2J"
FT STRAND 22..24
FT /evidence="ECO:0007829|PDB:2Q2J"
FT TURN 25..27
FT /evidence="ECO:0007829|PDB:2Q2J"
FT STRAND 28..31
FT /evidence="ECO:0007829|PDB:2Q2J"
FT HELIX 39..53
FT /evidence="ECO:0007829|PDB:2Q2J"
FT TURN 59..61
FT /evidence="ECO:0007829|PDB:2Q2J"
FT STRAND 66..68
FT /evidence="ECO:0007829|PDB:3CYL"
FT HELIX 69..71
FT /evidence="ECO:0007829|PDB:2Q2J"
FT HELIX 80..98
FT /evidence="ECO:0007829|PDB:2Q2J"
FT HELIX 99..102
FT /evidence="ECO:0007829|PDB:2Q2J"
FT HELIX 105..107
FT /evidence="ECO:0007829|PDB:2Q2J"
FT HELIX 112..114
FT /evidence="ECO:0007829|PDB:3CYL"
SQ SEQUENCE 121 AA; 13744 MW; 154C1BB79639893D CRC64;
SLFELGKMIL QETGKNPAKS YGAYGCNCGV LGRGKPKDAT DRCCYVHKCC YKKLTGCNPK
KDRYSYSWKD KTIVCGENNP CLKELCECDK AVAICLRENL GTYNKKYRYH LKPFCKKADD
C
