PA2HA_BOTAS
ID PA2HA_BOTAS Reviewed; 137 AA.
AC P0C616; B0FM89;
DT 15-JAN-2008, integrated into UniProtKB/Swiss-Prot.
DT 15-JAN-2008, sequence version 1.
DT 25-MAY-2022, entry version 45.
DE RecName: Full=Basic phospholipase A2 homolog 4a;
DE Short=svPLA2 homolog;
DE AltName: Full=Myotoxin IVa {ECO:0000303|PubMed:11240369};
DE Short=MT-IVa {ECO:0000303|PubMed:11240369};
DE Flags: Precursor;
OS Bothrops asper (Terciopelo).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Lepidosauria; Squamata; Bifurcata; Unidentata; Episquamata; Toxicofera;
OC Serpentes; Colubroidea; Viperidae; Crotalinae; Bothrops.
OX NCBI_TaxID=8722;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE, AND SUBCELLULAR
RP LOCATION.
RC TISSUE=Venom, and Venom gland;
RX PubMed=11240369; DOI=10.1016/s1357-2725(00)00073-x;
RA Lizano S., Lambeau G., Lazdunski M.;
RT "Cloning and cDNA sequence analysis of Lys(49) and Asp(49) basic
RT phospholipase A(2) myotoxin isoforms from Bothrops asper.";
RL Int. J. Biochem. Cell Biol. 33:127-132(2001).
CC -!- FUNCTION: Snake venom phospholipase A2 homolog that lacks enzymatic
CC activity (By similarity). Is myotoxic and displays edema-inducing
CC activities (By similarity). A model of myotoxic mechanism has been
CC 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:0000250|UniProtKB:Q90249}.
CC -!- SUBUNIT: Homodimer; non-covalently linked.
CC {ECO:0000250|UniProtKB:Q90249}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:11240369}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC {ECO:0000305|PubMed:11240369}.
CC -!- SIMILARITY: Belongs to the phospholipase A2 family. Group II subfamily.
CC K49 sub-subfamily. {ECO:0000305}.
CC -!- CAUTION: Does not bind calcium as three of the calcium binding ligands
CC are lost. {ECO:0000305}.
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DR EMBL; EU336943; ABY55159.1; -; mRNA.
DR AlphaFoldDB; P0C616; -.
DR SMR; P0C616; -.
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 CHAIN 17..137
FT /note="Basic phospholipase A2 homolog 4a"
FT /id="PRO_0000314776"
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 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; 15688 MW; 1DAC6BCF5FD60F7E CRC64;
MRTLWIVTVL LVGVEGSLVE LGKMILQETG KNPLTSYGVY GCNCGVGGRH KPKDGTDRCC
YVHKCCYKKM TDCDPKKDRY SYSWKDKTIV CDENNPCLKE LCECDKAVAI CLRENLDTYN
KKYKIYPKFF CKKAEPC
