PA2H2_BOTMA
ID PA2H2_BOTMA Reviewed; 106 AA.
AC P0DUP9;
DT 02-JUN-2021, integrated into UniProtKB/Swiss-Prot.
DT 02-JUN-2021, sequence version 1.
DT 25-MAY-2022, entry version 4.
DE RecName: Full=Basic phospholipase A2 homolog BmajPLA2-II {ECO:0000303|PubMed:28390830};
DE Short=svPLA2 homolog;
DE Flags: Fragments;
OS Bothrops marajoensis (Marajo lancehead).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Lepidosauria; Squamata; Bifurcata; Unidentata; Episquamata; Toxicofera;
OC Serpentes; Colubroidea; Viperidae; Crotalinae; Bothrops.
OX NCBI_TaxID=157554;
RN [1]
RP PROTEIN SEQUENCE, FUNCTION, MASS SPECTROMETRY, SUBUNIT, AND SUBCELLULAR
RP LOCATION.
RC TISSUE=Venom;
RX PubMed=28390830; DOI=10.1016/j.ijbiomac.2017.04.013;
RA Grabner A.N., Alfonso J., Kayano A.M., Moreira-Dill L.S.,
RA Dos Santos A.P.A., Caldeira C.A.S., Sobrinho J.C., Gomez A., Grabner F.P.,
RA Cardoso F.F., Zuliani J.P., Fontes M.R.M., Pimenta D.C., Gomez C.V.,
RA Teles C.B.G., Soares A.M., Calderon L.A.;
RT "BmajPLA2-II, a basic Lys49-phospholipase A2 homologue from Bothrops
RT marajoensis snake venom with parasiticidal potential.";
RL Int. J. Biol. Macromol. 102:571-581(2017).
CC -!- FUNCTION: Snake venom phospholipase A2 (PLA2) homolog that lacks
CC enzymatic activity (PubMed:28390830). Shows high myotoxin activities
CC (By similarity). Also shows neurotoxicity, since it induces muscle
CC paralysis when tested on mouse phrenic-diaphragm preparations (By
CC similarity). Displays edema-inducing activities (By similarity). Also
CC displays antimicrobial activity against E.coli and C.albicans, as well
CC as antitumoral activity against some human and mice cell lines (By
CC similarity). In addition, it is effective as parasiticidal agent
CC against Leishmania infantum promastigotes and Trypanosoma cruzi
CC epimastigotes (PubMed:28390830). It also disrupts negatively charged
CC liposomes in a dose- and temperature-dependent manner and shows
CC toxicity by intraperitoneal route (By similarity). In contrast to other
CC phospholipase A2-like toxins, this myotoxin does not require fatty acid
CC binding to be active (By similarity). A model of myotoxic mechanism has
CC been proposed: an apo Lys49-PLA2 is usually (but not here) 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:0000250|UniProtKB:Q9I834,
CC ECO:0000269|PubMed:28390830}.
CC -!- SUBUNIT: Monomer, and homodimer; non-covalently linked
CC (PubMed:28390830). Also found as trimer, tetramer, and pentamer
CC (PubMed:28390830). {ECO:0000269|PubMed:28390830}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:28390830}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC {ECO:0000305|PubMed:28390830}.
CC -!- MASS SPECTROMETRY: Mass=13956; Method=MALDI;
CC Evidence={ECO:0000269|PubMed:28390830};
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 39, which corresponds to 'Lys-49' in the
CC current nomenclature). {ECO:0000305}.
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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:0050832; P:defense response to fungus; IEA:UniProtKB-KW.
DR GO; GO:0031640; P:killing of cells of another organism; IEA:UniProtKB-KW.
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 PANTHER; PTHR11716; PTHR11716; 1.
DR Pfam; PF00068; Phospholip_A2_1; 1.
DR SMART; SM00085; PA2c; 1.
DR SUPFAM; SSF48619; SSF48619; 1.
PE 1: Evidence at protein level;
KW Antibiotic; Antimicrobial; Direct protein sequencing; Disulfide bond;
KW Fungicide; Myotoxin; Neurotoxin; Postsynaptic neurotoxin; Secreted; Toxin.
FT CHAIN 1..>106
FT /note="Basic phospholipase A2 homolog BmajPLA2-II"
FT /evidence="ECO:0000269|PubMed:28390830"
FT /id="PRO_0000453022"
FT SITE 15
FT /note="Cationic membrane-docking site (MDoS)"
FT /evidence="ECO:0000250|UniProtKB:Q9I834"
FT SITE 19
FT /note="Cationic membrane-docking site (MDoS)"
FT /evidence="ECO:0000250|UniProtKB:Q9I834"
FT SITE 96
FT /note="Important residue of the cationic membrane-docking
FT site (MDoS)"
FT /evidence="ECO:0000250|UniProtKB:I6L8L6,
FT ECO:0000250|UniProtKB:Q9I834"
FT SITE 103
FT /note="Hydrophobic membrane-disruption site (MDiS)"
FT /evidence="ECO:0000250|UniProtKB:I6L8L6"
FT SITE 104
FT /note="Cationic membrane-docking site (MDoS)"
FT /evidence="ECO:0000250|UniProtKB:I6L8L6"
FT SITE 106
FT /note="Hydrophobic membrane-disruption site (MDiS)"
FT /evidence="ECO:0000250|UniProtKB:I6L8L6"
FT DISULFID 26..?
FT /evidence="ECO:0000250|UniProtKB:Q9I834"
FT DISULFID 28..35
FT /evidence="ECO:0000250|UniProtKB:Q9I834"
FT DISULFID 34..86
FT /evidence="ECO:0000250|UniProtKB:Q9I834"
FT DISULFID 48..72
FT /evidence="ECO:0000250|UniProtKB:Q9I834"
FT DISULFID 66..77
FT /evidence="ECO:0000250|UniProtKB:Q9I834"
FT DISULFID 79..?
FT /evidence="ECO:0000250|UniProtKB:Q9I834"
FT NON_CONS 33..34
FT /evidence="ECO:0000305|PubMed:28390830"
FT NON_TER 106
FT /evidence="ECO:0000305|PubMed:28390830"
SQ SEQUENCE 106 AA; 11997 MW; 94B3A49700E1985F CRC64;
NLWQLGKMIL LETGKIPAKS YGAYGCNCGV LGRCCYVHKX XXXKLTGCDP KXXXYSYSWK
XXTIVCGENN SCLKELCECD KAVAICLREN LDTYNKXXXY NYLKPF
