PA2H_BOTSC
ID PA2H_BOTSC Reviewed; 137 AA.
AC P80963; Q8UVU8;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 25-NOV-2002, sequence version 2.
DT 25-MAY-2022, entry version 87.
DE RecName: Full=Basic phospholipase A2 homolog Bsc-K49 {ECO:0000303|PubMed:11594738};
DE Short=svPLA2 homolog;
DE AltName: Full=Myotoxin I {ECO:0000303|PubMed:9056257};
DE Flags: Precursor;
OS Bothriechis schlegelii (Eyelash palm pitviper).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Lepidosauria; Squamata; Bifurcata; Unidentata; Episquamata; Toxicofera;
OC Serpentes; Colubroidea; Viperidae; Crotalinae; Bothriechis.
OX NCBI_TaxID=44725;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 17-45, MASS SPECTROMETRY,
RP AND SUBCELLULAR LOCATION.
RC TISSUE=Venom, and Venom gland;
RX PubMed=11594738; DOI=10.1006/abbi.2001.2524;
RA Tsai I.-H., Chen Y.-H., Wang Y.-M., Tu M.-C., Tu A.T.;
RT "Purification, sequencing, and phylogenetic analyses of novel Lys-49
RT phospholipases A(2) from the venoms of rattlesnakes and other pit vipers.";
RL Arch. Biochem. Biophys. 394:236-244(2001).
RN [2]
RP PROTEIN SEQUENCE OF 17-41, FUNCTION, SUBUNIT, SUBCELLULAR LOCATION, AND
RP TOXIC DOSE.
RC TISSUE=Venom;
RX PubMed=9056257; DOI=10.1006/abbi.1996.9865;
RA Angulo Y., Chaves E., Alape A., Rucavado A., Gutierrez J.M., Lomonte B.;
RT "Isolation and characterization of a myotoxic phospholipase A2 from the
RT venom of the arboreal snake Bothriechis (Bothrops) schlegelii from Costa
RT Rica.";
RL Arch. Biochem. Biophys. 339:260-266(1997).
CC -!- FUNCTION: Snake venom phospholipase A2 that lacks enzymatic activity.
CC Is myotoxic, and displays edema-inducing activities (PubMed:9056257). A
CC model of myotoxic mechanism has been proposed: an apo Lys49-PLA2 is
CC activated by the entrance of a hydrophobic molecule (e.g. fatty acid)
CC at the hydrophobic channel of the protein leading to a reorientation of
CC a monomer (By similarity). This reorientation causes a transition
CC between 'inactive' to 'active' states, causing alignment of C-terminal
CC and membrane-docking sites (MDoS) side-by-side and putting the
CC membrane-disruption sites (MDiS) in the same plane, exposed to solvent
CC and in a symmetric position for both monomers (By similarity). The MDoS
CC region stabilizes the toxin on membrane by the interaction of charged
CC residues with phospholipid head groups (By similarity). Subsequently,
CC the MDiS region destabilizes the membrane with penetration of
CC hydrophobic residues (By similarity). This insertion causes a
CC disorganization of the membrane, allowing an uncontrolled influx of
CC ions (i.e. calcium and sodium), and eventually triggering irreversible
CC intracellular alterations and cell death (By similarity).
CC {ECO:0000250|UniProtKB:I6L8L6, ECO:0000269|PubMed:9056257}.
CC -!- SUBUNIT: Homodimer; non-covalently linked.
CC {ECO:0000250|UniProtKB:I6L8L6, ECO:0000269|PubMed:9056257}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:11594738,
CC ECO:0000269|PubMed:9056257}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC {ECO:0000305|PubMed:11594738, ECO:0000305|PubMed:9056257}.
CC -!- MASS SPECTROMETRY: Mass=13671; Method=Electrospray;
CC Evidence={ECO:0000269|PubMed:11594738};
CC -!- TOXIC DOSE: LD(50) is 2.5 mg/kg by intravenous injection into mice.
CC {ECO:0000269|PubMed:9056257}.
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 64, which corresponds to 'Lys-49' in the
CC current nomenclature). {ECO:0000305}.
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DR EMBL; AF374236; AAL39065.1; -; mRNA.
DR AlphaFoldDB; P80963; -.
DR SMR; P80963; -.
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 Direct protein sequencing; Disulfide bond; Myotoxin; Secreted; Signal;
KW Toxin.
FT SIGNAL 1..16
FT /evidence="ECO:0000269|PubMed:11594738,
FT ECO:0000269|PubMed:9056257"
FT CHAIN 17..137
FT /note="Basic phospholipase A2 homolog Bsc-K49"
FT /id="PRO_0000022822"
FT REGION 121..133
FT /note="Important for membrane-damaging activities in
FT eukaryotes and bacteria; heparin-binding"
FT /evidence="ECO:0000250|UniProtKB:P24605"
FT SITE 121
FT /note="Important residue of the cationic membrane-docking
FT site (MDoS)"
FT /evidence="ECO:0000250|UniProtKB:I6L8L6"
FT SITE 124
FT /note="Important residue of the cationic membrane-docking
FT site (MDoS)"
FT /evidence="ECO:0000250|UniProtKB:I6L8L6"
FT SITE 127
FT /note="Hydrophobic membrane-disruption site (MDiS)"
FT /evidence="ECO:0000250|UniProtKB:I6L8L6"
FT SITE 128
FT /note="Cationic membrane-docking site (MDoS)"
FT /evidence="ECO:0000250|UniProtKB:I6L8L6"
FT SITE 130
FT /note="Hydrophobic membrane-disruption site (MDiS)"
FT /evidence="ECO:0000250|UniProtKB:I6L8L6"
FT SITE 133
FT /note="Cationic membrane-docking site (MDoS)"
FT /evidence="ECO:0000250|UniProtKB:I6L8L6"
FT DISULFID 42..131
FT /evidence="ECO:0000250|UniProtKB:Q90249"
FT DISULFID 44..60
FT /evidence="ECO:0000250|UniProtKB:Q90249"
FT DISULFID 59..111
FT /evidence="ECO:0000250|UniProtKB:Q90249"
FT DISULFID 65..137
FT /evidence="ECO:0000250|UniProtKB:Q90249"
FT DISULFID 66..104
FT /evidence="ECO:0000250|UniProtKB:Q90249"
FT DISULFID 73..97
FT /evidence="ECO:0000250|UniProtKB:Q90249"
FT DISULFID 91..102
FT /evidence="ECO:0000250|UniProtKB:Q90249"
SQ SEQUENCE 137 AA; 15285 MW; 0D588DE1AC84D00D CRC64;
MRTLWIVAVL LVGVEGSMYE LGKMILLETG KNAATSYIAY GCNCGVGRRG QPLDATDRCC
YVHKCCYKKL TGCNPLTDRY SHSLKNKTIV CGENKPCLKE MCECDKALAI CLGKNVNTYN
KNYKITMKMF CKKPDAC
